Search

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide despite advances in cancer therapeutics. In several gynecological cancers, anti-Müllerian hormone receptor type 2 (AMHR2) mediates AMH-induced growth inhibition and is expressed at high levels. Furthermore, 5%-8% of NSCLCs exhibit high AMHR2 expression, suggesting that AMH may inhibit the progression of some lung cancers. However, the clinical relevance of AMHR2 expression and its role in lung cancer is not fully clarified., Methods: Immunostaining was performed on 79 surgical specimens of NSCLC. The Cancer Genome Atlas RNA-seq data for lung adenocarcinoma were analyzed, and gene ontology and gene set enrichment analyses were performed. In cellular experiments, AMHR2-overexpressing NSCLC cell lines were established, and the role of the AMH-AMHR2 pathway in cell proliferation with recombinant human AMH protein treatment was examined., Results: A total of 13 cases (16.5%) were positive for immunostaining in lung adenocarcinoma tissues; no positive signals were detected in lung squamous carcinoma tissues. Gene expression variation analysis using The Cancer Genome Atlas data showed that the expression of genes related to the cell cycle was downregulated in the AMHR2-high group. Cellular experiments showed that activation of the AMH-AMHR2 pathway suppressed cell proliferation., Conclusion: In lung adenocarcinoma tissues with high expression of AMHR2, activation of the AMH-AMHR2 pathway may suppress cell proliferation., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. The overall survival has not improved significantly over the last decades because no major therapeutic breakthroughs have been achieved for over 15 years., Methods: We analyzed a genome-wide loss-of-function screening database to identify vulnerabilities in SCLC for the development of urgently needed novel therapies., Results: We identified SKP2 (encoding S-phase kinase-associated protein 2) and CKS1B (encoding CDC28 protein kinase regulatory subunit 1B) as the two most essential genes in that order in SCLC. Notably, SKP2 and CKS1B comprise the p27 binding pocket of the E3 ubiquitin ligase SCF SKP2 complex. Immunohistochemistry on tissue microarrays revealed that SKP2 was expressed in >95% of samples at substantially higher levels than that observed for commonly used neuroendocrine markers. As expected, SCLC cell lines were sensitive to SKP2 inhibition. Furthermore, SKP2 or CKS1B knockdown induced apoptosis in RB1 mutant cells, whereas it induced senescence in RB1 wild-type cells., Conclusion: Although the mechanism underlying SKP2 knockdown-induced growth inhibition differs between RB1-wild-type and -mutant SCLC, SKP2 can be considered a novel therapeutic target for patients with SCLC regardless of the RB1 mutation status. Our findings indicate that SKP2 is a potential novel clinical diagnostic marker and therapeutic target in SCLC., Competing Interests: Declaration of competing interest Ken Tajima received research funding from Novartis. Kazuhisa Takahashi received research funding from Chugai Pharm, MSD, Ono Pharm, and Bristol-Myers Squibb. Additionally, Kazuhisa Takahashi acknowledges donations from Eli Lilly Japan, Teijin Pharm, Chugai Pharm, Nippon Boehringer Ingelheim, Kyorin Pharm, Taiho Pharm, and Sanofi. The other authors have no conflicts of interest., (Copyright © 2024 [The Author]. Published by Elsevier B.V. All rights reserved.)

Objective: We examined cases in which delirium developed after thoracic surgery under general anesthesia at our hospital to determine the predictive factors for postoperative delirium, as well as the perioperative findings in cases showing postoperative delirium., Methods: This retrospective study included 1674 patients who underwent surgery under general anesthesia at our hospital between 2012 and 2022, A psychiatrist diagnosed postoperative delirium using the Confusion Assessment Method., Results: There were 99 (5.9%) patients with postoperative delirium in our study, including 85 (86%) men, of whom 31 (31%) had a history of cerebrovascular disease. The incidence of postoperative delirium in patients aged > 80 years was 20% (36/182). The postoperative delirium group showed significantly longer hospital stays and more frequent postoperative complications than the group without postoperative delirium. In univariate analysis, age ≥ 80 years, male sex, history of cerebrovascular disease, hypertension, history of atrial fibrillation, and history of smoking were identified as significant factors, while multivariate analysis identified age ≥ 80 years, male sex, history of cerebrovascular disease, hypertension, and history of smoking as significant factors (odds ratios = 5.15, 2.04, 3.10, 1.67, and 2.36, respectively). In the 169 cases with none of these five factors, the postoperative delirium risk was 0% (0/169)., Conclusions: In patients undergoing thoracic surgery, predictive factors for postoperative delirium include age ≥ 80 years, male sex, history of cerebrovascular disease, hypertension, and smoking history. The findings also indicate that patients with these risk factors may require psychiatric consultation before surgery., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Background and Objective: Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease., Methods: We investigated the relative risk of developing lung cancer among patients diagnosed with LAM between 2001 and 2022 at a single high-volume centre in Japan, using data from the Japanese Cancer Registry as the reference population. Next-generation sequencing (NGS) was performed in cases where tumour samples were available., Results: Among 642 patients diagnosed with LAM (sporadic LAM, n = 557; tuberous sclerosis complex-LAM, n = 80; unclassified, n = 5), 13 (2.2%) were diagnosed with lung cancer during a median follow-up period of 5.13 years. All patients were female, 61.5% were never smokers, and the median age at lung cancer diagnosis was 53 years. Eight patients developed lung cancer after LAM diagnosis. The estimated incidence of lung cancer was 301.4 cases per 100,000 person-years, and the standardized incidence ratio was 13.6 (95% confidence interval, 6.2-21.0; p = 0.0008). Actionable genetic alterations were identified in 38.5% of the patients (EGFR: 3, ALK: 1 and ERBB2: 1). No findings suggested loss of TSC gene function in the two patients analysed by NGS., Conclusion: Our study revealed that patients diagnosed with LAM had a significantly increased risk of lung cancer. Further research is warranted to clarify the carcinogenesis of lung cancer in patients with LAM., (© 2024 Asian Pacific Society of Respirology.)

Identifying the mechanisms of action of anticancer drugs is an important step in the development of new drugs. In this study, we established a comprehensive screening platform consisting of 68 oncogenes (MANO panel), encompassing 243 genetic variants, to identify predictive markers for drug efficacy. Validation was performed using drugs that targeted EGFR, BRAF, and MAP2K1, which confirmed the utility of this functional screening panel. Screening of a BRCA2-knockout DLD1 cell line (DLD1-KO) revealed that cells expressing SMO and GLI1 were resistant to olaparib. Gene set enrichment analysis identified genes associated with DNA damage repair that were enriched in cells overexpressing SMO and GLI1. The expression of genes associated with homologous recombination repair (HR), such as the FANC family and BRCA1/2, was significantly upregulated by GLI1 expression, which is indicative of PARP inhibitor resistance. Although not all representative genes of the nucleotide excision repair (NER) pathway were upregulated, NER activity was enhanced by GLI1. The GLI1 inhibitor was effective against DLD1-KO cells overexpressing GLI1 both in vitro and in vivo. Furthermore, the combination therapy of olaparib and GLI1 inhibitor exhibited a synergistic effect on DLD1-KO, suggesting the possible clinical application of GLI1 inhibitor targeting cancer with defective DNA damage repair. This platform enables the identification of biomarkers associated with drug sensitivity, and is a useful tool for drug development., (© 2024. The Author(s).)

Purpose: We evaluated the surgical outcomes of salvage extended surgery after definitive medical treatment with an immune-checkpoint inhibitor (ICI) for locally advanced or unresectable non-small-cell lung cancer (NSCLC)., Methods: The subjects of this single-center retrospective analysis were 14 patients who underwent salvage surgery after ICI treatment between May, 2017 and April, 2023 at our institute. We reviewed the comprehensive surgical outcomes, including operative procedures, intraoperative findings, and postoperative morbidities. Overall survival (OS) was calculated using a Kaplan-Meier estimation., Results: The initial clinical stage before medical treatment (c-stage) was stage III in eight patients, stage IV in five patients, and one patient had postoperative lung cancer recurrence. The indications for surgery were as follows: local control for relapse or residual tumor in ten patients and discontinuation of systemic therapy because of treatment-related complications in four patients. The surgical modes were segmentectomy (n = 1), lobectomy (n = 4), bilobectomy (n = 3), pneumonectomy (n = 6), and bronchoplasty (n = 7). Grade 3 or higher postoperative morbidities were observed in six patients, including only one case of 90-day mortality., Conclusions: Our series demonstrated that the surgical outcome of salvage extended surgery after ICI therapy may be positive with careful selection of the procedure and indication., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Objectives: This study aimed to evaluate the safety and feasibility of early chest tube removal after anatomic pulmonary resection, regardless of the drainage volume., Methods: We conducted a multicenter, randomized, controlled, noninferiority trial. Patients with greater than 300 mL drainage volume during postoperative day 1 were randomly assigned to group A (tube removed on postoperative day 2) and group B (tube retained until drainage volume ≤300 mL/24 hours). The primary end point was the frequency of respiratory-related adverse events (grade 2 or higher based on the Clavien-Dindo classification) within 30 days postoperatively., Results: Between April 2019 and October 2021, 175 patients were assigned to group A (N = 88) or group B (N = 87). One patient in group B who experienced chylothorax was excluded from the study. Respiratory-related adverse events were observed in 10 patients (11.4%) in group A and 12 patients (14.0%) in group B (P = .008). The frequencies of thoracentesis or chest tube reinsertion were not significantly different (8.0% and 9.3% in groups A and B, respectively, P = .752). Additionally, the duration of chest tube placement was significantly shorter in group A than in group B (median, 2 vs 3 days; P < .001). No significant difference between groups A and B was found in postoperative hospital stay (median, 6 vs 7 days, P = .231)., Conclusions: Early chest tube removal, regardless of drainage volume, was safe and feasible in patients who underwent anatomic pulmonary resection., Competing Interests: Conflict of Interest Statement K.T.: honoraria from AstraZeneca, Chugai, Ono, Nippon Kayaku, Johnson & Johnson, and Covidien. T.H.: payment or honoraria from Intuitive Surgical and Johnson and Johnson. M.T.: payment or honoraria Johnson & Johnson Japan, AstraZeneca KK, Eli Lilly Japan, Chugai Pharmaceutical Co, Ltd, Taiho Pharma, Medtronic Japan, Ono Pharmaceutical Co, Ltd, MSD, Bristol-Myers Squibb KK, and Novartis. N.O.: payment or honoraria from Johnson & Johnson. N.I.: payment or honoraria from Taiho Pharma, Bristol Myers, Chugai Pharma, Fuji Film Nihon Mediphysics, MSD, Daiichi-Sankyo, Boehringer Ingelheim, Shionogi, Medtronic, Johnson & Johnson, Olympus, Roche, and Ono Pharma. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Non-small cell lung cancer (NSCLC) patients with pleural dissemination are generally contraindicated for surgery. This study aimed to investigate the survival benefits of primary tumor resection for NSCLC patients with unexpectedly detected pleural disseminated nodules during thoracotomy in the era of targeted therapy., Methods: Of the 4984 patients with NSCLC who underwent surgery without induction therapy between 2000 and 2021, we retrospectively evaluated 90 (1.8%) patients with unexpectedly detected pleural disseminated nodule. Survival analyses were performed with Kaplan-Meier methods and Cox proportional hazards regression., Results: Among the evaluated patients, 58 were male, the median age was 67, and 77 (86%) were diagnosed with adenocarcinoma. Exploratory thoracotomy was performed in 21 (23%), and primary tumor resection was performed in 69 (77%) patients, including pneumonectomy in four, lobectomy in 39, and sublobar resection in 26. Epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase rearrangement were detected in 33 (37%) and 4 (4%) cases, respectively. Among them, 31 patients received targeted therapy. The overall survival (OS) was not significantly different between patients with primary tumor resection and exploratory thoracotomy (5-year OS rate: 30.2% vs. 27.8%, p = 0.81). Multivariable analysis revealed that sex (p = 0.02) and targeted therapy (p < 0.01) were independent prognostic factors for OS. Survival outcomes in patients who received targeted therapy were significantly better regardless of primary tumor resection., Conclusions: Primary tumor resection might not affect the survival in NSCLC patients with unexpectedly detected pleural disseminated nodules in the era of targeted therapy., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Objectives: The long-term oncological outcomes and risk factors for recurrence after lung segmentectomy are unclear. The aims of this study were to investigate the long-term prognosis and to evaluate risk factors for recurrence after segmentectomy., Methods: Between January 2008 and December 2012, a total of 177 patients underwent segmentectomy for clinical stage I non-small cell lung cancer. The median follow-up period was 120.1 months. The overall survival (OS) and recurrence-free survival curves were analysed using the Kaplan-Meier method with a log-rank test. Univariable and multivariable analyses were used to identify significant factors that predicted recurrence., Results: The study included 177 patients with a median age of 67 years. The median operative time was 155 min. No 30-day deaths were observed. Nine patients (5.1%) had recurrences: loco-regional in 3, distant in 3 and both in 3. The 5-year and 10-year recurrence-free survival rates were 89.7% and 79.8%, and the OS rates were 90.9% and 80.4%, respectively. On multivariable analysis, the risk factor associated with recurrence was a pure solid tumour [hazard ratio, 23.151; 95% confidence interval 2.575-208.178; P = 0.005]. The non-pure solid tumour group had a significantly better probability of survival (5-year OS: 95.4% vs 77.2%; 10-year OS: 86.5% vs 61.8%; P < 0.0001). A total of 113 patients received preoperative positron emission tomography/computed tomography. Patients with a higher maximum standardized uptake value had a significantly higher recurrence rate., Conclusions: Segmentectomy for clinical stage I non-small cell lung cancer produced acceptable long-term outcomes. Pure solid radiographic appearance was associated with recurrence and decreased survival., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Purpose: Bronchopleural fistula (BPF) is a lethal complication, even in the modern era. Therefore, we investigated the details of patients with BPF to select an appropriate surgical strategy., Methods: This retrospective study included 4794 consecutive patients who underwent anatomical pulmonary resection between 2008 and 2022. We evaluated the predictors of BPF using a multivariable analysis and investigated the mortality and clinical course after BPF in detail., Results: BPF was observed in 32 patients (0.67%). In the multivariable analysis, the predictors for BPF were male sex (odds ratio [OR], 6.91), the body mass index (OR, 2.40), the vital capacity (%VC) (OR, 2.93), surgery performed (right lower lobectomy [OR, 10.92], right middle and lower lobectomy [OR, 6.97], and right pneumonectomy [OR, 16.68]), and additional resection of surrounding organs (OR, 3.47). Among the risk factors, surgery performed and male sex were very strong risk factors, with the frequency itself very low in females (0.1%). The 90-day mortality was 15.6%, and the 5-year overall survival in patients with BPF was 28.1%., Conclusion: Our study revealed that independent risk factors and consideration of the surgical methods and sex might help determine whether or not special attention should be given to the bronchial stump, which will be of great help in surgical strategies., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

We evaluated the prognostic role of the presence of a very small ground glass opacity (GGO) component in stage IA solid-predominant non-small cell lung cancer (NSCLC). We evaluated surgically resected 1471 patients diagnosed with stage IA solid-predominant NSCLC. They were classified into 3 groups; that is, GGO group (0.5

Introduction: Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein overexpressed in various cancer types. Although TROP2-targeting therapy is currently attracting attention, little is known about TROP2 expression in thymic carcinoma., Methods: TROP2 gene expression in thymic epithelial tumors was analyzed using RNA-sequencing (RNA-seq) data for 122 cases obtained from The Cancer Genome Atlas. Immunohistochemistry (IHC) staining with anti-TROP2 antibody (SP295) was performed in 26 cases of thymic carcinoma tissues surgically resected at Juntendo University., Results: RNA-seq data analysis from The Cancer Genome Atlas revealed that TACSTD2 (gene encoding TROP2) expression was significantly higher in thymic carcinoma than in thymoma (adjusted p  = 6.64e-05). There was also a trend of increasing expression in the order of thymoma type B1, B2, B3, and thymic carcinoma. As for IHC in thymic carcinoma, TROP2 expression was localized to the membrane of cancer cells. Intensity 0, 1, and 2 was observed in six (23.1%), 11 (42.3%), and nine (34.6%) cases, respectively, leading to TROP2 positivity in 20 cases (76.9%). The median proportion of TROP2-positive tumor cells and the median H-score were 25.0% (range: 0%-100%) and 25.0 (range: 0-200), respectively. No relevant factors were identified in the analysis of TROP2 expression and patient background. Although not significant, high TROP2 expression (H-score ≥ 50) tended to be associated with shorter survival., Conclusions: TROP2 expression in thymic carcinoma was confirmed by both RNA-seq and IHC, with high expression observed in IHC for intensity (76.9%) and proportion. TROP2 could be a potential target in thymic carcinoma., Competing Interests: Dr. Asao reports honoraria from AstraZeneca K.K., Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K, Merck Biopharma Co., Ltd., Merck Sharp & Dohme K.K, Nippon Boehringer Ingelheim Co., Ltd., Nippon Kayaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Pfizer Inc., Taiho Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Company Limited outside of the submitted work. Dr. Shukuya reports grants and honoraria from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., and Merck Sharp & Dohme K.K. and honoraria from Taiho Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Company, Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Company, Pfizer Inc., and Eisai Co., Ltd. outside of the submitted work. Dr. Fumiyuki Takahashi reports grants from 10.13039/100004325AstraZeneca, 10.13039/100017346Nippon Boehringer Ingelheim, 10.13039/100009947Merck Sharp & Dohme, 10.13039/100004336Novartis, and Lilly Japan outside of the submitted work. Dr. Kazuhisa Takahashi reports grants and honoraria from Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Pfizer Inc., Taiho Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Novartis Pharma K.K., Eli Lilly Japan K.K., Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Company Limited, and grants from 10.13039/100018036Nippon Shinyaku Co., Ltd., Tsumura & Co., Teijin Pharma Limited, 10.13039/100015990Sanofi K.K., Shionogi & Co., Ltd., Bayer Yakuhin, Ltd., 10.13039/501100002973Daiichi Sankyo Co., Ltd., Nipro Pharma Corporation, 10.13039/100010740Asahi Kasei Pharma Corporation, Kyowa Kirin Co., Ltd., and honoraria from Merck Sharp & Dohme K.K., AstraZeneca K.K., Merck Biopharma Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Bristol-Myers K.K., Meiji Seika Pharma Co., Ltd., Viatris Inc., Janssen Pharmaceutical K.K., Abbott Japan LLC, and Thermo Fisher Scientific Inc. outside the submitted work. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Objective: Clinical stage IA non-small cell lung cancer (NSCLC) showing a pure-solid appearance on computed tomography is associated with a worse prognosis. This study aimed to develop and validate machine-learning models using preoperative clinical and radiomic features to predict overall survival (OS) in clinical stage IA pure-solid NSCLC., Methods: Patients who underwent lung resection for NSCLC between January 2012 and December 2020 were reviewed. The radiomic features were extracted from the intratumoral and peritumoral regions on computed tomography. The machine-learning models were developed using random survival forest and eXtreme Gradient Boosting (XGBoost) algorithms, whereas the Cox regression model was set as a benchmark. Model performance was assessed using the integrated time-dependent area under the curve (iAUC) and validated by 5-fold cross-validation., Results: In total, 642 patients with clinical stage IA pure-solid NSCLC were included. Among 3748 radiomic and 34 preoperative clinical features, 42 features were selected. Both machine-learning models outperformed the Cox regression model (iAUC, 0.753; 95% confidence interval [CI], 0.629-0.829). The XGBoost model showed a better performance (iAUC, 0.832; 95% CI, 0.779-0.880) than the random survival forest model (iAUC, 0.795; 95% CI, 0.734-0.856). The XGBoost model showed an excellent survival stratification performance with a significant OS difference among the low-risk (5-year OS, 100.0%), moderate low-risk (5-year OS, 88.5%), moderate high-risk (5-year OS, 75.6%), and high-risk (5-year OS, 41.7%) groups (P < .0001)., Conclusions: A radiomics-based machine-learning model can preoperatively and accurately predict OS and improve survival stratification in clinical stage IA pure-solid NSCLC., Competing Interests: Conflict of Interest Statement K.T. receives personal fees from Johnson & Johnson, AstraZeneca, Eli Lilly, Chugai, Taiho, Medtronic, and Ono. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Evaluating the diffusing capacity for carbon monoxide (DLco) is crucial for patients with lung cancer and interstitial lung disease. However, the clinical significance of assessing exercise oxygen desaturation (EOD) remains unclear., Methods: We retrospectively analysed 186 consecutive patients with interstitial lung disease who underwent lobectomy for non-small-cell lung cancer. EOD was assessed using the two-flight test (TFT), with TFT positivity defined as ≥5% SpO2 reduction. We investigated the impact of EOD and predicted postoperative (ppo)%DLco on postoperative complications and prognosis., Results: A total of 106 (57%) patients were identified as TFT-positive, and 58 (31%) patients had ppo% DLco < 30%. Pulmonary complications were significantly more prevalent in TFT-positive patients than in TFT-negative patients (52% vs 19%, P < 0.001), and multivariable analysis revealed that TFT-positivity was an independent risk factor (odds ratio 3.46, 95% confidence interval 1.70-7.07, P < 0.001), whereas ppo%DLco was not (P = 0.09). In terms of long-term outcomes, both TFT positivity and ppo%DLco < 30% independently predicted overall survival. We divided the patients into 4 groups based on TFT positivity and ppo%DLco status. TFT-positive patients with ppo%DLco < 30% exhibited the significantly lowest 5-year overall survival among the 4 groups: ppo%DLco ≥ 30% and TFT-negative, 54.2%; ppo%DLco < 30% and TFT-negative, 68.8%; ppo%DLco ≥ 30% and TFT-positive, 38.1%; and ppo%DLco < 30% and TFT-positive, 16.7% (P = 0.001)., Conclusions: Incorporating EOD evaluation was useful for predicting postoperative complications and survival outcomes in patients with lung cancer and interstitial lung disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The pulmonary artery runs around the left upper bronchus, which poses the risk of blood vessel injury when cutting in the blind spot of the bronchus. During robotic surgery, the robotic arm holds the tissue under constant tension; therefore, even if the pulmonary artery is left for final transection, it is not injured by unexpected tension. In this study, we examined the usefulness of final transection of the proximal pulmonary artery in robotic left upper lobectomy., Methods: This retrospective single-institution study evaluated patients who had undergone robotic lung resection. Of the 453 robotic lung resections performed at our institution between 2017 and 2022, 49 patients who had undergone left upper lobectomy were evaluated. Patients who had undergone bronchial transection followed by pulmonary artery transection were assigned to the group, bronchus prior transection (BT group, n = 38), and those who had undergone pulmonary artery transection followed by bronchial transection were assigned to the group, pulmonary artery prior transection (AT group, n = 11). Patient characteristics and perioperative outcomes were compared between the groups., Results: The groups did not differ significantly in age, sex, smoking history, tumour size, complication rates or 30-day mortality. The BT group inclined to shorter operative times and lesser blood loss. No active intraoperative bleeding occurred in the BT group. However, the AT group had 2 cases of intraoperative pulmonary artery bleeding, one of which required urgent conversion to thoracotomy., Conclusions: Final transection of the proximal pulmonary artery is a novel and effective surgical technique for robotic left upper lobectomy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: This study aimed to investigate predictors of thoracic aortic invasion in lung cancer patients using preoperative clinical and imaging characteristics and elucidate surgical outcomes in cases of aortic invasion., Methods: Of the 4751 lung cancer patients who underwent surgery at our hospital, we included 126 (6.8%) who underwent left-sided surgery and in whom tumor appeared to be in contact with the thoracic aorta on preoperative imaging. The patients were divided into two groups: group A, 23 patients (18%) who underwent combined aortic resection (+); group B, 103 patients (82%) who did not undergo combined aortic resection (-)., Results: The percentage of aortic invasion for tumor diameter <3 cm, 3-4 cm, 4-5 cm, 5-7 cm, and >7 cm was 0%, 13%, 23%, 16%, and 35%, respectively. The percentages of aortic invasion were 27%, 16%, and 0% for tumor localization in the upper division, S6, and S10, respectively. Multivariate analysis revealed that aortic depression due to tumor or loss of fatty tissue between tumor and mediastinum in the chest CT significantly predicted aortic invasion (odds ratio = 23.83, 16.66). Group A demonstrated significantly more blood loss, longer operative time, prolonged hospital stay, and increased percentage of recurrent nerve palsy (13%) compared to group B. The 1-, 3-, and 5-year survival rates for patients in group A were 53.4%, 24.3%, and 24.3%, respectively., Conclusion: If the chest CT of a patient demonstrates aortic depression due to tumor or loss of fatty tissue between tumor and mediastinum, aortic complications should be considered when planning surgery., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Objectives: To validate or refute the hypothesis that non-small-cell lung cancers (NSCLC) with ground-glass areas (GGA+) within the tumour on high-resolution computed tomography are associated with a more favourable prognosis than those without GGA (GGA-)., Methods: We analysed data from a multicentre observational cohort study in Japan including 5005 patients with completely resected pathological stage I NSCLC, who were excluded from the Japan Clinical Oncology Group (JCOG) 0707 trial on oral adjuvant treatment during the enrolment period. The patients' medical and pathological records were assessed retrospectively by physicians and re-staged according to the 8th tumour, node, metastasis edition., Results: Of the 5005 patients, 2388 (48%) were ineligible for the JCOG0707 trial and 2617 (52%) were eligible but were not enrolled. A total of 958 patients (19.1%) died. Patients with GGA+ NSCLC and pathological invasion ≤3 cm showed significantly better overall survival than others. In patients with tumours with an invasive portion ≤4 cm, GGA+ was associated with better survival. The prognoses of patients with GGA+ T2a and GGA- T1c tumours were similar (5-year overall survival: 84.6% vs 83.1%, respectively). The survival with T2b or more tumours appeared unaffected by GGA, and GGA was not prognostic in these larger tumours., Conclusions: Patients with GGA+ NSCLC on high-resolution computed tomography and ≤4 cm invasion size may have a better prognosis than patients with solid GGA- tumours of the same T-stage. However, the presence or absence of radiological GGA has little impact on the prognosis of patients with NSCLC with greater (>4 cm) pathological invasion., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Purpose: To elucidate clinical outcomes using a digital drainage system (DDS) for massive air leakage (MAL) after pulmonary resection., Methods: A total of 135 consecutive patients with pulmonary resection air leakage of > 100 ml/min on the DDS were evaluated retrospectively. In this study, MAL was defined as ≥ 1000 ml/min on the DDS. We analyzed the clinical characteristics and surgical outcomes of patients with MAL compared with non-MAL (101-999 ml/min). Using the DDS data, the duration of the air leak was plotted with the Kaplan‒Meier method and compared using the log-rank test., Results: MAL was detected in 19 (14%) patients. The proportions of heavy smokers (P = 0.04) and patients with emphysematous lung (P = 0.03) and interstitial lung disease (P < 0.01) were higher in the MAL group than in the non-MAL group. The MAL group had a higher persistence rate of air leakage at 120 h after surgery than the non-MAL group (P < 0.01) and required significantly more frequent pleurodesis (P < 0.01). Drainage failure occurred in 2 (11%) and 5 (4%) patients from the MAL and non-MAL groups, respectively. Neither reoperation nor 30-day surgical mortality was observed in patients with MAL., Conclusions: MAL was able to be treated conservatively without surgery using the DDS., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

In the open-label, phase III CheckMate 816 study (NCT02998528), neoadjuvant nivolumab plus chemotherapy demonstrated statistically significant improvements in event-free survival (EFS) and pathological complete response (pCR) versus chemotherapy alone in patients with resectable non-small-cell lung cancer (NSCLC). Here we report efficacy and safety outcomes in the Japanese subpopulation. Patients with stage IB-IIIA, resectable NSCLC were randomized 1:1 to nivolumab plus chemotherapy or chemotherapy alone for three cycles before undergoing definitive surgery within 6 weeks of completing neoadjuvant treatment. The primary end-points (EFS and pCR) and safety were assessed in patients enrolled at 16 centers in Japan. Of the Japanese patients randomized, 93.9% (31/33) in the nivolumab plus chemotherapy arm and 82.9% (29/35) in the chemotherapy arm underwent surgery. At 21.5 months' minimum follow-up, median EFS was 30.6 months (95% confidence interval [CI], 16.8-not reached [NR]) with nivolumab plus chemotherapy versus 19.6 months (95% CI, 8.5-NR) with chemotherapy; hazard ratio, 0.60 (95% CI, 0.30-1.24). The pCR rate was 30.3% (95% CI, 15.6-48.7) versus 5.7% (95% CI, 0.7-19.2), respectively; odds ratio, 7.17 (95% CI, 1.44-35.85). Grade 3/4 treatment-related adverse events were reported in 59.4% versus 42.9% of patients, respectively, with no new safety signals identified. Neoadjuvant nivolumab plus chemotherapy resulted in longer EFS and a higher pCR rate versus chemotherapy alone in Japanese patients, consistent with findings in the global population. These data support nivolumab plus chemotherapy as a neoadjuvant treatment option in Japanese patients with resectable NSCLC., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

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.)

Objective: To investigate the influence of simple preoperative exercise tests as prognostic factors for early-stage lung cancer., Methods: This single-institution retrospective study included consecutive patients who underwent pulmonary resection for stage 0 to I lung cancer between April 2017 and December 2019. Before surgery, 7 metabolic equivalents of task in the double Master 2-step test were loaded into the exercise echocardiogram. The relationship between prognosis and exercise stress test results in terms of availability, symptoms, and saturation of percutaneous oxygen was investigated., Results: This study included 862 patients with pathological stage 0 to I lung cancer. Among the 862 patients, 673 patients (78.1%) who were able to complete 7 metabolic equivalents of task exercise for 3 minutes without assistance were classified into the complete group. The 5-year survival of the complete group was significantly better than that of the incomplete group. Multivariable analysis revealed that age (hazard ratio, 1.06; P = .008), male sex (hazard ratio, 2.23; P = .011), carcinoembryonic antigen level >5 ng/mL (hazard ratio, 2.33; P = .011), and inability to complete 7 metabolic equivalents of task exercise (hazard ratio, 3.90; P < .001) were the prognostic factors. Patients in the older group who had the ability to complete exercise had a better prognosis than those in the younger group without the ability (P = .003)., Conclusions: Preoperative exercise ability is a prognostic factor for early-stage lung cancer. Patients who can tolerate an exercise load of 7 metabolic equivalents of task, even if they are aged 70 years or older, have a better prognosis than patients younger than age 70 years without exercise tolerance., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: The phase III trial, Japan Clinical Oncology Group 0802, illustrated the superiority of sublobar resection for early-stage lung cancer in terms of overall survival, with more non-lung cancer-related deaths after a lobectomy. The advantages of sublobar resection may be more pronounced in high-risk patients. The goal of this study was to elucidate the prognoses of high-risk patients., Methods: Patients with a risk of being ineligible for Japan Clinical Oncology Group 0802 for general conditions were classified as the high-risk group, and those who were not at risk of being ineligible were classified as the normal-risk group. Overall survival and prognostic factors were analysed in the high-risk group., Results: There were 254 (19.4%) and 1054 patients in the high- and normal-risk groups, respectively. Five-year survival rates were 94.5% and 79.1% in the normal-risk and high-risk groups, respectively (P < 0.001). More patients in the high-risk group died of lung cancer (P < 0.001) and non-lung cancer deaths (P < 0.001) than patients in the normal-risk group.In the high-risk group, 151 lobectomies and 103 sublobar resections were performed. There was no significant difference in the numbers of lung cancer deaths and of non-lung cancer deaths between the procedures. Stratified survival analyses showed that the diffusing capacity of the lungs for carbon monoxide  < 40% tended to favour sublobar resection; being female and having a high carcinoembryonic antigen level tended to favour a lobectomy., Conclusions: Sublobar resection is not always superior for early-stage lung cancer. Even in such cases, the surgical method should be determined by taking into consideration the patient's background and lung cancer surveillance., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

A limited number of patients with lung squamous cell carcinoma (SCC) benefit clinically from molecular targeted drugs because of a lack of targetable driver alterations. We aimed to understand the prevalence and clinical significance of lysine-specific demethylase 5D (KDM5D) copy number loss in SCC and explore its potential as a predictive biomarker for ataxia-telangiectasia and Rad3-related (ATR) inhibitor treatment. We evaluated KDM5D copy number loss in 173 surgically resected SCCs from male patients using fluorescence in situ hybridization. KDM5D copy number loss was detected in 75 of the 173 patients (43%). Genome-wide expression profiles of the transcription start sites (TSSs) were obtained from 17 SCCs, for which the cap analysis of gene expression assay was performed, revealing that upregulated genes in tumors with the KDM5D copy number loss are associated with 'cell cycle', whereas downregulated genes in tumors with KDM5D copy number loss were associated with 'immune response'. Clinicopathologically, SCCs with KDM5D copy number loss were associated with late pathological stage (p = 0.0085) and high stromal content (p = 0.0254). Multiplexed fluorescent immunohistochemistry showed that the number of tumor-infiltrating CD8 + /T-bet + T cells was lower in SCCs with KDM5D copy number loss than in wild-type tumors. In conclusion, approximately 40% of the male patients with SCC exhibited KDM5D copy number loss. Tumors in patients who show this distinct phenotype can be 'cold tumors', which are characterized by the paucity of tumor T-cell infiltration and usually do not respond to immunotherapy. Thus, they may be candidates for trials with ATR inhibitors., (© 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Background: Adjuvant cisplatin-based chemotherapy improves the survival of patients with resected pathological stage II/III nonsmall cell lung cancer (NSCLC). However, the efficacy in patients with epidermal growth factor receptor (EGFR) mutations remains controversial., Methods: This retrospective study included 353 patients with resected pathological N1/N2 stage II/III NSCLC between 2010 and 2016. Mutant EGFR (mEGFR) was detected in 76 patients. Adjuvant chemotherapy (AC) was administered to 151 patients. We compared cancer-specific survival (CSS) and recurrence-free survival (RFS) between AC and surgery-alone (SA) groups, including patients with wild-type EGFR (wEGFR) and mEGFR. Using multivariate analysis, we evaluated the prognostic factors in patients with wEGFR and mEGFR., Results: The median follow-up time was 4.7 years. In patients with wEGFR, the differences in CSS and RFS between the AC ( n  = 114) and SA ( n  = 163) groups were significant (CSS: 66.8% [5 years] vs. 49.4% [5 years], p  = 0.001; RFS: 54.2% [5 years] vs. 39.2% [5 years], p  = 0.013). The significant prognostic factors were AC (vs. SA; p  < 0.0001), diffusing capacity of the lung for carbon monoxide  > 60% ( p  = 0.028), tumor size ( p  < 0.001), lymphatic permeation ( p  = 0.041), and pN1 (vs. pN2; p  < 0.001). However, the differences in CSS and RFS between the AC ( n  = 37) and SA ( n  = 39) groups were not significant (CSS: 64.0% [5 years] vs. 58.1% [5 years], p  = 0.065; RFS: 45.0% [5 years] vs. 33.8% [5 years], p  = 0.302). Multivariate analysis identified no significant prognostic factors in patients with mEGFR., Conclusion: We demonstrated the efficacy of AC in patients with mEGFR and wEGFR. The efficacy of AC may be lower in patients with mEGFR than in those with wEGFR., Competing Interests: None declared., (Thieme. All rights reserved.)

Objectives: We evaluated the clinicopathological and oncological characteristics of epidermal growth factor receptor-mutated clinical stage IA radiological pure-solid lung adenocarcinoma and compared them with those of a ground-glass opacity component., Methods: Between 2008 and 2020, data from 1014 surgically resected clinical stage 0-IA epidermal growth factor receptor-mutated lung adenocarcinomas were evaluated. Oncological outcomes were assessed using multivariable analysis. Overall survival was estimated using Kaplan-Meier analysis and the log-rank test. The cumulative incidence of recurrence was estimated using the Gray's test., Results: Of these, 233 (23%) were radiologically pure-solid tumors, which demonstrated a higher proportion of nodal metastasis, micropapillary component, spread through alveolar space, and Ex19 subtype compared with those of tumors with ground-glass opacity (P < .001). Multivariable analysis revealed that the presence of ground-glass opacity was an independently significant factor for overall survival (P = .037) and cumulative incidence of recurrence (P < .001). In cases where the oncological outcomes were stratified by the presence of ground-glass opacity component, the 5-year overall survival was excellent at more than 90% in tumors with ground-glass opacity despite clinical-T categories (P = .2044); however, tumor size significantly affected survival only in pure-solid tumors (T1a, 100%; T1b, 77.7%; T1c, 68.5%; P = .0056). Furthermore, the cumulative incidence of recurrence was low in tumors with ground-glass opacity despite the clinical-T categories, whereas tumor size significantly affected the cumulative incidence of recurrence only in pure-solid tumors (5-year cumulative incidence of recurrence: T1a-b, 18.9%; T1c, 41.3%; P < .001)., Conclusions: Oncologic behavior and prognosis of radiologically pure-solid tumors were significantly poorer than those of tumors with ground-glass opacity among patients with epidermal growth factor receptor-mutated early-stage lung adenocarcinoma. These findings imply distinct tumorigenesis based on the presence of ground-glass opacity, even in tumors with epidermal growth factor receptor mutations., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: We aimed to compare the outcomes of segmentectomy with those of lobectomy in T1c (>2-3 cm) radiological pure-solid non-small-cell lung cancer detected on thin-section computed tomography., Methods: This retrospective review compared the survival outcomes, causes of death and recurrence patterns between the segmentectomy and lobectomy in patients with c-T1cN0M0 radiological pure-solid non-small-cell lung cancer. Multivariable analysis was performed to control for confounders of survival. The overall survival (OS) and recurrence-free survival were analysed using the Kaplan-Meier method. Differences in cumulative incidence of recurrence between groups were assessed using the methods of Gray., Results: Of the 426 patients, lobectomy was performed in 381 patients and segmentectomy in 45 patients. Nodal metastasis was noted in 104 (24.4%) patients. Multivariable analysis revealed that lobectomy was an independent prognosticator of better OS (hazard ratio 0.596, 95% confidence interval 0.366-0.969; P = 0.037). Lobectomy arm showed favourable 5-year OS and recurrence-free survival (OS: 72.9% vs 59.7%, log-rank test P = 0.007; recurrence-free survival: 64.4% vs 48.7%, P = 0.034) (median follow-up: 53 months). Approximately 14% of the patients in the lobectomy group and 27% in the segmentectomy group died of lung cancer. Furthermore, 5-year cumulative incidence of loco-regional recurrence rate was significantly higher in the segmentectomy group (35.5% vs 15.8%, P < 0.001)., Conclusions: In T1c radiological pure-solid non-small-cell lung cancer, segmentectomy was significantly associated with worse survival and insufficient loco-regional cancer control. Lobectomy remains the standard surgical treatment; meanwhile, segmentectomy should be applied with great caution., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Based on the current World Health Organization classification criteria, five of 3895 consecutive cases of surgically resected primary lung carcinomas (0.13%) categorized as enteric-type were analyzed. Three cases completely comprised tumor cells that resemble colorectal adenocarcinoma, while the other two cases exhibited features of conventional adenocarcinomas admixed with enteric components. Immunohistochemically, all patients expressed at least three of the five intestinal markers: CDX2, CK20, HNF4α, MUC2, and SATB2. None of the patients expressed TTF-1 and NKX3.1. Three cases showed nuclear accumulation of β-catenin, indicating activation of the Wnt/β-catenin signaling pathway; APC mutations were detected in one of these cases. TP53 mutations were detected in three cases. Mutated EGFR or ALK fusions were not detected. Our study demonstrates that pulmonary enteric-type adenocarcinomas share immunohistochemical features and genetic alterations with colorectal adenocarcinomas, which are characterized by frequent activation of the Wnt/β-catenin signaling pathway and a lack of actionable mutations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Tumors invading the tracheobronchial angle or carina have long presented a challenge due to the complexity of airway reconstruction and management; thus, few medical centers have developed experience with this type of surgery. In this report, we review our experience with Sleeve Pneumonectomy (SP) and analyze both operative risks and outcomes., Materials and Methods: A retrospective review identified 34 patients who underwent SP: 19 underwent salvage SP and 15 underwent non-salvage SP. Salvage surgery was performed for recurrent lung cancer after chemoradiotherapy and could be considered if there were no other therapeutic options or in the presence of urgent symptoms, such as hemoptysis, obstructive pneumonia, superior vena cava syndrome, or tracheoesophageal fistula.The perioperative morbidity and oncological outcomes of salvage and non-salvage SP were analyzed., Results: Most cases were of lung cancer, whereas salvage SP included one case of SVC syndrome due to metastasis of colon cancer and one case of hemoptysis due to metastasis of leiomyosarcoma. Complications occurred in 47% of the non-salvage SP cases and 53% of the salvage SP cases. The 30-day mortality rates were zero in the non-salvage cases and 11% in the salvage cases. The 90-day mortality rates were 20% and 16% in the non-salvage and salvage groups, respectively., Conclusions: The salvage of SP after chemoradiotherapy or in the presence of urgent symptoms is feasible. We believe that it can be an option that improves quality of life (QOL) through longer desease-free survival (DFS) and alleviation of symptoms, rather than waiting for tumor growth progression and exacerbation of symptoms., Competing Interests: The authors declares that there are no conflicts of interest., (2023 ©The Juntendo Medical Society.)

Introduction: Invasive mucinous lung adenocarcinoma (IMA) has unique radiological findings and pathological characteristics. IMA is classified into solitary and pneumonic types; however, it is unclear whether these are biologically identical., Methods: A single-center retrospective analysis was performed for 70 IMA patients (solitary type [n = 38] and pneumonic type [n = 32]) who underwent pulmonary resection between January 2010 and December 2018. We compared clinical and biological characteristics between the two types., Results: The frequencies of genetic alternations such as EGFR, KRAS, BRAF, GNAS, ERBB2, TP53, NRG1, and MET were not different. Immunohistochemically, expression of MUC1 was significantly more common in the pneumonic type (5.0% versus 20.0%, p = 0.01) and diffuse MUC6 positive in the solitary type (39.0% versus 13.0%, p = 0.02). We further classified solitary types into those with or without ground-glass opacity (GGO) and pneumonic types into those with or without crazy-paving appearance (CPA), and evaluated their surgical outcomes. Five-year overall survival and relapse free survival rates were 95.8%/86.6%, 64.3%/70.7%, 74.6%/68.9%, and 50.0%/28.6% in patients with solitary type with GGO, solitary type without GGO, pneumonic type without CPA, and pneumonic type with CPA, respectively., Conclusions: There were no differences in genetic alternations; however, mucin expression pattern was different. Surgical outcomes were different according to the presence of GGO in the solitary type and the presence of CPA in the pneumonic type. These findings suggested a stepwise progression from solitary to pneumonic IMA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Clinical T factors in the 8th TNM classification of lung cancer have a practical problem. In some cases, it is difficult to measure the size of the solid components in part-solid tumors, and the classification of these tumors is controversial., Methods: We evaluated 590 resected cT1N0M0 stage IA non-small-cell lung cancers based on the 7th edition between 2009 and 2012. Tumor and solid component diameters were measured using thin-section computed tomography (CT). We defined tumors with difficulty in measuring the size of the solid components as lung cancers with scattered or mixed consolidation (LCSMCs). LCSMCs were observed in 79 (13.4%) patients. Other tumors were classified as cTis, cT1mi, cT1a, cT1b, and cT1c, according to the 8th edition. We compared prognosis and epidermal growth factor receptor mutations (EGFRm) status of LCSMCs with those of cT1a, cT1b, and cT1c., Results: The difference in overall survival (OS) among cT1a, cT1b, and cT1c was significant (5-year-OS: 96.9% vs. 76.8% vs. 65.0%). There was no significant difference in prognosis between LCSCs and cT1a (5-year-OS: 92.4% vs. 96.9%). A significant difference was observed in the frequency of EGFRm between cT1a, cT1b, and cT1c (52.4%, 42.4%, and 29.8%). The incidence of EGFRm in LCSMCs was 54.8% and there was no significant difference between LCSMCs and cT1a., Conclusions: The prognosis and frequency of EGFRm in LCSMCs were close to those in cT1a. As we cannot measure the diameter of the solid component in subsolid lung cancers, it may be appropriate to classify these tumors as cT1a tumors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Some patients have worse actual observed postoperative (apo) respiratory function values than predicted postoperative (ppo) values. The present study therefore clarified the predictive factors that hinder the recovery of the postoperative respiratory function., Methods: This study enrolled 255 patients who underwent anatomical pulmonary resection for lung cancer. A pulmonary function test (PFT) was carried out before surgery and at one, three, and six months after surgery. In each surgical procedures, the forced expiratory volume in 1 s (FEV1) ratio was calculated as the apo value divided by the ppo value. In addition, we investigated the predictive factors that inhibited postoperative respiratory function improvement in patients with an FEV1 ratio < 1.0 at 6 months after surgery., Results: The FEV1 ratio gradually improved over time in all surgical procedures. However, 49 of 196 patients who underwent a PFT at 6 months after surgery had an FEV1 ratio < 1.0. In a multivariate analysis, right side, upper lobe, segmentectomy and pleurodesis for prolonged air leakage were independent significant predictors of a decreased FEV1 ratio (p = 0.003, 0.006, 0.001, and 0.009, respectively)., Conclusion: Pleurodesis was the only controllable factor that might help preserve the postoperative respiratory function. Thus, the intraoperative management of air leakage is important., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Subtypes of small cell lung carcinoma (SCLC) are defined by the expression of ASCL1, NEUROD1, and POU2F3 markers. The aim of our study was to explore the extent to which the intratumoral heterogeneity of ASCL1, NEUROD1, and POU2F3 may lead to discrepancies in expression of these markers in surgical samples and their matched tissue microarray (TMA) and lymph node (LN) metastatic sites. METHODS AND RESULTS: The cohort included 77 patients with SCLC. Immunohistochemical examinations were performed on whole slides of the primary tumour, paired TMAs, and metastatic LN sites. Samples with H-scores >50 were considered positive. Based on the ASCL1, NEUROD1, and POU2F3 staining pattern, we grouped the tumours as follows: ASCL1-dominant (SCLC-A), NEUROD1-dominant (SCLC-N), ASCL1/NEUROD1 double-negative with POU2F3 expression (SCLC-P), and negative for all three markers (SCLC-I). In whole slides, 40 SCLC-A (52%), 20 SCLC-N (26%), 15 SCLC-P (20%), and two SCLC-I (3%) tumours were identified. Comparisons of TMAs or LN metastatic sites and corresponding surgical specimens showed that positivity for ASCL1, NEUROD1, and POU2F3 in TMAs (all P < 0.0001) or LN metastatic sites (ASCL1, P = 0.0047; NEUROD1, P = 0.0069; POU2F3, P < 0.0001) correlated significantly with that of corresponding surgical specimens. CONCLUSION: The positivity for these markers in TMAs and LN metastatic sites was significantly correlated with that of corresponding surgical specimens, indicating that biopsy specimens could be used to identify molecular subtypes of SCLC in patients., (© 2023 John Wiley & Sons Ltd.)

Aims: A distinct subset of lung adenocarcinomas (LADs), arising from a series of peripheral lung cells defined as the terminal respiratory unit (TRU), is characterised by thyroid transcription factor 1 (TTF-1) expression. The clinical relevance of transcription factors (TFs) other than TTF-1 remains unknown in LAD and was explored in the present study., Methods and Results: Seventy-one LAD samples were subjected to high-throughput transcriptome screening of LAD using cap analysis gene expression (CAGE) sequencing data; CAGE provides genome-wide expression levels of the transcription start sites (TSSs). In total, 1083 invasive LAD samples were subjected to immunohistochemical examination for paired box 9 (PAX9) and TTF-1 expression levels. PAX9 is an endoderm development-associated TF that most strongly and inversely correlates with the expression of TTF-1 TSS subsets. Immunohistochemically, PAX9 expression was restricted to the nuclei of ciliated epithelial and basal cells in the bronchi and bronchioles and the nuclei of epithelial cells of the bronchial glands; moreover, PAX9 expression was observed in 304 LADs (28%). PAX9-positive LADs were significantly associated with heavy smoking, non-lepidic subtype, EGFR wild-type tumours and PD-L1 expression (all P < 0.0001). All these characteristics were opposite to those of TRU-type LADs with TTF-1 expression. PAX9 expression was an independent prognostic factor for decreased overall survival (P = 0.022)., Conclusions: Our results revealed that PAX9 expression defines an aggressive subset of LADs preferentially occurring in smokers that may arise from bronchial or bronchiolar cells., (© 2022 John Wiley & Sons Ltd.)

Background: Thymic squamous cell carcinoma and type B3 thymoma are primary neoplasms of the anterior mediastinum that are sometimes difficult to differentiate from one another histologically. However, only a few immunohistochemical markers are available for the differential diagnosis. The purpose of this study was to discover a novel marker for differentiating between thymic squamous cell carcinoma and type B3 thymoma., Methods: We used histological samples of thymic carcinomas (n = 26) and type B3 thymomas (n = 38) which were resected between 1986 and 2017. To search for candidates of differential markers, gene expression levels were evaluated in samples using promoter analysis by cap analysis of gene expression (CAGE) sequencing., Results: Promoter level expression of CALML5 genes was significantly higher in thymic carcinomas than in type B3 thymomas. We further validated the results of the CAGE analysis in all 26 thymic carcinomas and 38 type B3 thymomas by immunohistochemistry (IHC). CALML5 was strongly expressed in the cytoplasm in 19 of 26 cases with thymic carcinoma, whereas positivity at the protein level was shown in two of 38 type B3 thymomas. Thus, the sensitivity (73.1%) and specificity (94.7%) of CALML5 as markers for immunohistochemical diagnosis of thymic carcinoma were extremely high., Conclusion: We identified CALML5 as a potential marker for differentiating thymic squamous cell carcinoma from type B3 thymoma. It is assumed that future clinical use of CALML5 may improve the diagnostic accuracy of differentiating between these two diseases., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Pulmonary artery intimal sarcoma (PAIS) is a rare but aggressive malignancy. This study clarified the problems and countermeasures of surgical treatment by examining surgical cases of PAIS., Methods: Between January 2007 and October 2020, 10 patients with PAIS who underwent surgery at our hospital were retrospectively examined., Results: The surgical procedure that aimed at complete resection was pulmonary resection only (three cases), along with pulmonary artery vascular replacement (six cases) and pulmonary endarterectomy (PE) (one case). The positive rate of vascular stumps was 7/10. In all cases, chest computed tomography scan showed positive margins of ≤20 mm between the tumor and surgical dissection (6/6). In addition, the distance between the location of the tumor on computed tomography and the dissection line during surgery needed to be at least 20 mm (2/3). However, even at a distance of 25 mm, one case with a positive margin was observed. Postoperative recurrence was 8/9 cases, and the median recurrence period was as short as 10 months (range, 3-19 months). Postoperative treatment was required in 7/9 cases (operation/chemotherapy/radiotherapy/chemoradiotherapy/heavy ion radiotherapy =1/2/2/1/1). The median survival was 15 months (range, 0.5-36 months)., Conclusions: Extended surgery should be performed as much as possible, with a distance of at least 20 mm between the location of the tumor on computed tomography scan and the incision line during surgery. The median postoperative recurrence period was as short as 10 months. Therefore, intensive care for intrathoracic recurrence follow-up is required for 1 year after surgery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-1945/coif). The authors have no conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)

Background: Acute exacerbation (AE) of interstitial lung disease (ILD) (AE-ILD) is a life-threatening condition and the leading cause of 30-day mortality among patients who underwent pulmonary resection for lung cancer in Japan. This study was conducted to clarify the characteristics of the immune environment of lung tissues before the onset of AE-ILD., Methods: This retrospective matched case-control study compared the immune phenotypes of helper T cells in lung tissues from patients with and without AE-ILD after surgery. In total, 135 patients who underwent surgical resection for lung cancer and were pathologically diagnosed with idiopathic interstitial pneumonia (IIP) at our institute between 2009 and 2018 were enrolled. Thirteen patients with AE-IIP and 122 patients without AE (non-AE) were matched using a propensity score analysis, and 12 cases in each group were compared. We evaluated the percentages of T helper (Th)1, Th2, Th17, regulatory T (Treg), and CD8 cells in CD3 + T cells and the Th1:Th2, Th17:Treg, and CD8:Treg ratios in patients with AE by immunostaining of lung tissues in the non-tumor area., Results: We found a significant difference in the lung Th17:Treg ratio between the AE and non-AE groups (1.47 and 0.79, p = 0.041). However, we detected no significant differences in the percentages of lung Th1 (21.3% and 29.0%), Th2 (34.2% and 42.7%), Th17 (22.3% and 21.6%), Treg (19.6% and 29.1%), and CD8 + T cells (47.2% and 42.2%) of CD3 + T cells between the AE and non-AE groups., Conclusion: The ratio of Th17:Treg cells in lung tissues was higher in participants in the AE group than in those in the non-AE group., Clinical Trial Registration: This study was approved by the ethics committee of our institute (2,016,095)., (© 2023. The Author(s).)

Aims: Bronchiolar adenoma (BA) is a novel entity in the 2021 WHO classification of lung tumours. The expression profile of mucin core proteins in BAs is not clear. The aim of this study was to clarify the expression profiles of mucins and to validate the clinicopathologic and molecular features of BAs., Methods and Results: We examined the clinicopathological, immunohistochemical, and molecular features of 20 BAs. Our cohort comprised 10 proximal and 10 distal BAs. Only seven of 18 patients (39%) were accurately diagnosed with BA at the time of intraoperative consultation. The frequent genetic alterations were BRAF V600E (35%) and KRAS (30%) mutations, which were mutually exclusive. The expression of MUC1, MUC4, and MUC5B was observed in all cases and that of MUC5AC and MUC6 was observed in nine (45%) and five (25%) cases, respectively. MUC4 was diffusely expressed in 18 cases. In contrast, MUC1, MUC5AC, MUC5B, and MUC6 displayed a patchy expression pattern. These expression patterns were similar to that of bronchiolar epithelium in normal lung tissue. In addition, overexpression of MUC1 and MUC4 on the entire cell surface was not observed in any of the BAs, suggesting their benign nature., Conclusion: BA commonly exhibits diffuse MUC4 and patchy MUC1 and MUC5B expression. Its unique expression pattern is probably attributed to mucin expression specific to the bronchiolar epithelium. These results confirm the clinicopathologic and molecular characteristics of BA, including the difficulty in intraoperative frozen section diagnosis and the broad morphologic spectrum of BA derived from the bronchiolar epithelium., (© 2022 John Wiley & Sons Ltd.)

Background: To investigate whether oxygen desaturation during low technology tests was associated with complications after lung resection., Methods: A retrospective cohort study was conducted on 1097 candidates for pulmonary resection; seven metabolic equivalents in the Master's double two-step test were loaded. The predicted postoperative (PPO) forced expiratory volume in 1 s and PPO diffusing capacity of the lung for carbon monoxide were estimated. The patients were divided into three groups: those with both values ≥60% (≥60% group (n=298)), either value <30% (<30% group (n=112)) and others (30%-60% group (n=687)). The relationships between postoperative cardiopulmonary complications and exercise stress test based on availability, symptoms and percutaneous oxygen saturation values were investigated in each group., Results: Τhe cardiopulmonary morbidity rates in the ≥60%, 30%-60%, and <30% groups were 7.7%, 14.6%, and 47.3%, respectively. Multivariate analyses revealed that predictors of complications were age (OR 0.96; p<0.001), male sex (OR 1.74; p=0.016) and exercise oxygen desaturation (EOD) >4% (OR 2.39; p=0.001) in the 30%-60% group, and male sex (OR 3.76; p=0.042) and EOD >4% (OR 2.28; p=0.030) in the <30% group.The two-flight test (TFT) was performed in 181 patients (22.8%); desaturation >4% in the TFT was also a predictor of complications., Conclusions: A low technology test is also valuable for high-risk patients. EOD >4% is a predictor of postoperative complications., Clinical Registration: This study is a non-interventional observational study and has not been registered in a public database. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology reporting guidelines.This study was approved by the Ethics Committee of the Juntendo University School of Medicine (no. 2016085)., 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: Preoperative staging of lymph node metastasis in patients with usual interstitial pneumonia (UIP) and non-small cell lung cancer (NSCLC) is difficult because inflammation can lead to false-positive imaging findings and clinical upstaging. We aimed to evaluate the accuracy of computed tomography (CT) and positron emission tomography (PET)/CT in nodal staging of NSCLC in patients with and without UIP., Methods: Between November 2016 and June 2018, 198 patients underwent both preoperative CT and PET/CT and anatomic lung resection with mediastinal nodal dissection at our institute. Diagnosis of interstitial pneumonia (IP) was based on the presence of UIP or probable UIP pattern on CT. We retrospectively evaluated the diagnostic performance of PET/CT in nodal staging of NSCLC in patients with and without IP, with or without 18 F-fluorodeoxyglucose (FDG) uptake in the lung., Results: The sensitivity, specificity, and accuracy for nodal staging were 36%, 94%, and 77%, respectively, in patients without IP and 25%, 89%, and 73%, respectively, in those with IP. Of 49 patients with IP, 23 had FDG uptake in the lung. The sensitivity, specificity, and accuracy were 13%, 93%, and 65%, respectively, in patients with IP with FDG uptake and 50%, 86%, and 81%, respectively, in those without FDG uptake., Conclusions: We showed that the diagnostic performance of PET/CT in patients with IP was lower than that in patients without IP. Furthermore, the accuracy of nodal staging in patients with NSCLC and IP with FDG uptake was further decreased., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: To date, no clinical trials on the use of induction therapy before surgery have focused solely on lung squamous cell carcinoma (LSCC). We report the results of the Personalized Induction Therapy-2 (PIT-2) trial, a multicenter phase II study, performed to investigate the efficacy and safety of S-1 + cisplatin with concurrent thoracic radiotherapy (TRT) followed by surgery in patients with stage IIIA (N2) LSCC., Methods: Patients with pathologically proven stage IIIA (N2) LSCC received induction therapy comprising three cycles of S-1 + cisplatin with concurrent TRT (45 Gy in 25 fractions) followed by surgery. S-1 was administered orally at a dose of 40 mg/m 2 twice daily on days 1-14, in addition to intravenous infusion of cisplatin (60 mg/m 2 ) on day 1. The primary endpoint was 2-year progression-free survival (PFS) rate., Results: Of 45 registered patients, 43 underwent induction therapy. Of the 43 patients, 39 (91%) underwent surgery (35 lobectomies, 3 pneumonectomies, and 1 wedge resection). The 2-year PFS, 2-year overall survival, objective response rate, and pathological complete response rates were 67% (90% confidence interval [CI] 54-78%), 70% (95% CI 53-81%), 86% (95% CI 76-96%), and 39% (95% CI 23-54%), respectively. No new treatment-related adverse events occurred during the induction therapy. One case of 90-day postoperative mortality involving a patient who underwent right pneumonectomy and developed pneumonia after discharge occurred., Conclusions: Induction therapy using S-1 + cisplatin with concurrent TRT followed by surgery is a feasible and promising treatment approach for stage IIIA (N2) LSCC., (© 2022. Society of Surgical Oncology.)

Introduction: A deeper understanding of intratumoral heterogeneity is essential for prognosis prediction or accurate treatment plan decisions in clinical practice. However, due to the cross-links and degradation of biomolecules within formalin-fixed paraffin-embedded (FFPE) specimens, it is challenging to analyze them. In this study, we aimed to optimize the simultaneous extraction of mRNA and DNA from microdissected FFPE tissues (φ = 100 µm) and apply the method to analyze tumor diversity in lung adenocarcinoma before and after erlotinib administration., Method: Two magnetic beads were used for the simultaneous extraction of mRNA and DNA. The decross-linking conditions were evaluated for gene mutation and gene expression analyses of microdissected FFPE tissues. Lung lymph nodes before treatment and lung adenocarcinoma after erlotinib administration were collected from the same patient and were preserved as FFPE specimens for 4 years. Gene expression and gene mutations between histologically classified regions of lung adenocarcinoma (pre-treatment tumor in lung lymph node biopsies and post-treatment tumor, normal lung, tumor stroma, and remission stroma, in resected lung tissue) were compared in a microdissection-based approach., Results: Using the optimized simultaneous extraction of DNA and mRNA and whole-genome amplification, we detected approximately 4,000-10,000 expressed genes and the epidermal growth factor receptor (EGFR) driver gene mutations from microdissected FFPE tissues. We found the differences in the highly expressed cancer-associated genes and the positive rate of EGFR exon 19 deletions among the tumor before and after treatment and tumor stroma, even though they were collected from tumors of the same patient or close regions of the same specimen., Conclusion: Our integrated spatial analysis method would be applied to various FFPE pathology specimens providing area-specific gene expression and gene mutation information., Competing Interests: HK is a founder and shareholder of Frontier Biosystems, Inc., which provides the microdissection punching system. The remaining 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 © 2022 Yamazaki, Hosokawa, Matsunaga, Arikawa, Takamochi, Suzuki, Hayashi, Kambara and Takeyama.)

Spatial transcriptome analysis of formalin-fixed paraffin-embedded (FFPE) tissues using RNA-sequencing (RNA-seq) provides interactive information on morphology and gene expression, which is useful for clinical applications. However, despite the advantages of long-term storage at room temperature, FFPE tissues may be severely damaged by methylene crosslinking and provide less gene information than fresh-frozen tissues. In this study, we proposed a sensitive FFPE micro-tissue RNA-seq method that combines the punching of tissue sections (diameter: 100 μm) and the direct construction of RNA-seq libraries. We evaluated a method using mouse liver tissues at two years after fixation and embedding and detected approximately 7000 genes in micro-punched tissue-spots (thickness: 10 μm), similar to that detected with purified total RNA (2.5 ng) equivalent to the several dozen cells in the spot. We applied this method to clinical FFPE specimens of lung cancer that had been fixed and embedded 6 years prior, and found that it was possible to determine characteristic gene expression in the microenvironment containing tumor and non-tumor cells of different morphologies. This result indicates that spatial gene expression analysis of the tumor microenvironment is feasible using FFPE tissue sections stored for extensive periods in medical facilities., (© 2022. The Author(s).)

Objectives: We aimed to compare the outcomes of segmentectomy with those of lobectomy in clinical-stage IA radiological solid-predominant non-small-cell lung cancer (NSCLC) >2 cm in maximum tumour size., Methods: A retrospective review was performed for radiological solid-predominant NSCLC >2-3 cm in maximum tumour size with a ground-glass opacity component on thin-section computed tomography. Multivariable or propensity score-matched analyses were performed to control for confounders for survival. Overall survival (OS) was analysed using a Kaplan-Meier estimation., Results: Of the 215 eligible cases, segmentectomy and lobectomy were performed in 46 and 169 patients. Multivariable analysis revealed that standardized uptake value (hazard ratio: 1.148, 95% confidence interval: 1.032-1.276, P = 0.011) was an independently significant prognosticators of OS, while the operative mode was not associated (hazard ratio: 0.635, 95% confidence interval: 0.132-3.049, P = 0.570). The 5 y-OS was excellent and did not differ significantly between segmentectomy and lobectomy (95.5% vs 90.2%; P = 0.697), which was also shown in the propensity score analysis (96.8% vs 94.0%; P = 0.406), with a median follow-up time of 5.2 years. Locoregional recurrence was found in 2 (4.3%) segmentectomy and 13 (7.7%) lobectomy (P = 0.443). In the subgroup analysis stratified by solid component size, the 5 y-OS was similar between segmentectomy and lobectomy in the c-T1b and c-T1c groups, respectively [c-T1b (n = 163): 94.1% vs 91.8%; P = 0.887 and c-T1c (n = 52): 100% vs 84.9%; P = 0.197]., Conclusions: Segmentectomy showed similar oncological results compared to lobectomy in solid-predominant NSCLC with a ground-glass opacity component >2-3 cm in maximum tumour size. More prospective randomized trials are needed to adequately expand the indication of anatomic segmentectomy for early-stage NSCLC., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: We primarily aimed to evaluate the operative techniques, clinicopathologic characteristics, and surgical outcomes after extended sleeve lobectomy (ESL). Additionally, we evaluated the feasibility of ESL for centrally located non-small cell lung cancer (NSCLC) compared with pneumonectomy (PN)., Methods: A retrospective review identified 119 patients who underwent pulmonary resections for centrally located NSCLC; of whom, 43 underwent ESLs and 76 underwent PNs. Perioperative morbidity and oncologic outcomes of ESL were analyzed. Postoperative morbidity was evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. Overall survival was evaluated using a Cox proportional hazard model., Results: According to the classifications of ESL, 10 patients comprised type A, 8 (19%) type B, 16 (37%) type C, and 9 (21%) type D. Pulmonary artery reconstructions were performed in 5 of type A, 8 of type B, 1 of type C, and 1 of type D, and pulmonary vein reconstructions occurred in 3 of type A and 2 of type C. After ESL, 30-day hospital mortality occurred in 1 patient (2.3%), and grade ≥3 morbidities occurred in 13 patients (30%). In particular, bronchial anastomosis/stump fistula was seen in 4 patients (9.3%) after ESL, and blood perfusion disorders due to the presence of thrombi were seen in 4 (9.3%). The 3-year overall survival was significantly better after ESL compared with that after PN (62.8% vs 45.2%, P = .047)., Conclusions: ESLs to preserve lung parenchyma will likely become a promising operative strategy in appropriately selected patients with centrally located NSCLC., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Pulmonary artery (PA) reconstruction is performed to avoid pneumonectomy for non-small cell lung cancer (NSCLC). Our objective was to assess the safety and efficacy of performing PA reconstruction without systemic heparinization during resections of NSCLC., Methods: Among 3537 patients with resected NSCLC between 2008 and 2019, 130 (3.7%) patients underwent PA reconstruction to avoid pneumonectomy without intraoperative systemic heparinization. We investigated surgical outcome. The median follow-up time was 37 months., Results: As to PA reconstruction, tangential suture, patch closure (autologous pericardium), end-to-end anastomosis, and conduit were performed in 56, 26, 32, and 16 patients (autologous pericardium, 13; resected pulmonary vein, 3), respectively. Combined bronchial sleeve resection was performed in 68 (52%) patients. The mean operative time was 261 minutes. The procedure-related complications were 2 PA thromboses with pericardial conduit requiring completion pneumonectomy and 2 massive hemoptysis of a bronchopulmonary fistula leading to death (operative mortality, 1.5%). PA bending and mechanical stenosis were due to the lengthening by the conduit. Seventy-five patients had other complications, the most frequent being arrhythmia. One patient was at stage 0 after induction chemoradiotherapy; 26, stage I (9 IA and 17 IB); 43, stage II (19 IA and 24 IB), 55 stage III (49 IIIA and 6 IIIB); and 5, stage IV. Five-year overall survival, cancer-specific survival, and recurrence-free survival rates were 49.2%, 61.8%, and 37.1%, respectively., Conclusions: PA reconstruction without intraoperative systemic heparinization during resections of NSCLC was performed with a very low risk of thrombosis as well as perioperative bleeding., (Copyright © 2022. Published by Elsevier Inc.)

Background: Personalized Induction Therapy-1 is a multicenter, randomized phase II selection design trial of the efficacy and safety of platinum-doublet induction chemotherapy plus angiogenesis inhibitors/concurrent thoracic radiotherapy (TRT) followed by surgery for stage IIIA (N2) nonsquamous non-small cell lung cancer (NSCLC)., Methods: Patients with pathologically proven stage IIIA (N2) nonsquamous NSCLC were assigned at random to 1 of 2 arms. Patients received (1:1) induction therapy with pemetrexed 500 mg/m 2 and cisplatin 75 mg/m 2 plus bevacizumab 15 mg/kg intravenously every 3 weeks for 3 cycles (bevacizumab arm) or concurrent TRT (45 Gy in 25 fractions; TRT arm) before surgery. The primary endpoint was the 2-year progression-free survival (PFS) rate., Results: Eighty-two patients were treated, including 42 in the bevacizumab arm and 40 in the TRT arm. Thirty-eight patients (90%) in the bevacizumab arm and 37 patients (93%) in the TRT arm underwent surgery. The objective response rates in the 2 groups were 50% and 60%, respectively (P = .36). The 2-year PFS and overall survival rates were 37% (95% confidence interval [CI], 22.4%-51.2%) and 50% (95% CI, 33.8%-64.2%) (hazard ratio [HR], 1.34; P = .28), respectively, and 81% (95% CI, 64.7%-89.7%) and 80% (95% CI, 64.0%-89.5%) (HR, 1.10; P = .83), respectively. Although grade 5 toxicity did not occur during induction therapy, 2 patients in the bevacizumab arm died due to bronchopleural fistula., Conclusions: Although not significant, the 2-year PFS rate was higher in the TRT arm than in the bevacizumab arm. Fatal surgical complications were observed only in the bevacizumab arm. Therefore, pemetrexed-cisplatin with concurrent TRT was chosen as the investigational induction treatment strategy for future phase III trials., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: General surgery for patients with lymphangioleiomyomatosis (LAM) is infrequent, however, general surgeons also occasionally experience it. Only a few reports have described the specific perioperative management appropriate for patients with LAM. Hence, in this case series, we aimed to investigate the surgical outcomes of LAM patients and their characteristics., Case Presentation: Medical records of 4482 patients who underwent thoracic surgery between 2009 and 2017 at our institution were assessed. Twelve patients were diagnosed with LAM. Details of the postoperative courses and surgical outcomes of LAM patients were retrospectively examined. All LAM patients were female (age 41.3 ± 10.6 years). Surgeries were performed for patients undergoing biopsy (n = 4) and those with pneumothorax (n = 3), lung cancer (n = 2), and other conditions (n = 3). The mortality rate was 0% and the length of hospital stay was 27.4 ± 8.9 days. Ten postoperative complications occurred in six patients (50%): hypoxemia (n = 5), chylothorax (n = 2), and prolonged air leakage (n = 3)., Conclusions: Thoracic surgery may pose a risk of postoperative complications and long hospitalization for patients with LAM, although it lowers the risk of fatality. Management of perioperative air and chyle leakages and lymphatic stasis in the lungs is important for preventing morbidities., (© 2022. The Author(s).)

A major challenge in treating superior sulcus tumors is achieving complete surgical resection because of technical difficulties associated with the anatomical structures and approaches to the thorax. Our technique combines posterior minimally invasive thoracotomy with robot-assisted right upper lobectomy, thereby reducing the invasiveness of the surgical approach and postoperative complications, including wound pain. In the presented case, the tumor was located on the apical right upper lobe, directly invading the apical thoracic wall structures. Hybrid robotic and minimally invasive thoracotomy with thoracic wall resection was performed. The postoperative course was uneventful. The patient discharged from our hospital with minimal wound pain., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Background: The initial surgery for lung cancer with interstitial lung disease (ILD) is often followed by passive treatment due to the surgery-induced deterioration in respiratory function, and only a few studies have summarized the findings associated with a second surgery for lung cancer patients with ILD., Methods: Of the 3932 lung cancer patients who underwent surgery at our hospital from August 2008 to July 2019, 404 (10%) patients (1) underwent preoperative computed tomography for imaging of interstitial pneumonia and (2) underwent initial surgery. We analyzed 45 cases (11%) suspected of showing metachronous lung cancer during the postoperative course., Results: Thirty-four patients (76%) underwent a second surgery. The group that underwent a second surgery showed a significantly better prognosis than the group that did not (p = 0.0009). The surgical procedure was wide-wedge resection/segmentectomy/lobectomy and above in 15/7/12 cases, respectively. Postoperative complications were observed in nine cases (26%) (prolonged pulmonary fistula in five cases, ILD acute exacerbation in two cases, and wound dissection in two cases). Mortality within 30 days occurred in one case (ILD acute exacerbation at postoperative day 15). Twelve patients (35%) experienced recurrence. In the wide-wedge resection group, 2/15 (13%) patients showed stump recurrence. The 1-, 2-, 3-, and 5-year survival rates after surgery for secondary lung cancer were 80.4, 72.5, 68.2, and 39.4%, respectively., Conclusion: Surgery can be considered an effective treatment method for secondary lung cancer with ILD if the cases are carefully selected., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)