High oxygen exposure's impact on newborn mice: Temporal changes observed via micro-computed tomography.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) impacts life expectancy and long-term quality of life. Currently, BPD mouse models exposed to high oxygen are frequently used, but to reevaluate their relevance to human BPD, we attempted an assessment using micro-computed tomography (µCT). METHODS: Newborn wildtype male mice underwent either 21% or 95% oxygen exposure for 4 days, followed until 8 wk. Weekly µCT scans and lung histological evaluations were performed independently. RESULTS: Neonatal hyperoxia for 4 days hindered lung development, causing alveolar expansion and simplification. Histologically, during the first postnatal week, the exposed group showed a longer mean linear intercept, enlarged alveolar area, and a decrease in alveolar number, diminishing by week 4. Weekly µCT scans supported these findings, revealing initially lower lung density in newborn mice, increasing with age. However, the high-oxygen group displayed higher lung density initially. This difference diminished over time, with no significant contrast to controls at 3 wk. Although no significant difference in total lung volume was observed at week 1, the high-oxygen group exhibited a decrease by week 2, persisting until 8 wk. CONCLUSION: This study highlights µCT-detected changes in mice exposed to high oxygen. BPD mouse models might follow a different recovery trajectory than humans, suggesting the need for further optimization.

Prognostic Significance of the Maximum Standardized Uptake Value on the Prognosis of Clinical Stage IA Lung Adenocarcinoma Based on the 8th Edition TNM Classification.

BACKGROUND: There are few reports on the utility of the maximum standardized uptake value (SUVmax) for predicting the prognosis of early-stage lung adenocarcinoma based on the latest tumor-node-metastasis (TNM) classification. This study aimed to determine whether clinicopathologic factors, including the SUVmax, affect prognosis in these patients. PATIENTS AND METHODS: We enrolled 527 patients with c-stage IA lung adenocarcinoma who underwent lobectomy or greater resection between 2011 and 2017. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and compared using the log-rank test. Factors associated with RFS and OS were determined using the Cox proportional hazards model. RESULTS: RFS was significantly different based on tumor stage. In contrast, there was no significant difference in OS between patients with stage IA2 and IA3 disease (p = 0.794), although there were significant differences in OS between patients with stage IA1 and IA2 disease (p = 0.024) and between patients with stage IA1 and IA3 disease (p = 0.012). Multivariate analysis demonstrated that SUVmax was independently associated with both RFS and OS among patients with c-stage IA lung adenocarcinoma (RFS, p = 0.017; OS, p = 0.047). Further, even though there was no significant difference in OS between patients with stage IA2 and IA3 disease (n = 410), SUVmax was able to stratify patients with high and low RFS and OS among these patients (RFS, p < 0.001; OS, p < 0.001). CONCLUSION: SUVmax was an important preoperative factor to evaluate prognosis among patients with c-stage IA lung adenocarcinoma as well as the current TNM classification.

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.

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.

[Thoracoscopic Segmentectomy Using Three-dimensional Image Simulation of the Pulmonary Artery Perfusion Area and Indocyanine Green( ICG) Intravenous Injection Method].

PURPOSE: When performing segmentectomy, we aim to keep adequate distance from the tumor using three-dimensional( 3D) images of the pulmonary artery perfusion area and the indocyanine green( ICG) injection method. The effectiveness and improvement of this method were examined. PATIENTS AND METHOD: We retrospectively investigated 50 consecutive patients who underwent segmentectomy with this method. In simulation, we measured the predicted margin distance( PMD) on a 3D image. Then, we measured the actual margin distance (AMD) on resected specimens fixed in formalin. We compared these two distances and evaluated factors influencing shorter AMD. RESULTS: The median AMD was 1.7 cm, and there was no positive margin case. The median ratio of AMD/PMD was 0.73. In multivariate analysis, shorter PMD and no resection of subsegment bronchi next to the tumor were significant factors associated with shorter AMD( p<0.001, p=0.014). CONCLUSIONS: Our method was effective for segmentectomy. For adequate AMD, a longer PMD in simulation and subsegmental bronchi resection next to the tumor should be considered.

[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.

Prognostic factors for relapse-free survival in stage IB-IIIA primary lung adenocarcinoma by epidermal growth factor receptor mutation status.

BACKGROUND: Pathological stage IB-IIIA lung adenocarcinoma with an epidermal growth factor receptor (EGFR) mutation (Mt) has a high recurrence rate even after complete resection. However, there have been few reports on the risk factors for Mt recurrence. This study aimed to analyze the clinicopathological factors related to the relapse-free survival (RFS) of patients with pathological stage IB-IIIA primary lung adenocarcinoma with and without an EGFR mutation. METHODS: Patients who underwent curative surgery for Mt (n = 208) harboring the EGFR exon 21 L858R point mutation or EGFR exon 19 deletion mutation and EGFR mutation wild-type lung adenocarcinoma (Wt, n = 358) between January 2010 and December 2020 were included. Patients who received adjuvant EGFR-tyrosine kinase inhibitors were excluded. The prognostic factors for RFS were analyzed using a multivariable Cox regression analysis. RESULTS: The 5-year RFS rates in the Mt and Wt groups were 43.5 and 52.3%, respectively (p = 0.907). Prognostic factors for RFS in the Mt group included smoking history (hazard ratio [HR], 1.49; p = 0.049), blood vessel invasion (HR, 1.84; p = 0.023), and lymph node metastasis (HR, 1.96; p = 0.005). However, adjuvant chemotherapy was not a prognostic factor (HR, 1.02; p = 0.906). In contrast, positron emission tomography (PET) max standardized uptake value (SUV) ≥ 6.0 (HR, 1.53; p = 0.042), lymphatic vessel invasion (HR, 1.54; p = 0.036), lymph node metastasis (HR, 1.79; p = 0.002), and adjuvant chemotherapy (HR, 0.60; p = 0.008) were prognostic factors for RFS in the Wt group. CONCLUSIONS: Prognostic factors for RFS in stage IB-IIIA primary lung adenocarcinoma differ by epidermal growth factor receptor mutation status. The impact of adjuvant chemotherapy on RFS also differed by EGFR mutation status.

Diagnosis of SLC25A46-related pontocerebellar hypoplasia in two siblings with fulminant neonatal course: role of postmortem CT and whole genomic analysis: a case report.

BACKGROUND: Pontocerebellar hypoplasia (PCH) is increasingly known as a degenerative disease rather than simple "hypoplasia". At least 21 disease-causing genes have been identified for PCH so far. Because PCH is very heterogenous, prognostic prediction based solely on clinical or radiologic findings is not feasible. CASE PRESENTATION: Here, we report two siblings who had a fulminant neonatal course. The documentation of pontocerebellar hypoplasia by postmortem brain CT imaging in one of the siblings and a subsequent complex and comprehensive whole genome analysis established that both siblings had bi-allelic compound heterozygous variants (a splicing variant and a deletion) in the SLC25A46 gene which encodes a solute carrier protein essential for mitochondrial function. Long-read whole genome sequencing was required to confirm the presence of the deletion. The fulminant courses suggest that SLC25A46-related PCH is an acutely progressive degenerative condition starting in utero, rather than a simple static hypoplasia. CONCLUSION: The genomic analysis was instrumental and essential to solving the enigma of the unexplained neonatal deaths of these two siblings and to provide accurate genetic counseling.

[Early Experience with MRI-Ultrasound Fusion-Guided Prostate Biopsy in Our Institution].

A total of 100 patients were retrospectively analyzed with magnetic resonance imaging-ultrasonography (MRI-US) fusion biopsy(KOELIS, TRINITY®) at our institution between October 2019 and May 2020. The median patient age was 71 years, median prostate specific antigen (PSA) level was 7.4 ng/ml, and median PSA-density was 0.183 mg/ml. Sixty-one of the patients were positive for cancer ; 14 of them were positive by targeted biopsy only, 9 were positive by systematic biopsy only, and 38 were positive by both. Clinically significant prostate cancer (CPSC ; Gleason Score ≥3＋4 and % core ≥50%) was detected by target biopsies in 46 patients and by systematic biopsies in 33 patients. The positive core detection rate for CSPC was 32.5% for targeted biopsies and 7.0% for systematic biopsies(P＜0.0001), with a significantly higher rate for targeted biopsies. These results indicate that in MRI-US fusion biopsy, targeted biopsy has a higher detection rate for cancer and a significantly higher detection rate for clinically significant prostate cancer compared with systematic biopsy.

Detection of Pathologic Heart Murmurs Using a Piezoelectric Sensor.

This study aimed to evaluate the capability of a piezoelectric sensor to detect a heart murmur in patients with congenital heart defects. Heart sounds and murmurs were recorded using a piezoelectric sensor and an electronic stethoscope in healthy neonates (n = 9) and in neonates with systolic murmurs caused by congenital heart defects (n = 9) who were born at a hospital. Signal data were digitally filtered by high-pass filtering, and the envelope of the processed signals was calculated. The amplitudes of systolic murmurs were evaluated using the signal-to-noise ratio and compared between healthy neonates and those with congenital heart defects. In addition, the correlation between the amplitudes of systolic murmurs recorded by the piezoelectric sensor and electronic stethoscope was determined. The amplitudes of systolic murmurs detected by the piezoelectric sensor were significantly higher in neonates with congenital heart defects than in healthy neonates (p < 0.01). Systolic murmurs recorded by the piezoelectric sensor had a strong correlation with those recorded by the electronic stethoscope (ρ = 0.899 and p < 0.01, respectively). The piezoelectric sensor can detect heart murmurs objectively. Mechanical improvement and automatic analysis algorithms are expected to improve recording in the future.

Fetal goiter identified in a pregnant woman with triiodothyronine-predominant graves' disease: a case report.

BACKGROUND: Approximately 10% of all Graves' disease cases are triiodothyronine (T3)-predominant. T3-predominance is characterized by higher T3 levels than thyroxine (T4) levels. Thyroid stimulating hormone receptor autoantibody (TRAb) levels are higher in T3-predominant Graves' disease cases than in non-T3-predominant Graves' disease cases. Treatment with oral drugs is difficult. Here, we report a case of fetal goiter in a pregnant woman with T3-predominant Graves' disease. CASE PRESENTATION: A 31-year-old woman had unstable thyroid function during the third trimester of pregnancy, making it impossible to reduce her dosage of antithyroid medication. She was admitted to our hospital at 34 weeks of gestation owing to hydramnios and signs of threatened premature labor, and fetal goiter (thyromegaly) was detected. The dose of her antithyroid medication was reduced, based on the assumption that it had migrated to the fetus. Subsequently, the fetal goiter decreased in size, and the hydramnios improved. The patient underwent elective cesarean delivery at 36 weeks and 5 days of gestation. The infant presented with temporary symptoms of hyperthyroidism that improved over time. CONCLUSIONS: The recommended perinatal management of Graves' disease is to adjust free T4 within a range from the upper limit of normal to a slightly elevated level in order to maintain the thyroid function of the fetus. However, in T3-predominant cases, free T4 levels may drop during the long-term course of the pregnancy owing to attempts to control the mother's symptoms of thyrotoxicosis. Little is known about the perinatal management and appropriate therapeutic strategy for T3-predominant cases and fetal goiter. Therefore, further investigation is necessary.

The F-actin-binding RapGEF GflB is required for efficient macropinocytosis in Dictyostelium.

Macropinocytosis involves the uptake of large volumes of fluid, which is regulated by various small GTPases. The Dictyostelium discoideum protein GflB is a guanine nucleotide exchange factor (GEF) of Rap1, and is involved in chemotaxis. Here, we studied the role of GflB in macropinocytosis, phagocytosis and cytokinesis. In plate culture of vegetative cells, compared with the parental strain AX2, gflB-knockout (KO) cells were flatter and more polarized, whereas GflB-overproducing cells were rounder. The gflB-KO cells exhibited impaired crown formation and retraction, particularly retraction, resulting in more crowns (macropinocytic cups) per cell and longer crown lifetimes. Accordingly, gflB-KO cells showed defects in macropinocytosis and also in phagocytosis and cytokinesis. F-actin levels were elevated in gflB-KO cells. GflB localized to the actin cortex most prominently at crowns and phagocytic cups. The villin headpiece domain (VHP)-like N-terminal domain of GflB directly interacted with F-actin in vitro Furthermore, a domain enriched in basic amino acids interacted with specific membrane cortex structures such as the cleavage furrow. In conclusion, GflB acts as a key local regulator of actin-driven membrane protrusion possibly by modulating Rap1 signaling pathways.

Novel TRAPPC2 mutation in a boy with X-linked spondylo-epiphyseal dysplasia tarda.

X-linked spondylo-epiphyseal dysplasia tarda (SEDT) is an X-linked recessive, late-onset, progressive skeletal disorder characterized by mild-to-moderate short-trunked short stature. X-linked SEDT is caused by mutations in the gene TRAPPC2, which is located on chromosome Xp22. In the present study, we identified a novel splice-site mutation, c.93+1G>A, in TRAPPC2 in a 9-year-old Japanese patient who had X-linked SEDT and no family history of the disease. On reverse transcription-polymerase chain reaction, the mutation resulted in a 4 bp frame-shift insertion between exon 3 and exon 4. The present case highlights the importance of genetic analysis for confirmatory diagnosis of X-linked SEDT, especially in cases without a positive family history.

Novel mutation in the TMPRSS6 gene with iron-refractory iron deficiency anemia.

Iron-refractory iron deficiency anemia (IRIDA) is a rare autosomal recessive disease characterized by congenital hypochromic microcytic anemia, low transferrin saturation, low serum iron, normal-high serum ferritin, and increased hepcidin. This disease is caused by loss-of-function mutations in TMPRSS6 that lead to high hepcidin and result in severe anemia. We report our experience with an 11-year-old Japanese girl with hypochromic microcytic anemia, low serum iron, and high serum ferritin, with anemia that was refractory to the oral iron that was prescribed frequently from early childhood. Presence of high hepcidin suggested a diagnosis of IRIDA, which was eventually confirmed by identification of a novel homozygous mutation, p.Pro354Leu, in the TMPRSS6 gene. This case suggests that serum hepcidin should be routinely measured for differential diagnosis when patients with IDA are unresponsive to oral iron or have unusual clinical features.

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.

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.

Primary lung chordoma: a case report.

BACKGROUND: Chordoma, a rare malignant tumor arising from notochordal tissue, usually occurs along the spinal axis. Only a few published reports of primary lung chordomas exist. Herein, we present a case of primary lung chordoma and discuss important considerations for diagnosing rare chordomas. CASE PRESENTATION: We report a case of primary lung chordoma in a 39-year-old male with a history of testicular mixed germ-cell tumor of yolk sac and teratoma. Computed tomography revealed slow-growing solid lesions in the left lower lobe. We performed wedge resection for suspected germ-cell tumor lung metastasis. Histologically, large round or oval cells with eosinophilic cytoplasm were surrounded by large cells with granular, lightly eosinophilic cytoplasm. Tumor cells were physaliphorous. Immunohistochemistry was positive for brachyury, S-100 protein, epithelial membrane antigen, vimentin, and cytokeratin AE1/AE3, suggesting pulmonary chordoma. Re-examination of the testicular mixed germ-cell tumor revealed no notochordal elements. Although some areas were positive for brachyury staining, hematoxylin and eosin (HE) staining did not show morphological features typical of chordoma. Complementary fluorescence in situ hybridization (FISH) of the lung tumor confirmed the absence of isochromosome 12p and 12p amplification. Thus, a final diagnosis of primary lung chordoma was established. CONCLUSIONS: In patients with a history of testicular mixed germ cell tumors, comparison of histomorphology using HE and Brachyury staining of lung and testicular tumors, and analyzing isochromosome 12p and 12p amplification in lung tumors using FISH is pivotal for the diagnosis of rare lung chordomas.

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.

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.