Comparison of SP263 and 22C3 pharmDx assays to test programmed death ligand-1 (PD-L1) expression in surgically resected non-small cell lung cancer.

BACKGROUND: Atezolizumab, one of the immune checkpoint inhibitors, has been approved as an adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II-IIIA non-small cell lung cancer with 1% or more programmed death ligand-1 (PD-L1) expression. The Food and Drug Administration (FDA) has approved SP263 as a companion diagnostic assay for adjuvant treatment with atezolizumab; however, in clinical practice, the 22C3 assay is most commonly used for advanced non-small cell lung cancer. Therefore, our study aimed to compare two PD-L1 assays, SP263 and 22C3, to evaluate whether 22C3 could replace SP263 when deciding whether to administer adjuvant atezolizumab. METHODS: We retrospectively and prospectively analyzed 98 patients who underwent surgical resection at Kanagawa Cancer Center (Japan). An immunohistochemistry assay was performed for all the cases with both SP263 and 22C3. We statistically analyzed the concordance of PD-L1 expression between SP263 and 22C3 assays. RESULTS: The concordance between the two assays using Cohen's kappa was κ = 0.670 (95% CI: 0.522-0.818) at the 1% cutoff and κ = 0.796 (95% CI: 0.639-0.954) at the 50% cutoff. The Spearman correlation coefficient of 0.874 (p < 0.01) indicated high concordance. PD-L1 expression with 22C3 resulted slightly higher than that with SP263. CONCLUSIONS: This study showed a high concordance of PD-L1 expression with the SP263 and 22C3 assays. Further studies examining the therapeutic effects of adjuvant atezolizumab are required.

Genetic Ablation of Pyruvate Dehydrogenase Kinase Isoform 4 Gene Enhances Recovery from Hyperoxic Lung Injury: Insights into Antioxidant and Inflammatory Mechanisms.

BACKGROUND: Pyruvate dehydrogenase kinase isoform 4 (PDK4) plays a pivotal role in the regulation of cellular proliferation and apoptosis. The objective of this study was to examine whether the genetic depletion of the PDK4 gene attenuates hyperoxia-induced lung injury in neonatal mice. METHODS: Neonatal PDK4-/- mice and wild-type (WT) mice were exposed to oxygen concentrations of 21% (normoxia) and 95% (hyperoxia) for the first 4 days of life. Pulmonary histological assessments were performed, and the mRNA levels of lung PDK4, monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-6 were assessed. The levels of inflammatory cytokines in lung tissue were quantified. RESULTS: Following convalescence from neonatal hyperoxia, PDK4-/- mice exhibited improved lung alveolarization. Notably, PDK4-/- mice displayed significantly elevated MCP-1 protein levels in pulmonary tissues following 4 days of hyperoxic exposure, whereas WT mice showed increased IL-6 protein levels under similar conditions. Furthermore, neonatal PDK4-/- mice subjected to hyperoxia demonstrated markedly higher MCP-1 mRNA expression at 4 days of age compared to WT mice, while IL-6 mRNA expression remained unaffected in PDK4-/- mice. CONCLUSIONS: Newborn PDK4-/- mice exhibited notable recovery from hyperoxia-induced lung injury, suggesting the potential protective role of PDK4 depletion in mitigating lung damage.

Suitable Patient Selection and Optimal Timing of Treatment for Persistent Air Leak after Lung Resection.

OBJECTIVES: The choice of therapeutic intervention for postoperative air leak varies between institutions. We aimed to identify the optimal timing and patient criteria for therapeutic intervention in cases of postoperative air leaks after lung resection. METHODS: This study utilized data from a prospective multicenter observational study conducted in 2019. Among the 2187 cases in the database, 420 cases with air leaks on postoperative day 1 were identified. The intervention group underwent therapeutic interventions, such as pleurodesis or surgery, while the observation group was monitored without intervention. A comparison between the intervention group and the observation group were analyzed using the cumulative distribution and hazard functions. RESULTS: Forty-six patients (11.0%) were included in the intervention group. The multivariate analysis revealed that low body mass index (p = 0.019), partial resection (p = 0.010), intraoperative use of fibrin glue (p = 0.008), severe air leak on postoperative day 1 (p < 0.001), and high forced expiratory volume in 1 s (p = 0.021) were significant predictors of the requirement for intervention. The proportion of patients with persistent air leak in the observation group was 20% on postoperative day 5 and 94% on postoperative day 7. The hazard of air leak cessation peaked from postoperative day 3 to postoperative day 7. CONCLUSIONS: This research contributes valuable insights into predicting therapeutic interventions for postoperative air leaks and identifies scenarios where spontaneous cessation is probable. A validation through prospective studies is warranted to affirm these findings.

Contributions of the light environment and co-sleeping to sleep consolidation into nighttime in early infants: A pilot study.

BACKGROUND: Sleep consolidation into nighttime is considered the primary goal of sleep development in early infants. However, factors contributing to sleep consolidation into nighttime remain unclear. AIM: To clarify the influences of the light environment and nighttime co-sleeping on sleep consolidation into nighttime in early infants. STUDY DESIGN: Cross-sectional study. SUBJECTS AND METHODS: Sleep-wake time and light stimulation were measured in infants for 4 consecutive days using actigraphy. The infants' mothers were asked to complete a sleep events diary and a questionnaire about childcare, including "co-sleeping", defined as when the infant and mother slept on the same surface throughout the night. OUTCOME MEASURES: The data were analyzed with a focus on daytime and nighttime sleep parameters. RESULTS: Daytime light stimulation reduced daytime "active sleep", tended to reduce daytime sleep, and increased daytime waking. Nighttime light stimulation reduced nighttime "quiet sleep" and nighttime sleep and increased nighttime waking. Co-sleeping reduced nighttime waking, and, as a result, nighttime sleep time and sleep efficiency increased. Co-sleeping reduced daytime sleep and tended to increase daytime waking. Consequently, co-sleeping tended to increase the ratio of nighttime sleep to daytime sleep. CONCLUSIONS: The present findings suggest that an appropriate light environment promotes daytime waking and nighttime sleep in early infants, but it does not contribute to sleep consolidation into nighttime by itself. On the other hand, co-sleeping may promote sleep consolidation into nighttime. Therefore, further methods for safe co-sleeping need to be established while avoiding risk factors for sudden unexpected death in infancy/sudden infant death syndrome.

Risk Factors for Recurrence of Stage I Epidermal Growth Factor Receptor Mutated Lung Adenocarcinoma.

BACKGROUND: We aimed to clarify the risk factors for postoperative recurrence in patients with epidermal growth factor receptor (EGFR)-mutated stage I lung adenocarcinoma, using EGFR wild-type adenocarcinoma as a comparator, to select optimal candidates for adjuvant therapy with EGFR tyrosine kinase inhibitor (TKI). METHODS: Data of patients with pathologic stage I EGFR-mutated (n = 713) and wild-type (n = 673) adenocarcinoma who did not receive adjuvant therapy were retrospectively analyzed. The cumulative incidence of recurrence (CIR) was estimated using Gray's method, and multivariable Fine-Gray competing risk models identified independent risk factors associated with recurrence. RESULTS: The CIR did not differ significantly between patients with EGFR-mutated and wild-type adenocarcinoma (P = .32). Multivariable analysis revealed that greater size (cm) of invasive tumor (hazard ratio 1.539; 95% CI, 1.077-2.201), lymphovascular invasion (hazard ratio 5.180; 95% CI, 2.208-12.15), pleural invasion (hazard ratio 3.388; 95% CI, 1.524-7.533), and high-grade histologic subtype (hazard ratio 4.295; 95% CI, 1.539-11.99) were independent risk factors for recurrence in patients with EGFR-mutated adenocarcinoma. The 5-year CIR was significantly higher among patients with these factors (tumor size greater than 2 cm, 15.9%; lymphovascular invasion, 26.9%; pleural invasion, 39.3%; and high-grade subtype, 44.4%) than among patients without them (4.4%, 2.2%, 3.9%, and 5%, respectively; P < .001). For patients with EGFR wild-type adenocarcinoma, independent risk factors for recurrence were invasive tumor size, lymphovascular invasion, and pleural invasion, but not histologic subtypes. CONCLUSIONS: Even for patients with EGFR-mutated stage I lung adenocarcinoma, recurrence risk is stratified. Adjuvant therapy may be considered if they have high-risk factors for recurrence.

Benefit of Adjuvant Chemotherapy for Patients Older Than 75 Years With Completely Resected p-Stage II-IIIA Non-Small-Cell Lung Cancer: A Retrospective Cohort Study Using Japanese Nationwide Real-World Data.

BACKGROUND: The efficacy of adjuvant chemotherapy (ACT) in elderly patients with completely resected p-stage II-IIIA non-small-cell lung cancer (NSCLC) remains unclear because all previous randomized controlled trials on ACT have been conducted among patients aged <75 years. Thus, this study aimed to evaluate the effectiveness of ACT in elderly patients with completely resected NSCLC. PATIENTS: We extracted the nationwide data of 812 patients aged ≥75 years who underwent lobectomy with mediastinal nodal dissection in 2010 and were diagnosed with p-stage II-IIIA NSCLC, from nationwide registry data accumulated in 2016. METHODS: We classified the 812 patients into 2 groups based on the ACT administration status and analyzed the differences in their postoperative overall survival (OS). RESULTS: Overall, 295 patients received ACT (36.3%; group A), whereas 517 patients did not (63.70%; group N). Group A showed significantly better OS as a whole (hazard ratio [HR]: 0.650 [95% confidence interval {CI}: 0.526-0.804]), in the p-stage II subset (HR: 0.688 [95% CI: 0.513-0.925]), and p-stage IIIA subset (HR: 0.547 [95% CI: 0.402-0.743]) than group N. Even after propensity score matching, group A showed significantly better OS as a whole (HR: 0.626 [95% CI: 0.495-0.792]), in the p-stage II subset (HR: 0.690 [95% CI: 0.493-0.964]), and p-stage IIIA subset (HR: 0.554 [95% CI: 0.398-0.772]) than group N. CONCLUSION: ACT is recommended even in elderly patients with completely resected p-stage II-IIIA NSCLC. Hence, physicians should not avoid ACT in patients with completely resected NSCLC based solely on age.

Osimertinib versus comparator first-generation epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment in patients with advanced EGFR-mutated non-small cell lung cancer: a Chinese, multicenter, real-world cohort study.

Background: In the phase 3 FLAURA trial, osimertinib was compared with first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as a first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib showed longer progression-free survival (PFS), overall survival (OS), and a similar safety profile. However, more studies demonstrating the effectiveness and safety of osimertinib as a first-line strategy are needed in real-world populations. Methods: We enrolled 1,556 patients with EGFR-mutated stage IIIc-IV NSCLC from the CAPTRA-Lung database. All patients received either osimertinib (n=202) or a first-generation EGFR-TKI (n=1,354) as their initial treatment. To adjust for differences in baseline characteristics between two groups, 1:2 propensity score matching (PSM) was performed. Propensity scores included gender, age, Eastern Cooperative Oncology Group performance status score, smoking history, family history of tumor, pathology, EGFR mutations, and central nervous system (CNS) metastases. The standardized mean differences (SMD) before and after PSM were calculated to examine the balance of covariate distributions between two groups. Results: After PSM, 202 patients receiving osimertinib and 404 patients receiving first-generation EGFR-TKIs were finally identified. SMD of each matched variable is less than 0.10. The median PFS was 19.4 months [95% confidence interval (CI): 14.3-24.4] in the osimertinib arm and 10.9 months (95% CI: 9.3-12.5) in the comparator arm [hazard ratio (HR) for progression, 0.47; 95% CI: 0.38-0.59; P<0.001). The median OS was 40.5 months (95% CI: 27.1-54.0) vs. 34.3 months (95% CI: 30.6-38.0) in two groups, respectively (HR for death, 0.76; 95% CI: 0.58-1.00; P=0.045). The incidence of grade 3 adverse events (AEs) between the two groups was 1% and 4.2%, respectively. No grade 4 AEs and treatment-related deaths were reported in both groups. Conclusions: In real-world settings, osimertinib demonstrates longer PFS and OS, with a similar safety profile to that of comparator EGFR-TKIs when used as a first-line strategy in NSCLC patients.

Preoperative predictors for recurrence sites associated with poor post-recurrence survival after surgery of non-small cell lung cancer: a multicenter study.

BACKGROUND: The recurrence site that influences post-recurrence survival (PRS) in patients with non-small cell lung cancer (NSCLC) undergoing surgery and the preoperative predictors of recurrence remain unclear. METHODS: Cohorts 1 and 2 had 4520 (who underwent complete resection for p-stage 0-IIIA NSCLC) and 727 (who experienced recurrence after surgery) patients, respectively. The initial sites of recurrence were the lungs (309 cases), thoracic lymph nodes (225 cases), pleura (112 cases), bone (110 cases), central nervous system (86 cases), adrenal gland (25 cases), abdomen (60 cases), cervical and axillary lymph nodes (38 cases), chest wall (13 cases), skin (5 cases), and eye and tongue (3 cases). For cohort 2 analysis, the initial recurrence site that resulted in poor PRS was analyzed by multivariable analysis using a Cox proportional hazard model. For cohort 1 analysis, the preoperative predictors of recurrence patterns with poor PRS were analyzed by multivariable analysis using a logistic regression model. RESULTS: In cohort 2 analysis, recurrence in the central nervous system (hazard ratio [HR], 1.70; p < 0.001), bone (HR, 1.75; p < 0.001), abdomen (HR, 2.39; p < 0.001), and pleura (HR, 1.69; p < 0.001) were independent poor prognostic recurrent sites for PRS and they were high-risk sites (HRS). Intrathoracic lymph nodes, cervical and axillary lymph nodes, lungs, chest wall, adrenal gland, eye and tongue, and skin were low-risk sites (LRS) that did not affect PRS. Patients with multiple LRS without HRS recurrence had a worse prognosis than those with a single LRS without HRS recurrence (5-year PRS 20.2% vs. 37.7%, p < 0.001) and were comparable to those with HRS recurrence (p = 1.000). In cohort 1 analysis, preoperative predictors for HRS and multiple LRS recurrences were positron emission tomography (PET) maximum standardized uptake value (maxSUV) ≥ 3.2 (HR, 5.09; p < 0.001), clinical nodal metastasis (HR, 2.00; p < 0.001), tumor size ≥ 2.4 cm (HR, 1.96; p < 0.001) and carcinoembryonic antigen (CEA) ≥ 5 ng/ml (HR, 1.41; p = 0.004). The cumulative incidence rates of HRS and multiple LRS recurrences within 5 years were 55.9%, 40.9%, 26.3%, 11.1%, and 3.5% (p < 0.001) in patients with 4, 3, 2, 1 and 0 of the above risks, respectively. CONCLUSIONS: HRS and multiple LRS were vital recurrences associated with poor PRS. Preoperative PET maxSUV, clinical nodal metastasis, tumor size, and CEA level predicted the incidence of vital recurrence.

Impact of RBM10 and PD-L1 expression on the prognosis of pathologic N1-N2 epidermal growth factor receptor mutant lung adenocarcinoma.

Background: Impact of RNA-binding motif protein 10 (RBM10) and programmed death-ligand 1 (PD-L1) on the postoperative prognosis of patients with epidermal growth factor receptor gene mutation (EGFR-Mt) lung adenocarcinoma with pathological lymph node metastasis is still unclear. Methods: Patients who underwent curative surgery for pN1-N2 EGFR-Mt lung adenocarcinoma (n=129) harboring the EGFR exon 19 deletion mutation (Ex19) (n=66) or EGFR exon 21 L858R mutation (Ex21) (n=63) between January 2010 and December 2020 were included in this retrospective study. The prognoses of patients with low/high cytoplasmic RBM10 expression and PD-L1 negativity/positivity based on immunohistochemistry (IHC) of resected specimens were compared using the log-rank test. The effects of RBM10 and PD-L1 expression on overall survival (OS) were examined via multivariable analysis using the Cox proportional hazards regression model. The effects of RBM10 and PD-L1 expression on progression-free survival (PFS) of EGFR-tyrosine kinase inhibitors (TKIs) therapy among patients with recurrent pN1-N2 EGFR-Mt lung adenocarcinoma (n=67) were examined using log-rank tests. Results: The RBM10 low expression group showed significantly better 5-year OS than the RBM10 high expression group (89.4% vs. 71.5%, P=0.020), and the PD-L1 negative group tended to have longer 5-year OS than the PD-L1 positive group (86.4% vs. 68.4%, P=0.050). Multivariable analysis showed that high RBM10 expression [hazard ratio (HR), 3.12; 95% confidence interval (CI): 1.19-8.17; P=0.021] and PD-L1 positivity (HR, 3.80; 95% CI: 1.64-8.84; P=0.002) were independent poor prognostic factors for OS. PFS of patients with relapse and first-line EGFR-TKI treatment was significantly better in the PD-L1-negative group than in the PD-L1-positive group (34.5 vs. 12.1 months, P=0.045). PFS of patients with Ex21 relapse and first-line EGFR-TKI treatment was significantly better in the RBM10 low expression group than in the RBM10 high expression group (25.5 vs. 13.0 months, P=0.025). Conclusions: High RBM10 expression and PD-L1 positivity are poor prognostic factors for OS in patients with pN1-N2 EGFR-Mt lung adenocarcinoma after curative surgery. In patients with recurrent pN1-N2 EGFR-Mt lung adenocarcinoma, PD-L1 and RBM10 expression may influence response to EGFR-TKIs.

Wedge resection vs. segmentectomy for lung cancer measuring ≤ 2 cm with consolidation tumor ratio > 0.25.

Objectives: We aimed to clarify the differences in prognosis between wedge resection and segmentectomy performed for cN0 non-small cell lung cancer (NSCLC) measuring ≤ 2 cm, with consolidation tumor ratio (CTR) > 0.25. Methods: This multicenter study included 570 patients with cN0 NSCLC (tumor size ≤ 2 cm, CTR > 0.25) who underwent wedge resection (n = 244) and segmentectomy (n = 326) between January 2010 and December 2018. After propensity score matching (PSM, 1:1 method), 182 patients were matched for clinical characteristics (age, sex, laterality, smoking index, tumor size, CTR, carcinoembryonic antigen value, positron-emission tomography-documented maximum standardized uptake value, clinical stage, and tumor disappearance rate) and intergroup comparison of disease-free survival (DFS) and overall survival (OS). Using Gray's test, an intergroup comparison of the cumulative incidence of lung cancer-specific mortality was performed. Results: After PSM, similar DFS (5-year DFS, 79.9% vs. 87.1%, p = 0.103) and OS (5-year OS, 88.7% vs. 88.9%, p = 0.719) rates were observed in the wedge resection and segmentectomy groups. We observed no significant intergroup differences in lung cancer-specific mortality (5-year cumulative incidence: 4.6% vs. 3.5%; p = 0.235). Subgroup analysis revealed no specific subgroup demonstrating improved DFS or OS after undergoing wedge resection or segmentectomy. Conclusion: DFS, OS, and lung cancer-specific mortality were comparable between wedge resection and segmentectomy of cN0 NSCLC-tumor size ≤ 2 cm and CTR > 0.25. Large-scale prospective clinical trials are warranted to compare the prognoses of wedge resection and segmentectomy for these tumors.

Long-term changes in psoas muscle mass after lobectomy and segmentectomy for early-stage lung cancer.

BACKGROUND: Segmentectomy is considered a less invasive procedure than lobectomy for patients with non-small cell lung cancer (NSCLC); however, little is known about the physiological mechanism underlying the lower invasiveness of segmentectomy. This study is aimed to compare the differences in the long-term changes in the psoas muscle mass after segmentectomy and lobectomy in patients with NSCLC. METHODS: Overall 315 recurrence-free patients who underwent segmentectomy (n = 93) or lobectomy (n = 222) for clinical stage 0-I NSCLC between January 2016 and December 2018 and underwent computed tomography during the entire period of 6 months ≤ postoperative year (POY) 0.5 < 12 months, 12 months ≤ POY 1 < 24 months, 24 months ≤ POY 2 < 36 months, and 36 months ≤ POY 3 < 48 months were included. Bilateral psoas muscle area (PMA) at the L3 level was measured using each cross-sectional computed tomography scan. Differences between the segmentectomy and lobectomy groups in the mean change of postoperative PMA from the preoperative period were analysed using Student's t-test and mixed analysis of variance. Multivariable analysis was performed to identify the risk factors for PMA loss on POY 3 using logistic regression analysis. RESULTS: The lobectomy group had a significantly larger PMA change than the segmentectomy group during each postoperative period (P < 0.001). Mixed analysis of variance revealed that the mean PMA change was significantly smaller in the segmentectomy group than in the lobectomy group during the observation period (P < 0.001). The mean change in the PMA was significantly larger from POY1 (-2.5%) to POY2 (-3.9%) and POY3 (-4.7%) in the lobectomy group (P = 0.003 and P < 0.001). However, PMA remained unchanged during the postoperative observation period in the segmentectomy group. In the multivariable analysis, the risk factors for PMA change ≤-3.3% (cut-off: mean change of PMA) at POY3 included lobectomy [odds ratio (OR), 3.32; 95% confidence interval (CI), 1.90-5.82; P < 0.001], male sex (OR, 1.92; 95% CI, 1.02-3.62; P = 0.044) and open thoracotomy (OR, 1.84; 95% CI, 1.11-3.05; P = 0.017). After propensity score matching, the mean change in PMA was smaller in the segmentectomy group (n = 75) than in the lobectomy group (n = 75) during the postoperative observation period (P < 0.001). CONCLUSIONS: Psoas muscle mass was better maintained during the postoperative period by segmentectomy than by lobectomy. Psoas muscle mass reduction progressed over a long postoperative period after lobectomy. Segmentectomy via complete video-assisted thoracic surgery is associated with a lower likelihood of sarcopenia progression.

Designing artificial circadian environments with multisensory cares for supporting preterm infants' growth in NICUs.

Previous studies suggest the importance of stable circadian environments for fetuses to achieve sound physiology and intrauterine development. This idea is also supported by epidemiological and animal studies, in which pregnant females exposed to repeated shifting of light-dark cycles had increased rates of reproductive abnormalities and adverse pregnancy outcomes. In response to such findings, artificial circadian environments with light-dark (LD) cycles have been introduced to NICUs to promote better physical development of preterm infants. Such LD cycles, however, may not be fully effective for preterm infants who are less than 30 weeks gestational age (WGA) since they are too premature to be adequately responsive to light. Instead, circadian rhythmicity of incubated preterm infants less than 30 WGA may be able to be developed through stimulation of the non-visual senses such as touch and sound.

Is adjuvant chemotherapy for completely resected p-stage IA (>2 cm) and stage IB non-small-cell lung cancer beneficial for elderly patients? A large, retrospective cohort study based on real-world data from Japan.

OBJECTIVE: The efficacy of tegafur-uracil as adjuvant chemotherapy for patients with completely resected stage I non-small-cell lung cancer is proven; however, its efficacy for elderly patients remains unclear. Herein, we evaluated the effectiveness of adjuvant chemotherapy for elderly patients with completely resected stage I non-small-cell lung cancer based on real-world Japanese data using propensity score matching. METHODS: This retrospective study extracted data from a nationwide registry study, performed in 2016, on patients ≥75 years who underwent lobectomy with mediastinal nodal dissection for non-small-cell lung cancer in 2010 and were diagnosed with p-stage IA (>2 cm) or stage IB non-small-cell lung cancer. We classified the 1294 patients into two groups-Group A, postoperative adjuvant chemotherapy (n = 295, 22.8%) and Group N, no adjuvant chemotherapy (n = 999, 77.2%)-and analyzed differences in postoperative overall survival between groups. RESULTS: Group A showed no advantage in overall survival over Group N as a whole (hazard ratio: 0.824 [95% confidence interval: 0.631-1.076]), in p-stage IA (hazard ratio: 0.617 [95% confidence interval: 0.330-1.156]) and in p-stage IB (hazard ratio: 0.806 [95% confidence interval: 0.597-1.088]) subsets. Even after propensity score matching, Group A showed no significant advantage in overall survival over Group N as a whole (hazard ratio: 0.975 [95% confidence interval: 0.688-1.381]), in p-stage IA (hazard ratio: 1.390 [95% confidence interval: 0.539-3.586]) and in p-stage IB (hazard ratio: 0.922 [95% confidence interval: 0.633-1.343]). CONCLUSIONS: adjuvant chemotherapy for completely resected p-stage IA (>2 cm) and stage IB non-small-cell lung cancer showed no benefit for recommendation for elderly patients; considering the risk of adverse events, we do not recommend adjuvant chemotherapy for elderly patients.

Effect of Surgical Treatment for N2-Positive c-stage III Non-Small Cell Lung Carcinoma in the "PACIFIC" Era.

BACKGROUND: The PACIFIC trial findings drastically changed the c-stage III non-small cell lung cancer (NSCLC) treatment strategy. However, it remains uncertain whether surgery is no longer needed for treatment. We aimed to evaluate the efficacy of surgery and explore the prognostic factors of better outcomes in surgery-treated patients than in PACIFIC regimen-treated patients. PATIENTS AND METHODS: From 2010 to 2020, 107 patients with clinical N2-stage III NSCLC underwent lung resection in our institute. We analyzed and compared the yearly postoperative overall survival (OS) benchmarks of these patients to those of patients treated in the PACIFIC trial. RESULTS: The 1-, 2-, 3-, 4-, and 5-year OS rates of patients were 87.7%, 73.9%, 64.9%, 58.2%, and 55.4%, respectively, all of which were superior to those of PACIFIC regimen-treated patients. However, patients with cT3/T4 tumors and skip, multistation, distant, and bulky N2 metastases, as well as those who underwent bronchoplasty, showed inferior results in several yearly benchmarks than in PACIFIC regimen-treated patients. Multivariate analyses conducted among factors mentioned above showed that cT3/T4 tumor was a worse prognostic factor for surgery-treated patients than for PACIFIC regimen-treated patients (hazard ratio [HR] 1.89, P = .036). Distant N2 metastasis was also a worse prognostic factor, although its effect was not statistically significant (HR 1.81, P = .082). CONCLUSION: Surgery remains the mainstay of N2-positive c-stage III NSCLC treatment, and the PACIFIC regimen may be suitable only for patients with unresectable disease. However, surgery should be cautiously considered for patients with cT3/4 disease.

Segmentectomy for cancer control in radiologically pure-solid clinical stage IA3 lung cancer.

OBJECTIVES: This study aimed to compare cancer control after segmentectomy and lobectomy in patients with radiologically pure-solid clinical stage IA3 non-small-cell lung cancer (NSCLC). METHODS: Patients with radiologically pure-solid clinical stage IA3 NSCLC who underwent lobectomy or segmentectomy at 3 institutions between 2010 and 2019 were identified. We estimated propensity scores to adjust for confounding variables regarding tumour malignancy, including age, sex, smoking history, tumour size, maximum standardized uptake value on 18F-fluorodeoxyglucose positron emission tomography, lymph node dissection, histological type and lymphatic, vascular and pleural invasion. Cumulative incidence of recurrence (CIR) was evaluated as a primary end point. RESULTS: Among 412 patients, postoperative recurrence occurred in 7 of 44 patients (15.9%) undergoing segmentectomy, and 71 of 368 patients (19.3%) undergoing lobectomy. CIR was comparable between patients undergoing segmentectomy (5-year rate, 21.9%) and those undergoing lobectomy (5-year rate, 20.8%; P = 0.88). Locoregional recurrence did not differ between patients undergoing segmentectomy (6.8%) and those undergoing lobectomy (9.0%). In multivariable analysis, segmentectomy (versus lobectomy) was not identified as an independent prognostic factor for CIR (hazard ratio, 1.045; 95% confidence interval, 0.475-2.298; P = 0.91). In propensity score matching of 40 pairs, CIR was not significantly different between patients undergoing segmentectomy (5-year rate, 20.7%) and those undergoing lobectomy (5-year rate, 18.4%; P = 0.81). CONCLUSIONS: Cancer control may be comparable between segmentectomy and lobectomy in patients with radiologically pure-solid clinical stage IA3 NSCLC. Further studies are warranted to clarify the survival benefits of segmentectomy in these patients.

[Standard Approach and Education of Video-assisted Thoracoscopic Surgery for Anterior Mediastinal Tumors].

There are various approaches to surgery for anterior mediastinal tumors, including median sternotomy, multi-port and single-port video-assisted thoracic surgery, and robot-assisted thoracic surgery. According to the 2017 Annual Report of The Japanese Association for Thoracic Surgery, mediastinal tumor resection is about one-tenth of lung resection. Therefore, we consider that it is necessary to standardize the technique at each institution to acquire stable minimally invasive surgical techniques. We reported on our center's techniques and innovations in minimally invasive surgery for anterior mediastinal tumors, and used a learning curve to reveal that sharing knowledge within the team can reduce operative time.

Left lower lobectomy without pericardial reconstruction in a patient with a congenital pericardium defect.

Pericardial defects are rare congenital disorders. We report a case of a left lower lobectomy in a patient with lung cancer, a congenital complete left-sided pericardial defect and severe pleural adhesions. The pleural adhesions between the epicardium and lungs were carefully dissected. A left lower lobectomy with mediastinal nodal dissection was performed under complete video-assisted thoracoscopic surgery without pericardial reconstruction. The patient remained asymptomatic for 20 months postoperatively. Careful dissection of severe adhesions is necessary in patients with severe cardiac pulsations.

Extracellular vesicle-associated microRNA signatures related to lymphovascular invasion in early-stage lung adenocarcinoma.

Lymphovascular invasion (LVI) is a fundamental step toward the spread of cancer. Extracellular vesicles (EVs) promote cellular communication by shuttling cargo, such as microRNAs (miRNAs). However, whether EV-associated miRNAs serve as biomarkers for LVI remains unclear. This study aimed to identify EV-associated miRNAs related to LVI and validate the miRNA levels from patients with early-stage lung adenocarcinoma (LADC). Blood samples were collected from patients undergoing pulmonary resection for stage I LADC before surgery. The patients were classified into three groups according to the presence of LVI and postoperative recurrence. Serum-derived EVs in the derivation cohort were used for small RNA sequencing, while the selected LVI miRNA candidates were validated via real-time quantitative polymerase chain reaction using 44 patient and 16 healthy donor samples as the validation cohorts. Five miRNAs (miR-99b-3p, miR-26a-5p, miR-93-5p, miR-30d-5p, and miR-365b-3p) were assessed, and miR-30d-5p (p = 0.036) levels were significantly downregulated in the LVI-positive group. miR-30d-5p levels in healthy donors were lower than those in LADC patients. Patients with high miR-30d-5p levels had favorable survival compared to those with low miR-30d-5p levels. miR-30d-5p level in EVs may serve as a promising biomarker for detecting LVI in patients with early-stage LADC.