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Background: Solid-predominant lung adenocarcinoma (SPA), which is one of the high-risk subtypes with poor prognosis and unsatisfactory response to chemotherapy and targeted therapy in lung adenocarcinoma, remains molecular profile unclarified. Weighted correlation network analysis (WGCNA) was used for data mining, especially for studying biological networks based on pairwise correlations between variables. This study aimed to identify disease-related protein co-expression networks associated with early-stage SPA., Methods: We assessed cancerous cells laser-microdissected from formalin-fixed paraffin-embedded (FFPE) tissues of a SPA group ( n = 5), referencing a low-risk subtype, a lepidic predominant subtype group (LPA) ( n = 4), and another high-risk subtype, micropapillary predominant subtype (MPA) group ( n = 3) and performed mass spectrometry-based proteomic analysis. Disease-related co-expression networks associated with the SPA subtype were identified by WGCNA and their upstream regulators and causal networks were predicted by Ingenuity Pathway Analysis., Results: Among the forty WGCNA network modules identified, two network modules were found to be associated significantly with the SPA subtype. Canonical enriched pathways were highly associated with cellular growth, proliferation, and immune response. Upregulated HLA class I molecules HLA-G and HLA-B implicated high mutation burden and T cell activation in the SPA subtype. Upstream analysis implicated the involvement of highly activated oncogenic regulators, MYC, MLXIPL, MYCN, the redox master regulator NFE2L2, and the highly inhibited LARP1, leading to oncogenic IRES-dependent translation, and also regulators of the adaptive immune response, including highly activated IFNG, TCRD, CD3-TCR, CD8A, CD8B, CD3, CD80/CD86, and highly inhibited LILRB2. Interestingly, the immune checkpoint molecule HLA-G, which is the counterpart of LILRB2, was highly expressed characteristically in the SPA subtype and might be associated with antitumor immunity., Conclusion: Our findings provide a disease molecular profile based on protein co-expression networks identified for the high-risk solid predominant adenocarcinoma, which will help develop future therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nishimura, Végvári, Nakamura, Fujii, Sakai, Naruki, Furuya and Saji.)

Background: Although segmentectomy was better than lobectomy in terms of overall survival for patients with non-small-cell lung cancer (NSCLC) with a pure-solid tumour appearance on thin-section CT in the open-label, multicentre, randomised, controlled, phase 3 JCOG0802/WJOG4607L trial, the reasons why segmentectomy was associated with better overall survival were unclear. We aimed to compare the survival, cause of death, and recurrence patterns after segmentectomy versus lobectomy in trial participants with NSCLC with a pure-solid appearance METHODS: We conducted a post-hoc supplemental analysis of the JCO0802/WJOG4607L randomised, controlled, non-inferiority trial for the patients (aged 20-85 years) with small-sized NSCLC with radiologically pure-solid appearance on thin-section CT (≤2 cm, consolidation tumour ratio 1·0). The primary aim was to compare the overall and relapse-free survival, cause of death, and recurrence patterns associated with segmentectomy and lobectomy for patients with radiologically pure-solid NSCLC to determine why the overall survival of segmentectomy was superior to that of lobectomy, even for oncologically invasive lung cancers. JCO0802/WJOG4607L is registered with the UMIN Clinical Trials Registry, UMIN000002317, and is complete., Findings: Between Aug 10, 2009, and Oct 21, 2014, 1106 patients were randomly assigned to undergo either lobectomy or segmentectomy. Of these participants, 553 (50%) had radiologically pure-solid NSCLC and were eligible for this post-hoc supplemental analysis. Of these 553 participants, 274 (50%) patients underwent lobectomy and 279 (50%) underwent segmentectomy. Median patient age was 67 years (IQR 61-73), 347 (63%) of 553 patients were male and 206 (37%) were female, and data on race and ethnicity were not collected. As of data cutoff (June 13, 2020), after a median follow-up of 7·3 years (IQR 6·0-8·5), the 5-year overall survival rate was significantly higher after segmentectomy than after lobectomy (86·1% [95% CI 81·4-89·7] in the lobectomy group, with 55 deaths vs 92·4% [88·6-95·0] in the segmentectomy group, with 38 deaths; hazard ratio (HR) 0·64 [95% CI 0·41-0·97]; log-rank test p=0·033), whereas the 5-year relapse-free survival was similar between the groups (81·7% [95% CI 76·5-85·8], with 34 events vs 82·0% [76·9-86·0], with 52 events; HR 1·01 [95% CI 0·72-1·42]; p=0·94). Deaths after a median follow-up of 7·3 years due to lung cancer occurred in 20 (7%) of 274 patients after lobectomy and 19 (7%) of 279 after segmentectomy, and deaths due to other causes occurred in 35 (13%) patients after lobectomy compared with 19 (7%) after segmentectomy (lung cancer death vs other cause of death, p=0·19). The locoregional recurrence was higher after segmentectomy (21 [8%] vs 45 [16%]; p=0·0021). In subgroup analyses, better 5-year overall survival after segmentectomy than after lobectomy was observed in the subgroup of patients aged 70 years or older (77·1% [95% CI 68·2-83·8] with lobectomy vs 85·6% [77·5-90·9] with segmentectomy; p=0·013) and in male patients (80·5% [73·7-85·7] vs 92·1% [87·0-95·2]; p=0·0085). By contrast, better 5-year relapse-free survival after lobectomy than after segmentectomy was observed in the subgroup younger than 70 years (87·4% [95% CI 81·2-91·7] with lobectomy vs 84·4% [77·9-89·1] with segmentectomy; p=0·049) and in female patients (94·2% [87·6-97·4] vs 82·2% [73·2-88·4]; p=0·047)., Interpretation: This post-hoc analysis showed improved overall survival after segmentectomy in patients with pure-solid NSCLC compared with lobectomy. However, survival outcomes of segmentectomy depend on the patient's age and sex. Given the results of this exploratory analysis, further research is necessary to determine clinically relevant indications for segmentectomy in radiologically pure-solid NSCLC., Funding: Japanese National Cancer Center Research and Development Fund and Practical Research for Innovative Cancer Control Fund, and a Grant-in-Aid for Scientific Research from the Ministry of Health, Labor, and Welfare of Japan., Competing Interests: Declaration of interests AH, KS, KT, YT, RN, KA, HS, MT, MO, HA, and SW report research funding from the National Cancer Center Research and Development Fund by the National Cancer Center, Practical Research for Innovative Cancer Control Fund by Japan Agency for Medical Research and Development and a Grant-in-Aid for Scientific Research from the Ministry of Health, Labor, and Welfare of Japan. MW reports honoraria from Nihon Medi-Physics. HS reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from MSD, Boehringer Ingelheim, Ethicon, Covidien, Chugai Pharmaceutical, Astellas Pharma, Fujifilm Medical, and Bristol Myers Squibb. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to identify the risk factors for pulmonary functional deterioration after wedge resection for early-stage lung cancer with ground-glass opacity, which remain unclear, particularly in low-risk patients., Methods: We analysed 237 patients who underwent wedge resection for peripheral early-stage lung cancer in JCOG0804/WJOG4507L, a phase III, single-arm confirmatory trial. The changes in forced expiratory volume in 1 s were calculated pre- and postoperatively, and a cutoff value of -10%, the previously reported reduction rate after lobectomy, was used to divide the patients into 2 groups: the severely reduced group (≤-10%) and normal group (>-10%). These groups were compared to identify predictors for severe reduction., Results: Thirty-seven (16%) patients experienced severe reduction. Lesions with a total tumour size ≥1 cm were significantly more frequent in the severely reduced group than in the normal group (89.2% vs 71.5%; P = 0.024). A total tumour size of ≥1 cm [odds ratio (OR), 3.287; 95% confidence interval (CI), 1.114-9.699: P = 0.031] and pleural indentation (OR, 2.474; 95% CI, 1.039-5.890: P = 0.041) were significant predictive factors in the univariable analysis. In the multivariable analysis, pleural indentation (OR, 2.667; 95% CI, 1.082-6.574; P = 0.033) was an independent predictive factor, whereas smoking status and total tumour size were marginally significant., Conclusions: Of the low-risk patients who underwent pulmonary wedge resection for early-stage lung cancer, 16% experienced severe reduction in pulmonary function. Pleural indentation may be a risk factor for severely reduced pulmonary function in pulmonary wedge resection., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: This study aimed to evaluate the long-term prognosis of patients with peripheral small ground-glass opacity-dominant lung cancer after sublobar resection. We have already reported the 5-year safety and efficacy of sublobar resection and report the long-term outcomes after a 10-year follow-up period., Methods: Between May 2009 and April 2011, 333 patients with radiologically noninvasive peripheral lung cancer were enrolled from 51 institutions (median age, 62 years at registration) and followed up until May 6, 2021. Of these patients, sublobar resections with wedge resection as the first choice were performed in 314 patients (258 wedge resections and 56 segmentectomies), conversion lobectomies were performed in 11 patients, and 8 patients were ineligible., Results: The 10-year relapse-free survival and overall survival for the 314 patients with sublobar resections were 98.6% (95% confidence interval, 96.2-99.5) and 98.5% (95% confidence interval, 96.1-99.4), respectively. There was 1 local recurrence at the resection margin. Among the patients, second cancers were observed in 43 patients (13.4%; 95% confidence interval, 9.8-17.6), of which 18 were second lung cancers (5.8%; 95% confidence interval, 3.5-8.9)., Conclusions: Peripheral ground-glass opacity-dominant lung cancer is cured by sublobar resection, with wedge resection as the first choice, and the indications for other treatment options should be further investigated. The incidence of second cancer is similar to that in the general Japanese population., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Segmentectomy is a good surgical option for peripheral, early, non-small cell lung cancer (NSCLC) ≤2 cm. However, the role of sublobar resection including wedge resection and segmentectomy remains unclear for octogenarians with >2-cm but ≤4-cm early-stage NSCLC, for which lobectomy is a standard treatment., Methods: By use of a prospective registry, 892 patients aged ≥80 years with operable lung cancer were enrolled at 82 institutions. Of these, we analyzed the clinicopathologic findings and surgical outcomes of 419 patients with NSCLC tumors of 2 to 4 cm during a median follow-up of 50.9 months between April 2015 and December 2016., Results: Five-year overall survival (OS) was slightly but not significantly worse after sublobar resection than after lobectomy in the entire cohort (54.7% [95% CI, 43.2%-93.0%] vs 66.8% [95% CI, 60.8%-72.1%]; P = .09). Multivariable Cox regression analysis of OS revealed that these surgical procedures were not independent prognostic predictors (hazard ratio, 0.8 [0.5-1.1]; P = .16). The 5-year OS was comparable between 192 patients who could tolerate lobectomy but were treated by sublobar resection or lobectomy (67.5% [95% CI, 48.8%-80.6%] vs 71.5% [95% CI, 62.9%-78.4%]; P = .79). Recurrence after sublobar resection and lobectomy was locoregional in 11 (11%) of 97 and in 23 (7%) of 322 patients, respectively., Conclusions: OS might be equivalent between sublobar resection with a secure surgical margin and lobectomy for selected patients aged ≥80 years with peripheral early-stage NSCLC tumors of 2 to 4 cm who can tolerate lobectomy., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to investigate the associated factors of insulation failure (IF) in reusable endoscopic instruments. The insulation coating of reusable endoscopic instruments underwent routine visual checks, hand washing to remove visible stains, and mechanized sterilization. We recorded the cleaning number and usage period of all instruments. The instruments were tested for IF using a detector. IF was found in eight of 69 devices (11.6%). Examining by clinical specialty, we found IF in 4 of 28 gastrointestinal (14.3%), 3 of 20 gynecological (15.0%), 1 of 12 urological (8.3%), and none of the nine thoracic devices. The median distance from the tip to the damaged part was 5 cm (3-5 cm). In the IF and the intact groups, the period of use [7 years (6-8) versus 7 years (4-8), P = 0.90] and the number of cleanings [281 (261-323) versus 261 (179-320), P = 0.27] were not significantly different. The IF group included products of three different companies; however, six of the eight (75.0%) were from the same company. Cleaning methods and usage period have a lower impact on IF. The use of reusable forceps as a monopolar device was found to pose a higher risk, requiring regular assessments., (© 2023. Springer Nature Limited.)

Background: Although segmentectomy is a widely used surgical procedure, lobectomy is the standard procedure for resectable non-small-cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and safety of segmentectomy for NSCLC up to 3 cm in size, including ground-glass opacity (GGO) and predominant GGO., Methods: A multicentre, single-arm, confirmatory phase 3 trial was conducted across 42 institutions (hospitals, university hospitals, and cancer centres) in Japan. Segmentectomy with hilar, interlobar, and intrapulmonary lymph node dissection was performed as protocol surgery for patients with a tumour diameter of up to 3 cm, including GGO and dominant GGO. Eligible patients were those aged 20-79 years with an Eastern Cooperative Oncology Group performance score of 0 or 1 and clinical stage IA tumour confirmed by thin-sliced CT. The primary endpoint was 5-year relapse-free survival (RFS). This study is registered with the University Hospital Medical Information Network Clinical Trials (UMIN000011819), and is ongoing., Findings: A total of 396 patients were registered from Sept 20, 2013, to Nov 13, 2015, of whom 357 underwent segmentectomy. At a median follow-up of 5·4 years (IQR 5·0-6·0), the 5-year RFS was 98·0% (95% CI 95·9-99·1). This finding exceeded the 87% of the pre-set threshold 5-year RFS and the primary endpoint was met. Grade 3 or 4 early postoperative complications occurred in seven patients (2%), but no grade 5 treatment-related deaths occurred., Interpretation: Segmentectomy should be considered as part of standard treatment for patients with predominantly GGO NSCLC with a tumour size of 3 cm or less in diameter, including GGO even if it exceeds 2 cm., Funding: National Cancer Centre Research and Development Fund and Japan Agency for Medical Research and Development., Competing Interests: Declaration of interests KA, AH, HI, TK, HK, TMiy, RN, YO, MO, JO, YT, and SW report research funding from the National Cancer Center Research and Development Fund by the National Cancer Center and Practical Research for Innovative Cancer Control Fund by Japan Agency for Medical Research and Development. HF reports lecture fees from Chugai Pharmaceuticals, outside of the submitted work. MW reports honoraria from Nihon Medi-Physics outside of the submitted work. MTs reports research funding from Boehringer-Ingelheim Japan and commissioned research for clinical trials from MSD, Astrazeneca, Ono Pharmaceutical, Bristol-Myers Squibb, Eli Lilly Japan, Novartis, and BMG; lecture fees from Johnson & Johnson Japan, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, MSD, Bristol-Myers Squibb, Teijin Pharma, Taiho Pharma, Medtronic Japan, ONO Pharmaceutical, Daiichi-Sankyo, and Novartis, outside of the submitted work; is on the advisory board of AstraZeneca, Chugai Pharmaceutical, MSD, Novartis, and Eli Lilly, outside of the submitted work; and also is on the committee of Japan Lung Cancer Society and Japanese Association of Chest Surgery, Cancer Net Japan, Japanese Organization for Research, and Treatment of Cancer, outside of the submitted work. TMim reports research funding from the Japan Society for the Promotion of Science KAKENHI (grant number 20K09177) by the Japan Society for Promotion of Science, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In Japan, cotton is commonly used in thoracic surgery for the gentle handling of organs as well as obtaining a good surgical field. While uniportal video-assisted thoracoscopic surgery is being recognized as a major surgical approach, use of cotton is not noted in this technique. Uniportal video-assisted thoracoscopic surgery needs curved instruments because they are effective in preventing the interference of instruments. Thus, we developed a novel curved cotton instrument, known as the "CS Two-Way Handle TM ", for uniportal video-assisted thoracoscopic surgery. The CS Two-Way Handle TM can be used not only as a cotton bar but also as a suction aid. Moreover, surgical smoke can be suctioned with the insertion of cotton. This instrument was introduced in our institution in September 2019, along with some other prototypes. When anatomical lung resection using uniportal video-assisted thoracoscopic surgery was first introduced, there were some instances of conversion to conventional multiportal video-assisted thoracoscopic surgery. However, after the CS Two-Way Handle TM introduction, the procedure has become easy to perform and the need for conversion to conventional methods has reduced. The main uses of the CS Two-Way Handle TM are: (I) exposure of the surgical view, (II) lymph node dissection, (III) bleeding control, (IV) suction, and (V) evacuation of surgical smoke. We present our experiences using the CS Two-Way Handle TM in uniportal video-assisted thoracoscopic surgery., Competing Interests: Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1602/coif). The author has no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

There are few prospective reports of transbronchial lung cryobiopsy (TBLC) for malignant tumors in combination with forceps biopsy. We investigated the clinical parameters in which TBLC is superior to forceps biopsy. This is a prospective cohort study to analyse the efficacy of TBLC for suspected malignancy. TBLC was performed after brushing cytology and forceps biopsy, and the diagnostic yield for TBLC, brushing cytology, and forceps biopsy were examined. Adverse events were defined as those requiring additional procedures. Next-generation sequencing (NGS) analysis was performed in each case of non-small cell lung cancer. Of the 100 patients, malignancy was confirmed in 94 cases. The diagnostic yield for TBLC/forceps biopsy/brushing cytology was 86/81/82% respectively, while the diagnostic yield for all procedures combined was 94%. There was no significant difference in the diagnostic yield between TBLC and forceps biopsy. When comparing the biopsy site, the diagnostic yield for TBLC at the lower lobe was significantly higher than forceps biopsy (P < 0.01). Endobronchial ultrasonography imaging using a guide-sheath did not significantly differ in the diagnostic yield of TBLC. The success rate of NGS for TBLC specimens was 100% (26 cases). Adverse events included two cases of severe bleeding. TBLC of peripheral lesions may improve the diagnostic yield when combined with forceps biopsy and brushing cytology. The diagnostic yield of TBLC was higher at the lower lobes. Furthermore, TBLC provided sufficient specimen quality for NGS., (© 2023. The Author(s).)

Purpose: To establish the prognostic significance of C-reactive protein (CRP) and albumin in octogenarians with non-small cell lung cancer (NSCLC) based on the study of the Japanese Association for Chest Surgery (JACS 1303)., Methods: A total of 618 octogenarians with pathological stage I NSCLC, who underwent pulmonary resection, were included in the analysis. We conducted multivariable Cox regression analysis to evaluate the CRP to albumin ratio (CAR) as a potential prognostic factor. Other clinicopathological factors were also evaluated., Results: The median age was 82 years. Operations included lobectomy (n = 388; 62.8%) segmentectomy (n = 95; 15%), and wedge resection (n = 135; 22%). Pathological stage IA was diagnosed in 380 (61.5%) patients. The 3-year (OS) and cancer-specific survival (CS) rates were 86.7% and 94.6%, respectively. OS was significantly higher for patients with low CAR (< 0.106) than for those with high CAR (≥ 0.106) (hazard ratio = 3.13, 95% confidence interval: 1.99-4.93, p < 0.0001). Univariate analysis identified sex, poor performance status, smoking status, comorbidity, solid tumor, histology, high Glasgow prognostic scale, and high CAR as significant prognostic factors. Multivariate analysis identified only the CAR as a significant prognostic factor for both OS and CS., Conclusions: Our analysis of the nationwide data demonstrated that the CAR is a useful prognostic factor for elderly patients with stage I NSCLC., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Genetic panel tests require sufficient tissue samples, and therefore, cannot always be performed. Although collecting cytological specimens is easier than tissue collection, there are no validation studies on the diagnostic accuracy of lung cancer gene panel tests using cytology samples. Methods: Using an amplicon-based high-sensitivity next-generation sequencing panel test capable of measuring eight druggable genes, we prospectively enrolled consecutive patients who underwent diagnostic procedures. We evaluated the analysis accuracy rate, nucleic acid yield, and the quality of cytological specimens under brushing, needle aspiration, and pleural effusion. We then compared these specimens with collected tissue samples. Results: In 163 prospectively enrolled cases, nucleic acid extraction and analysis accuracy was 100% in cases diagnosed with adenocarcinoma. Gene mutations were found in 68.7% of cases with 99.5% (95% CI: 98.2-99.9) concordance to companion diagnostics. The median DNA/RNA yield and DNA/RNA integrity number were 475/321 ng and 7.9/5.7, respectively. The correlation coefficient of the gene allele ratio in 64 cases compared with tissue samples was 0.711. Conclusion: The success of gene analysis using cytological specimens was high, and the yield and quality of the extracted nucleic acid were sufficient for panel analysis. Moreover, the allele frequency of gene mutations in cytological specimens showed high correlations with tissue specimens.

Introduction: The prognostic significance of mediastinal lymph node dissection (MLND) in elderly patients with non-small cell lung cancer (NSCLC) remains unclear. This post hoc analysis of a nationwide multicenter cohort study (JACS1303) evaluated the prognostic significance of MLND in octogenarians with NSCLC., Materials and Methods: We included 622 octogenarians with NSCLC who underwent lobectomy. The median follow-up duration was 41.1 months. We compared survival and perioperative outcomes between patients who did and did not undergo MLND., Results: In total, 414 (67%) patients underwent MLND (ND2 group), whereas 208 (33%) did not undergo MLND (ND0-1 group). The disease stage was more advanced in the ND2 group than in the ND0-1 group. Disease-free survival was slightly greater in the ND0-1 group with marginal significance (P= .079). In the matched cohort (N = 228), which mainly consisted of patients with clinical stage I disease (96%), there was no significant difference between the 2 groups regarding overall and disease-free survival (P= .908 and P = .916, respectively). Operative time and blood loss were significantly lower in the ND0-1 group than in the ND2 group in the entire cohort (P< .001 and P = .050, respectively) and in the matched cohort (P = .003 and P= .046, respectively)., Conclusion: Based on a nationwide prospective database, we found limited prognostic impact of MLND, suggesting that MLND can be omitted for octogenarians with early-stage NSCLC., (Copyright © 2021. Published by Elsevier Inc.)

Background: Lobectomy is the standard of care for early-stage non-small-cell lung cancer (NSCLC). The survival and clinical benefits of segmentectomy have not been investigated in a randomised trial setting. We aimed to investigate if segmentectomy was non-inferior to lobectomy in patients with small-sized peripheral NSCLC., Methods: We conducted this randomised, controlled, non-inferiority trial at 70 institutions in Japan. Patients with clinical stage IA NSCLC (tumour diameter ≤2 cm; consolidation-to-tumour ratio >0·5) were randomly assigned 1:1 to receive either lobectomy or segmentectomy. Randomisation was done via the minimisation method, with balancing for the institution, histological type, sex, age, and thin-section CT findings. Treatment allocation was not concealed from investigators and patients. The primary endpoint was overall survival for all randomly assigned patients. The secondary endpoints were postoperative respiratory function (6 months and 12 months), relapse-free survival, proportion of local relapse, adverse events, proportion of segmentectomy completion, duration of hospital stay, duration of chest tube placement, duration of surgery, amount of blood loss, and the number of automatic surgical staples used. Overall survival was analysed on an intention-to-treat basis with a non-inferiority margin of 1·54 for the upper limit of the 95% CI of the hazard ratio (HR) and estimated using a stratified Cox regression model. This study is registered with UMIN Clinical Trials Registry, UMIN000002317., Findings: Between Aug, 10, 2009, and Oct 21, 2014, 1106 patients (intention-to-treat population) were enrolled to receive lobectomy (n=554) or segmentectomy (n=552). Patient baseline clinicopathological factors were well balanced between the groups. In the segmentectomy group, 22 patients were switched to lobectomies and one patient received wide wedge resection. At a median follow-up of 7·3 years (range 0·0-10·9), the 5-year overall survival was 94·3% (92·1-96·0) for segmentectomy and 91·1% for lobectomy (95% CI 88·4-93·2); superiority and non-inferiority in overall survival were confirmed using a stratified Cox regression model (HR 0·663; 95% CI 0·474-0·927; one-sided p<0·0001 for non-inferiority; p=0·0082 for superiority). Improved overall survival was observed consistently across all predefined subgroups in the segmentectomy group. At 1 year follow-up, the significant difference in the reduction of median forced expiratory volume in 1 sec between the two groups was 3·5% (p<0·0001), which did not reach the predefined threshold for clinical significance of 10%. The 5-year relapse-free survival was 88·0% (95% CI 85·0-90·4) for segmentectomy and 87·9% (84·8-90·3) for lobectomy (HR 0·998; 95% CI 0·753-1·323; p=0·9889). The proportions of patients with local relapse were 10·5% for segmentectomy and 5·4% for lobectomy (p=0·0018). 52 (63%) of 83 patients and 27 (47%) of 58 patients died of other diseases after lobectomy and segmentectomy, respectively. No 30-day or 90-day mortality was observed. One or more postoperative complications of grade 2 or worse occurred at similar frequencies in both groups (142 [26%] patients who received lobectomy, 148 [27%] who received segmentectomy)., Interpretation: To our knowledge, this study was the first phase 3 trial to show the benefits of segmentectomy versus lobectomy in overall survival of patients with small-peripheral NSCLC. The findings suggest that segmentectomy should be the standard surgical procedure for this population of patients., Funding: National Cancer Center Research and the Ministry of Health, Labour, and Welfare of Japan., Competing Interests: Declaration of interests HS reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from MSD, Boehringer Ingelheim, Ethicon, Covidien, Chugai Pharmaceutical, Astellas Pharma, Fujifilm Medical, and Bristol Myers Squibb. MO reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from MSD, Ethicon, Covidien, Chugai Pharmaceutical, ONO Pharmaceutical, AstraZeneca, and Bristol Myers Squibb. MT reports grants from Boehringer Ingelheim Japan, MSD, AstraZeneca, ONO Pharmaceutical, MSD, Bristol Myers Squibb, and Eli Lilly Japan; consulting fees from AstraZeneca, Chugai Pharmaceutical, MSD, and Novartis; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Johnson & Johnson Japan, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, Taiho Pharmaceutical, Medtronic Japan, ONO Pharmaceutical, MSD, Bristol Myers Squibb, and Teijin Pharmaceutical. KS reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Boehringer Ingelheim, Ethicon, Covidien, Chugai Pharmaceutical, Astellas Pharma, Intuitive, and Bristol Myers Squibb. KA reports consulting fees from TAIHO pharma, Olympus medical, AstraZeneca, Covidien, Johnson & Johnson, and Care-net; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from MSD, Mochida Pharmaceutical, Johnson & Johnson, Covidien, Chugai Pharmaceutical, Bristol Myers Squibb, Eli-lilly, and Teijin healthcare. IY reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from MSD, Boehringer Ingelheim, Ethicon, Covidien, Chugai Pharmaceutical, Astellas Pharma, Fujifilm Medical, and Bristol Myers Squibb. NI reports grants from AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, Pfizer, Taiho Pharmaceutical, Eli Lilly, ONO Pharmaceutical, Bristol-Meyers Squibb, MSD, Nihon Medi-Physics, Teijin Pharmaceutical, Kyowa Kirin, Sanofi, Eisai, Astellas Pharma, Shionogi, Daiichi-Sankyo, and Roche Diagnostics; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, Pfizer, Taiho Pharmaceutical, Eli Lilly, ONO Pharmaceutical, Bristol-Meyers Squibb, MSD, Nihon Medi-physics, Teijin Pharmaceutical, Johnson & Johnson, and Olympus Corporation. MW reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Chugai Pharmaceutical and Johnson & Johnson. HF reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Chugai Pharmaceutical. TM reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Boehringer Ingelheim, Novartis, Chugai Pharmaceutical, MSD, Bristol-Meyers Squibb, ONO Pharmaceutical, Taiho Pharmaceutical, Merck Biopharmaceutical, Pfizer, Takeda, BeiGene, and Daiichi-Sankyo. SI-W reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Johnson & Johnson, Medtronics, MSD, AstraZeneca, and Striker. HA reports grants from Johnson & Johnson, Medtronic, Astellas, Taiho Pharmaceutical, AstraZeneca, and Eli Lilly. RN, TA, JO, HI, NO, MY, KN, and SN declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: The first surge in severe acute respiratory syndrome coronavirus 2 infection had a significant impact on health care institutions. Understanding how the pandemic affected general thoracic surgery would provide valuable data for establishing a health care protocol for upcoming surges., Methods: A questionnaire survey on coronavirus disease-related patient statistics and health care was conducted between February 2020 and June 2020 across 14 facilities affiliated with the Kanagawa General Thoracic Surgery Study Group., Results: The average number of newly referred patients from February to June 2020 was 65% of that during the same period in 2019. Six facilities placed restrictions on medical care services, among which four restricted surgeries. At all institutions and those placed on surgical restriction, the total number of surgeries under general anesthesia was 92% and 78%, the total number of primary lung cancers was 94% and 86%, and the total number of surgeries for pneumothorax was 71% and 77% of that in the preceding year, respectively. Infection control and insufficient resources of the medical material were the most influential factors impacting the medical institutions' decision to restrict the services provided., Conclusions: Restrictions on surgery had a significant impact on the care provided by general thoracic surgery departments. To avoid patient inconvenience, establishing a collaborative system that refers patients to operational medical institutions in case of medical treatment restrictions may be useful., (© 2021. The Japanese Association for Thoracic Surgery.)

Background: The optimal mode of surgery for ground-glass opacity dominant peripheral lung cancer defined with thoracic thin-section computed tomography remains unknown., Methods: We conducted a single-arm confirmatory trial to evaluate the efficacy and safety of sublobar resection for ground-glass opacity dominant peripheral lung cancer. Lung cancer with maximum tumor diameter 2.0 cm or less and with consolidation tumor ratio 0.25 or less based on thin-section computed tomography were registered. The primary end point was 5-year relapse-free survival. The planned sample size was 330 with the expected 5-year relapse-free survival of 98%, threshold of 95%, 1-sided α of 5%, and power of 90%. The trial is registered with University Hospital Medical Information Network Clinical Trials Registry, number University Hospital Medical Information Network 000002008., Results: Between May 2009 and April 2011, 333 patients were enrolled from 51 institutions. Median age was 62 years (interquartile range, 56-68), and 109 were smokers. Median maximum tumor diameter was 1.20 cm (1.00-1.54). Median maximum tumor diameter of consolidation was 0 (0.00-0.20). The primary end point, 5-year relapse-free survival, was estimated on 314 patients who underwent sublobar resection. Operative modes were 258 wide wedge resections and 56 segmentectomies. Median pathological surgical margin was 15 mm (0-55). The 5-year relapse-free survival was 99.7% (90% confidence interval, 98.3-99.9), which met the primary end point. There was no local relapse. Grade 3 or higher postoperative complications based on Common Terminology Criteria for Adverse Effect v3.0 were observed in 17 patients (5.4%), without any grade 4 or 5., Conclusions: Sublobar resection with enough surgical margin offered sufficient local control and relapse-free survival for lung cancer clinically resectable N0 staged by computed tomography with 3 or fewer peripheral lesions 2.0 cm or less amenable to sublobar resection and with a consolidation tumor ratio of 0.25 or less., (Copyright © 2020. Published by Elsevier Inc.)

Background: Anatomic resection with lymph node dissection or sampling is the standard treatment for early non-small cell lung cancer (NSCLC), and wedge resection is an option for compromised patients. This study aimed to determine whether wedge resection can provide comparable prognoses for elderly patients with NSCLC., Methods: The study analyzed the clinicopathologic findings and surgical outcomes during a median follow-up period of 39.6 months for 156 patients with solid dominant (consolidation-to-tumor ratio > 0.5) small (whole tumor size ≤ 2 cm) NSCLC among 892 patients 80 years of age or older with medically operable lung cancer between April 2015 and December 2016., Results: The 3-year overall survival (OS) rates after wedge resection and after segmentectomy plus lobectomy did not differ significantly (86.5 %; 95 % confidence interval [CI], 74.6-93.0 % vs 83.7 % 95 % CI, 74.0-90.0 %; P = 0.92). Multivariable Cox regression analysis of OS with propensity scores showed that the surgical procedure was not an independent prognostic predictor (hazard ratio [HR], 0.84; 95 % CI, 0.39-1.8; P = 0.64). The 3-year OS rates were slightly better after wedge resection for 97 patients who could tolerate lobectomy than after segmentectomy plus lobectomy (89.4 %; 95 % CI, 73.8-95.9 % vs 75.8 %; 95 % CI, 62.0-85.2 %; P = 0.14). The cumulative incidence of other causes for death was marginally higher after segmentectomy plus lobectomy than after wedge resection (P = 0.079)., Conclusions: Wedge resection might be equivalent to lobectomy or segmentectomy for selected patients 80 years of age or older with early-stage NSCLC who can tolerate lobectomy., (© 2021. Society of Surgical Oncology.)

Objective: We performed a validation study to confirm the prognostic importance of the presence of a ground-glass opacity component based on data of the Japan Clinical Oncology Group study, JCOG0201, which was a prospective observational study to predict the pathological noninvasiveness of clinical stage IA lung cancer in Japan., Methods: Among the 811 patients registered in JCOG0201, 671 were confirmed eligible by study monitoring and a central review of computed tomography. Registered c-stage IA lung cancer was less than 30 mm in maximum tumor size, which was classified into a with ground-glass opacity group (pure ground-glass opacity and part-solid tumor) or solid group based on the status of a ground-glass opacity component. T staging was reassigned in accordance with the 8th edition of the TNM staging system. To validate the prognostic impact, overall survival was estimated., Results: Of the cases, 432 (64%) were in the with ground-glass opacity group and 239 (36%) were in the solid group with a median follow-up time of 10.1 years. The 5-year overall survival was significantly different between the with ground-glass opacity group and solid group (95.1% vs 81.1%). The 5-year overall survival was excellent regardless of the solid component size in the with ground-glass opacity group (c-T1a or less: 97.2%, c-T1b: 93.4%, c-T1c: 91.7%). In contrast, prognostic impact of the tumor size was definitive in the solid group (c-T1a: 87.5%, c-T1b: 85.9%, c-T1c: 73.7%)., Conclusions: Favorable prognostic impact of the presence of a ground-glass opacity component was demonstrated in JCOG0201. The presence or absence of a ground-glass opacity should be considered as an important parameter in the next clinical T classification., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to determine the relationship of programmed death-ligand 1 (PD-L1) expression and standardized uptake values in fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) with prognosis in non-small-cell lung cancer (NSCLC)., Methods: We retrospectively analyzed 328 NSCLC patients who underwent lobectomy/segmentectomy with lymph node dissection. PD-L1 expression was detected by immunohistochemically stained using the murine monoclonal antibody clone 22C3. The preoperative maximum standardized uptake value (SUV max ) of FDG-PET/CT at the primary lesion; pathological factors including histological type, microscopic lymphatic, venous, and pleural invasion; and lymph node metastases in resected specimens was determined. Significant prognostic clinicopathologic factors were analyzed by univariate and multivariate analyses., Results: PD-L1 expression was higher in men, smokers, squamous cell carcinoma, advanced pathologic stages, positive venous invasion, positive pleural invasion, and high preoperative SUV max (≥3). Postoperative survival analysis showed that both PD-L1 expression and preoperative SUV max were significantly negative prognostic factors in univariate analysis for overall survival (OS) ( P = 0.0123 and P < 0.0001) and relapse-free survival (RFS) ( P = 0.0012 and P < 0.0001). Kaplan-Meier survival curves showed that the OS and RFS were the best in patients with negative PD-L1 expression and SUV max < 3, intermediate in patients with positive PD-L1 expression and SUV max < 3 and those with negative PD-L1 expression and SUV max ≥ 3, and poor in patients with positive PD-L1 expression and SUV max ≥ 3., Conclusion: Combining PD-L1 expression and preoperative FDG-PET/CT SUV max in primary tumor might help in accurate prediction of postoperative prognosis in NSCLC patients.

The relatively low toxicity profile of nab-paclitaxel plus carboplatin and its feasibility as an adjuvant administration was reported previously. This study aimed to evaluate the survival efficacy for completely resected patients with stage IB, II, and IIIA nonsmall cell lung cancer (NSCLC). Twenty-nine eligible patients with NSCLC who received surgical resection for pathological stage IB, II, or IIIA, followed by postoperative adjuvant chemotherapy with modified 3-week cycles of either nab-paclitaxel (nab-P) (100 mg/m) on days 1 and 8 followed by carboplatin area (area under the curve = 6) on day 1 were prospectively enrolled and assessed for survival outcomes against patients with the same stages who received other postoperative adjuvant chemotherapy regimens during the same period. There were no significant differences in clinicopathological features, including age, gender, smoking status, performance status, surgical procedures, tumor histology, and pathological stage between the two groups. The cumulative overall survival (OS) rates at 5 years of the experimental and control groups in pathological stage IB-IIIA were 85.4% and 63.9%, respectively (P = 0.598), while recurrence-free survival (RFS) rates in these groups at 5 years were 65.2% and 34.8%, respectively (P = 0.344). Moreover, the cumulative OS rates of the experimental and control groups in pathological stage II-IIIA were 83.6% and 63.6%, respectively (P = 0.970), while RFS rates in these groups at 5 years were 61.1% and 37.3%, respectively (P = 0.460). This new regimen was considered an attractive alternative postoperative adjuvant chemotherapy option with relatively low toxicity and moderate survival outcomes for completely resected NSCLC.

In the original publication of the article, the corresponding author email address was published wrongly.

Background: No definitive comparisons of surgical morbidity between segmentectomy and lobectomy for non-small cell lung cancer have been reported., Methods: We conducted a randomized controlled trial to confirm the noninferiority of segmentectomy to lobectomy in regard to prognosis (trial No. JCOG0802/WJOG4607L). Patients with invasive peripheral non-small cell lung cancer tumor of a diameter ≤2 cm were randomized to undergo either lobectomy or segmentectomy. The primary end point was overall survival. Here, we have focused on morbidity and mortality. Predictors of surgical morbidity were evaluated by the mode of surgery. Segmentectomy was categorized into simple and complex. Simple segmentectomy was defined as segmental resection of the right or left segment 6, left superior, or lingular segment. Complex segmentectomy was resection of the other segment. This trial is registered with the University Hospital Medical Information Network--Clinical Trial Registry (UMIN000002317)., Results: Between August 10, 2009, and October 21, 2014, 1106 patients (lobectomy n = 554 and segmentectomy n = 552) were enrolled. No mortality was noted. Complications (grade ≥ 2) occurred in 26.2% and 27.4% in the lobectomy and segmentectomy arms (P = .68), respectively. Fistula/pulmonary-lung (air leak) was detected in 21 (3.8%) and 36 (6.5%) patients in the lobectomy and segmentectomy arms (P = .04), respectively. Multivariable analysis revealed that predictors of pulmonary complications, including air leak and empyema (grade ≥ 2) were complex segmentectomy (vs lobectomy) (odds ratio, 2.07; 95% confidence interval, 1.11-3.88; P = .023), and > 20 pack-years of smoking (odds ratio, 2.61; 95% confidence interval, 1.14-5.97; P = .023)., Conclusions: There was no difference in almost any postoperative measure of intraoperative and postoperative complication in segmentectomy and lobectomy patients, except more air leakage was observed in the segmentectomy arm. Segmentectomy will be a standard treatment if the superior pulmonary function and noninferiority in overall survival are confirmed., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: The molecular underpinnings that may prognosticate survival and increase our understanding of tumor development and progression are still poorly understood. This study aimed to define the molecular signatures for malignancy in small cell lung carcinoma (SCLC), which is known for its highly aggressive clinical features and poor prognosis., Experimental Design: Using clinical specimens, the authors perform a comparative proteomic analysis of high-grade SCLCs and low-grade pulmonary carcinoid tumors (PCTs), both of which are types of neuroendocrine tumors. A label-free LC-MS-based quantitative proteomic analysis is applied to tumor cells laser-microdissected from their formalin-fixed paraffin-embedded (FFPE) tissues obtained from six patients each., Results: Overall, 1991 proteins are identified from tumor cells in the FFPE tissues. Through the protein-protein interaction network analysis of 201 proteins significantly, the authors find that SCLC is functionally characterized by activation of molecular pathways for spliceosome, RNA transport, and DNA replication and cell cycle. Particularly, 11 proteins involved in tumor proliferation (MCM2, 4, 6, 7, and MSH2), metastasis (RCC2, CORO1C, CHD4, and IPO9), and cancer metabolism (PHGDH and TYMP) are identified as SCLC-specific proteins. Furthermore, their prognostic significances are demonstrated by online Kaplan-Meier survival analysis., Conclusions and Clinical Relevance: These clinical tissue proteomic approach for SCLC reveals the proteins associated with aggressiveness and poor prognosis. The identified SCLC-specific proteins represent potential therapeutic targets. Moreover, MCMs and PHGDH can be poor prognostic factors for lung cancer., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The reliability of the cobas EGFR assay to detect epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) as an in vitro diagnostic test was compared with 3 laboratory-developed tests (LDTs)., Materials and Methods: After screening for EGFR mutations using formalin-fixed-paraffin-embedded NSCLC tissue sections using the cobas EGFR assay, 151 samples were further tested with 3 LDTs; the peptide nucleic acid-locked nucleic acid polymerase chain reaction (PCR) clamp, PCR invader, and Cycleave assays. The cobas EGFR assay performance was evaluated by determining the concordance rate and κ-coefficient between the assays. In samples exhibiting discrepancies in the EGFR mutation status in the 4 assays, next-generation sequencing was performed to confirm mutated sequences., Results: Concordance rates and κ-coefficients between the cobas EGFR assay and the other tests were 96.0% and 0.921 for the peptide nucleic acid-locked nucleic acid PCR clamp assay, 94.0% and 0.881 for the PCR invader assay, and 96.7% and 0.934 for the Cycleave assay, respectively. Data showed very good agreement with the other assays. Precise mutated sequences or exons in the EGFR gene matched in 137 samples (90.7%). Different results were obtained in 4 samples (2.6%), owing to systemic limitations of the assay. Next-generation sequencing of 10 (6.6%) samples with discordant results exhibited a concordance rate of 60% to 80% in each assay., Conclusions: The cobas EGFR assay showed high concordance rates and κ-coefficients between the 3 compared LDTs and can be used to select patients who would benefit from EGFR-tyrosine kinase inhibitors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In January 2017, the Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group commenced a randomized Phase III trial to confirm the clinical benefit of lobe-specific nodal dissection for clinical Stage I-II non-small cell lung cancer. The primary endpoint is overall survival, and the main objective is to confirm the non-inferiority of lobe-specific in comparison to systematic nodal dissection with regard to lobectomy. The secondary endpoints are relapse-free survival, %local recurrence, %regional lymph node recurrence, operation time, blood loss, length of hospitalization, duration of chest tube placement and adverse events. A total of 1700 patients will be accrued from 44 Japanese institutions within 5 years. This study is the first and large prospective trial to evaluate whether the difference in the area of nodal dissection affects the overall survival of patients with relatively early-stage non-small cell lung cancer. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000025530., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The treatments for advanced non-small cell lung cancer (NSCLC) should control both local and microscopic systemic disease, because the 5-year survival of patients with Stage III NSCLC who underwent surgical resection alone has been dismal. One way to improve surgical outcome is the administration of chemotherapy before or after the surgical procedure. During the last two decades, many clinical studies have focused on developing optimal adjuvant or neoadjuvant chemotherapy regimens that can be combined with surgical treatment and/or radiotherapy. Based on the results of those clinical studies, multimodality therapy is considered to be an appropriate treatment approach for Stage IIIA NSCLC patients; although, optimal treatment strategies are still evolving. When N2 nodal involvement is discovered postoperatively, adjuvant cisplatin-based chemotherapy confers an overall survival benefit. The addition of postoperative radiotherapy might be considered for patients with nodal metastases. Although definitive chemoradiation remains a standard of care for cN2 NSCLC, alternative approaches such as induction chemotherapy or chemoradiotherapy and surgery can be considered for a selective group of patients. When surgical resection can be performed after induction therapy with low risk and a good chance of complete resection, the outcome may be optimal. The decision to proceed with resection after induction therapy must include a detailed preoperative pulmonary function evaluation as well as a critical intraoperative assessment of the feasibility of complete resection., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although tracheobronchial stents are widely used for tracheal obstruction due to malignant or benign stenosis, stent migration has been reported as a major postoperative complication. A self-expandable metallic stent (SEMS) is more easily introduced compared with silicone stents. However, it is also difficult to remove or replace without complications. We report a new technique for successful SEMS adjustment using a flexible bronchoscope with two biopsy forceps.

Introduction: Lobectomy has been the standard surgery for even stage I lung cancer since the validity of limited resection for stage I lung cancer was denied by the randomized study reported in 1995. The aim of this non-randomized confirmatory going on since September 2013 is to confirm the efficacy of a segmentectomy for clinical T1N0 lung cancer with dominant ground glass opacity based on thin-slice computed tomography., Method: A total of 390 patients from 42 Japanese institutions are recruited within 4 years. The primary endpoint of this study is a 5-year relapse-free survival in all of the patients who undergo a segmentectomy for a lung nodule. The secondary endpoints are overall survival, annual relapse-free survival, disease-free survival, proportion of local relapse, postoperative pulmonary function, proportion of segmentectomy completion, proportion of R0 resection completion by segmentectomy, adverse events, and serious adverse events. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000011819 ( http://www.umin.ac.jp/ctr/ )., Results: Patient's accrual has been already finished in November, 2015 and the primary analysis will be performed in 2021., Conclusion: This study is one of the pivotal trial of lung segmentectomy for early lung cancer. The result will provide a clear evidence for our daily clinics and will be possible contribution to preserving pulmonary function for lung cancer patients.

Background  To assess the reliability of maximum standardized uptake values (SUVmax) at the primary lesion in 18-fluorodeoxyglucose positron emission tomography combined with computed tomography ( 18 FDG-PET/CT) for identifying patients with lung cancer who were most likely to be cured by sublobar resection (SR). Methods  We retrospectively reviewed the medical records of 120 patients who underwent SR for clinical (c)-stage IA + IB lung cancer after 18 FDG-PET/CT. Various factors, including tumor size, SUVmax at the primary site, and microscopic tumor invasion, were examined to identify their association with postsurgical survival. Prognoses of patients undergoing SR were compared with those of 272 patients undergoing lobectomy and lymphadenectomy during the same period. Results  The 5-year recurrence-free survival (RFS) and overall survival (OS) rates in all patients undergoing SR for c-stage IA + IB disease were 79.5% and 82.2%, respectively. In multivariate analysis, a lack of microscopic pleural invasion and SUVmax ≤ 3.0 significantly correlated with better RFS and OS in patients undergoing SR. Though there were no significant differences in RFS and OS following SR and lobectomy for c-stage IA + IB or IA disease, RFS was significantly inferior in nonintentional SR (NISR) than in lobectomy in c-stage IA disease ( p  < 0.01). However, in NISR identified based on SUVmax ≤ 2.0, RFS was comparable to those in lobectomy ( p  = 0.5371). Conclusion  When certain subgroups of patients are accurately identified based on preoperative SUVmax, SR can be a highly curative surgical method for lung cancer., (Georg Thieme Verlag KG Stuttgart · New York.)

Since 'radical lobectomy' was reported by Cahan in 1960, the standard surgical care for lung cancer has been lobectomy, in which units of the lobe are excised with their specific regional hilar and mediastinal lymphatics. However, pulmonary function-preserving limited resection for lung cancer has gradually become more prevalent in the late 20th century. In 1995, Ginsberg et al. conducted a randomized controlled trial in which limited resection (segmentectomy and wide-wedge resection) and lobectomy for stage I lung cancer were compared and reported that limited resection should not be applied to healthy patients with clinical stage IA lung cancer. The detection of small-sized and early-stage lung cancers has improved with advancement in diagnostic technology. Ground-glass opacity of lung nodules, as recognized on thin-slice computed tomography, has also been widely recognized as being correlated with less-invasive pathological findings of alveolar epithelial cell replacement of cancer cells. The Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group conducted a cohort study of early peripheral lung cancer and investigated the validity thin-slice computed tomography criteria to diagnose non-invasive lung adenocarcinoma for the preoperative prediction of pathological non-invasive cancer. Following this observational study, the on-going JCOG0802/WJOG4607L, JCOG0804/WJOG4507L and JCOG1211 trials were initiated to confirm the validity of limited resection for stage I lung cancer patients stratified according to preoperative thin-slice computed tomography findings; these trials will clarify whether limited resection for lung cancer is not function-preserving but also only curative surgery., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

According to the 2012 annual report of the Japanese Association for Thoracic Surgery, the total number of surgical procedures performed for the treatment of lung cancer had reached 35,667. Patients over 70 years of age comprised 52% of those surgical cases, and those over 80 years 12%. This tendency has been increasing annually. Although hospital mortality rates in elderly patients over 80 years of age and others were almost the same, 30% of elderly patients died from other diseases, as reported by the Japanese Joint Committee of the Lung Cancer Registry in 1999. Therefore, current preoperative physiological and oncological risk evaluations of elderly patients do not appear to be sufficient. The Japanese Association for Chest Surgery planned and performed a multiinstitutional prospective cohort study of elderly patients with lung cancer who underwent thoracic surgery to answer clinical questions surrounding such risk evaluations.

Background: Microscopic vascular invasion (MVI) in patients with non-small cell lung cancer (NSCLC) has been reported to be a strong predictor of poor outcomes but it has not been a descriptor of the TNM classification. The purposes of this study were to determine whether the presence of MVI is related to a predictor of poor outcomes and to explore the degree of MVI according to tumor size., Methods: A total of 1,884 patients with stage pT1-4N0-2 NSCLC who underwent complete resection comprised the study sample. Overall survival (OS) and recurrence-free proportion were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to assess independent predictors of poor outcomes., Results: Of 1,884 patients, 1,097 (58.2%) had MVI. Multivariate analysis showed MVI was a significant independent predictor of unfavorable OS (hazard ratio, 1.666; P < .001) and recurrence (hazard ratio, 2.268; P < .001). The frequency of MVI varied according to tumor size, and in each cohort of tumor sizes ≤ 2 cm, > 2 to 3 cm, and > 3 to 5 cm, there were significant differences in survival outcome by MVI status. The proportions of patients with a 5-year recurrence-free period with tumor sizes ≤ 2 cm, > 2 to 3 cm, and > 3 to 5 cm between MVI (+) and MVI (-) were 93.0% and 72.5% (P < .001), 90.8% and 63.3% (P < .001), and 86.4% and 59.9% (P < .001), respectively., Conclusions: This study demonstrated that MVI was a strong predictor of poor outcomes and that the effect is more prominent in patients with tumor sizes ≤ 5 cm. Further analysis of survival and MVI should be collected for future revision of the TNM system., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: Lung cancers in patients with combined pulmonary fibrosis and emphysema (CPFE) are increasing. Objective of this investigation was to identify which clinicopathological features significantly affected surgical outcome of these patients., Methods: Among 4313 patients with primary lung cancers who underwent surgery between January 2008 and December 2010 in nine institutions in Japan, 265 had CPFE. We retrospectively compared 2176 and 157 patients without and with CPFE, respectively, and further analyzed 233 patients with CPFE whose detailed information was available. CPFE was defined as upper lobe emphysema and lower lobe fibrosis., Results: The rates of postoperative morbidity and mortality were higher and overall survival was poorer in patients with, than without CPFE. Among 233 patients with CPFE, the median values of %VC and FEV1.0 % were 98.4 and 71.5 %, respectively. The histological types comprised 111 squamous cell carcinomas and 84 adenocarcinomas. Surgical procedures included 203 standard lobectomies/pneumonectomies and 30 lesser resections. Five patients (2 %) developed postoperative acute exacerbation of interstitial pneumonia. Six and 15 patients (3 and 6 %) died within 30- and 90-postoperative-day, respectively. Cancer was the cause of death at 90-day in only one patient. The 3-year overall survival rate for all patients was 58.4 %. Multivariate analysis showed that male sex, advanced age, advanced clinical stage and lower %VC predict a poor prognosis., Conclusions: Patients with lung cancer and CPFE had poor prognoses regardless of apparently good pulmonary function and showed quite high postoperative mortality rates. A lower %VC that might reflect the severity of pulmonary fibrosis was associated with poor prognoses.

Purpose: Maximum standardized uptake values (SUVmax) at the primary lesions of non-small-cell lung cancer in (18)F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT), and the microscopic local extension of tumors were examined to develop reliable criteria to determine candidates for sublobar resection., Methods: We retrospectively analyzed 209 patients who underwent lobectomy, bilobectomy, or pneumonectomy with systematic lymph node dissection. Preoperative SUVmax at the primary lesion, microscopic lymphatic, venous, and pleural invasion in addition to lymph node metastases in the resected specimens were examined. Receiver operating characteristic analyses were used to predict an optimal cutoff for lymph node metastases., Results: With receiver operating characteristic analysis, the areas under the curve for SUVmax and tumor size were 0.693 and 0.545, respectively, suggesting SUVmax superiority for prediction of lymph node metastases with a cutoff of 2.9. When a tumor was ≤2.0 cm (n = 41, 19.6 %), the percentages of microscopic lymphatic invasion, venous invasion, pleural invasion, and lymph node metastases were 12.2, 7.3, 4.9, and 17.1 %, respectively. When SUVmax was <3.0 (n = 91, 43.5 %), these percentages were 15.4, 3.3, 7.7, and 8.8 %, showing that SUVmax could efficiently exclude nodal metastases in more cases than tumor size. The postoperative 5-year survival rate was 86.6 % in patients with SUVmax < 3.0 and 58.1 % in patients with SUVmax ≥ 3.0 (p < 0.001)., Conclusions: (18)F-FDG uptake value was more useful than tumor size for selecting patients with non-small-cell lung cancer suitable for intentional sublobar resection.

The anterior transcervical-thoracic approach clearly exposes the subclavian vessels and brachial plexus. We believe that this approach is optimal when a superior sulcus tumor (SST) invades the anterior part of the thoracic inlet. However, this approach is not yet widely applied because anatomical relationships in this procedure are difficult to visualize. Three-dimensional tomography can considerably improve preoperative planning, enhance the surgeon's skill and simplify the approach to complex surgical procedures. We applied preoperative 3-dimensional multidetector computed tomography to a case where an SST had invaded the anterior part of the thoracic inlet including the clavicle, sternoclavicular joint, first rib, subclavian vessels and brachial plexus. After the patient underwent induction chemotherapy, we performed the transmanubrial osteomuscular-sparing approach and added a third anterolateral thoracotomy with a hemi-clamshell incision and completely resected the tumor.

Unlabelled: Epidermal growth factor receptor (EGFR) status and pathological stage (p-stage) were shown to be essential prognostic factors for estimating survival after recurrence of lung adenocarcinoma. In patients with EGFR mutations, those with early p-stage tumors showed better survival after disease recurrence than those with advanced p-stage tumors. The EGFR mutation status and p-stage could also prompt the design of clinical trials on adjuvant therapy for patients after complete surgical resection., Background: The current staging system and epidermal growth factor receptor (EGFR) mutation status are key factors for predicting survival. However, the significance of these factors as predictors of survival after disease recurrence (PRS) has not been sufficiently elucidated. The objective of this study was to investigate the clinicopathological factors, particularly the EGFR mutation status and pathological stage (p-stage), which affect PRS in patients with completely resected lung adenocarcinoma., Patients and Methods: We retrospectively reviewed the data of 198 consecutive lung adenocarcinoma patients with disease recurrence who previously underwent complete surgical resection in our hospital., Results: Of the 198 patients, 117 were examined for EGFR mutations (mutants). Mutants were detected in 57 patients (28.7%). The patients with mutants had a significantly better 3-year PRS (3y-PRS) rate (68.6%) than those with an EGFR wild type (WT) status (51.7%) or an unknown (UN) status (27.0%). The 3y-PRS rates for p-stage I to II (p-I-II) and p-stage III (p-III) were 52.5% and 29.3%, respectively. Multivariate survival analysis showed that the EGFR mutation status and p-stage had significant associations with favorable PRS. The 3y-PRS rate for mutants/p-I-II (81.4%) was significantly better than that for mutants/p-III (48.0%). Conversely, there was no significant difference between mutants/p-III and WT/UN/p-I-II (3y-PRS: 40.7%) or between mutants/p-III and WT/UN/p-III (3y-PRS: 24.4%)., Conclusion: EGFR status and p-stage were shown to be essential prognostic factors for estimating PRS. In patients with mutants, those with early p-stage tumors showed better PRS than those with advanced p-stage tumors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The relationships between the subtypes defined by the new international histologic classification of lung adenocarcinoma (IASLC/ATS/ERS) and epidermal growth factor receptor (EGFR) mutations were studied., Patients and Methods: We retrospectively reviewed 320 patients with lung adenocarcinoma (162 women, 158 men; mean age, 69 years) who had undergone complete resection, focusing on the new histologic subtypes and EGFR mutations. The clinical stage was IA in 196 patients, IB in 95, IIA in 10, IIB in 10, IIIA in 6, and IV in 3., Results: The most prevalent subtype was papillary (35.0%), followed by acinar (29.4%), lepidic (13.1%), solid (7.2%), adenocarcinoma in situ (6.6%), minimally invasive adenocarcinoma (6.3%), micropapillary (1.6%), and invasive mucinous adenocarcinoma (1.0%). These subtypes were predictive for both postoperative disease-free and overall survival. EGFR mutations, detected in 40.6% of all cases, were most frequent in acinar (48.4%), followed by minimally invasive adenocarcinoma (45.0%) and papillary (43.8%). They were least frequent in the solid subtype (17.4%). EGFR mutation status did not affect postoperative disease-free or overall survival., Conclusion: The outcome after complete resection for lung adenocarcinoma was predicted by the proposed subtype classification. Because EGFR mutations were found in all subtypes, mutation analyses are essential to identify patients with postoperative relapse who would benefit from EGFR-tyrosine kinase inhibitor therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The four major histological types of lung cancer are adenocarcinoma, squamous cell carcinoma (SQ), large cell carcinoma and small cell carcinoma. Over the past few decades, the incidence of lung adenocarcinoma has increased gradually in most countries as the most frequently occurring histological type, displacing SQ. Adenocarcinoma is the predominant type of lung cancer among lifelong non-smokers and among females. Especially in East Asian countries, the cause(s) of the increase in adenocarcinomas are not clear. Several genetic mutations specific to lung adenocarcinomas have been found, representing attractive targets for molecular therapy. Recently, the pathological classification of lung adenocarcinoma was revised by integrating the newer clinical and biological knowledge concerning this prevailing type. Additional epidemiological, pathological and genetic studies are required to better understand this type of lung cancer.

Background: We previously reported the prognostic impact of the number of involved lymph nodes (LNs) on survival in non-small cell lung cancer (NSCLC). However, it remains unknown whether the total number or anatomic location of involved LNs is a superior prognostic factor., Methods: A total of 689 patients with NSCLC who underwent complete resection involving dissection of the hilar and mediastinal LNs with curative intent of ≥ 10 LNs were enrolled. The association between the total number of LNs (nN) involved and survival was assessed by comparison with the anatomic location of LN involvement (pathologic lymph node [pN]), the present nodal category., Results: We classified the patients into five categories according to the combined pN and nN status as follows: pN0-nN0, pN1-nN1-3, pN1-nN4-, pN2-nN1-3, and pN2-nN4. Although there was no statistically significant difference between the pN1-nN4- and pN2-nN1-3 categories, pN2-nN1-3 had better prognoses than pN1-nN4-. On multivariate analysis, the nN category was an independent prognostic factor for overall survival and disease-free survival (vs nN4-; the hazard ratios of nN0 and nN1-3 for overall survival were 0.223 and 0.369, respectively, P &lt; .0001 for all), similar to the pN category. We propose a new classification based on a combination of the pN and nN categories: namely, N0 becomes pN0-nN0, the N1 category becomes pN1-nN1-3, the N2a category becomes pN2-nN1-3 + pN1-nN4-, and the N2b category becomes pN2-nN4. Each survival curve was proportional and was well distributed among the curves., Conclusions: A combined anatomically based pN stage classification and numerically based nN stage classification is a more accurate prognostic determinant in patients with NSCLC, especially in the prognostically heterogeneous pN1 and pN2 cases. Further large-scale international cohort validation analyses are warranted.

Objective: The objective of this study was to identify the clinicopathologic factors influencing postrecurrence survival (PRS) in and the effect of postrecurrence therapy (PRT) on patients with completely resected stage I non-small cell lung cancer (NSCLC)., Methods: We reviewed the data of 919 patients in whom complete resection of stage I NSCLC had been performed., Results: Of the 919 patients, 170 (18.5%) had recurrent disease. Initial PRT was performed in 118 patients (69.1%) (surgery in eight, chemotherapy in 79, radiotherapy in 10, and chemoradiotherapy in 21). On multivariate analyses, PRT (hazard ratio [HR], 0.542; 95% CI, 0.344-0.853; P = .008), female sex (HR, 0.487; 95% CI, 0.297-0.801; P = .005), and differentiation (HR, 1.810; 95% CI, 1.194-2.743; P = .005) demonstrated a statistically significant association with favorable PRS. Bone metastasis (HR, 3.288; 95% CI, 1.783-6.062; P &lt; .001), liver metastasis (HR, 4.518; 95% CI, 1.793-11.379; P = .001), chemotherapy (HR, 0.478; 95% CI, 0.236-0.975; P = .040), epidermal growth factor receptor-tyrosine kinase inhibitors treatment (EGFR-TKIs) (HR, 0.460; 95% CI, 0.245-0.862; P = .015), and nonadenocarcinoma (HR, 2.136; 95% CI, 1.273-3.585; P = .004) were independently and significantly associated with PRS in the 118 patients who underwent any PRT. Subgroup analysis with a combination of these five PRS factors in the patients who underwent any PRT revealed median PRS times of 42.4 months for 20 patients lacking all five risk factors and 18.8 months for 98 patients with at least one of these risk factors (P = .001)., Conclusions: PRT, sex, and differentiation were independently associated with PRS. In the patients who underwent any PRT, PRS was related to EGFR-TKIs, chemotherapy, histology, and initial recurrence sites. One challenge for the future will be to create systematic treatment strategies for recurrent NSCLC according to the risk factor status of individual patients.

We present a case of an aged male with invasive thymoma that extended into the right atrium and led to superior and inferior vena cava syndrome. The patient initially presented with edema of the face and bilateral lower extremities. Echocardiography revealed a mass within the right atrium. Imaging studies demonstrated an anterior mediastinal tumor that continuously occupied the bilateral brachiocephalic veins, superior vena cava, and right atrium. Pathological diagnosis of the tumor biopsy was highly suspicious of thymoma. Due to the high risk of wide spread of the tumor, treatments including resection of the tumor were impossible. Several days later he died, and an autopsy was performed. The tumor was type B2 thymoma invading bilateral brachiocephalic veins, superior vena cava and right atrium. Multiple tumor emboli within the pulmonary arteries were identified. Direct cause of death was deemed to be tumor strangulation at the tricuspid orifice. In addition to the superior vena cava syndrome, inferior vena cava syndrome including ectasia of the intrahepatic vessels was confirmed along with pericarditis. To our knowledge, this is the first English report of an autopsy case of intracardiac thymoma extension, and a detailed literature review of similar cases is also presented., (© 2012 The Authors. Pathology International © 2012 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)

Background: The purpose of the present study was to determine the nodal spread patterns of pN2 non-small cell lung cancer (NSCLC) according to tumor location, and to attempt to evaluate the possible indications of selective lymph node dissection (SLND)., Methods: We retrospectively analyzed nodal spread patterns in 207 patients with NSCLC of less than 5 cm with N2 involvement., Results: The tumor location was right upper lobe (RUL) in 79, middle lobe in 12, right lower lobe (RLL) in 40, left upper division (LUD) in 41, lingular division in 11, and left lower lobe (LLL) in 24. Both RUL and LUD tumors showed a higher incidence of upper mediastinal (UM) involvement (96 and 100%, respectively) and a lower incidence of subcarinal involvement (15 and 10%, respectively) than lower lobe tumors (UM; RLL 60%, LLL 42%; subcarinal: RLL 60%, LLL 46%, respectively). Among the patients with 24 right UM-positive RLL and 10 left UM-positive LLL tumors, 2 showed negative hilar, subcarinal, and lower mediastinal involvement, and cT1, suggesting that UM dissection may be unnecessary in lower lobe tumors with no metastasis to hilar, subcarinal, and lower mediastinal nodes on frozen sections according to the preoperative T status. Among the patients with 12 subcarinal-positive RUL and 4 subcarinal-positive LUD tumors, one showed negative hilar or UM involvement, suggesting that subcarinal dissection may be unnecessary in RUL or LUD tumors with no metastasis to hilar and UM nodes on frozen sections., Conclusions: The present study appears to provide one of the supportive results regarding the treatment strategies for tumor location-specific SLND.

Introduction: The appropriate therapeutic strategy and postoperative management for patients with stage IA non-small-cell lung cancer (NSCLC) still remain a matter of debate because of the prognostic heterogeneity of this population, including the risk of cancer recurrence. The objective of the current study was to identify the clinicopathological factors that affect overall prognosis and cancer recurrence of stage IA NSCLC., Methods: We reviewed the data of 532 patients in whom complete resection of stage IA NSCLC had been performed. Overall survival and recurrence-free proportion (RFP) were estimated using the Kaplan-Meier method. RFP was estimated from the date of the primary tumor resection to the date of the first recurrence or last follow-up. We performed univariate and multivariate analyses to determine the independent prognostic factors., Results: On multivariate analyses, three variables were shown to be independently significant recurrence risk factors: histological differentiation (hazard ratio [HR] = 1.925), blood-vessel invasion (HR = 1.712), and lymph-vessel invasion (HR = 1.751). On subgroup analyses combining these risk factors, the 5-year RFP was 91.3% for patients with no risk factors, 79.5% for those with either poorly differentiated carcinoma or vascular invasion, (p < 0.001 for both), and 62.9% for those with both poorly differentiated carcinoma and vascular invasion (p = 0.068)., Conclusion: These results indicated that vascular invasion and tumor differentiation have a significant impact on the prediction of cancer recurrence in patients with stage IA NSCLC. Patients with these predictive factors of recurrence may be good candidates for adjuvant chemotherapy.

Background: Lymph node (LN) status is a major determinant of stage and survival in patients with lung cancer. In the 7th edition of the TNM Classification of Malignant Tumors, the number of involved LNs is included in the definition of pN factors in breast, stomach, esophageal, and colorectal cancer, and the pN status significantly correlates with prognosis., Methods: We retrospectively investigated the prognostic impact of the number of resected LNs (RLNs) and involved LNs in the context of other established clinical prognostic factors, in a series of 928 consecutive patients with non-small cell lung cancer (NSCLC) who underwent complete resection at our institution between 2000 and 2007., Results: The mean number of RLNs was 15. There was a significant difference in the total number of RLNs categorized between less than 10 and ≥10 (p = 0.0129). Although the incidence of LN involvement was statistically associated with poor prognosis, the largest statistically significant increase in overall survival was observed between 0 to 3 and ≥4 involved LNs (hazard ratio = 7.680; 95% confidence interval = 5.051-11.655, p < 0.0001). On multivariate analysis, we used the ratio between the number of involved LNs and RLNs. The number of RLNs was found to be a strong independent prognostic factor for NSCLC (hazard ratio = 6.803; 95% confidence interval = 4.137-11.186, p < 0.0001)., Conclusion: Complete resection including 10 or more LNs influenced survival at complete NSCLC resection. Four involved LNs seemed to be a benchmark for NSCLC prognosis. The number of involved LNs is a strong independent prognostic factor in NSCLC, and the results of this study may provide new information for determining the N category in the next tumor, node, metastasis classification.