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Purpose: This study examined the learning curve of segmentectomy using the "fused surgery" approach., Methods: We retrospectively collected data from 100 patients who underwent segmentectomy via fused robot-assisted thoracoscopy at our institution between September 2020 and February 2024. The learning curve was evaluated using the cumulative sum of the operative times in all cases and was analyzed separately for simple and complex segmentectomies., Results: After applying the cumulative sum method to all cases, we obtained a graph of the operative time that showed three well-differentiated phases: phase 1 (n = 23), the initial learning phase; phase 2 (n = 28), the increased competence phase; and phase 3 (n = 49), the highest skill phase. Comparing phases 1 and 2 with phase 3, we found significant differences in operative time (P < 0.001); however, no significant differences were observed in bleeding or rate of postoperative complications. We observed a significant reduction in operative time after 25 simple segmentectomies and 22 complex segmentectomies., Conclusions: The data suggested that the inflection point of the learning curve was achieved in 51 cases. Complex segmentectomy requires the same cases to achieve the same level of competence as simple segmentectomy., Competing Interests: Declarations Conflict of interest Yugo Tanaka received lecture fees from Ethicon Inc. (Cincinnati, OH, USA). The authors declare no conflicts of interest., (© 2024. The Author(s).)

Purpose: Robotic-assisted thoracoscopic surgery (RATS) is a relatively new approach to lung cancer surgery. To promote the development of RATS procedures, we investigated the factors related to short-term postoperative outcomes., Methods: We analyzed the records of patients who underwent RATS lobectomy for primary lung cancer at our institution between June, 2018 and January, 2023. The primary outcome was operative time, and the estimated value of surgery-related factors was calculated by linear regression analysis. The secondary outcome was surgical morbidity and the risk was assessed by logistic regression analysis., Results: The study cohort comprised 238 patients. Left upper lobectomy had the longest mean operative time, followed by right upper lobectomy. Postoperative complications occurred in 13.0% of the patients. Multivariate analysis revealed that upper lobectomy, the number of staples used for interlobular fissures, and the number of cases experienced by the surgeon were significantly associated with a longer operative time. The only significant risk factor for postoperative complications was heavy smoking., Conclusion: Patients with well-lobulated middle or lower lobe lung cancer who are not heavy smokers are recommended for the introductory period of RATS lobectomy. Improving the procedures for upper lobectomy and dividing incomplete interlobular fissures will promote the further development of RATS., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: To evaluate the safety and efficacy of new staple-line reinforcement (SLR) in pulmonary resection through a prospective study and to compare the results of this study with historical control data in an exploratory study., Methods: The subjects of this study were 48 patients who underwent thoracoscopic lobectomy. The primary endpoint was air leakage from the staple line. The secondary endpoints were the location of air leakage, duration of air leakage, and postoperative pulmonary complications., Results: The incidence of intraoperative air leakage from the staple line was 6.3%. Three patients had prolonged air leakage as a postoperative pulmonary complication. No malfunction was found in patients who underwent SLR with the stapling device. When compared with the historical group, the SLR group had a significantly lower incidence of air leakage from the staple line (6.3% vs. 28.5%, P < 0.001) and significantly shorter indwelling chest drainage time (P = 0.049) and length of hospital stay (P < 0.001)., Conclusions: The use of SLR in pulmonary resection was safe and effective. When compared with conventional products, SLR could control intraoperative air leakage from the staple line and shorten time needed for indwelling chest drainage and the length of hospital stay., (© 2024. The Author(s).)

In the last decade, even thoracic surgery has seen an increase in the use of robotic surgical systems, and robot-assisted thoracic surgery (RATS) is considered one of the main issues. While RATS is associated with solo manipulative freedom and high-definition optical systems, several disadvantages, such as the lack of tactile sensation and difficult learning curves for the whole team, have been raised. Therefore, to overcome these issues, we developed a 'fusion surgery' approach combining a robotic procedure with manual maneuvers, where the table surgeon retracts the lung and staples the pulmonary vasculature and bronchus. Herein, we introduce our 'fusion surgery' procedure and elaborate on its advantage from technical and educational perspectives., (© 2023. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Purpose: Many effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed, but a weaker response in individuals undergoing anticancer treatment has been reported. This study evaluates the immunogenic status and safety of SARS-CoV-2 vaccines for patients with non-small-cell lung cancer (NSCLC), receiving tegafur-uracil (UFT) as postoperative adjuvant chemotherapy., Methods: The subjects of this prospective study were 40 patients who underwent surgery for NSCLC and received SARS-CoV-2 vaccines postoperatively. We compared the antibody titers of SARS-CoV-2 vaccines and the adverse events between patients who received adjuvant UFT and patients who did not., Results: The mean anti-S1 IgG titers were not significantly different between the UFT and without-UFT groups (mean optimal density, 0.194 vs. 0.205; P = 0.76). Multivariate analysis identified the period after the second vaccination as an independent predictor of anti-S1 IgG titer (P = 0.049), but not the UFT status (with or without-UFT treatment; P = 0.47). The prevalence of adverse events did not differ significantly between the groups, and no severe adverse events occurred., Conclusions: The efficacy and safety of the SARS-CoV-2 vaccines for NSCLC patients who received postoperative adjuvant UFT chemotherapy were comparable to those for NSCLC patients who did not receive postoperative adjuvant UFT chemotherapy., Clinical Trial Registration: This study was registered with the University Hospital Medical Information Network (UMIN) in Japan (UMIN000047380)., (© 2023. The Author(s).)

Background: Identifying the preoperative risk factors for lymph node upstaging could contribute to the development of individualized perioperative treatment for patients with non-small cell lung cancer (NSCLC). The current study aimed to evaluate the risk factors for lymph node upstaging, including gene mutation and programmed death ligand-1 expression in patients with resectable NSCLC., Methods: Data on the clinicopathological characteristics of patients who underwent lobectomy for clinical N0 NSCLC at our institution were collected. The clinicopathological findings of the pathological N0 and lymph node upstaging groups were then analyzed. Univariate and multivariate analyses were performed to examine the predictive factors for nodal upstaging., Results: Of 291 patients, 40 had postoperative nodal upstaging (n = 25, N1; n = 15, N2). Large tumor size and high maximum standardized uptake value were significantly associated with nodal upstaging. The nodal upstaging group had a higher proportion of patients with solid adenocarcinoma and lymphatic, vascular, and pleural invasion than the pathological N0 group. Further, the nodal upstaging group had a higher proportion of patients with positive programmed death ligand-1 expression than the pathological N0 group. Univariate and multivariate analyses showed that tumor size and positive programmed death ligand-1 expression were associated with nodal upstaging., Conclusion: The appropriate therapeutic strategy including preoperative treatment and resection should be cautiously considered preoperatively in patients with clinical N0 NSCLC who have large tumors and positive programmed death ligand-1 expression., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Myasthenia gravis (MG) is the most common paraneoplastic syndrome in thymoma. However, the association between MG and postoperative outcomes is controversial. Therefore, we examined the effect of MG on the surgical outcomes of patients with thymoma., Methods: This study enrolled 145 consecutive patients with thymoma who underwent surgical resection at our institution between January 2000 and December 2020. The patients were classified into thymoma with MG (MG group) and without MG (non-MG group). Data about characteristics of patients, surgical outcomes, and prognostic factors were compared between the two groups., Results: Of 145 patients, 47 (32%) presented with MG and 98 (68%) did not. There was no significant difference in terms of the incidence of postoperative complications, overall survival (OS), and recurrence-free survival (RFS) between the two groups. The deaths were not caused by thymoma. Among the patients aged >60 years, the MG group had a lower survival rate than the non-MG group. In the univariate analysis, age ≥60 years was a poor prognostic factor for OS, whereas in the multivariate analysis, Masaoka stage III and IV classifications were poor prognostic factors for RFS., Conclusion: The incidence of postoperative complications did not differ between patients with thymoma and without MG. In the MG group, age ≥60 years was a poor prognostic factor for OS. The postoperative follow-up of patients aged ≥60 years with thymoma with MG should focus on not only recurrence but also progression of diseases other than thymoma.

Background: The number of surgical procedures has increased among patients with early-stage lung cancer. If the poor prognostic factors for stage I non-small cell lung cancer (NSCLC) can be simply validated preoperatively, appropriate treatment will be provided. The current study aimed to evaluate the prognostic value of preoperative plasma fibrinogen levels in patients with resected stage I NSCLC., Methods: We retrospectively analyzed the clinicopathological information of patients (n = 149) who underwent lobectomy for stage I NSCLC between May 2014 and July 2016. Data about peripheral blood analysis, histopathological finding, and follow-up assessment results were collected from the databases. Patients were divided into the low and high fibrinogen groups. Univariate and multivariate analyses were performed to evaluate the predictors of recurrence and survival., Results: Compared with the low fibrinogen group (<377 mg/dl), the high fibrinogen group (≥377 mg/dl) had a significantly greater number of male participants (p = 0.04), smokers (p < 0.001), and those with elevated cytokeratin antigen levels (p = 0.04), lymphatic invasion (p = 0.007), and squamous cell carcinoma (p < 0.001). Plasma fibrinogen level was considered a significant independent factor for recurrence and overall survival on both the univariate and multivariate analyses (p < 0.001 and p = 0.010) and the multivariate analysis alone (p = 0.020 and p < 0.012)., Conclusion: Preoperative plasma fibrinogen level might be a useful predictor of recurrence and survival in patients with stage I NSCLC. The treatment strategy for patients with high fibrinogen levels could be cautiously considered preoperatively., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Managing thoracic empyema with massive air leakage can be challenging. We present a case with thoracic empyema with multiple bronchopleural fistulae and extensive lung parenchymal necrosis due to drain injury. Emergency surgery was performed for respiratory distress due to massive air leakage. As direct sutures could not be achieved due to extensive parenchymal necrosis, polyglycolic acid and oxidized regenerated cellulose sheets were packed into the lesion. Although open-window thoracostomy was required for bronchopleural fistulae, the stoma closure was achieved via vacuum-assisted closure therapy. The dual sheet coverings contributed to the successful recovery by resolving multiple bronchopleural fistulae.

Adhesiolysis is often necessary in intrathoracic adhesion during ipsilateral repeat lung resection. This procedure has a risk of surgical complications, including unintentional intraoperative damage of the pulmonary vessels or lung parenchyma. We used an oxidized regenerated cellulose (ORC) sheet to prevent intrathoracic adhesion after lung resection in 55 patients. The sheet was placed on the surface of the resected region and on the lung surface under the wound. No major postoperative complications were observed. Three cases underwent ipsilateral thoracic surgery for the treatment of lung malignancies, and there were no intrathoracic adhesions around the ORC sheet-covered area.

Background: Fibrous bands (FBs) are one of the histological features in tumors which can be confirmed by hematoxylin and eosin (H&E)-stained slides. FBs have been reported to correlate with malignancy in various tumors. This study aimed to investigate whether the presence of FBs is associated with malignancy in thymoma., Methods: A total of 123 consecutive patients with thymoma who underwent microscopically complete resections from January 2000 to December 2018 were enrolled into this study. H&E-stained slides of all thymoma patients were re-examined. Study patients were classified into two groups: with FBs (n = 36) and without FBs (n = 87). Clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) were compared between the two groups. Furthermore, multivariate analyses were performed to identify whether the presence of FBs was associated with higher Masaoka stage and poor prognosis in patients with thymoma., Results: The Masaoka stage was found to be higher and recurrence more likely in thymoma patients with FBs than in those without. RFS was significantly poorer in thymoma patients with FBs than in those without, although no significant difference was observed in OS between them. The presence of FBs was significantly associated with higher Masaoka stage in the multivariate analysis using logistic regression. Additionally, the presence of FBs was an independent prognostic factor for poor RFS in multivariate analysis using Cox's proportional hazards model., Conclusions: The presence of FBs in patients with thymoma was associated with higher Masaoka stage, higher recurrence rate, and poorer RFS., Key Points: SIGNIFICANT FINDINGS OF THE STUDY: Fibrous bands (FBs) are bands of fibrosis dividing tumors into different-sized irregular islands. The presence of FBs is associated with higher Masaoka stage and poor recurrence-free survival in patients with thymoma., What This Study Adds: The presence of fibrous bands might be associated with the malignant behavior of thymoma. Confirming the presence or absence of FBs may result in personalized medication for patients with thymoma., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Backgrounds and Objectives: Recent studies have suggested that insulinoma-associated protein 1 (INSM1) is a useful marker for pathological diagnosis of pulmonary neuroendocrine tumors. In the present study, we investigated the association between INSM1 expression and prognosis in patients with pulmonary high-grade neuroendocrine carcinomas (HGNEC) and assessed the usefulness of INSM1 as a prognostic biomarker in these patients., Methods: Seventy-five consecutive patients with HGNEC who underwent complete surgical resections from January 2000 to December 2018 were enrolled in this study. We classified these patients into two groups: the INSM1-positive group (n = 59) and INSM1-negative group (n = 16). We compared the clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) between the groups. In addition, we performed univariate and multivariate analyses to identify the prognostic factors associated with postoperative survival., Results: Significant differences in tumor diameter and vascular invasion between the groups were found. OS and RFS were significantly poorer in the INSM1-positive group than in the INSM1-negative group. Univariate and multivariate analyses revealed that INSM1 expression was the strongest predictor of poor prognosis for OS and RFS., Conclusions: INSM1 expression had the greatest influence on the prognosis in patients with HGNEC and may be a prognostic biomarker in these patients., (© 2020 Wiley Periodicals, Inc.)

Soft tissue myoepithelial tumors are very rare mesenchymal tumors that are currently categorized as miscellaneous neoplasms with uncertain differentiation. Although the molecular pathogenesis of soft tissue myoepithelial tumors remains unclear, EWSR1 gene fusions with a variety of partner genes are regarded as one of the major pathogenic driver events in these tumors. We herein present a case of a deep soft tissue malignant myoepithelial tumor arising in the thigh with multiple pulmonary metastases. This tumor displayed diverse and unique histological features, namely, an epithelioid glandular growth pattern, pseudorosette-like formation, and a diffuse nest and cord-like pattern within an abundant myxoid matrix. Next-generation RNA sequencing identified a novel fusion transcript, in which the in-frame junctional reads contained exon 9 of EWSR1 and exon 2 of VGLL1, resulting in the formation of a putative chimeric protein with the N-terminal transcriptional activation domain of EWSR1 and C-terminal full length of the VGLL1 protein. EWSR1-VGLL1 fusion has not been described in neoplasm before. Further molecular and functional experiments on the present EWSR1-VGLL1 fusion gene are required to elucidate its tumorigenic effect., (© 2019 Wiley Periodicals, Inc.)

Malignant pleural mesothelioma (MPM), associated with unfavorable outcomes, is closely associated with asbestos exposure. Early detection and treatment are critical to prolong survival of patients with MPM because of the rapid progression and resistance to treatment. The recently defined malignant mesothelioma in situ (MIS) has been gaining increasing attention with advances in genome-based methods including fluorescence in situ hybridization (FISH) as well as immunohistochemistry. We herein report the case of a MIS in a 73-year-old male with a history of asbestos exposure presenting with massive pleural effusion in the right thoracic cavity. Video-assisted thoracoscopic surgery with pleural biopsy of the right side revealed a single layer of atypical mesothelial cells without invasive lesions by hematoxylin and eosin staining. However, these mesothelial cells exhibited a loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry and homozygous deletion of CDKN2A (p16) by FISH, leading to the diagnosis of MIS.

Mediastinal leiomyosarcoma is an aggressive tumor that primarily occurs in the posterior mediastinum. A bronchogenic cyst is a benign lesion that often develops in the mediastinum close to the thoracic trachea and has been reported to be the origin of certain malignancies. The present study reports an extremely rare case of an anterior mediastinal leiomyosarcoma that was considered to have originated from a bronchogenic cyst. An 82-year-old woman complained of chest pain, presenting an abnormal 70 mm mass shadow in the anterior mediastinum of a chest CT scan. Mediastinal tumor resection was performed and the tumor was diagnosed as a leiomyosarcoma. As the tumor was located adjacent to a bronchogenic cyst, it was considered to have originated from the remnant tissue of the cyst. Recurrent lesions were noted in the right lower lobe on CT scan 24 months after surgery., (Copyright: © Kimura et al.)

Objectives: During video-assisted thoracoscopic surgery (VATS), blood oozing from the surface of the access port wound can hamper the surgical view. Although this oozing is difficult to prevent, it can be decreased by placing a wound edge protector with oxidized regenerated cellulose (ORC) on the surface of the access port wound, thereby improving the surgical outcomes and safety of VATS., Methods: We conducted a prospective, single-centre, open-label, randomized clinical trial to evaluate the operative outcomes of VATS when using the ORC (ORC group) compared with operative outcomes without using the ORC (non-ORC group). The primary end point was interruption of the operation as a result of blood oozing from the surface of the access port wound. The secondary end points were the other intraoperative and postoperative outcomes., Results: A total of 108 patients were divided into the ORC group (n = 54) and the non-ORC group (n = 54). Compared with the non-ORC group, the ORC group had fewer patients with an interruption in the operation (11.1% vs 51.8%; P < 0.001), less need for wound haemostasis of the access ports during wound closure (44.4% vs 72.2%; P = 0.003), similar rates of postoperative deaths and complications and a tendency for shorter operation times (149.3 vs 168.8 min, respectively; P = 0.083)., Conclusion: The use of an ORC sheet around a wound edge protector for haemostasis can ensure a clear view during VATS., Clinical Trial Registration Number: UMIN000031112., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

A 39-year-old man was admitted to our hospital with back pain and numbness of the left leg. Computed tomography (CT) showed a giant bulla and tumor in the right lung, mediastinal shift to the left side and lesions suggestive of metastatic sacral tumor. Three days later, the patient visited the emergency room with dyspnea and tachycardia. Chest CT showed the progression of mediastinal shift due to the rapid expansion of the giant bulla, and an emergency surgery was performed. After induction of anesthesia, sudden respiratory and circulatory failure occurred. Considering further expansion of the giant bulla by positive pressure ventilation, veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) was applied. After establishing ECMO, the condition of the patient became stable and the giant bulla could be resected successfully.

Background: The efficacy of diaphragmatic plication (DP) has been proven in many studies. However, there are few reports on DP for patients with severe respiratory conditions requiring mechanical ventilation. The study aim was to demonstrate the efficacy of DP for patients with severe respiratory insufficiency after cardiothoracic surgeries., Methods: We retrospectively reviewed 10 patients who underwent DP for severe respiratory insufficiency due to postoperative diaphragmatic paralysis; eight of them required mechanical ventilation, and two needed high-flow oxygen therapy prior to DP. The symptoms, lung function, and elevation of the diaphragm were assessed before and after DP., Results: All patients were successfully withdrawn from mechanical ventilation after DP and discharged without the need for oxygen therapy. The mean perioperative Medical Research Council (MRC) dyspnea scale (ATS/ERS 2004) score improved in 30 days (from 4 to 1.8) and in 90 days (from 4 to 0.6) after DP. Lung dynamic compliance was also ameliorated (mean improvement: 41.9 to 60.7 mL/cmH2O). Radiography revealed improved elevation of the diaphragm (mean improvement of 1.8 intercostal spaces, range, 1-2). Mean hospital stay after DP was 65.5 days (range, 25-187 days). One patient who underwent DP with endostapler-only suturing required re-operation because of staple line ruptures., Conclusions: DP was found to be an effective form of treatment for patients with severe respiratory insufficiency after cardiothoracic surgery., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Journal of Thoracic Disease. All rights reserved.)

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disease characterized by hypophosphatemia and skeletal undermineralization. Overproduction of fibroblast growth factor 23( FGF23) from the responsible tumor is reported to be a causative factor. Removing the tumor is the only effective treatment for TIO, but identifying the tumor is sometimes difficult. A 43-year-old man complained of heel pain 4 years earlier, and the pain gradually expanded to the whole body. As a blood test showed the elevation of the serum FGF23 level and hypophosphatemia, he was diagnosed with FGF23-related hypophosphatemia. Chest computed tomography (CT) showed a 10-mm nodule in the right chest wall. Venous sampling for FGF23 revealed considerable elevation of the FGF23 level in the right subclavian vein. Therefore, a chest wall tumor was suspected as the tumor responsible for TIO, and surgical resection was performed. After surgery, hypophosphatemia improved within several days, and the FGF23 level also normalized.

Background: Large-cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are categorized as high-grade neuroendocrine carcinoma (HGNEC). We analyzed the efficacy of perioperative chemotherapy for HGNEC and the prognostic factors., Methods: We retrospectively reviewed the medical records of patients who underwent tumor resection and were diagnosed with HGNEC between January 2001 and December 2014. The overall survival (OS) was estimated by the Kaplan-Meier method. Propensity score matching was performed to compare the OS between the treatment groups. Multivariate analyses using a Cox proportional hazards model were performed to search for prognostic factors for HGNEC., Results: We analyzed 146 HGNEC patients (LCNEC n=92, SCLC n=54) without synchronous multiple cancers, who underwent complete resection. Seventy patients (LCNEC n=31, SCLC n=32) received perioperative chemotherapy and all of them received a platinum-based anticancer drug. Perioperative chemotherapy significantly improved the 5-year OS rates of HGNEC patients (all stages: 74.5% vs. 34.7%, P<0.01, stage I: 88.5% vs. 40.0%, P<0.01). The efficacy of perioperative chemotherapy was similar between LCNEC and SCLC patients [LCNEC all stages: hazard ratio (HR) 0.27, P<0.01, LCNEC stage I: HR 0.27, P=0.01; SCLC all stages: HR 0.38, P=0.02, SCLC stage I: HR 0.34, P=0.06]. The survival benefit of perioperative chemotherapy for HGNEC patients was confirmed by propensity score matching analysis (HR 0.31, P<0.01). The multivariate analysis revealed that perioperative chemotherapy (HR 0.29, P<0.01), sublobar resection (HR 2.11, P=0.04), and lymph node metastasis (HR 3.34, P<0.01) were independently associated with survival., Conclusions: Surgical resection combined with perioperative chemotherapy was considered to be effective even for stage I HGNEC patients. Sublobar resection might increase the risk of death in HGNEC patients., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

ROS proto-oncogene 1 receptor tyrosine kinase (ROS1)-rearranged lung cancer is rare and comprises only 1% of lung adenocarcinoma cases. It has recently been reported to have good response to crizotinib, a tyrosine kinase inhibitor of anaplastic lymphoma kinase. Driver oncogene mutations with approved therapies seldom coexist with a high expression of Programmed death-ligand 1 (PD-L1). The present case report describes a rare case of ROS1 rearrangement with high-PD-L1-expressing occult lung adenocarcinoma. A 32-year-old woman presented with chest pain and a prolonged cough. Chest computed tomography (CT) revealed a 57×36-mm tumor in the mediastinum, with no tumors detected in other regions. Positron emission tomography (PET)-CT showed a strong fluorodeoxyglucose accumulation in the tumor (SUVmax 13.2). Mediastinal tumor resection was completely resected using a video-assisted thoracic surgery approach. Pathological examination showed the tumor cells were positive for thyroid transcription factor 1, Napsin-A, ROS1, and PD-L1 (tumor proportion score >99%). ROS1 rearrangement was confirmed by fluorescence in situ hybridization. The mediastinal tumor was diagnosed as mediastinal lymph node metastasis of ROS1-rearranged PD-L1 high-expression undifferentiated lung adenocarcinoma (pathological stage 3, TxN2M0). Two months after the operation, the CT scan showed multiple mediastinum lymph nodes metastases with rapid tumor growth. The patient achieved a complete response after three cycles of S-1 plus cisplatin with concurrent radiotherapy 60 Gy/30 Fr.

Background: Advances in the development of staplers for pulmonary vessels have contributed to safe and convenient procedures in thoracic surgery. However, adverse events (AEs) can occur during vascular stapling and cause fatal hemorrhage. We aimed to assess the risk level of using the vessel stapling procedure to reduce such AEs., Methods: First, an animal experiment using pig cardiopulmonary blocks was conducted. Pulmonary arteries were closed with staplers under stressful conditions such as lifting or twisting; vessel stump endurance was analyzed through different methods. Second, AEs associated with clinical stapler use for pulmonary vessels were retrospectively reviewed by studying clinical videos of 263 patients., Results: In the animal experiment, the pressure resistance was significantly lower in the twisted group than in the no strain group (no strain vs. lifting: P=0.2008, no strain vs. twisting: P=0.002, no strain vs . twisting and lifting: P<0.0001). Regarding clinical stapler use, 754 staplers were used against the vessels. AEs occurred in 9 cases, and 7 cases were suspected to be caused by vessel tension., Conclusions: The pulmonary vessel stapling causes stress due to twisting and lifting that decreased stump durability. Avoiding such stress when using stapler for vessels leads to a safer thoracic surgery., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objective: Radical resection for thoracic malignancies that invade the great vessels or heart structure is an uncommon, high-risk operation. To help surgeons determine therapeutic strategy, we reviewed the patient characteristics and outcomes of combined thoracic and cardiovascular surgery for thoracic malignancies., Methods: Surgical resections of lung cancer, mediastinal tumor and pulmonary artery sarcoma invading great vessels or heart structures were reviewed from the literature., Results: Pneumonectomy was often performed for lung cancer invading the aorta, superior vena cava, and left atrium. Complete resection (R0), no mediastinal lymph node metastasis and without using cardiopulmonary bypass led to a good prognosis. Induction therapy was often performed for complete resection. Regarding mediastinal tumors, thymic epithelial tumors or germ cell tumors occasionally invaded the great vessels or heart structures. For these malignancies, multimodality therapy was often performed, and complete resection could be one of the prognostic factors. The resection of primary pulmonary artery sarcoma (PPAS) is also a combined thoracic and cardiovascular surgery. The primary treatment for PPAS is surgical resection; specifically, pulmonary endarterectomy and pneumonectomy, because PPAS has substantial resistance to chemotherapy or radiotherapy. The prognosis of PPAS is poor, but surgical resection has potential for long-term survival., Conclusion: Although these surgeries are uncommon and invasive for the patients, selecting appropriate patients, aggressive multimodality therapy, and performing combined thoracic and cardiovascular surgery can contribute to a good outcome.

Objectives: Partner of Sld five (Psf) 3 is a member of the evolutionarily conserved heterotetrameric complex GINS (Go-Ichi-Ni-San). We previously reported that Psf3 could serve as a biomarker of poor prognosis in lung adenocarcinoma. Here, we used tissue microarrays to analyse Psf3 expression in lung adenocarcinoma and investigated whether its expression is associated with survival outcomes., Methods: The study included 864 consecutive patients with lung adenocarcinoma who underwent complete resection at Hyogo Cancer Center between January 2002 and December 2009. Tissue microarrays were prepared, and Psf3 was detected using mouse antihuman Psf3 primary monoclonal antibodies. The status of Psf3 expression was determined using these microarrays., Results: Of the 864 patients, 375 had high-positive Psf3 expression and 489 had low-positive expression. Psf3 expression was significantly associated with age, sex, T factor, lymph node metastasis, stage and P factor. The 5-year disease-free survival (DFS) rate was significantly lower in patients with high-positive Psf3 expression than in those with low-positive expression, and Psf3 expression, sex, age, T factor and lymph node metastasis were identified as independent and significant prognostic determinants. Among patients with Stage I adenocarcinoma, the 5-year DFS rate was significantly lower in those with high-positive Psf3 expression than in those with low-positive expression, and Psf3 expression was the most powerful survival predictor., Conclusions: The present findings strengthened our previous data demonstrating that high Psf3 expression in primary lung adenocarcinoma plays an important role in disease progression and is a prognostic indicator, particularly in early-stage adenocarcinoma., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Disturbance of the surgical view during video-assisted thoracic surgery (VATS) as a result of blood oozing from the wound surface of the access port may lead to additional stress on surgeons and is difficult to prevent. We used a wound edge protector with oxidized regenerated cellulose (ORC) rings for the wound surfaces of the access ports and eliminated the problem. Furthermore, no hemostatic procedure was required for the wound surface before wound closure because the ORC rings completely stopped wound surface bleeding during the operation. ORC rings enhanced protection of the thoracoscopic port and the quality of VATS., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The GINS complex associates with cell division cycle (Cdc) protein 45 and mini-chromosome maintenance (Mcm) proteins 2-7 to form the Cdc45-Mcm-GINS (CMG) complex, which is essential for DNA duplication. One member of the GINS complex is Psf3. We previously found that increased Psf3 expression was strongly associated with poor survival in lung adenocarcinoma. Here, we investigated the role of Psf3 expression in non-small-cell lung cancer (NSCLC). We verified Psf3 expression in human NSCLC tissues (180 patients) and cell lines. Immunohistochemical analysis revealed that the overexpression of Psf3 was significantly associated with vessel invasion (P = 0.016), lymphatic invasion (P = 0.002), and pleural invasion (P = 0.036). The overall survival rate in patients with Psf3 overexpression was significantly lower than that in patients without Psf3 overexpression (P = 0.006). Multivariate survival analysis revealed Psf3 expression to be an independent risk factor for an unfavorable outcome (P = 0.049). A proximal ligation assay showed interactions between Psf3 and other CMG components (such as Mcm2 and Cdc45) in both NSCLC specimens and cell lines, indicating that Psf3 acted as the CMG complex, which could lead to excessive proliferation. Knockdown of Psf3 inhibited the proliferation of both cell lines by delaying the S phase, which revealed that Psf3 played an important role in cancer proliferation. Thus, Psf3 acted as the CMG complex, promoting excessive proliferation. These results suggest that Psf3 inhibition might be a therapeutic target for NSCLC with Psf3 overexpression., (© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

Aim: We examined the advantages of thoracoscopy over thoracotomy in terms of perioperative outcomes and toleration of adjuvant chemotherapy., Methods: Between April 2010 and March 2013, 657 patients with non-small-cell lung cancer who underwent lobectomy were classified into thoracoscopy (308 patients) and thoracotomy (349 patients) groups and compared., Results: The thoracoscopy group had less blood loss compared to the thoracotomy group (p < 0.001). When limiting the analysis to pathological stage I patients, the results were similar (p < 0.001). In addition, the difference in blood loss between the 2 groups was greater in patients with severe pleural adhesions. The postoperative morbidity of the thoracoscopy group was significantly less than that of the thoracotomy group (13.3% vs. 21.2%, p < 0.001), and this result was similar when analyzing the pathological stage I patients (12.6% vs. 20.6%, p = 0.001). A higher percentage of the thoracoscopy group received both the full planned course and dose of adjuvant chemotherapy compared to the thoracotomy group (84.2% vs. 65.8%, p = 0.032)., Conclusions: These results indicate that totally thoracoscopic lobectomy is the more beneficial surgical approach with regard to the incidence of postoperative complications and toleration of adjuvant chemotherapy., (© The Author(s) 2015.)

A thymoma is a neoplasm that arises from the epithelial cells of the thymus, and may cause various signs and symptoms dependent upon its local extent. A non-traumatic hemothorax is extremely rare. The present study reports the case of a 77-year-old female who presented with an acute onset of chest pain. Imaging procedures revealed a mass occupying the anterior mediastinum and left hemithorax, and a left pleural effusion. Progressive anemia was noted following admission. Left hemothorax due to rupture of the anterior mediastinal mass was suspected, and emergency surgery was performed. Hemorrhage was observed on the cut surface of the tumor. An analysis of frozen sections indicated a thymoma, and a thymo-partial thymectomy was subsequently performed to remove as much of the hematoma as possible. The patient was discharged on post-operative day 13 following an uneventful recovery. The present case suggests that in previously healthy individuals, sudden-onset dyspnea and chest pain co-occurring with an acute widening of the mediastinum observed on roentgenograph may be indicative of a ruptured thymoma.

Objectives: We evaluated the clinical benefit of segmentectomy for patients with cT1bN0M0 lung cancer., Methods: We retrospectively reviewed the medical records of 178 patients who underwent lobectomy or segmentectomy for cT1bN0M0 lung adenocarcinoma and squamous cell carcinoma from January 1995 to December 2005. We investigated the association of surgical outcomes with the presence of pathological invasion., Results: The median follow-up period was 93.4 months. Of 178 patients, 37 were scheduled for segmentectomy, but 6 of these patients were switched to receive lobectomy due to surgical N1 or N2 in 3 patients and insufficient surgical margins in 3 patients. In total, 31 patients underwent segmentectomy, and 147 underwent lobectomy. The 5-year overall survival (OS) was similar between the patients who underwent lobectomy (5-year OS, 81.6%) and segmentectomy (5-year OS, 77.4%, P = 0.73). Among pN0 patients without pathological invasion, there was no difference in OS between patients who underwent lobectomy (5-year OS, 89.9%) and segmentectomy (5-year OS, 88.9%, P = 0.80). In contrast, among pN0 patients with pathological invasion, OS was greater in patients who underwent lobectomy (5-year OS, 80.9%) than in those who underwent segmentectomy (5-year OS, 54.6%; P = 0.19). Moreover, a significantly higher rate of local and local + distant recurrence was observed in patients who underwent segmentectomy (45%) than in those who underwent lobectomy (15%) in this group (P = 0.02)., Conclusions: The results of our study suggest that segmentectomy may not be recommended for cT1b tumours if pathological invasion is suspected before surgery., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The mediastinal mature teratoma is uncommon in adult and sometimes ruptures. We present a case of perforation of mediastinal mature teratoma. A 22-year-old man, who had been scheduled for surgery to resect anterior mediastinal teratoma, was referred to our hospital due to sudden chest pain. The enhanced computed tomography findings suggested a perforation of the teratoma and the emergency surgery was performed. Extirpation of the tumor with partial resection of right upper lung, pericardium, and superior vena cava was performed. The histological diagnosis was mature teratoma and the defect of the mediastinal pleura was found to be the site of perforation. The patient was well and discharged from the hospital without complications.

We previously reported that cancer cells may be detected through pleural lavage cytology (PLC). In this study, we sought to re-examine the prognostic significance of the PLC status based on an extended dataset with an additional follow-up period. Pleural lavage following thoracotomy was cytologically examined in 1,317 consecutive patients who were diagnosed with NSCLC between 1987 and 2004 at the Thoracic Surgery Units of Kobe University Graduate School of Medicine and Hyogo Cancer Center. Among the investigated patients, 46 exhibited positive cytological findings. The prognosis of these patients was significantly worse compared to that of patients without positive PLC. Of the 844 pathological stage I patients, 18 had a positive PLC status and their prognosis was significantly worse compared to that of patients with stage I disease without positive PLC. In conclusion, positive PLC findings were associated with a poor prognosis and this finding was significant for patients with stage I disease. These results suggest the need for PLC status evaluation during staging and treatment planning in patients with NSCLC.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive malignant tumor, which was proposed as a novel type of neuroendocrine tumor in 1991. Although it is categorized as a non-small cell lung carcinoma, the precise pathological condition is unknown due to its rare occurrence. The present study outlines the case of a patient presenting with an LCNEC that exhibited pagetoid spread from the region of the primary tumor to the bronchial epithelium (distance, >30 mm). The pagetoid spread was unconfirmed preoperatively, however, was identified by intraoperative rapid diagnosis. This caused us to suffer the perioperative decision of additional resection and resulted in an incomplete resection, as suture of the bronchus was not possible. Pagetoid spread, which is often apparent in the breast, presents as a rare pattern of infiltration of cancer cells when a massive carcinoma is identified beneath the intraepithelial spread. Although preoperative diagnosis of pagetoid spread is difficult due to its rarity and undefined clinical features, it is important for surgeons and pathologists treating lung cancer patients to be aware of potential pagetoid spread in the thoracic region.

The histological subtype of non-small-cell lung cancer (NSCLC) is a significant factor when selecting treatment strategies. However, cases are occasionally encountered that are diagnosed as 'not otherwise specified' (NOS) prior to surgery, due to an uncertain histological subtype. The present study investigated the prognostic significance of the NOS subtype for patients with resectable NSCLC. Between 2001 and 2011, 1,913 patients were diagnosed with NSCLC using transbronchial biopsy and underwent surgical resection at two facilities in Japan. Of these patients, 151 (7.9%) were pre-operatively diagnosed with NSCLC-NOS (NOS group) and the remainder had confirmed histological subtypes (confirmed group). The present study compared the clinicopathological features and prognoses of these groups. Analyses of resected specimens revealed that pleomorphic cell carcinoma, large cell neuroendocrine cell carcinoma, large cell carcinoma and adenosquamous carcinoma were significantly more common in the NOS group than in the confirmed group (P<0.001, P=0.002, P=0.019 and P=0.014, respectively). The five-year survival rate was significantly poorer in the NOS group (60.5 vs. 67.1%; P=0.010), particularly for stage I disease (70.8 vs. 80.7%; P=0.007). The results of a multivariate analysis of overall survival indicated that NOS was a significant independent prognostic factor (hazard ratio, 1.40; 95% confidence interval, 1.02-1.86; P=0.041). These results indicated that pre-operative NOS was significantly associated with poorer survival, including for stage I disease. In conjunction with other clinicopathological parameters, NOS can be a useful prognostic factor when deciding on a treatment strategy for NSCLC.

Sirtuin 1 (Sirt1) is a nicotinamide adenine dinucleotide-dependent class III histone deacetylase. It reportedly can repress cellular apoptosis and senescence to affect DNA repair, stress response and aging. Notably, previous data have indicated that Sirt1 is both a tumor promoter and a tumor suppressor in tumorigenesis. However, Sirt1 expression in primary lung adenocarcinoma remains unknown. Immunohistochemical staining was performed to investigate Sirt1 expression in cancer cells in 125 consecutive resected cases of primary lung adenocarcinoma. Sirt1 expression was found to be increased in 26 (20.8%) of the 125 cases, which correlated significantly with five clinicopathological factors: Ki67 index, hypoxia-inducible factor 1 (HIF1) molecule expression, tumor-node-metastasis (TNM) classification, pulmonary vein invasion and lymphatic duct invasion. In the Sirt1-positive expression group, Sirt1 expression correlated with a higher Ki67 index and higher TNM classification, particularly for lymph node invasion and metastasis, and with a higher number of pulmonary vein invasion and lymphatic duct invasion. Additionally, a negative correlation was identified between HIF1-positive expression and Sirt1-negative expression. These results indicate that Sirt1 overexpression plays a promotional role in tumorigenesis and is closely associated with invasion and metastasis and, thus, it may be associated with prognosis.

Objectives: The purpose of this study was to compare the efficacy of 320-detector row computed tomography (CT) with that of 64-detector row CT for three-dimensional assessment of pulmonary vasculature of candidates for pulmonary segmentectomy., Methods: We included 32 patients who underwent both 320- and 64-detector CT before pulmonary segmentectomy, which was performed by cutting the pulmonary artery and bronchi of the affected segment followed by dissection of the intersegmental plane along the intersegmental vein. Before the operation, three-dimensional pulmonary vasculature images were obtained for each patient, and the arteries and intersegmental veins of the affected segments were identified. Two thoracic surgeons independently assessed the vessels with visual scoring systems, and kappa analysis was used to determine interobserver agreement. The Wilcoxon signed-rank test was used to compare the visual scores for the assessment of the visualization capabilities of the two methods. In addition, the final determination of pulmonary vasculature at a given site was made by consensus from thoracic surgeons during operation, and receiver operating characteristic analysis was performed to compare their efficacy of pulmonary vasculature assessment. Sensitivity, specificity and accuracy of either method were also compared by means of McNemar's test., Results: Of the 32 cases, there were no operative complications, but 1 patient died of postoperative idiopathic interstitial pneumonia. Visualization scores for the pulmonary vessels were significantly higher for 320- than those for 64-detector CT (P < 0.0001 for the affected arteries and P < 0.0001 for the intersegmental veins). As for pulmonary vasculature assessment, the areas under the curve showed no statistically significant differences in between the two methods, while the specificity and accuracy of intersegemental vein assessment were significantly better for 320- than those for 64-detector row CT (P < 0.05). Interobserver agreement for the assessment yielded by either method was almost perfect for all cases., Conclusions: Three hundred and twenty-detector row CT is more useful than conventional 64-detector row CT for preoperative three-dimensional assessment of pulmonary vasculature, especially when we identify the intersegmental veins, in candidates for pulmonary segmentectomy.

Nectin-like molecule-5 (Necl-5) is an immunoglobulin-like molecule that was originally identified as a poliovirus receptor and is often upregulated in cancer cells. It has been said that Necl-5 plays a role in not only cell-cell adhesion, but also cell migration, proliferation, and metastasis. In this study, we used a bronchioloalveolar carcinoma (BAC) cell line and fibroblasts to assess the expression of Necl-5 in the development of cancer-stroma communication by using an easy-to-prepare double-layered collagen gel hemisphere (DL-CGH) system that enables visualization of cell migration during invasion. The expression of Necl-5 was higher in BAC cells than in fibroblasts. This tendency didn't change even when the BAC cells were mixed with fibroblasts. To assess the role of Necl-5 in the invasive activity of the BAC cells, we knocked down its expression using RNA interference (RNAi). The invasion assay with DL-CGH revealed that inhibition of Necl-5 expression in the BAC cells was associated with suppressed invasiveness. In addition, Necl-5 knockdown inhibited the movement and proliferation of the BAC cells. Necl-5 expression in lung cancer cells is crucial for their invasiveness in the cancer-stromal interaction, suggesting that Necl-5 could be a favorable molecular target for the suppression of invasiveness in lung adenocarcinoma., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Psf3 is a member of the evolutionarily conserved heterotetrameric complex GINS (Go-Ichi-Ni-San), which consists of Sld5, Psf1, Psf2, and Psf3. Previous studies have suggested that some GINS complex members are upregulated in cancer, but the status of Psf3 expression in lung adenocarcinoma has not been investigated. The objective of the current study was to determine whether Psf3 plays a role in lung adenocarcinoma by investigating clinical samples. We investigated the status of Psf3 expression in cancer cells of 125 consecutive resected lung adenocarcinomas by immunohistochemistry. Increased Psf3 expression was observed in 27 (21.6%) of the 125 cases. Further, univariate analysis and log-rank test indicated a significant association between Psf3 expression and lower overall survival rate (P = 0.0001 and P < 0.0001, respectively). Multivariate analysis also indicated a statistically significant association between increased Psf3 expression and lower overall survival rate (hazard ratio, 5.2; P = 0.0027). In a subgroup analysis of only stage I patients, increased Psf3 expression was also significantly associated with a lower overall survival rate (P = 0.0008, log-rank test). Moreover, the Ki67 index level was higher in the Psf3-positive group than in the Psf3-low positive group (P < 0.0001, Mann-Whitney U-test). Our results indicated that Psf3 can serve as a prognostic biomarker in lung adenocarcinoma., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

We report 2 cases of lung cancer incidentally detected following pneumothorax. Case 1:A 40-year-old man complaining of dyspnea was admitted with right pneumothorax. Chest computed tomography (CT) after chest drainage showed a cavitary nodule with pleural indentations in the right lower lobe. It was indicated at surgery that pneumothorax was caused by perforation of the tumor into the pleural cavity. Right lower lobectomy was performed because the pathological diagnosis of the nodule was a large cell carcinoma. The final histopathological diagnosis was stage II A (pT2aN1M0). The patient died of recurrence 14 months after surgery. Case 2:A 47-year-old man who admitted with right pneumothorax was found to have a nodule with pleural indentations closely a bulla at the apex of the right lung by chest CT after chest drainage. Pneumothorax was indicated to be caused by rupture of the bulla at surgery. Right upper lobectomy was performed because the pathological diagnosis of the nodule was a squamous carcinoma. The final histopathological diagnosis was stage I A (pT1bN0M0). The patient is alive at 2 years after the operation without recurrence. Lung cancer detected following pneumothorax which was caused by perforation of the tumor is generally considered to have poor prognosis. Whereas, prognosis of lung cancer incidentally detected following pneumothorax depends on its staging.

A 76-year-old female was admitted to our hospital because of an abnormal shadow on chest computed tomography (CT) which showed the tumor extending from left lower end of the thyroid to the aortic window along the left side of the trachea, indicating the retrosternal goiter. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were within normal ranges. The tumor was resected through cervical collar incision and median sternotomy. The pathological diagnosis was an adenomatous goiter. The patient was discharged without complications.

A 39-year-old woman was referred to our hospital because of pneumothorax related to menstruation. Chest X-ray showed right pneumothorax. Right thoracoscopy revealed 3 fenestrations on the diaphragm. Partial resection of the diaphragm including these lesions were performed. Intrathoracic minocycline was applied expecting pleural adhesion after surgery. Histopathological examination confirmed the presence of endometriosis on the resected diaphragm.