Prior coronary stent does not exclude major pulmonary resection regardless of antiplatelet therapy.

PURPOSE: We assessed the safety of general thoracic surgery in patients with prior coronary stents undergoing lung resection, based on differences in perioperative antiplatelet therapy management. METHODS: We retrospectively examined 150 patients with coronary artery stents who underwent pulmonary resection between July 2009 and July 2018. The impact of the antiplatelet agent on thoracic surgery safety was assessed by comparing perioperative outcomes, including major adverse cardiac and cerebrovascular events, among the discontinued antiplatelet therapy (group D), heparin bridging (group H), and continuous antiplatelet therapy (group C) groups. RESULTS: Groups D, H, and C included twenty-four, eighty-four, and forty-two patients, respectively. Second-generation drug-eluting stents were used in > 50% of the patients. No significant differences were found in the estimated blood loss, transfusion rate, or operative duration. Major adverse cardiac and cerebrovascular events occurred in four (2.7%) patients, which was comparable among the groups. In group H, postoperative heart failure and transient ischemic attack with stroke occurred in one patient each. Major bleeding occurred in two (4.7%) patients in group C. CONCLUSIONS: Pulmonary resection surgical outcomes in patients with coronary artery stents were feasible regardless of antiplatelet therapy continuation. However, discontinuing dual-antiplatelet or single-antiplatelet therapy in such patients may be reasonable because this generation of drug-eluting stents has a higher safety profile than bare-metal and first-generation drug-eluting stents.

Simple endoscopic estimation to predict anastomotic complications after bronchoplastic procedures.

OBJECTIVES: Endoscopic evaluation of anastomosis is effective for the early detection of anastomotic complications after a bronchoplastic procedure. Herein, we aimed to clarify important findings for predicting anastomotic complications. METHODS: This single-centre retrospective study included patients who underwent bronchoplastic surgery between April 2013 and September 2023. Only cases in which bronchoscopy was performed both 1 and 2 weeks after surgery were included. Endoscopic findings (classification by Ludwig and Stoelben, mucosa colour, oedema, slough area and colour, and depression) were reviewed for all cases. The accuracy of these findings for predicting anastomotic complications was evaluated. RESULTS: Of the 190 patients included in this study, 14 (7.4%) experienced anastomotic abnormalities, 11 had fistulas (5.8%), and 7 had stenosis (3.7%). The onsets of fistula and stenosis were 20-28 and 20-44 days after surgery, respectively. In 102 patients (53.7%), the slough worsened from the first to the second week post-surgery. Therefore, it was easier to evaluate slough 2 weeks post-surgery rather than 1-week post-surgery. The positive/negative predicted values of anastomotic complications in endoscopic findings 2 weeks post-surgery were circular slough, 34.2%/99.3%; slough with dark colour, 39.3%/98.1%; and depression, 54.2%/99.4%. The incidence of anastomotic abnormalities was 0% in cases without the three findings, 10% in cases with at least one finding, and 67% in cases with all three findings. CONCLUSIONS: The endoscopic findings of slough on the anastomosis 2 weeks after bronchoplasty can be easily evaluated and accurately predict complications. Three important endoscopic findings were circular slough, dark colour, and depression.

Anti-Müllerian hormone type II receptor protein expression in non-small cell lung cancer and the effect of AMH/AMHR2 signaling on cancer cell proliferation.

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.

Clinical potential of SKP2 as diagnostic marker and therapeutic target in small cell lung cancer.

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 SCFSKP2 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.

GLI1 confers resistance to PARP inhibitors by activating the DNA damage repair pathway.

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.

No survival benefit of primary tumor resection for non-small cell lung cancer patients with unexpectedly detected pleural disseminated nodules in the era of targeted therapy.

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.

Long-term outcomes and risk factors for recurrence after lung segmentectomy.

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.

Trophoblast Cell Surface Antigen 2 Expression in Thymic Carcinoma: Brief Report.

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.

Preoperatively predicting survival outcome for clinical stage IA pure-solid non-small cell lung cancer by radiomics-based machine learning.

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.

Usefulness of final transection of the proximal pulmonary artery in robotic left upper lobectomy.

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.

Significance of preoperative exercise oxygen desaturation in lung cancer with interstitial lung disease.

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.

Investigating the predictive factors of thoracic aortic invasion and surgical outcomes in patients with primary lung cancer: A retrospective study.

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.

Lymphangioleiomyomatosis as a potent lung cancer risk factor: Insights from a Japanese large cohort study.

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.

Prognostic significance of ground-glass areas within tumours in non-small-cell lung cancer.

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.

Salvage extended surgery after immune-checkpoint inhibitor treatment for advanced non-small cell lung cancer.

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.

Predictive factors for postoperative delirium in thoracic surgery.

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.

Early chest tube removal regardless of drainage volume after anatomic pulmonary resection: A multicenter, randomized, controlled trial.

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.

Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer with radiologically pure-solid appearance in Japan (JCOG0802/WJOG4607L): a post-hoc supplemental analysis of a multicentre, open-label, phase 3 trial.

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.

Prognostic significance of preoperative exercise tolerance in patients with early-stage lung cancer.

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.