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Purpose: Nutritional scores have been reported to be useful prognostic factors for various cancers. This study evaluated the usefulness of the preoperative controlling nutritional status (CONUT) score as a predictor of recurrence of non-small cell lung cancer (NSCLC)., Methods: The present study included 422 patients with stage I-IIIA NSCLC who underwent complete resection at Tohoku University Hospital between January 2010 and December 2016. The patients were divided into the low-CONUT and high-CONUT groups based on their CONUT scores. Overall survival (OS), recurrence-free survival (RFS), and cumulative recurrence rates in the low- and high-CONUT groups were evaluated retrospectively., Results: One hundred forty-seven patients (34.8%) were assigned to the high-CONUT group. The high-CONUT group had a significantly worse performance status, pleural invasion, vascular invasion, and lung metastasis. In the whole cohort, the low-CONUT group showed better overall survival, recurrence-free survival, and a low cumulative recurrence rate in comparison to the high-CONUT group. There was no significant difference in prognosis or recurrence between the low- and high-CONUT groups after propensity score matching., Conclusion: Patients with a high CONUT score may be at high risk of recurrence because of the high frequency of pleural invasion, vascular invasion, and lung metastasis., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest in association with the present study., (© 2024. The Author(s).)

Background: Lung transplantation is a vital option for patients with end-stage lung disease. However, it faces a significant challenge due to the shortage of compatible donors, which particularly affects individuals with small chest cavities and pediatric patients. The novel approach of cadaveric lobar lung transplantation is a promising solution to alleviate the donor shortage crisis. Both the mid-term and long-term outcomes of lobar lung transplantation are comparable to those of standard lung transplantation. However, patients undergoing lobar lung transplantation reported a significantly higher rate of primary graft dysfunction compared to patients undergoing standard lung transplantation. Therefore, careful donor selection is critical to improve outcomes after lobar transplantation. However, no established method exists to evaluate each lung lobar graft of deceased donors. This case report describes a case of cadaveric lobar lung transplantation to overcome size mismatch and donor shortage, with particular emphasis on lobar graft evaluation., Case Presentation: A 39-year-old woman with scleroderma-related respiratory failure was listed for deceased donor lung transplantation due to a rapidly progressing disease. Faced with a long waiting list and impending mortality, she underwent bilateral living-donor lobar lung transplantation donated by her relatives. Post-transplant complications included progressive pulmonary vein obstruction and pleural effusion, which ultimately required retransplantation. An oversized donor with pneumonia in the bilateral lower lobes was allocated. Lung ultrasound was used to evaluate each lung lobar graft during procurement. The right upper and middle lobes and left upper lobe were confirmed to be transplantable, and lobar lung redo transplantation was performed. The patient's post-transplant course was uneventful, and she was discharged home and returned to her daily activities., Conclusions: This case highlights the clinical impact of cadaveric lobar lung transplantation as a feasible and effective strategy to overcome the shortage of donor lungs, especially in patients with small thoracic cavities. By establishing donor lung evaluation techniques and overcoming anatomical and logistical challenges, cadaveric lobar lung transplantation can significantly expand the donor pool and offer hope to those previously considered ineligible for transplantation., (© 2024. The Author(s).)

Purposes: Delayed chest closure (DCC) is a widely accepted procedure in the context of lung transplantation (LTx); yet there are few reports detailing its long-term survival and clinical outcomes., Methods: We reviewed the medical records of recipients who underwent deceased-donor lung transplantation (LTx) at Tohoku University Hospital. Long-term survival, including overall survival, freedom from chronic lung allograft dysfunction (CLAD), and CLAD-free survival and the clinical outcomes of graft function and physical performance and constitution were reviewed in recipients with DCC., Results: Between 2009 and 2022, 116 patients underwent LTx, 33 of whom (28.4%) required DCC. The intra-and post-operative courses of the recipients who required DCC were more complicated than those of the recipients who underwent primary chest closure (PCC), with frequent volume reduction surgery and longer periods of invasive mechanical ventilation. Pulmonary vascular disease was considered a risk factor for these complications and DCC. Nonetheless, long-term survival and graft functions were comparable between the DCC and PCC groups. The physical performance and constitution of recipients who required DCC continued to improve, and by 2 years after transplantation, exhibited almost no difference from those who underwent PCC., Conclusions: In view of the profoundly complicated intra- and post-operative courses, DCC should be performed cautiously and only when clinically indicated, despite which it can result in equivalent long-term survival and acceptable outcomes to PCC., (© 2024. The Author(s).)

This single-arm multi-institutional prospective study aimed to evaluate the 10-year outcomes of sublobar resection for small-sized ground-glass opacity-dominant lung cancer. Among 73 patients prospectively enrolled from 13 institutions between November 2006 and April 2012, 53 ground-glass opacity-dominant lung cancer patients underwent sublobar resection with wedge resection as the first choice. The inclusion criteria were maximum tumor size of 8-20 mm; ≥ 80% ground-glass opacity ratio on high-resolution computed tomography; lower 18 F-fluorodeoxyglucose accumulation than the mediastinum; intraoperative pathological diagnosis of adenocarcinoma in situ; and no cancer cells on intraoperative cut margins. The primary endpoint was a 10-year disease-specific survival. The 53 eligible patients had a mean tumor size of 14 ± 3.4 mm and a mean ground-glass opacity ratio of 95.9 ± 7.2%. Wedge resection and segmentectomy were performed in 39 and 14 patients, respectively. The final pathological diagnoses were adenocarcinoma in situ in 47 patients (88.7%) and adenocarcinoma with mixed subtype in 6 patients (11.3%). The 10-year disease-specific survival and overall survival were 100% and 96.2%, respectively, during a median follow-up period of 120 months (range, 37-162 months). Ground-glass opacity-dominant small lung cancer is cured by sublobar resection when patients are strictly selected by the inclusion criteria of this study., (© 2024. The Author(s).)

Purpose: This single-institution retrospective cohort study was conducted to assess the prognostic significance of perioperative changes in the prognostic nutritional index (PNI) in patients who underwent surgery for non-small cell lung cancer (NSCLC)., Methods: Clinicopathological data were collected from 441 patients who underwent lobectomy for NSCLC between 2010 and 2016.The PNI ratio (postoperative PNI/preoperative PNI) was used as an indicator of perioperative PNI changes. Prognostic differences were investigated based on PNI ratios., Results: The optimal cut-off value of the PNI ratio for overall survival (OS) was set at 0.88 using a receiver operating characteristic curve. The PNI ratio was inversely related to a high smoking index, interstitial lung disease, and postoperative pulmonary complications. The 5-year OS rates for the high vs. low PNI ratio groups were 88.2% vs. 68.5%, respectively (hazard ratio [HR]: 3.04, 95% confidence interval [CI]: 1.90-4.86). Multivariable analysis revealed that a low PNI ratio was significantly associated with poor prognosis (HR: 2.94, 95% CI: 1.77-4.87). The PNI ratio was a more sensitive indicator than postoperative PNI status alone for identifying patients at high risk of mortality, particularly those with non-lung cancer causes., Conclusion: The perioperative PNI change is a significant prognostic factor for patients with NSCLC., (© 2024. The Author(s).)

Purpose: To investigate the surgical outcomes and postoperative survival prognostic factors of intractable secondary spontaneous pneumothorax., Methods: A total of 95 patients who underwent thoracoscopic surgery for intractable secondary spontaneous pneumothorax between April 2010 and March 2020 were included in this study. These patients were classified into interstitial pneumonia and non-interstitial pneumonia groups, and a comparative study was performed on surgical outcomes and postoperative survival prognostic factors., Results: There was no difference in the 1-year overall survival rate between the two groups. However, the 3-year overall survival rate was significantly lower in the interstitial pneumonia group than in the non-interstitial pneumonia group. The differences in short-term surgical outcomes (persistent air leakage, postoperative complications, etc.) were not significant between the two groups. Univariate analysis revealed that the drainage period, the development of postoperative complications, and recurrence were significant independent postoperative survival prognostic factors for all cases. Postoperative complications were the only associated postoperative survival prognostic factor for interstitial pneumonia pneumothorax in the multivariate analysis., Conclusion: The development of postoperative complications can cause poor postoperative survival prognosis of intractable secondary spontaneous pneumothorax due to interstitial pneumonia., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: This study aims to compare the post-transplant survival of untwinned single lung transplantation (SLT) to twinned SLT. In untwinned SLT, the contralateral lung is judged unsuitable for transplantation and might affect the lung graft within the donor body and recipient survival after SLT., Methods: A retrospective analysis was conducted on 84 SLT recipients at our center, divided into untwinned SLT and twinned SLT groups. The demographics of donors and recipients, surgical characteristics, complications, mortality, and survival rates were compared., Results: There were no significant differences in recipient and donor demographics between the two groups. Surgical characteristics showed no significant differences. Microbiological findings of the transplanted lungs indicated a low incidence of positive cultures in both groups. 3-month to 1-year mortality and overall survival rates were comparable between the two groups., Conclusion: At our institution, both untwinned and twinned SLT procedures exhibited excellent survival rates without significant differences between the two procedures. The favorable outcomes observed may be associated with the strategic advantages of Japan's MC system and the diligent management of marginal donor lungs although this requires further investigation to elucidate the specific contributory factors., (© 2023. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Recent advancements in computed tomography (CT) scanning have improved the detection rates of peripheral pulmonary nodules, including those with ground-glass opacities (GGOs). This study focuses on part-solid pure ground-glass nodules (GGNs) and aims to identify imaging predictors that can reliably differentiate primary lung cancer from nodules with other diagnoses among part-solid GGNs on high-resolution CT (HRCT). A retrospective study was conducted on 609 patients who underwent surgical treatment or observation for lung nodules. Radiological findings from pre-operative HRCT scans were reviewed and several CT imaging features of part-solid GGNs were examined for their positive predictive value to identify primary lung cancer. The proportions of the nodules with a final diagnosis of primary lung cancer were significantly higher in part-solid GGNs (91.9%) compared with solid nodules (70.3%) or pure GGNs (66.7%). Among CT imaging features of part-solid GGNs that were evaluated, consolidation-to-tumor ratio (CTR) < 0.5 (98.1%), pleural indentation (96.4%), and clear tumor border (96.7%) had high positive predictive value to identify primary lung cancer. When two imaging features were combined, the combination of CTR < 0.5 and a clear tumor border was identified to have 100% positive predictive values with a sensitivity of 40.8%. Thus we conclude that part-solid GGNs with a CTR < 0.5 accompanied by a clear tumor border evaluated by HRCT are very likely to be primary lung cancers with an acceptable sensitivity. Preoperative diagnostic procedures to obtain a pathological diagnosis may potentially be omitted in patients harboring such part-solid GGNs.

Non-islet cell tumor hypoglycemia (NICTH) is one of the paraneoplastic syndromes manifesting severe hypoglycemia caused by aberrant production of high-molecular-weight insulin-like growth factor 2 (big-IGF2). Two surgical cases of extremely large thoracic solitary fibrous tumors (SFT) with unusual history of NICTH are presented. One case manifested severe hypoglycemia after four years of the first complete surgical resection of the tumor with potential malignant transformation, and the other case showed severe hypoglycemia after ten years of the first detection of the tumor. Meticulous laboratory testing, including serum endocrinological tests and western immunoblotting before and after surgery was performed, and both cases were diagnosed as NICTH. Both patients underwent open thoracic surgery. The patients showed normal glucose and hormone levels immediately after the resection of responsible tumors with elevated blood insulin concentration. SFTs are generally considered benign; however, life-threatening hypoglycemia can happen regardless of treatment. Careful follow-up of the tumor growth is warranted.

Background: Interstitial lung disease (ILD) represents a heterogeneous group of lung disorders characterized by fibrotic lung tissue changes. In regions with severe donor shortages, single-lung transplantation (SLTx) is often preferred over bilateral lung transplantation for advanced ILD. However, temporal changes and complications in the retained native lung remain poorly understood., Methods: A retrospective analysis of 149 recipients who had undergone SLTx was conducted, including 34 ILD SLTx recipients. Native-lung volume, radiological alterations, and perfusion were assessed at distinct post-SLTx time points. Statistical analyses compared ILD and non-ILD SLTx groups., Results: Our study revealed a progressive reduction in native-lung volume over time, accompanied by radiographic deterioration and declining perfusion. Complications in the retained native lung were observed, such as pneumothorax (29.4%), pulmonary aspergillosis (11.8%), and acute exacerbation (8.9%). Long-term survival rates were similar between ILD and non-ILD SLTx recipients., Conclusions: This study illuminates the unique challenges and complications with respect to the native lung following SLTx for ILD. Ongoing monitoring and tailored management are essential. Despite limitations, this research contributes to our understanding of the temporal progression of native-lung complications post-SLTx for ILD, underscoring the need for further investigation., (© 2024. The Author(s).)

Whole lung engineering and the transplantation of its products is an ambitious goal and ultimately a viable solution for alleviating the donor-shortage crisis for lung transplants. There are several limitations currently impeding progress in the field with a major obstacle being efficient revascularization of decellularized scaffolds, which requires an extremely large number of cells when using larger pre-clinical animal models. Here, we developed a simple but effective experimental pulmonary bioengineering platform by utilizing the lung as a scaffold. Revascularization of pulmonary vasculature using human umbilical cord vein endothelial cells was feasible using a novel in-house developed perfusion-based bioreactor. The endothelial lumens formed in the peripheral alveolar area were confirmed using a transmission electron microscope. The quality of engineered lung vasculature was evaluated using box-counting analysis of histological images. The engineered mouse lungs were successfully transplanted into the orthotopic thoracic cavity. The engineered vasculature in the lung scaffold showed blood perfusion after transplantation without significant hemorrhage. The mouse-based lung bioengineering system can be utilized as an efficient ex-vivo screening platform for lung tissue engineering., (© 2024. The Author(s).)

Objectives: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation., Methods: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center., Results: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis., Conclusion: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis., 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 © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study is to identify the clinical, genomic, and transcriptomic features of patients with lung adenocarcinoma (LUAD) harboring uncommon epidermal growth factor receptor (EGFR) mutations (UCM) compared with common EGFR mutations (CM)., Materials and Methods: In this multicenter retrospective cohort study, clinicopathological data were collected from 1047 consecutive patients who underwent complete surgical resection for LUAD, as well as EGFR mutation analysis, between 2005 and 2012 at 4 institutions. Differences in postoperative overall survival (OS) and recurrence-free survival (RFS) according to EGFR mutation status were evaluated. For the genomic and transcriptomic analyses, 5 cohorts from public databases were evaluated., Results: Of 466 eligible patients, 415 (89.1%) and 51 (10.9%) had CM and UCM, respectively. The 5-year OS and RFS rates in the CM/UCM groups were 86.8%/77.0% and 74.8%/59.0%, respectively. OS and RFS were significantly shorter in the UCM than CM group (both P < .01). Multivariable analysis of OS showed that UCM was an independent prognostic factor (hazard ratio 1.72, 95% confidential interval 1.01-2.93). According to the genomic analysis, tumors with UCM had a significantly higher tumor mutation burden and TP53 mutation frequency. Transcriptomic analysis showed that the T-cell-inflamed gene signature, a biomarker of the treatment for immunotherapy, was significantly associated with tumors with UCM., Conclusion: UCM were associated with a poor prognosis in patients with surgically resected EGFR-mutated LUAD. Tumors with UCM had unique genomic and transcriptomic features suggestive of a tumor microenvironment responsive to immunotherapy., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The ADAURA trial reported that osimertinib improved overall survival (OS) as an adjuvant chemotherapy for pathological stage IB-IIIA epidermal growth factor receptor (EGFR) mutant lung cancer compared with a placebo. Currently, platinum-based adjuvant chemotherapy is the standard treatment for patients with or without EGFR mutations. This study aimed to evaluate the efficacy of platinum-based adjuvant chemotherapy in patient with stage II-IIIA EGFR mutant lung adenocarcinoma., Methods: We collected the medical records of consecutive patients who underwent surgical resection for lung adenocarcinoma between 2005 and 2012 at the four participating institutions. The data of 173 patients with different EGFR mutation status were retrospectively evaluated to determine the efficacy of platinum-based adjuvant chemotherapy for OS and recurrence-free survival (RFS). We further analyzed OS using the inverse probability of treatment weighting method with propensity scores., Results: The median age was 69 years (range, 45-85 years); 95 (54.9%) were male and 74 (42.8%) had EGFR mutations. A total of 43 patients with EGFR mutants (58.1%) and 43 patients with wild-type EGFR tumors (43.4%) received platinum-based adjuvant chemotherapy. No differences in RFS and OS were observed between EGFR mutant and wild-type EGFR in lung adenocarcinoma without adjuvant therapy. However, wild-type EGFR showed an improvement in OS with platinum-based adjuvant chemotherapy in inverse probability of treatment weighting analysis, whereas those with EGFR mutations showed no significant difference in OS between the surgery-only group and the adjuvant group. The deletion of exon 19 and exon 21 L858R point mutation showed no significant differences in OS between the surgery-only group and the adjuvant group, respectively. The hazard ratio (HR) exceeded 1 for uncommon EGFR mutations., Conclusions: Platinum-based adjuvant chemotherapy may be less effective for EGFR-mutant lung adenocarcinoma, regardless of the mutation type., 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-23-1323/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: Systemic-to-pulmonary artery shunt (SPAS) is a rare condition that can occur as a result of congenital heart disease or chronic pulmonary inflammation, occasionally leading to life-threatening hemoptysis. Computed tomography (CT) imaging is crucial in the diagnosis of SPAS, and the optimal management approach for SPAS remains uncertain. This case report presents a novel approach to the treatment of SPAS, consisting of transcatheter arterial embolization of the systemic artery followed by lung segmentectomy., Case Presentation: A 42-year-old man with abnormal chest findings was referred to us and a diagnosis of SPAS was established based on the CT findings showing a blood flow regurgitation from the dilated left 4th intercostal artery to the Lt. A6. The patient was asymptomatic but we decided to treat him to prevent a risk of future hemoptysis. Transcatheter arterial embolization (TAE) of systemic arteries followed by S6 segmentectomy was successfully performed with minimal blood loss and complete removal of the dilated intra-pulmonary blood vessels. Histological analysis confirmed the diagnosis of SPAS., Conclusion: We reported a case of SPAS, who was successfully treated with the combination of TAE and subsequent segmentectomy. The blood loss during surgery was minimal and this strategy appeared to minimize future recanalization and hemoptysis. Further studies and long-term follow-up of SPAS patients are required to establish standardized management guidelines for this rare condition., (© 2023. The Author(s).)

Objectives: Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors were recently reported to be effective as adjuvant therapy for resected lung adenocarcinoma (ADC) harbouring common EGFR mutations. However, whether the EGFR mutation is a direct risk factor for postoperative recurrence remains unknown. Therefore, we conducted a multi-institutional observational study to compare postoperative survival according to EGFR mutation status., Methods: We collected the medical records of consecutive patients who underwent surgical resection for ADC between 2005 and 2012 at 4 participating institutions. Recurrence-free survival (RFS) and overall survival (OS) associated with EGFR mutation status were evaluated. We further analysed survival after pair-matching patients' clinicopathological characteristics., Results: EGFR mutations were harboured by 401 of 840 (48%) enrolled patients. The number of patients with an EGFR mutation (M group) differed from that with the EGFR wild-type sequence (W group) in terms of sex, smoking history and pathological stage. The median follow-up period was 85 months. The five-year RFS/OS rates of the M and W groups were 70%/85% and 61%/75%, respectively (P < 0.001 for both groups). However, multivariable analysis revealed that EGFR mutation status was not independently related with both RFS and OS. In pair-matched analysis, the RFS and OS curves of the patients with an EGFR mutation and wild-type sequence were not statistically different, either., Conclusions: Long-term follow-up of consecutive patients did not show that a common EGFR mutation was an independent risk factor of recurrence or prognostic factor for completely resected lung ADC., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4/ILT3) is an up-and-coming molecule that promotes immune evasion. We have previously reported that LILRB4 facilitates myeloid-derived suppressor cells (MDSCs)-mediated tumor metastasis in mice. This study aimed to investigate the impact of the LILRB4 expression levels on tumor-infiltrating cells on the prognosis of non-small cell lung cancer (NSCLC) patients., Methods: We immunohistochemically evaluated the LILRB4 expression levels of completely resected 239 NSCLC specimens. Whether the blocking of LILRB4 on human PBMC-derived CD33 + MDSCs inhibited the migration ability of lung cancer cells was also examined using transwell migration assay., Results: The LILRB4 high group, in which patients with a high LILRB4 expression level on tumor-infiltrating cells, showed a shorter overall survival (OS) (p = 0.013) and relapse-free survival (RFS) (p = 0.0017) compared to the LILRB4 low group. Multivariate analyses revealed that a high LILRB4 expression was an independent factor for postoperative recurrence, poor OS and RFS. Even in the cohort background aligned by propensity score matching, OS (p = 0.023) and RFS (p = 0.0046) in the LILRB4 high group were shorter than in the LILRB4 low group. Some of the LILRB4 positive cells were positive for MDSC markers, CD33 and CD14. Transwell migration assay demonstrated that blocking LILRB4 significantly inhibited the migration of human lung cancer cells cocultured with CD33 + MDSCs., Conclusion: Together, signals through LILRB4 on tumor-infiltrating cells, including MDSCs, play an essential role in promoting tumor evasion and cancer progression, impacting the recurrence and poor prognosis of patients with resected NSCLC., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Neurological paraneoplastic syndrome is a relatively rare condition in patients with malignant tumors. Recently, it has been reported that anti-Aquaporin 4 (AQP4) antibody is highly specific for neuromyelitis optica. The patient was a 76-year-old man. He underwent right upper lobectomy for squamous cell carcinoma of the lung. Although the immediate postoperative course was uneventful, neurological symptoms became apparent from postoperative day (POD) 4. Magnetic resonance imaging showed longitudinally extended edematous lesions in the spinal cord, and a cerebrospinal fluid examination was positive for anti-AQP4 antibody, leading to the diagnosis of paraneoplastic neuromyelitis optica. Despite multiple rounds of steroid pulse therapy and plasma exchange, the neurological symptoms worsened and the patient died on POD 46. The development of neuromyelitis optica in the early postoperative period could be related to the influence of surgical stress or epidural anesthesia.

In this study, we sought to elucidate the roles of the interleukin (IL)-32β and IL-32γ in mesothelioma cell growth, and vascular endothelial growth factor (VEGF)-A and C-X-C motif chemokine ligand 8 (CXCL8) expression. IL-32 elicited a growth-promoting effect against one of the six mesotheliomas lines and exerted diverse regulatory functions in VEGF-A and CXCL8 secretion from mesotheliomas stimulated with or without IL-17A. Retroviral-mediated transduction of mesothelioma lines with IL-32γ resulted in enhanced IL-32β expression, which facilitated or suppressed the in vitro growth, and VEGF-A and CXCL8 expression. Overexpressed IL-32β-augmented growth and VEGF-A and CXCL8 production were mainly mediated through the phosphatidylinositol-3 kinase (PI3K) signaling pathway. On the other hand, overexpressed IL-32β-deceased growth was mediated through mitogen-activated protein kinase (MAPK) pathway. NCI-H2373IL-32γ tumors grew faster than NCI-H2373Neo tumors in a xenograft model, which was associated with increased vascularity. These findings indicate that IL-32 are involved in the regulation of growth and angiogenic factor production in mesotheliomas., 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 © 2022 Elsevier Inc. All rights reserved.)

Background: Aortopulmonary mediastinal paragangliomas are rare. Complete resection of the tumor is desirable regardless of tumor size in view of the risk of sudden death induced by adjacent organ compression and poor prognosis after partial resection or untreated observation. Due to the hypervascularity of the tumor, the risk of intraoperative bleeding is significant, and cardiopulmonary bypass is often required for complete resection., Case Presentation: The patient was diagnosed as having bilateral carotid body tumors and supposedly an aortic body tumor at the age of 43 and eventually underwent resections of bilateral carotid body tumors at the age of 52. The pathology of the carotid body tumors was compatible with paraganglioma on both sides. A familial succinate dehydrogenase subunit D mutation was subsequently identified. Five years later, a contrast-enhanced computed tomography scan showed an enlarged tumor of 45 mm in size in the aortopulmonary mediastinum. Based on the previously known genetic mutation, the tumor was thought to be a paraganglioma. After confirming with an endocrinologist that the aortic body tumor was non-functional, radiologists performed preoperative embolization of the feeding vessels. Subsequently, a surgical team consisting of thoracic and cardiovascular surgeons resected the aortic body tumor using a video-assisted small left thoracotomy approach combined with a median sternotomy approach. The procedure was completed without cardiopulmonary bypass or blood transfusion. The patient was discharged home on postoperative day 9 uneventfully., Conclusions: After conduction of preceding interventional embolization of multiple feeding vessels, we employed a video-assisted thoracoscopic surgical approach to dissect the aspects of the tumor adjacent to the esophagus, descending thoracic aorta, and left pulmonary artery, followed by a median sternotomy approach to dissect the other aspects of the tumor adjacent to the ascending aorta, aortic arch, right pulmonary artery, and trachea. There have been no reports on scheduled preoperative embolization of feeding vessels to an aortopulmonary mediastinal paraganglioma. Multidisciplinary approach was effective for complete resection of this challenging rare mediastinal tumor., (© 2022. The Author(s).)

As shown in our previous studies, the intratracheal-administration of STC1 (stanniocalcin-1) ameliorates pulmonary fibrosis by reducing oxidative and endoplasmic reticulum stress through the uncoupling of respiration in a bleomycin-treated mouse model. However, the overall effect of STC1 on metabolism was not examined. Therefore, we first conducted a comprehensive metabolomics analysis to screen the overall metabolic changes induced by STC1 in an alveolar epithelial cell line using capillary electrophoresis time-of-flight mass spectrometry. The results were subsequently validated in multiple alveolar epithelial and fibroblast cell lines by performing precise analyses of each substance. STC1 stimulated glycolysis, acetyl-CoA synthesis, and the methionine and cysteine-glutathione pathways, which are closely related to the uncoupling of respiration, modulation of epigenetics, and reduction in oxidative stress. These results are consistent with our previous study. Subsequently, we focused on the inhibitory factor SMAD7, which exerts an antifibrotic effect and is susceptible to epigenetic regulation. STC1 upregulates SMAD7 in an uncoupling protein 2-dependent manner, induces demethylation of the SMAD7 promoter region and acetylation of the SMAD7 protein in human alveolar epithelial and fibroblast cell lines and a bleomycin-treated mouse model, and subsequently attenuates fibrosis. The antifibrotic effects of STC1 may partially depend on the regulation of SMAD7. In the evaluation using lung tissue from patients with idiopathic pulmonary fibrosis, SMAD7 expression and acetylation were high in the alveolar structure-preserving region and low in the fibrotic region. The intratracheal administration of STC1 may prevent the development of pulmonary fibrosis by regulating the metabolism-mediated epigenetic modification of SMAD7 in patients.

Introduction: Mutations in BRAF occur in 2% to 4% of patients with lung adenocarcinoma. Combination dabrafenib and trametinib, or single-agent vemurafenib is approved only for patients with cancers driven by the V600E BRAF mutation. Targeted therapy is not currently available for patients harboring non-V600 BRAF mutations., Methods: A lung adenocarcinoma patient-derived xenograft model (PHLC12) with wild-type and nonamplified EGFR was tested for response to EGFR tyrosine kinase inhibitors (TKIs). A cell line derived from this model (X12CL) was also used to evaluate drug sensitivity and to identify potential drivers by small interfering RNA knockdown. Kinase assays were used to test direct targeting of the candidate driver by the EGFR TKIs. Structural modeling including, molecular dynamics simulations, and binding assays were conducted to explore the mechanism of off-target inhibition by EGFR TKIs on the model 12 driver., Results: Both patient-derived xenograft PHLC12 and the X12CL cell line were sensitive to multiple EGFR TKIs. The BRAF G469V mutation was found to be the only known oncogenic mutation in this model. Small interfering RNA knockdown of BRAF, but not the EGFR, killed X12CL, confirming BRAF G469V as the oncogenic driver. Kinase activity of the BRAF protein isolated from X12CL was inhibited by treatment with the EGFR TKIs gefitinib and osimertinib, and expression of BRAF G469V in non-EGFR-expressing NR6 cells promoted growth in low serum condition, which was also sensitive to EGFR TKIs. Structural modeling, molecular dynamic simulations, and in vitro binding assays support BRAF G469V being a direct target of the TKIs., Conclusions: Clinically approved EGFR TKIs can be repurposed to treat patients with non-small cell lung cancer harboring the BRAF G469V mutation., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

The patient was a 41-year-old man. He was diagnosed with pleurisy and came to our hospital. The pleural effusion and pleurisy remained even after administration of sufficient doses of antibiotics. A thorough examination revealed an anterior mediastinal tumor. Six months later, pericarditis also developed. Autoimmune diseases, infections, and malignant diseases were suspected, but a definitive diagnosis could not be made. In order to confirm the diagnosis, anterior mediastinal tumor resection and pleural biopsy were performed. The anterior mediastinal tumor was diagnosed as cholesterin granuloma pathollogically. Cholesterin granuloma is a granuloma formed by deposition of cholesterin crystals and cholesterin granuloma occurring in the mediastinum is extremely rare.

Background: As lung transplantation (LTX) is a valuable treatment procedure for end-stage pulmonary disease, delayed referral to a transplant center should be avoided. We aimed to conduct a single-center analysis of the survival time after listing for LTX and waitlist mortality in each disease category in a Japanese population., Methods: We included patients listed for LTX at Tohoku University Hospital from January 2007 to December 2020 who were followed up until March 2021. Pulmonary disease was categorized into the Obstructive, Vascular, Suppurative, Fibrosis, and Allogeneic groups. Risk factors for waitlist mortality were assessed using a Cox proportional hazards model. The Kaplan-Meier method was used to model time to death., Results: We included 269 LTX candidates. Of those, 100, 72, and 97 patients were transplanted, waiting, and dead, respectively. The median time to LTX and time to death were 796 days (interquartile range [IQR] 579-1056) and 323 days (IQR 129-528), respectively. The Fibrosis group showed the highest mortality (50.9%; p < .001), followed by the Allogeneic (35.0%), Suppurative (33.3%), Vascular (32.1%), and Obstructive (13.1%) groups. The Fibrosis group showed a remarkable risk for waitlist mortality (hazard ratio 3.32, 95% CI 2.11-4.85)., Conclusions: In Japan, the waiting time is extremely long and candidates with Fibrosis have high mortality. There is a need to document outcomes based on the underlying disease for listed LTX candidates to help determine the optimal timing for listing patients based on the estimated local waiting time., (© 2021. The Author(s).)

Background: While lung transplant (LTX) can be an effective therapy to provide the survival benefit in selected populations, post-transplant outcome in LTX recipients with bronchiectasis other than cystic fibrosis (CF) has been less studied. Pseudomonas aeruginosa, often associated with exacerbations in bronchiectasis, is the most common micro-organism isolated from LTX recipients. We aimed to see the outcomes of patients with bronchiectasis other than CF after LTX and seek the risk factors associated with pre- and post-transplant Pseudomonas status., Methods: Patients who underwent LTX at Tohoku University Hospital between January 2000 and December 2020 were consecutively included into the retrospective cohort study. Pre- and post-transplant prevalence of Pseudomonas colonization between bronchiectasis and other diseases was reviewed. Post-transplant outcomes (mortality and the development of chronic lung allograft dysfunction (CLAD)) were assessed using a Cox proportional hazards and time-to-event outcomes were estimated using the Kaplan-Meier method., Results: LTX recipients with bronchiectasis experienced a high rate of pre- and post-transplant Pseudomonas colonization compared to other diseases with statistical significance (p < 0.001 and p < 0.001, respectively). Nevertheless, long-term survival in bronchiectasis was as great as non-bronchiectasis (Log-rank p = 0.522), and the bronchiectasis was not a trigger for death (HR 1.62, 95% CI 0.63-4.19). On the other hand, the chance of CLAD onset in bronchiectasis was comparable to non-bronchiectasis (Log-rank p = 0.221), and bronchiectasis was not a predictor of the development of CLAD (HR 1.88, 95% CI 0.65-5.40)., Conclusions: Despite high prevalence of pre- and post-transplant Pseudomonas colonization, the outcome in LTX recipients with bronchiectasis other than CF was comparable to those without bronchiectasis., (© 2021. The Author(s).)