Search

Purpose: Higher serum 25-hydroxyvitamin D (25(OH)D) levels are reportedly associated with better survival in early-stage non–small cell lung cancer (NSCLC). Therefore, whether vitamin D supplementation can improve the prognosis of patients with NSCLC was examined (UMIN000001869).Patients and Methods: A randomized, double-blind trial comparing vitamin D supplements (1,200 IU/day) with placebo for 1 year after operation was conducted. The primary and secondary outcomes were relapse-free survival (RFS) and overall survival (OS), respectively. Prespecified subgroup analyses were performed with stratification by stage (early vs. advanced), pathology (adenocarcinoma vs. others), and 25(OH)D levels (low, Results: Patients with NSCLC (n = 155) were randomly assigned to receive vitamin D (n = 77) or placebo (n = 78) and followed for a median of 3.3 years. Relapse and death occurred in 40 (28%) and 24 (17%) patients, respectively. In the total study population, no significant difference in either RFS or OS was seen with vitamin D compared with the placebo group. However, by restricting the analysis to the subgroup with early-stage adenocarcinoma with low 25(OH)D, the vitamin D group showed significantly better 5-year RFS (86% vs. 50%, P = 0.04) and OS (91% vs. 48%, P = 0.02) than the placebo group. Among the examined polymorphisms, DBP1 (rs7041) TT and CDX2 (rs11568820) AA/AG genotypes were markers of better prognosis, even with multivariate adjustment.Conclusions: In patients with NSCLC, vitamin D supplementation may improve survival of patients with early-stage lung adenocarcinoma with lower 25(OH)D levels. Clin Cancer Res; 24(17); 4089–97. ©2018 AACR.

Figure S1. Relapse-free survival curves (A) and overall survival curves (B) of patients stratified by 25(OH)D equal to or greater than 30 ng/mL. Figure S2. Kaplan-Meier curves of patients restricted only to adenocarcinoma, or both early stages (IA - IIB) and adenocarcinoma. Figure S3. Relapse-free survival curves (A) and overall survival curves (B) of patients stratified by SNPs of FokI. Mean (SD) of 25(OH)D in each genotype are as follows; FokI CC, 19.9 (6.2) ng/ml; CT, 21.8 (6.6) ng/ml; TT 21.4 (7.9) ng/ml. Figure S4. Relapse-free survival curves (A) and overall survival curves (B) of patients stratified by SNPs of BsmI. Mean (SD) of 25(OH)D in each genotype are as follows: BsmI AA, 15 (-) ng/ml; AG, 20.2 (6.4) ng/ml; GG 21.7 (6.8) ng/ml. Figure S6. Relapse-free survival curves (A) and overall survival curves (B) of patients stratified by SNPs of ApaI. Mean (SD) of 25(OH)D in each genotype are as follows: ApaI GG, 21.2 (7.2) ng/ml; GT, 21.4 (6.3) ng/ml; TT, 21.5 (7.7) ng/ml. Figure S7. Relapse-free survival curves (A) and overall survival curves (B) of patients stratified by SNPs of TaqI. Mean (SD) of 25(OH)D in each genotype are as follows: TaqI TT, 21.7 (6.7) ng/ml; TG, 20.4 (6.9) ng/ml; GG, - (-) ng/ml. Figure S8. Relapse-free survival curves (A) and overall survival curves (B) of patients stratified by SNPs of DBP1. Mean (SD) of 25(OH)D in each genotype are as follows: DBP1 TT, 21.3 (7.0) ng/ml; TG, 20.8 (6.0) ng/ml; GG, 23.6 (7.9) ng/ml. Figure S9. Relapse-free survival curves (A) and overall survival curves (B) of patients stratified by SNPs of DBP2. Mean (SD) of 25(OH)D in each genotype are as follows: DBP2 CC, 22.7 (6.6) ng/ml; CA, 20.0 (6.3) ng/ml; AA, 12.8 (1.5) ng/ml.

This study evaluated the feasibility of performing non-intubated video-assisted thoracoscopic surgery (VATS) with local anesthesia for parapneumonic effusion and empyema resistant to conservative treatment.We retrospectively reviewed 80 patients who underwent surgery for parapneumonic effusions and empyema between 2015 and 2021. Patients were divided into those who received non-intubated local anesthesia and general anesthesia during surgery. Patient demographics, characteristics, laboratory findings, treatment progress, and treatment outcomes were compared. The primary outcomes were duration of postoperative drainage, postoperative complication rate, and postoperative mortality rate within 30 days.Among patients who received local (n = 21) and general anesthesia (n = 59), there was a significant difference in age (median 79.0 years [interquartile range (IQR) 77.0-80.0] vs. 68.0 years [IQR 54.5-77.5]; p 0.001), preoperative performance status (3.0 [IQR 2.0-4.0] vs. 2.0 [IQR 1.0-3.0]; p 0.001), and operative time (69 min [IQR 50-128] vs. 150 min [IQR 107-198]; p 0.001) but not in preoperative white blood cell count (12,100/μL [IQR 8,400-18000] vs. 12,220/μL [IQR 8,950-16,724]; p = 0.840), C-reactive protein (15.2 mg/dL [8.8-21.3] vs. 17.9 mg/dL [IQR 9.5-23.6]; p = 0.623), postoperative drainage period (11 days [IQR 7-14] vs. 9 days [7-13]; p = 0.216), postoperative hospital stay (22 days [IQR 16-53] vs. 18 days [IQR 12-26]; p = 0.094), reoperation rate (9.5% vs. 15.3%; p = 0.775), postoperative complication rate (19.0% vs. 18.6%; p = 0.132), or postoperative 30-day mortality rate (4.8% vs. 0%; p = 0.587).VATS using local anesthesia is feasible for patients with treatment-resistant parapneumonic effusion and empyema with poor general condition.

Background Whole-layer laparoscopic cholecystectomy (W-LC) has recently been advocated as a total biopsy for potentially malignant neoplasms of the gallbladder; however, it is not an injury-proof procedure. This study reports W-LC using the segment IV approach (technique for securing the whole-layer gallbladder at the medial origin of the cystic plate).MethodsTwenty among twenty-five patients diagnosed with potentially malignant gallbladder polyps underwent this technique.ResultsMostly, W-LC was performed successfully (median operative time 135 min) without intraoperative and postoperative complications. Pathological findings indicated that cholesteric polyps was the most common type (n=13), followed by adenomatous polyps (25%) and carcinoma in situ (5%).ConclusionsWe conclude that the segment IV approach is appropriate for performing total biopsy in patients diagnosed with potentially malignant gallbladder polyps.

Ferroptosis is a necrotic form of regulated cell death (RCD) mediated by phospholipid peroxidation in association with free iron-mediated Fenton reactions. Disrupted iron homeostasis resulting in excessive oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, we demonstrate the involvement of ferroptosis in COPD pathogenesis. Our in vivo and in vitro models show labile iron accumulation and enhanced lipid peroxidation with concomitant non-apoptotic cell death during cigarette smoke (CS) exposure, which are negatively regulated by GPx4 activity. Treatment with deferoxamine and ferrostatin-1, in addition to GPx4 knockdown, illuminate the role of ferroptosis in CS-treated lung epithelial cells. NCOA4-mediated ferritin selective autophagy (ferritinophagy) is initiated during ferritin degradation in response to CS treatment. CS exposure models, using both GPx4-deficient and overexpressing mice, clarify the pivotal role of GPx4-regulated cell death during COPD. These findings support a role for cigarette smoke-induced ferroptosis in the pathogenesis of COPD., Altered iron homeostasis resulting in excessive oxidative stress has been implicated in smoke-induced lung diseases. Here the authors show that ferroptosis of lung epithelial cells, potentially resulting from excessive ferritinophagy, is involved in the pathogenesis of COPD.

OBJECTIVES Difficult thoracoscopic surgery sometimes requires a long operative time. It is unclear whether patients benefit from such thoracoscopic surgeries. We investigated whether thoracoscopic surgery for difficult cases contributed to improvements in perioperative outcomes. METHODS We retrospectively reviewed cases of anatomical lung resection with thoracoscopic surgery, including conversion to thoracotomy, between January 2006 and December 2016 and compared patient demographics and perioperative outcomes of the long (≥360 min) and the normal operative time groups (

Background: The present study evaluated the impact of the introduction of thoracoscopic lung lobectomy (TL) for non-small cell lung cancer at our institution. Methods: This study retrospectively compared surgical and oncological outcomes in the period before and after the introduction of TL for non-small cell lung cancer. Propensity score-matched analysis was performed with respect to baseline patient variables and tumor characteristics. Results: Patients were divided into two groups: those who underwent lung lobectomy in the period before (BI group, n=261) and after (AI group, n=261) the introduction of TL. The proportion of TLs at our institution increased from 1.3% in the BI group to 93% in the AI group. The AI group experienced a longer duration of surgery, lesser intraoperative blood loss, and a significantly shorter postoperative hospital stay (POHS). There were no significant differences in postoperative complications between the two groups. The median follow-up period was 50 months in both groups. No significant differences were observed between the BI and AI groups with respect to 5-year overall survival (OS) (76.1% and 71.7%, respectively; P=0.1973) and disease-free survival (DFS) (67.6% and 66.1%, respectively; P=0.4071). On multivariate analysis, pathological N1–2 status was an independent predictor of survival. AI group and TL showed no independent association with survival. Conclusions: The introduction of TL represented a positive change at our institution owing to decreased invasiveness and oncological equivalence of the surgical treatment for non-small cell lung cancer.

Background: We assessed how the severity of chronic obstructive pulmonary disease (COPD) and other comorbidities affect long-term survival after thoracoscopic lung resection for c-stage I non-small cell lung cancer (NSCLC). Methods: Patients with c-stage I NSCLC who underwent thoracoscopic lung resection at our hospital between 2006 to 2014 were retrospectively analyzed. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric grades were used to classify the severity of COPD, and comorbidity was classified according to the Charlson comorbidity index (CCI). Various outcomes were assessed and compared. Results: The cohort comprised 404 patients with NSCLC, of whom 133 were diagnosed with COPD (51 as GOLD 1, 79 as GOLD 2, and 3 as GOLD 3) and 271 were diagnosed without COPD. The 5-year overall survival (OS) rates were 86.0%, 80.2%, and 71.1% for the non-COPD, GOLD 1, and GOLD 2/3 groups, respectively (P=0.0221); the corresponding 5-year disease-specific survival (DSS) rates were 91.7%, 86.9%, and 85.1% (P=0.2136). Univariate analysis indicated that sex, smoking status, pathology, COPD severity, CCI, and pathological stage were associated with OS, and multivariate analysis confirmed the association with CCI and pathological stage. Postoperative complications were significantly more frequent in the GOLD 1 (21.5%) and GOLD 2/3 (26.8%) groups than in the non-COPD group (12.1%) (P=0.0040). Conclusions: Following thoracoscopic surgery (TS) for NSCLC, patients with COPD had a poorer OS than patients without COPD. However, the CCI and not the COPD severity was the independent prognostic factor for OS. Comorbidities adversely affected long-term survival of patients with stage I NSCLC and COPD after TS, and the same effect can be oncologically expected regardless of the COPD severity.

Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor β) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development. Human lung fibroblasts (LF) were used to evaluate TGFB-induced myofibroblast differentiation. With respect to NOX4 regulation via proteostasis, assays for macroautophagy/autophagy, the unfolded protein response (UPR), and proteasome activity were performed. The potential anti-fibrotic property of AZM was examined by using bleomycin (BLM)-induced lung fibrosis mouse models. TGFB-induced NOX4 and myofibroblast differentiation were clearly inhibited by AZM treatment in LF. AZM-mediated NOX4 reduction was restored by treatment with MG132, a proteasome inhibitor. AZM inhibited autophagy and enhanced the UPR. Autophagy inhibition by AZM was linked to ubiquitination of NOX4 via increased protein levels of STUB1 (STIP1 homology and U-box containing protein 1), an E3 ubiquitin ligase. An increased UPR by AZM was associated with enhanced proteasome activity. AZM suppressed lung fibrosis development induced by BLM with concomitantly reduced NOX4 protein levels and enhanced proteasome activation. These results suggest that AZM suppresses NOX4 by promoting proteasomal degradation, resulting in inhibition of TGFB-induced myofibroblast differentiation and lung fibrosis development. AZM may be a candidate for the treatment of the fibrotic lung disease IPF.

Objectives For the purpose of simulating thoracoscopic surgery, we have conducted stepwise development of a life-like chest model including thorax and intrathoracic organs. Methods First, CT data of the human chest were obtained. First-generation model: based on the CT data, each component of the chest was made from a 3D printer. A hard resin was used for the bony thorax and a rubber-like resin for the vessels and bronchi. Lung parenchyma, muscles and skin were not created. Second-generation model: in addition to the 3D printer, a cast moulding method was used. Each part was casted using a 3D printed master and then assembled. The vasculature and bronchi were casted using silicon resin. The lung parenchyma and mediastinum organs were casted using urethane foam. Chest wall and bony thorax were also casted using a silicon resin. Third-generation model: foamed polyvinyl alcohol (PVA) was newly developed and casted onto the lung parenchyma. The vasculature and bronchi were developed using a soft resin. A PVA plate was made as the mediastinum, and all were combined. Results The first-generation model showed real distribution of the vasculature and bronchi; it enabled an understanding of the anatomy within the lung. The second-generation model is a total chest dry model, which enabled observation of the total anatomy of the organs and thorax. The third-generation model is a wet organ model. It allowed for realistic simulation of surgical procedures, such as cutting, suturing, stapling and energy device use. This single-use model achieved realistic simulation of thoracoscopic surgery. Conclusions As the generation advances, the model provides a more realistic simulation of thoracoscopic surgery. Further improvement of the model is needed.

OBJECTIVES Thoracoscopic surgery is widely used for the surgical treatment of thymoma. However, large-sized thymomas are typically treated using open surgery. This study evaluated the feasibility of performing thoracoscopic thymectomy (TT) for thymoma ≥50 mm. METHODS A retrospective review was conducted on 135 patients who underwent TT or open thymectomy (OT) for Masaoka stage I-IVa thymoma between 1996 and 2014. RESULTS Patients were first divided into two groups based on thymoma size: thymoma ≥50 mm and thymoma

Background Minimally invasive thoracoscopic lobectomy is the recommended surgery for clinical stage I non-small cell lung cancer (NSCLC). The purpose of this study was to identify the risk factors, including sarcopenia, for postoperative complications in patients undergoing a complete single-lobe thoracoscopic lobectomy for clinical stage I NSCLC, as well as the impact of complications on disease-free survival. Methods We retrospectively investigated 173 patients with pathologically-diagnosed NSCLC who underwent curative thoracoscopic lobectomies between April 2013 and March 2018. Sarcopenia was assessed using the psoas muscle index calculated from preoperative computed tomography images at the third lumbar vertebral level. Results Complications developed in 38 (22%) patients, including 21 with prolonged air leak. In univariate analysis, the significant risk factors for complications were advanced age, male sex, higher Charlson Comorbidity Index (CCI) score, lower cholinesterase, lower albumin, higher creatinine level, pleural adhesion, operative time ≥ five hours, nonadenocarcinoma cancer, and larger tumor size. Multivariate analysis showed that age ≥ 75 years (P = 0.002) and pleural adhesion (P = 0.026) were significant independent risk factors for complications. Compared with the patient group without complications, postoperative complications were independently associated with shorter disease-free survival (P = 0.01). Conclusions Advanced age and pleural adhesion were independent risk factors for complications after complete single-lobe thoracoscopic lobectomies for clinical stage I NSCLC, and postoperative complications were statistically associated with poor prognosis. Surgical teams should ensure an experienced surgeon leads the operation for patients at higher risk to avoid prolonged postoperative hospitalization and a possible poor prognosis.

Fibroblastic foci, known to be the leading edge of fibrosis development in idiopathic pulmonary fibrosis (IPF), are composed of fibrogenic myofibroblasts. Autophagy has been implicated in the regulation of myofibroblast differentiation. Insufficient mitophagy, the mitochondria-selective autophagy, results in increased reactive oxygen species, which may modulate cell signaling pathways for myofibroblast differentiation. Therefore, we sought to investigate the regulatory role of mitophagy in myofibroblast differentiation as a part of IPF pathogenesis. Lung fibroblasts were used in in vitro experiments. Immunohistochemical evaluation in IPF lung tissues was performed. PARK2 was examined as a target molecule for mitophagy regulation, and a PARK2 knockout mouse was employed in a bleomycin-induced lung fibrosis model. We demonstrated that PARK2 knockdown-mediated mitophagy inhibition was involved in the mechanism for activation of the platelet-derived growth factor receptor (PDGFR)/PI3K/AKT signaling pathway accompanied by enhanced myofibroblast differentiation and proliferation, which were clearly inhibited by treatment with both antioxidants and AG1296, a PDGFR inhibitor. Mitophagy inhibition–mediated activation of PDGFR signaling was responsible for further autophagy suppression, suggesting the existence of a self-amplifying loop of mitophagy inhibition and PDGFR activation. IPF lung demonstrated reduced PARK2 with concomitantly increased PDGFR phosphorylation. Furthermore, bleomycin-induced lung fibrosis was enhanced in PARK2 knockout mice and subsequently inhibited by AG1296. These findings suggest that insufficient mitophagy-mediated PDGFR/PI3K/AKT activation, which is mainly attributed to reduced PARK2 expression, is a potent underlying mechanism for myofibroblast differentiation and proliferation in fibroblastic foci formation during IPF pathogenesis.

Downregulation of lamin B1 has been recognized as a crucial step for development of full senescence. Accelerated cellular senescence linked to mechanistic target of rapamycin kinase (MTOR) signaling and accumulation of mitochondrial damage has been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. We hypothesized that lamin B1 protein levels are reduced in COPD lungs, contributing to the process of cigarette smoke (CS)–induced cellular senescence via dysregulation of MTOR and mitochondrial integrity. To illuminate the role of lamin B1 in COPD pathogenesis, lamin B1 protein levels, MTOR activation, mitochondrial mass, and cellular senescence were evaluated in CS extract (CSE)–treated human bronchial epithelial cells (HBEC), CS-exposed mice, and COPD lungs. We showed that lamin B1 was reduced by exposure to CSE and that autophagy was responsible for lamin B1 degradation in HBEC. Lamin B1 reduction was linked to MTOR activation through DEP domain–containing MTOR-interacting protein (DEPTOR) downregulation, resulting in accelerated cellular senescence. Aberrant MTOR activation was associated with increased mitochondrial mass, which can be attributed to peroxisome proliferator-activated receptor γ coactivator-1β–mediated mitochondrial biogenesis. CS-exposed mouse lungs and COPD lungs also showed reduced lamin B1 and DEPTOR protein levels, along with MTOR activation accompanied by increased mitochondrial mass and cellular senescence. Antidiabetic metformin prevented CSE-induced HBEC senescence and mitochondrial accumulation via increased DEPTOR expression. These findings suggest that lamin B1 reduction is not only a hallmark of lung aging but is also involved in the progression of cellular senescence during COPD pathogenesis through aberrant MTOR signaling.

Purpose: Higher serum 25-hydroxyvitamin D (25(OH)D) levels are reportedly associated with better survival in early-stage non–small cell lung cancer (NSCLC). Therefore, whether vitamin D supplementation can improve the prognosis of patients with NSCLC was examined (UMIN000001869). Patients and Methods: A randomized, double-blind trial comparing vitamin D supplements (1,200 IU/day) with placebo for 1 year after operation was conducted. The primary and secondary outcomes were relapse-free survival (RFS) and overall survival (OS), respectively. Prespecified subgroup analyses were performed with stratification by stage (early vs. advanced), pathology (adenocarcinoma vs. others), and 25(OH)D levels (low, Results: Patients with NSCLC (n = 155) were randomly assigned to receive vitamin D (n = 77) or placebo (n = 78) and followed for a median of 3.3 years. Relapse and death occurred in 40 (28%) and 24 (17%) patients, respectively. In the total study population, no significant difference in either RFS or OS was seen with vitamin D compared with the placebo group. However, by restricting the analysis to the subgroup with early-stage adenocarcinoma with low 25(OH)D, the vitamin D group showed significantly better 5-year RFS (86% vs. 50%, P = 0.04) and OS (91% vs. 48%, P = 0.02) than the placebo group. Among the examined polymorphisms, DBP1 (rs7041) TT and CDX2 (rs11568820) AA/AG genotypes were markers of better prognosis, even with multivariate adjustment. Conclusions: In patients with NSCLC, vitamin D supplementation may improve survival of patients with early-stage lung adenocarcinoma with lower 25(OH)D levels. Clin Cancer Res; 24(17); 4089–97. ©2018 AACR.

Introduction The objective of this study was to evaluate the feasibility of thoracoscopic thymectomy (TT) for treatment of early-stage thymoma and to compare the outcomes with those after open thymectomy (OT). Methods A retrospective review of 98 patients who underwent TT or OT of Masaoka stage I-II thymoma without thymic cancer between 1996 and 2013 was performed. Results Thoracoscopic thymectomy was performed in 67 patients, and OT was performed in 31 patients. The intraoperative blood loss amounts differed significantly between the TT group and OT group (100 vs 185 mL, P = 0.0070). The postoperative hospital stay was significantly shorter in the TT group than in the OT group (4 vs 12 days, P

Background Pirfenidone (PFD) is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis (IPF), but its precise mechanism of action remains elusive. Accumulation of profibrotic myofibroblasts is a crucial process for fibrotic remodeling in IPF. Recent findings show participation of autophagy/mitophagy, part of the lysosomal degradation machinery, in IPF pathogenesis. Mitophagy has been implicated in myofibroblast differentiation through regulating mitochondrial reactive oxygen species (ROS)-mediated platelet-derived growth factor receptor (PDGFR) activation. In this study, the effect of PFD on autophagy/mitophagy activation in lung fibroblasts (LF) was evaluated, specifically the anti-fibrotic property of PFD for modulation of myofibroblast differentiation during insufficient mitophagy. Methods Transforming growth factor-β (TGF-β)-induced or ATG5, ATG7, and PARK2 knockdown-mediated myofibroblast differentiation in LF were used for in vitro models. The anti-fibrotic role of PFD was examined in a bleomycin (BLM)-induced lung fibrosis model using PARK2 knockout (KO) mice. Results We found that PFD induced autophagy/mitophagy activation via enhanced PARK2 expression, which was partly involved in the inhibition of myofibroblast differentiation in the presence of TGF-β. PFD inhibited the myofibroblast differentiation induced by PARK2 knockdown by reducing mitochondrial ROS and PDGFR-PI3K-Akt activation. BLM-treated PARK2 KO mice demonstrated augmentation of lung fibrosis and oxidative modifications compared to those of BLM-treated wild type mice, which were efficiently attenuated by PFD. Conclusions These results suggest that PFD induces PARK2-mediated mitophagy and also inhibits lung fibrosis development in the setting of insufficient mitophagy, which may at least partly explain the anti-fibrotic mechanisms of PFD for IPF treatment.

Thymoma remains the most common primary anterior mediastinal neoplasm. Surgical resection remains central to the treatment of thymoma, with thoracoscopic thymectomy (TT) being increasingly performed. This present review article aimed to summarize current studies comparing TT and open thymectomy (OT). Recently, most patients with Masaoka stage I-II thymoma have been receiving TT. This procedure is associated with a significantly shorter post-operative hospital stay, decreased intraoperative blood loss, and fewer complications compared with OT. Recurrence rates of thymoma after TT range from 0% to 6.7%, and the 5-year disease-free survival (DFS) ranges from 83.3% to 96%. The oncological outcomes of TT are comparable to that of OT. Masaoka stage and the World Health Organization (WHO) type classification are valuable predictors of the prognosis of thymoma; hence, the optimal treatment for thymoma should be performed according to these two. TT is less invasive, with equivalent oncological outcomes, when compared with the OT. Minimally invasive surgery including TT for stage I-II thymomas is becoming the mainstay of therapy.

Precise imaging modalities are necessary during pulmonary resection to assess nodules that are otherwise difficult to diagnose. Studies have demonstrated that partial lung resection can completely cure adenocarcinoma in situ and minimally invasive adenocarcinoma. The important considerations for partial lung resection are: (I) to accurately identify the location of a small tumor intraoperatively and (II) to ensure a sufficient resection margin and preserve the remaining lung function. Hence, precise detection of hardly palpable or invisible tumors is essential. Although some reports describe methods for marking tumor locations, these processes are both invasive and complicated. Here, we describe a novel intraoperative navigation system that easily feeds image information to the operator on-site and evaluated its feasibility in three cases of partial lung resection. Implementing the software developed by Amin Inc. allowed three-dimensional scaling, rotation, transparency display, and calculation of tumor volumes in real time using a tablet computer (TC) interfaced with a hand tracking and voice control device. The surgeon, assistant, and digital imaging assistant can preoperatively verify the image using a TC by simulating the virtual resection line and insertion angle of the endoscopic stapler. During surgery, the tumor was assessed with a thoracoscope in comparison with the constructed three-dimensional image. Partial resection was successfully performed and pathological excision margins were negative in all cases. Other than prolonged air leakage in one case, no other complications were encountered. This novel navigation system appears to be safe and effective for less invasive partial lung resection.

This study evaluated the feasibility of thoracoscopic thymectomy (TT) for the treatment of early- and advanced-stage thymoma and compared patient outcomes with those following open thymectomy (OT). A retrospective review was conducted for 140 patients who underwent TT or OT for Masaoka stage I–IV thymoma between 1996 and 2014. TT was performed in 88 patients and OT in 52 patients. The postoperative hospital stay was significantly shorter in the TT group than in the OT group (4 and 13 days, respectively; P

Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence. Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation. Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis. Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC). Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation. To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed. PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry. We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence. CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC. Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs. These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC. Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD.