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Thymic epithelial tumors (TETs) are rare tumors arising from the mediastinum. Among TETs, thymoma type B2, B3 and thymic carcinoma are highly malignant and often present invasion and dissemination. However, the biological characteristics of TETs have not been thoroughly studied, and their mechanisms of invasion and dissemination are largely unknown. α-Actinin 4 (ACTN4) is a member of actin-binding proteins and reportedly plays important roles in the progression of several cancers. In this study, we investigated the relationship between ACTN4 and characteristics of the malignant potential of TETs, such as invasion and dissemination. In vitro experiments using Ty-82 thymic carcinoma cells revealed that overexpression of ACTN4 enhanced the proliferative and invasive ability of Ty-82 cells; conversely, knockdown of ACTN4 attenuated the proliferative and invasive potential of Ty-82 cells. In western blotting (WB) experiments, ACTN4 induced the phosphorylation of extracellular signal-regulated kinase and glycogen synthase kinase 3β to regulate the β-catenin/Slug pathway. Furthermore, WB analysis of cancer tissue-origin spheroids from patients with TETs showed results similar to those for Ty-82 cells. In vivo experiments showed that the knockdown of ACTN4 significantly suppressed the dissemination of Ty-82 cells. A WB and immunohistochemistry staining comparison of primary and disseminated lesions of TETs using surgical specimens showed upregulated expression of ACTN4, β-catenin, and Slug proteins in disseminated lesions. In summary, our study suggests ACTN4 is associated with malignant potential characteristics such as invasion and dissemination in TETs via the β-catenin/Slug pathway., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

High-energy-density laser facilities and advances in dynamic compression techniques have expanded access to material states in the Terapascal regime relevant to inertial confinement fusion, planetary science, and geophysics. However, experimentally determining the material temperature in these extreme conditions has remained a difficult challenge. Extended X-ray Absorption Fine Structure (EXAFS), referring to the modulations in x-ray absorption above an absorption edge from photoelectrons' interactions with neighboring atoms, has proven to be a versatile and robust technique for probing material temperature and density for mid-to-high Z elements under dynamic compression. The current platform at the National Ignition Facility has developed six configurations for EXAFS measurements between 7 and 18 keV for different absorption edges (Fe K, Co K, Cu K, Ta L3, Pb L3, and Zr K) using a curved-crystal spectrometer and a bright, continuum foil x-ray source. In this work, we describe the platform geometry, x-ray source performance, spectrometer resolution and throughput, design considerations, and data in ambient and dynamic-compression conditions., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Purpose: Single lung transplantation (SLT) is a viable option for patients with end-stage pulmonary parenchymal and vascular diseases. However, various diseases can occur in native lungs after SLT., Methods: Between January 2000 and December 2021, 35 patients underwent cadaveric SLT and survived for more than 30 days in our hospital. Among these 35 patients, 10 required surgery for diseases that developed in their native lungs. The clinical characteristics of these 10 patients and the outcomes of native lung surgery (NLS) were investigated., Results: Among these ten patients, the indications for lung transplantation were chronic obstructive pulmonary disease and idiopathic interstitial pneumonia in three patients each, and lymphangioleiomyomatosis and collagen vascular disease-related interstitial pneumoniain two patients each. The causes of NLS included pneumothorax (n = 4), primary lung cancer (n = 2), native lung hyperinflation (n = 2), and pulmonary aspergilloma (n = 2). The surgical procedures were pneumonectomy (n = 7), lobectomy (n = 2), and alveolar-pleural fistula repair (n = 1). Only one postoperative complication, empyema, was treated with antibiotics. The 5-year overall survival rates after transplantation with and without NLS were 70.0% and 80.0%, respectively, and did not differ to a statistically extent (p = 0.56)., Conclusion: NLS is an effective treatment option for diseases that develop in the native lungs after SLT., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: The hemiclamshell (HCS) approach provides a comprehensive view of the anterior mediastinum, whereas the transmanubrial osteomuscular sparing approach (TMA) allows sufficient exposure of the cervico-thoracic transition. We assessed the effectiveness and the outcomes of the combined HCS plus TMA approach to resect thoracic malignant tumors., Methods: We reviewed five patients with thoracic malignant tumors invading the thoracic outlet who underwent surgery using an HCS and TMA approach between 2018 and 2021., Results: The preoperative diagnosis was myxofibrosarcoma, lung cancer, thymic cancer, thymoma, and neurofibromatosis type1 in one patient each, respectively. Cardiovascular reconstruction was done on the aortic arch in two patients, on the descending aorta in one, and on the superior vena cava in one, combined with resection of the vagus nerve in three patients, of the phrenic nerve in two, and of vertebra in one, with overlap in some cases. The TMA was added because all patients required dissection of the periphery of the subclavian artery, and two had tumor extension to the neck. Macroscopic complete resection was achieved in four patients. There was no postoperative mortality., Conclusion: The combination of the HCS and TMA approaches at the same operation provides a comprehensive view of the mediastinum, lung, and cervico-thoracic transition and allows safe access to the thoracic great vessels and subclavian vessels., (© 2024. The Author(s).)

Background: Cholesterol granuloma (CG) is a benign entity characterized by the presence of cholesterol crystals and foreign body giant cells. This condition can be attributed to cholesterol crystals that are deposited in the tissues and react with foreign body giant cells, resulting in granuloma formation. Lesions commonly develop in the otolaryngeal region, such as the middle ear. However, crystals rarely form in the thymus, accounting for 1% of all mediastinal tumors. Herein, we present five cases of mediastinal CG., Case Presentation: The patients were aged 49-61 (mean, 55.4) years. Among them, three were men and two women. One patient had fever, and four patients were asymptomatic. The patients' lesions were detected during follow-up of other diseases or medical examinations showing the presence of abnormal chest shadows. The patients did not have a history of trauma or surgery. All lesions were located within the thymus gland. Three patients presented with multifocal lesions and two with a single lesion. Four patients had contrast effect on computed tomography scan. Four patients had abnormal fluorodeoxyglucose accumulation (mean maximum standardized uptake value, 4.67) on positron emission tomography-computed tomography. Four patients underwent complete surgical resection. The size of the resected lesions ranged from 1.8 to 5.1 (mean, 3.24) cm. Histologically, all patients presented with small nodules with cholesterol clefts and foreign body giant cells and histiocyte infiltration within the thymic tissue. The postoperative course was excellent. None of the patients who underwent complete resection presented with recurrence. Moreover, the patient who underwent partial resection did not have lesion enlargement., Conclusions: CG in the thymus is clinically challenging to differentiate from malignant lesions, and histologic diagnosis via surgical resection is required., (© 2024. The Author(s).)

Purpose: Fibroblast activation protein (FAP) is a serine integral membrane protease, the expression of which has been confirmed in various cancer types. Solitary fibrous tumors of the pleura (SFTP) are rare mesenchymal fibroblastic neoplasms. We present a case of 18 F-labeled FAP inhibitor ([ 18 F]FAPI-74) PET imaging and its correlation with histological FAP expression and review an SFTP series at our institution in relation to the extent of FAP expression., Methods: This retrospective study included 13 patients who underwent surgery between March 2011 and December 2022 at our institute. One of the patients also underwent [ 18 F]FAPI-74 PET imaging. We semi-quantitatively evaluated FAP expression in SFTPs using immunohistochemical staining and H-scores., Results: Nine of the 13 patients were male, with a median age of 64 years (range, 28-79 years). The median tumor size was 6.6 cm (1.1, 16 cm). In the pathological findings, expression levels of Ki67 were 1-5% in 12 of 13 cases. Furthermore, FAP expression was observed in all patients, and the median H-score was 160 (range, 10-280). The H-score of FAP expression in two of the 13 patients was low (10 in both), and that in two of the 13 patients was high (240 and 280). The SUVmax value of [ 18 F]FAPI-74 PET was 3.57 in a patient in whom the H-score of FAP expression was 180., Conclusions: SFTPs expressed FAP to varying degrees in different patients and the [ 18 F]FAPI-74 PET results in one patient reflected FAP expression in the tumor tissue., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Toru Kimura reports financial support was provided by Japan Society for the Promotion of Science. Toru Kimura reports financial support was provided by The Japan Lung Cancer Society. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Although lung transplantation (LTx) is the last resort for patients with end-stage lymphangioleiomyomatosis (LAM), the high waitlist mortality is a source of concern in Japan. Discontinuation of mechanistic target of rapamycin (mTOR) inhibitors prior to LTx is recommended due to the incidence of severe adverse events. Therefore, we hypothesized that mTOR inhibitors may affect the mortality of patients with LAM on the LTx waitlist., Methods: We retrospectively compared the characteristics of consecutive patients with LAM on the LTx waitlist who were and were not receiving mTOR inhibitors., Results: Twenty-nine consecutive patients with LAM who listed our center between January 2004 and December 2021 were selected from the database and enrolled in the present study. Seventeen patients (58.6%) were receiving a mTOR inhibitor, sirolimus (treatment group). During a median listing period of 1277 days, 12 patients (41.4%) were hospitalized, six patients (20.7%) died from disease before LTx, and 15 patients underwent LTx. Among the deceased patients, four patients (66.6%) had pneumothoraces. The waitlist mortality in the treatment group was significantly lower than that in the non-treatment group (p = 0.03). Among the six patients who discontinued sirolimus in the treatment group, four patients (66.6%) were hospitalized with respiratory complications after the discontinuation of sirolimus. No mTOR inhibitor-related complications arose in the treatment group undergoing LTx (n = 7), including those on a reduced sirolimus dose., Conclusions: Administration of an mTOR inhibitor until LTx may decrease waitlist mortality. Due to life-threatening events after discontinuing sirolimus pre-LTx, a reduced dose until LTx is permissible., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Purposes: Some predictive markers of death have been reported for patients on the waiting list for lung transplantation (LTx). We assessed whether or not the preoperative psoas muscle index (PMI) correlates with waitlist mortality., Methods: In 81 patients with end-stage lung disease on the waiting list for LTx between 2011 and 2020 at Osaka University Hospital, we examined the association between baseline characteristics, including the diagnosis, respiratory function test results, blood collection items, steroid use, and psoas muscle mass on computed tomography, and survival during the waiting period using Kaplan-Meier curves and Cox proportional hazard regression models., Results: Thirty-three patients (41%) died during follow-up. Univariate and multivariate analyses showed that patients with a low PMI had a higher rate of death during follow-up than those with a high PMI (p < 0.0001 and 0.0002, respectively). In addition, a diagnosis of interstitial pneumonia (hazard ratio 3.30, 95% confidence interval 1.52-7.17, p = 0.0025) and low albumin level (hazard ratio 2.21, 95% confidence interval 1.02-4.80, p = 0.0449) were also significant predictors of survival., Conclusion: A low PMI at registration is associated with a decreased survival time among LTx candidates and it may be a predictive factor of mortality in patients waiting for LTx., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: There has been little information on the actual diagnosis of pulmonary lesions in patients with a history of urinary tract transitional cell carcinoma (TCC) and short- and long- outcomes of pulmonary resection for these patients., Methods: In the present study, the data of 37 consecutive patients with a history of TCC who underwent pulmonary resection for solitary pulmonary lesions were reviewed, and the clinical factors and short- and long-term outcomes were analyzed., Results: The study population included 35 male patients, and 2 female patients. The mean age was 72.5 years. Twenty patients (80%) were smokers and showed a high incidence of chronic obstructive pulmonary disease. Pulmonary lesions and primary TCC were detected simultaneously in 5 patients and metachronously in 32 patients. The median interval between treatment for primary TCC and the detection of pulmonary lesion was 43 months. The mean tumor diameter was 23 mm. The types of resection included lobectomy (n = 19), segmentectomy (n = 8), and partial resection (n = 10). Twelve of 37 patients (32%) developed postoperative complications. The pathological diagnoses included primary lung cancer (n = 28), pulmonary metastasis from TCC (n = 7), and others (n = 2). The 5-year overall survival rate for all patients was 72%. The 5-year overall survival rate of patients with primary lung cancer was 74%, while that of patients with pulmonary metastasis from TCC was 57%., Conclusions: Surgery can be proactively considered for treating pulmonary lesions in patients with a previous history of TCC, as it provides favorable long-term outcomes., (© 2024. The Author(s).)

Background: Adipose-derived stem cells (ADSCs) are well-recognized for their remarkable ability to suppress ischemia-reperfusion lung injury (IRLI). The primary objective of this investigation was to elucidate the underlying mechanism through which ADSCs exert protective effects against IRLI., Methods: A warm hilar occlusion model in C57BL6J mice was used. Hilar occlusion was achieved for 1 hour (ischemic), and after 1 hour the occlusion was released (reperfusion) to recover for 3 hours. RNA sequencing, the physiological function, pathway activation, and expression of inflammatory cytokines were evaluated., Results: Lung gas exchange and pulmonary edema were significantly improved in the IRLI/ADSCs group compared with the IRLI group. RNA sequencing results suggested that the peroxisome proliferator-activated receptor gamma (PPARγ)/nuclear factor-kappa B (NF-κB) pathway was involved in the effect of the ADSCs. Administration of a PPARγ antagonist in the IRLI/ADSC group resulted in the deterioration of the physiological function. Furthermore, the PPARγ protein expression level decreased, the NF-κB protein expression level increased, and inflammatory cytokine parameters from lung tissue and blood sample worsened in the PPARγ antagonist-administered group., Conclusion: Administration of ADSCs exerted a significant protective effect against IRLI in mice, and the effect is attributed to the activation of the PPARγ/NF-κB pathway., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Mediastinal lymphatic tumors are relatively rare. The prognosis is poor but has improved due to recent advances in treatment strategies. Herein, we report a case of mediastinal lymphoma diagnosed using surgical biopsy, which was complicated by mediastinal mass syndrome due to general anesthesia., Case Presentation: A 25-year-old man with cough, fever, dyspnea, and night sweats was transferred to our hospital for resection of a large anterior mediastinal tumor. Although his preoperative diagnosis was WHO type B1 thymoma, the clinical findings suggested a lymphoma. A repeat surgical biopsy was performed under general anesthesia. Immediately after extubation, the patient developed acute respiratory failure with hypolucency of the right lung field on chest radiography. He was reintubated immediately and was diagnosed with negative pressure pulmonary edema in the right lung. He was managed with positive-pressure ventilation and his respiratory distress resolved within 5 days. Pathological examination of surgical specimens confirmed the diagnosis of lymphoma., Conclusion: Surgical biopsy is useful for the diagnosis of mediastinal tumors. However, the risk of perioperative mediastinal mass syndrome should be carefully assessed before administering general anesthesia., (© 2024. The Author(s).)

Background: Congenital bronchial atresia (CBA) is a rare bronchial abnormality. Adult patients with CBA generally do not show any symptoms. Although surgical resection is the first-line treatment, the indication for the surgical intervention is controversial, especially in mildly symptomatic or asymptomatic patients. Recently, thoracoscopic surgery is the commonly preferred approach to treat this condition., Case Presentation: Case 1: A woman in her 20s suffered from repeating episodes of fever and cough due to left CBA with the interruption of B9 and B10. Uniportal thoracoscopic left lower lobe wedge resection was performed, following which the symptoms disappeared. Case 2: A woman in her 40s presented to the clinic with dyspnea on exertion, and the computed tomography image revealed the absence of B2. Multiportal thoracoscopic right S2 segmentectomy was performed on her, after which the symptoms of dyspnea improved. Case 3: A woman in her 40s visited the hospital with symptoms of intermittent cough, sputum, and slight fever for 7 months. The examinations identified the absence of B6a. Right S6 segmentectomy and S2 wedge resection were carried out by multiportal thoracoscopic approach. The patient is now asymptomatic., Conclusions: Based on our experiences in the three adult CBA surgery cases, the three-dimensional image reconstruction system is very useful for diagnosis and surgical decisions with regard to this disease. Even for CBA patients with subtle symptoms, early surgical treatments may be beneficial from the point of view of minimally invasive interventions, and sublobar resection will be sufficient for treatments and preservation of respiratory function., (© 2023. The Author(s).)

Purpose: As the number of long-term survivors of pancreatic cancer is expected to increase thanks to recent advances in multidisciplinary treatment and earlier diagnoses of pancreatic cancer, we are likely to encounter more cases of postoperative pulmonary nodules. We analyzed the clinical course and prognosis of resection of pulmonary metastases from pancreatic cancer to clarify the prognostic implication of pulmonary metastasectomy for pancreatic cancer., Method: We retrospectively analyzed 35 patients who underwent resection of lung metastases after pancreatic cancer surgery. Short- and long-term outcomes and factors associated with the prognosis were analyzed., Results: The observation period was 20 (range, 1-101) months, with 3- and 5-year survival rates of 88.3% and 64.5% from pancreatectomy and 44.1% and 28.3% from lung resection, respectively. A univariate analysis revealed that a period from pancreatic cancer resection to pulmonary nodule shadow detection of < 15 months was associated with a significantly lower overall survival from pancreatic resection than a longer period. Conversely, histological type, stage, size of lung metastases, and resection technique were not associated with the overall survival., Conclusion: A long-term prognosis may be expected in some cases with a disease-free interval of ≥ 15 months. Our findings suggest that the disease-free interval may influence the prognosis., (© 2023. The Author(s).)

Purpose of the Report: L-type amino acid transporter-1 (LAT1) is a tumor-specific transporter expressed in various tumor types, with minimal expression in normal organs. We previously demonstrated 18F-fluoro-borono-phenylalanine (18F-FBPA) as a selective PET probe for LAT1 in a preclinical study. Herein, we evaluated LAT1 expression in preoperative patients with lung or mediastinal tumors using 18F-FBPA PET and immunofluorescence staining., Patients and Methods: The study population included patients with histopathological diagnosis (n = 55): primary lung cancers (n = 21), lung metastases (n = 6), mediastinal tumors (n = 15), and benign lesion (n = 13). PET scanning was performed 1 hour after the injection of 18F-FBPA (232 ± 32 MBq). Immunofluorescence staining was performed on the resected tumor sections using LAT1 antibody. LAT1 staining was graded on a 4-grade scale and compared with the SUVmax on 18F-FBPA PET., Results: A positive correlation was observed between the SUVmax of 18F-FBPA PET and LAT1 expression by immunofluorescence staining (r = 0.611, P < 0.001). The SUVmax of 18F-FBPA was 3.92 ± 1.46 in grade 3, 3.21 ± 1.82 in grade 2, 2.33 ± 0.93 in grade 1, and 1.50 ± 0.39 in grade 0 of LAT1 expression. Although 18F-FBPA PET showed variable uptake in lung cancers and mediastinal tumors, benign lesions showed significantly lower SUVmax than those in malignant lesions (P < 0.01)., Conclusions: Uptake on 18F-FBPA PET reflected the expression level of LAT1 in lung and mediastinal tumors. It was suggested that 18F-FBPA PET can be used for the precise characterization of the tumor in pretreatment evaluation., Competing Interests: Conflicts of interest and sources of funding: The authors declare no potential conflicts of interest relevant to this study. This study was funded by the QiSS program of OPERA (grant number: JPMJOP1721) from the Japan Science and Technology Agency., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The first lung transplant procedure in the world was performed in 1983, while in Japan that was first accomplished in 1998. Over the following 25 years, lung transplantation has become a viable treatment option for Japanese patients with a variety of end-stage lung diseases. Seventy cadaveric-donor lung (41 single, 29 bilateral), 11 bilateral living-donor lobar lung, and three heart-lung transplants have been performed with use of an integrated cardiothoracic team approach at medical facilities associated with Osaka University. Extremely advanced clinical and surgical skill sets are required to complete a lung transplant procedure, including surgical knowledge and techniques, as well as management of cardiovascular surgery, especially in regard to mechanical circulatory support (MCS), vascular anastomosis in difficult cases, and concomitant cardiac surgery. We have found that a collaborative effort by general thoracic and cardiac surgeons is an important key for success with lung transplantation. Complex lung transplant surgery and management in Japan are performed by use of an integrated cardiothoracic team approach, which has led to a synergistic impact on successful lung transplantation cases by capitalizing greatly on the experiences, techniques, and expertise of cardiac and thoracic experts. The present review is focused on the role of cardiac surgeons from the viewpoint of our experience with these cases., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1720/coif). The special series “Why is the Outcome Good? Secrets of Lung Transplantation in Japan” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: Necroptosis, one of the types of regulated necrosis, causes ischemia-reperfusion (IR) lung injury. N-acetyl-leucyl-leucyl-norleucinal (ALLN), a calpain inhibitor, is known to attenuate necroptosis and apoptosis, and the purpose of this study was to evaluate the protective effect of ALLN during cold ischemia against IR injury in a rat lung transplant model., Methods: Male Lewis rats (250-350 g) were divided into 3 groups: sham group (n = 4), nontransplantation; control group (n = 8), transplantation with IR lung injury; and ALLN group (n = 8), transplantation with IR lung injury/ALLN. Rats in the sham group underwent a simple thoracotomy, and the remaining 2 groups of rats underwent an orthotopic left lung transplant. Cold ischemic time was 15 h. After 2 h of reperfusion, physiological function, inflammatory cytokine expression, pathway activation, and the degrees of necroptosis and apoptosis were evaluated., Results: Lung gas exchange (PaO 2 /FiO 2 ) was significantly better, and pulmonary edema was significantly improved in the ALLN group compared with the control group ( P = 0.0009, P = 0.0014). Plasma expression of interleukin-1β was significantly lower in the ALLN group than in the control group ( P = 0.0313). The proportion of necroptotic and apoptotic cells was significantly lower in the ALLN group than in the control group ( P = 0.0009), whereas the proportion of apoptotic cells remained unchanged ( P = 0.372); therefore, the calpain inhibitor was thought to suppress necroptosis., Conclusions: The administration of ALLN during cold ischemia appears to improve IR lung injury in a lung transplant animal model via the inhibition of necroptosis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Limited treatment options are available for non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD). The rationale for immunotherapy and its adverse events for NSCLC with ILD remains unclear. In this study, we examined T cell profiles and functions in the lung tissues of NSCLC patients with or without ILD to provide evidence for the potential mechanism of immune checkpoint inhibitor (ICI)-related pneumonitis in NSCLC patients with ILD., Material and Methods: We investigated T cell immunity in the lung tissues of NSCLC patients with ILD to support the application of immunotherapy for these patients. We analyzed T cell profiles and functions in surgically resected lung tissues from NSCLC patients with and without ILD. The T cell profiles of infiltrating cells in lung tissues were analyzed by flow cytometry. T cell functions were measured based on cytokine production by T cells stimulated with phorbol 12-myristate 13-acetate and ionomycin., Results: The percentages of CD4 +  T cells expressing immune checkpoint molecules (Tim-3, ICOS, and 4-1BB), CD103 + CD8 +  T cells, and regulatory T (Treg) cells were higher in NSCLC patients with than in those without ILD. A functional analysis of T cells in lung tissues indicated that CD103 + CD8 +  T cells positively correlated with IFNγ production, whereas Treg cells negatively correlated with IFNγ and TNFα production. Cytokine production by CD4 +  and CD8 +  T cells did not significantly differ between NSCLC patients with and without ILD, except for TNFα production by CD4 +  T cells being lower in the former than in the latter., Conclusion: In NSCLC patients with ILD stable for surgery, T cells were active participants and balanced in part by Treg cells in lung tissues, suggesting the potential development of ICI-related pneumonitis in NSCLC patients with ILD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Neuroendocrine tumors of a thymus (NETTs) are rare, accounting for approximately 2-5% of all thymic epithelial tumors, and have a poor prognosis due to frequent lymph nodes or distant metastasis., Methods: We retrospectively reviewed the clinicopathological background and outcomes of 40 patients who underwent resection or surgical biopsy with histologically diagnosed NETTs from 1986 to 2022., Results: The most common pathological type was atypical carcinoid. Surgical resection was performed in 35 patients, with lymph node dissection in 33 and surgical biopsy in five. The overall survival (OS) rate for all patients was 81.4% and 52.3% at 5 and 10 years, respectively. The 2-year survival rate was 20% for the biopsy group, which was significantly worse than that of the resected group ( p < 0.001). The relapse-free survival rates were 61.7% and 37.6% at 5 and 10 years, respectively, in 34 patients with complete resection. The univariate analysis revealed better the OS rate in the resected cases but with no significant differences between histological grade, lymph node metastasis, tumor size, or Ki67 index., Conclusions: Surgical complete resection is considered to improve prognosis regardless of histologic type. NETTs frequently develop lymph node metastasis, thus, lymph node dissection seems necessary for complete resection.

Background: In lung transplantation, vascular complications are relatively rare. However, severe pulmonary artery stenosis after lung transplantation can cause clinical symptoms and lead to graft dysfunction., Case Presentation: The present patient underwent right lung transplantation for severe chronic obstructive pulmonary disease. After lung transplantation, pulmonary blood flow scintigraphy showed a decreased blood flow to the transplanted lung, and contrast-enhanced computed tomography showed pulmonary artery anastomotic stenosis. As the initial treatment, balloon dilation of the pulmonary artery was attempted and unsuccessful. Right pulmonary artery plasty was then performed 5 months after lung transplantation. Following the procedure, the pulmonary artery stenosis was released, and the blood flow to the transplanted lung improved., Conclusion: Surgical treatment should be considered for pulmonary artery stenosis after lung transplantation if minimally invasive intervention is not effective., (© 2023. The Author(s).)

Background: The CyberKnife system features a robotically-positioned linear accelerator to deliver real-time image-guided stereotactic ablative body radiotherapy (SABR). It achieves steep dose gradients using irradiation from hundreds of different directions and increases the central dose of the gross tumor volume (GTV) without increasing the marginal dose to the planning target volume. We evaluated the effectiveness and safety of SABR with a central high dose using CyberKnife for metastatic lung tumors., Methods: A total of 73 patients with 112 metastatic lung tumors treated with CyberKnife were retrospectively analyzed. Local control, progression-free survival, and overall survival were calculated using the Kaplan-Meier method. The median age was 69.2 years. The most common primary sites were the uterus (n = 34), colorectum (n = 24), head and neck (n = 17), and esophagus (n = 16). For peripheral lung tumors, the median radiation dose was 52 Gy in 4 fractions, whereas for centrally located lung tumors, it was 60 Gy in 8-10 fractions. The dose prescription was defined as 99% of the solid tumor components of the GTV. The median maximum dose within the GTV was 61.0 Gy. The GTV and planning target volume were enclosed conformally by the 80% and 70% isodose lines of the maximum dose, respectively. The median follow-up period was extended to 24.7 months; it was 33.0 months for survivors., Results: The 2-year local control, progression-free survival, and overall survival rates were 89.1%, 37.1%, and 71.3%, respectively. Toxicities of grade ≥ 2 were noted as grade 2 and 3 radiation pneumonitis in one patient each. The two patients with grade 2 or higher radiation pneumonitis had both received simultaneous irradiation at two or three metastatic lung tumor sites. No toxicity of grade ≥ 2 was observed in patients with metastasis in one lung only., Conclusions: SABR with a central high dose using CyberKnife for metastatic lung tumors is effective with acceptable toxicity., Trial Registration: Number: 20557, Name: Stereotactic ablative radiotherapy using CyberKnife for metastatic lung tumor, URL: http://www.radonc.med.osaka-u.ac.jp/pdf/SBRT.pdf , Date of registration: April 1, 2021 (retrospectively registered), Date of enrollment: May 1, 2014., (© 2023. The Author(s).)

Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer death worldwide. The most common lung cancer is non-small cell lung cancer (NSCLC), with an overall 5-year survival rate of around 20% because NSCLC is a metastatic disease. A better understanding of the mechanism underlying lung cancer metastasis is therefore urgently needed. The tumor microenvironment involves different types of stromal cells and functions as key components in the progression of NSCLC. Through epithelial-mesenchymal transition (EMT), in which epithelial cells lose their polarity and acquire mesenchymal potential, cancer cells acquire metastatic abilities, as well as cancer stem-cell-like potential. We previously reported that cancer-associated fibroblasts (CAFs) interact with lung cancer cells to allow for the acquisition of malignancy and treatment resistance by paracrine loops via EMT signals in the tumor microenvironment. Furthermore, CAFs regulate the cytotoxic activity of immune cells via various cytokines and chemokines, creating a microenvironment of immune tolerance. Regulation of CAFs can therefore affect immune responses. Recent research has shown several roles of CAFs in NSCLC tumorigenesis, owing to their heterogeneity, so molecular markers of CAFs should be elucidated to better classify tumor-promoting subtypes and facilitate the establishment of CAF-specific targeted therapies. CAF-targeted cancer treatments may suppress EMT and regulate the niche of cancer stem cells and the immunosuppressive network and thus may prove useful for NSCLC treatment through multiple mechanisms.

Our department has been performing uniportal thoracoscopic lobectomy since April 2019 and now also performs segmentectomy for small malignant tumors. A skin incision of approximately 4 cm is created between the anterior fifth intercostal space on the left and right sides. Based on our experience, uniportal segmentectomy does not follow the learning curve unique to segmentectomy. For dissection of segmental surface, an automatic suture is used to prevent pulmonary fistulas. If the cutting line between the segments is straight, dissection can be performed easily even in uniportal surgery, in which the automatic suturing device is inserted from one direction. For inter-area identification, we use an air-containing collapsed line with normal ventilation, after which thoracoscopic indocyanine green( ICG) imaging is introduced. However, there have been cases in which a difference in inter-area identification occurred between ICG identification and the air-containing collapsed line. As such, it is better to utilize both methods in cases with masses close to the inter-areas.

Purpose: This study aimed to explore the clinical implications and prognostic value of the number of organ/structure invasions (NOI) in patients with thymoma after curative surgical resection., Methods: We retrospectively analyzed 306 consecutive Japanese patients with thymoma who underwent curative surgical resection. Tumor invasions of pericardium, mediastinal pleura, phrenic nerve, lung, and venous structures were examined histopathologically. Cases were classified into four subgroups according to NOI: group 0, no tumor invasion; group 1, tumor invasion into single organ/structure; group 2, tumor invasion of two organs/structures; group 3, invasion of three or more organs/structures. Associations with NOI and several clinical characteristics and their prognostic significance were analyzed., Results: Pleural invasion was found in 100 cases (32.7%), lung invasion in 48 cases (15.7%), pericardial invasion in 46 cases (15%), phrenic nerve invasion in 29 (9.5%), and venous invasion in 22 cases (7.2%). NOI was classed as group 0 in 201 cases (65.0%), group 1 in 42 cases (13.7%), group 2 in 20 cases (6.5%), and group 3 in 43 cases (14.1%). Cases with higher NOI showed significantly worse relapse-free survival (RFS) and overall survival (OS). Cox's proportional hazard model analysis also identified NOI as a prognostic factor affecting RFS and OS., Conclusions: Cases with higher NOI of thymoma after radical surgical resection showed significantly worse recurrence rates and survival., (© 2022. Society of Surgical Oncology.)

Objectives: The surgical Apgar score (SAS) is a simple score that predicts postoperative complications based on 3 intraoperative valuables. The present study evaluated the association between the SAS and postoperative outcomes in non-small-cell lung cancer patients who underwent surgery., Methods: A total of 585 patients who underwent lung resection were enrolled in the present study. We calculated the SAS of each patient and investigated its influence on the short- and long-term outcomes., Results: Postoperative complications of any grade were detected in 164 cases (28%). The morbidity rate increased with decreasing SAS. When all the patients were divided into 2 groups (SAS <7 vs ≥7), postoperative complications were observed more frequently in the SAS <7 group than in the SAS ≥7 group (41% vs 25%, P < 0.001). In the multivariate analysis, the SAS was an independent risk factor for postoperative complications (odds ratio: 1.64 [1.03-2.61], P = 0.036). In terms of long-term outcomes, the 5-year disease-free survival (54.1% vs 73.2%, P < 0.001) and overall survival (73.8% vs 83.0%, P = 0.031) were significantly worse in the SAS <7 group than in the SAS ≥7 group. In a multivariate analysis, however, the SAS was not found to be an independent prognostic factor for either disease-free survival (hazard ratio: 1.39 [0.97-2.00], P = 0.075) or overall survival (hazard ratio: 0.90 [0.57-1.42], P = 0.642)., Conclusions: The SAS reflected preoperative and intraoperative characteristics and was able to stratify the morbidity rate, suggesting it to be a useful predictor of short-term outcomes in non-small-cell lung cancer patients who undergo surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)