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A 70-year-old man was referred for an abnormal chest shadow. Enhanced computed tomography (CT) revealed a well-circumscribed lung tumor of 53 mm in diameter in the left upper lobe with slight enhancement. Positron emission tomography-CT showed a high maximum standardized uptake value for the tumor but no metastasis in the lymph nodes or other organs. Although a definitive diagnosis could not be made by transbronchial biopsy, the tumor was highly suspected to be malignant based on the radiological findings, and a left upper lobectomy with mediastinal lymph nodes dissection was performed for definitive diagnosis and treatment. A pathological examination showed the tumor to be composed of mitotic spindle-shaped cells, which were positive for α-smooth muscle actin, desmin, and caldesmon. The MIB-1 labelling index was 60~70%. According to these pathologic findings, the tumor was identified as a leiomyosarcoma. Metastases to the skin of chest and hilar lymph nodes were noted six months after the surgery for which radiotherapy was performed.

Although concurrent chemoradiotherapy (CRT) followed by consolidation immunotherapy considerably improves the duration of survival in patients with unresectable stage III non-small cell lung cancer (NSCLC), few data are available on the management of local relapse after therapy. We present a patient with initially unresectable NSCLC who underwent a right upper lobectomy with reconstruction of the bronchus and pulmonary artery after definitive CRT, followed by consolidation durvalumab. No postoperative complications occurred, and he was recurrence-free at the 10-month follow-up. Salvage surgery might be a viable option for local relapse of NSCLC treated with definitive CRT and durvalumab.

Paragangliomas in the diaphragm are extremely rare. We report the case of a 27‐year‐old woman with a nonfunctioning paraganglioma protruding superiorly from the right diaphragm. The patient underwent an anterior thoracotomy, and a supradiaphragmatic tumor (70 mm in diameter), which compressed the inferior vena cava and the right hepatic vein, was completely resected by combined partial resection of the right diaphragm and pericardium. To our knowledge, this is the first report of a paraganglioma situated both on the diaphragm and close to the inferior vena cava and hepatic vein. Key points, Herein, we report the case of a 27‐year‐old woman with a nonfunctioning paraganglioma protruding superiorly from the right diaphragm. A supradiaphragmatic tumor, 70 mm in diameter, which was compressing the inferior vena cava and right hepatic vein, was completely resected with combined partial resection of the right diaphragm and pericardium. To our knowledge, this is the first report of a paraganglioma arising from the diaphragm in such close proximity to the inferior vena cava and hepatic vein.

Immunoglobulin G4 (IgG4)‐related disease is established as a new clinical entity, characterized by high levels of plasma IgG4 and IgG4‐positive plasma cell infiltration. However, the elevation of plasma IgG4 and infiltration of IgG4‐positive cells have been observed in other diseases, including malignancy. We experienced a case of prominent IgG4‐positive lymphadenopathy, which was diagnosed as a reactive lesion in response to lung cancer. The cancerous lesion was so small in size that it was difficult to reveal the coexisting lung cancer. Surgical lymph node biopsy and endobronchial ultrasound‐guided transbronchial needle aspiration did not reveal lymph node metastasis of cancer. Mediastinal lymph node dissection finally revealed it. After the right upper lobectomy, the patient underwent postoperative chemotherapy and remains cancer‐free after 1 year. Our case suggests that close examination and careful follow‐up are necessary when IgG4‐positive lymphadenopathy is observed., This article discussed a case in which prominent lymphadenopathy with immunoglobulin G4‐positive cell infiltration was caused in response to microscopic lung cancer. Surgical lymph node biopsy, as well as endobronchial ultrasound‐guided transbronchial needle aspiration, could not reveal coexisting malignant cells in the mediastinal lymph node.

Kentaro Minegishi,1 Yoh Dobashi,2,3 Hiroyoshi Tsubochi,1 Koichi Hagiwara,4 Yuko Ishibashi,5,6 Sachiyo Nomura,7 Ritsuko Nakamura,8 Yasukazu Ohmoto,9 Shunsuke Endo1 1Department of Thoracic Surgery, Saitama Medical Center, Jichi Medical University, Saitama, Japan; 2Department of Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan; 3Department of Pathology, School of Medicine, International University of Health and Welfare, Tochigi, Japan; 4Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, Tochigi, Japan; 5Department of Breast and Endocrine Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 6Division of Breast Surgery, Hospital of the National Center for the Global Health and Medicine, Tokyo, Japan; 7Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 8Department of Molecular and Cellular Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan; 9Tokushima University Industry-University R&D Startup Leading Institute, Tokushima, JapanCorrespondence: Yoh DobashiDepartment of Pathology, School of Medicine, International University of Health and Welfare, 537-3 Iguchi, Nasushiobara, Tochigi, 329-2763, JapanTel +81-287-37-2221Fax +81-287-39-3001Email ydobashi2@iuhw.ac.jpIntroduction: Trefoil Factor (TFF) is a member of a protein family comprised of three isoforms, of which TFF-1 exhibits antithetical functions; promotion or suppression of cell proliferation, survival and invasion, depending on the cancer type. However, the pathobiological function of TFF-1 in lung carcinoma has been still unclear.Methods: We examined the expression and secretion of TFF-1 using cultured human lung carcinoma cells by immunoblotting, immunofluorescence, enzyme-linked immunosorbent assay and quantitative real-time PCR analyses. The effects of TFF-1 on various phenotypes were analyzed in two cell lines, including those transfected with cDNA encoding TFF-1. Cell proliferation and death were examined by hemocytometer cell counting and by colorimetric viability/cytotoxicity assay. Cell cycle profile, migration and invasion were also examined by flow cytometry, wound healing assay and Matrigel Transwell assay, respectively. The effect of TFF-1 overexpression was confirmed by additional transfection of TFF-1-specific siRNA.Results: Endogenous TFF-1 protein expression and secretion into the media were observed exclusively in adenocarcinoma-derived cell lines. Forced overexpression of TFF-1 drove cell cycle transition, while the proliferation decreased by 19% to 25% due to increased cell death. This cell death was predominantly caused by apoptosis, as assessed by the activation of caspase 3/7. Cell migration was also suppressed by 71% to 82% in TFF-1-transfected cells. The suppressive effect of TFF-1 on proliferation and migration was restored by transfection of TFF-1 siRNA. Moreover, invasion was also suppressed to 77% to 83% in TFF-1-transfected cells.Conclusion: These findings reveal that TFF-1 functions as a suppressor of cancer proliferation by induction of apoptosis, cell migration and invasion and thus may provide a synergistic target for potential treatment strategies for human lung carcinoma.Keywords: TFF-1, lung carcinoma cells, growth inhibition, apoptosis, migration, invasion

Metaplastic thymoma is a rare histologic variant of thymic epithelial tumors and is characterized by a biphasic growth pattern. We herein report the case of 44-year-old woman who underwent surgery for metaplastic thymoma. Computed tomography scan revealed a well-circumscribed mediastinal tumor: 56 mm in diameter with homogenous enhancement. The tumor was suspected to be a non-invasive thymoma, and thymomectomy with resection of the surrounding thymus was performed using thoracoscopy. The resected tumor measured 60 mm and was grossly well-encapsulated. The cut surface was gray to white and homogenous. Microscopically, the epithelial components took the form of an anastomosing nest to broad trabeculae intertwining with the bundle of spindle cells. Mitosis was not found and the Ki-67 index was1%. Cytokeratin 5/6 was strongly positive in the epithelial components composed of polygonal cells. Terminal deoxynucleotidyl transferase positive immature T cells were not observed. Based on these pathologic findings, the tumor was identified as metaplastic thymoma.

When the first intervention for lung cancer is anatomical resection, the ipsilateral repeat anatomical resection for metachronous second lung cancer becomes technically challenging. Herein, we report the outcomes of second anatomical pulmonary resection for ipsilateral metachronous lung cancer at our institution.Sixteen consecutive patients[ 10 men and 6 women, average age 70( range 59~81) years] were reviewed in this retrospective study. These patients underwent ipsilateral repeat anatomical resection for metachronous second lung cancer between 2009 and 2020.All case required right-sided lung resections. The previous interventions of patients included upper lobectomy, lower lobectomy, middle lobectomy, S2 segmentectomy, and S6 and S10a segmentectomy in 9, 4, 1, 1, and 1 case, respectively. The second surgical interventions were middle lobectomy, S6 segmentectomy, upper lobectomy, lower lobectomy, S1 segmentectomy, and S2 segmentectomy, in 6, 4, 2, 2, 1, and 1 case, respectively. Postoperative complications occurred in three patients. The median follow-up period was 53.5 months. Three patients died during the follow-up period. Of the 13 patients still alive, 6 had recurrence. The five-year overall survival rate was 80%.Although only a few cases were assessed, the prognosis after second anatomical pulmonary resection for ipsilateral metachronous lung cancer at our institution was satisfactory.

The morbidity and mortality after completion pneumonectomy (CP) are reportedly high. We, herein, report the outcomes of CP at our institution.Nine consecutive patients [7 men and 2 women, average age of 72 years(range 44~84 years)] who underwent CP for recurrence of lung cancer during 2012~2018 were retrospectively reviewed.Right-sided sleeve CP was performed in two cases and left-sided CP in seven cases. The indications for surgery were lymph node metastasis of the cancer, pulmonary metastasis, and bronchial stump recurrence in 4, 3, and 2 cases, respectively. Postoperative complications occurred in six patients. One of the patients who underwent right sleeve pneumonectomy developed bronchopleural fistula and died 68 days after the surgery. The mean follow-up period was 33 months, and four patients died during follow-up. Of the 5 patients still alive, 4 had no recurrence and 1 had recurrence in the stump of the main bronchus. The five-year overall survival rate was 78%.Although only few cases were assessed, the prognosis after CP at our institution was relatively good.

Background A longer left superior pulmonary vein (LSPV) stump may increase the risk for postoperative cerebral infarction. Although the residual stump is generally longer after left upper lobectomy (LUL) than for other lobectomies, the length of the LSPV stump after LUL may be influenced by the anatomical relationship between the left atrial appendage (LAA) and the LSPV. Our aim in this study was to investigate the influence of this anatomical relationship on the residual length of the LSPV stump after LUL. Methods This was a retrospective analysis of 85 patients who underwent LUL at our institution, between January 2014 and March 2018. Based on pre-operative computed tomography (CT) images, the anatomical relationship between the LSPV and the LAA was classified into two patterns, namely an antero-superior and a postero-inferior pattern. The length of the LSPV stump for these two patterns was evaluated on postoperative CT images and compared between the two groups. Results Of the 85 patients, 49 were classified in the antero-superior pattern and 36 in the postero-inferior pattern. The mean length of the LSPV stump after LUL, overall, was 21.9 (range, 15-38) mm, with the stump being significantly longer for the antero-posterior (24.2 mm) than postero-inferior (18.9 mm) pattern. Conclusions The anatomical relationship between the LSPV and LAA, identified on pre-operative CT images, was associated with the length of the LSPV stump after LUL.

Objectives Selection criteria for palliative limited surgery in patients with non-small cell lung cancer (NSCLC) can vary by institution or surgeon. We retrospectively reviewed outcomes of poor-risk patients who underwent palliative segmentectomy (PS), using the National Clinical Database Risk Calculator (RC). Methods We retrospectively analyzed medical records of patients with NSCLC tumors ≥ 20 mm and consolidation/tumor ratios ≥ 0.5 on computed tomography, who underwent PS from January 2009 to March 2016. Median follow-up time was 47 months (range 2–102 months). Results We enrolled 67 patients (median age: 73.0 years), of whom 54 received thoracoscopic surgery and 28 received medial lymph-node dissection. The RC’s mean predictive probability rate for perioperative mortality or severe complications was 7.1%. Of the 67 patients, 24 patients (43.0%) suffered post-surgical complications, including 2 (3%) who died in hospital; 17 eventually suffered NSCLC recurrences and/or metastases, 11 eventually died from NSCLC, and 17 died from other diseases. Five-year overall survival (OS) was 59.4%. When the patients were divided into high-risk (HR) and low-risk (LR) groups based on the RC, 5-year OS was significantly less in the HR group (43.9%) than in the LR group (82.2%; P Conclusion The RC, which was developed primarily to determine perioperative risk, can predict long-term prognosis for compromised patients who undergo PS.

We previously reported that miR-200a was highly up-regulated in lung carcinoma, exhibiting a copy number increase (CNI) of the AKT2 gene (AKT2+ group) in defined subsets, i.e., adenocarcinoma and early stages of carcinoma (pStage I/II). In this study, we searched possible targets of miR-200a in these subsets by IHC analyses focusing on the expression of known target proteins of miR-200a: beta-catenin, EphA2, ZEB1, PTEN, and YAP-1, as well as E-cadherin, the expression of which is suppressed by ZEB1. Among those 6 proteins, when all 38 cases of surgically resected specimens were analyzed as a whole, IHC score of ZEB1 was inversely (ρ=-.417) and E-cadherin was positively (ρ=.345) correlated with miR-200a expression. However, only EphA2 was inversely correlated with the expression of miR-200a in adenocarcinoma (ρ=-.496) and in pStage I/II group (ρ=-.547), while no correlation was seen in non-adenocarcinoma, squamous cell carcinoma, or pStage III carcinoma. Furthermore, by comparison of 3 groups categorized according to the AKT gene increase, only EphA2 was down-regulated to a statistically significant level in the AKT2+ group in both adenocarcinoma (p=.0447) and pStage I/II carcinoma (p=.0458). These results suggest that in lung carcinomas, higher Akt activation caused by increased AKT2 gene copy number leads to the upregulation of miR-200a, which exerts its function as a suppressor of EphA2 in adenocarcinoma and the early stages of carcinomas.

Aspergillus empyema is usually reported as a complication of surgical procedures, and spontaneous cases are quite rare. Here, we describe the case of a 16-year-old man who suddenly developed dyspnea despite previously being healthy. Chest computed tomography showed multiple mass-containing cavity lesions, pneumothorax, and pleural effusion in the left thorax. Within 2 weeks, Aspergillus fumigatus grew from his pleural effusion, thus he was diagnosed with Aspergillus empyema. He also developed severe eosinophilia after admission, and was treated with anti-fungal drugs. Although there are many factors that can cause eosinophilia, we suspect that infection with Aspergillus fumigatus was the major cause of the eosinophilia in this patient. The lack of bronchial symptoms and lesions were not consistent with a diagnosis of allergic bronchopulmonary aspergillosis. As far as we know, this is the first case of spontaneous Aspergillus empyema resulting in severe eosinophilia.

The most important step in lung segmentectomy is to determine an appropriate intersegmental plane to obtain sufficient pre- and intraoperative margins. Inappropriate dissection of the lung parenchyma leads to loss of oncological validity and additionally causes various complications such as pneumonia, prolonged air leakage, lung congestion, and atelectasis.In this study, we evaluated the validity of segmentectomy for non-small cell lung cancer (NSCLC) based on evaluation of survival outcomes and recurrence patterns.In principle, we usually perform video-assisted thoracic surgery segmentectomy. Hilar dissection is performed along the intersegmental vein under ultrasonographic guidance, and the peripheral lung parenchyma is subsequently stapled. We usually create inflation-deflation lines from before to determine the intersegmental lines. Recently, near-infrared fluorescence imaging with indocyanine green is also used.We retrospectively reviewed data of 101 patients who underwent segmentectomy for lung cancer between 2007 and 2014.The 5- and 10-year overall survival rates were 84% and 62%, respectively. The 5- and 10-year recurrence-free survival rates were 83% and 63%, respectively. Recurrence at the surgical margin occurred in 5 patients( pulmonary stump:4 patients, bronchial stump:1 patient).Segmentectomy may be acceptable for patients with Stage I NSCLC. Accurate determination of the intersegmental plane is essential to avoid stump recurrence.

We report a case of intractable chylothorax after right upper lobectomy and nodal dissection via median sternotomy for lung cancer in a 67-year-old man. Lymphangiography (LAG) with lipiodol and sequential computed tomography showed the thoracic duct in the left posterior mediastinum and massive lymphatic leakage in the anterior and middle mediastinum. The Chylous leakage was resolved by LAG with lipiodol. Our findings suggest that variation of the thoracic duct should be evaluated by LAG when intractable chylothorax or chylomediastinum develops after anterior mediastinal surgery.

Treatments for lung cancer include therapies targeting aberrant oncoproteins, but there remains a high medical need for novel therapies. Our previous studies showed that gene amplification/high-level polysomy of

Median sternotomy is the standard procedure for mediastinal, cardiovascular, and bilateral thoracic disease, among other conditions, and an increasing number of patients undergo reoperation via median sternotomy after previous thoracic procedures. However, reentry into the mediastinum can cause catastrophic hemorrhage, and major vessels and cardiac structures are sometimes injured because of dense adhesion between the posterior wall of the sternum and anterior mediastinum (1). When a patient undergoes extended thymothymectomy, dense adhesion of the left innominate vein to the sternum should be considered during resternotomy. We describe the successful use of a “mini-clamshell approach” through the 3rd intercostal space for complete resection of local recurrence in a 41-year-old man after extended thymothymectomy for thymic carcinoid tumor.

Background Postoperative bronchopleural fistula is one of the most life-threatening complications after anatomical pulmonary resection. Bronchopleural fistula may cause empyema and aspiration pneumonia with subsequent acute respiratory distress syndrome. Surgical interventions for bronchopleural fistula can prolong hospitalization and impair postoperative quality of life. Postoperative care requires minimally invasive endoscopic occlusion. Methods We retrospectively reviewed the records of 7 patients who developed bronchopleural fistula among 689 patients who underwent segmentectomy or lobectomy without sleeve resection for lung cancer in Jichi Medical University from 2009 to 2013. Bronchopleural fistula occurred in the right lower bronchial stump in 3 patients, in the superior segmental bronchus of the right lower lobe in 2, in the superior segmental bronchus of the left lower lobe in one, and in the right intermediate bronchus in one. Flexible bronchoscopy was used to occlude 3-mm fistulas with polyglycolic acid mesh in 2 patients. Larger fistulas in 5 patients were occluded with polyglycolic acid mesh plus fibrin glue to secure the mesh. The median procedure was 37 min. Procedures were considered complete upon resolution of air leakage from the chest drainage system. Results Bronchoscopic interventions for bronchopleural fistula were repeated an average of 2 times. No procedure-related complications or death occurred. Bronchoscopic interventions were successful in all patients. Conclusions Bronchoscopic occlusion with polyglycolic acid mesh with or without fibrin glue is easy and feasible as the first step in postoperative management of bronchopleural fistula.

Down-regulation of cyclin-dependent kinase inhibitor protein p27, due to enhanced degradation, is frequently observed in various cancers. The ubiquitin ligases that mediate this degradation have been identified as S-phase kinase-associated protein-2 (Skp2), Kip1 ubiquitylation-promoting complex (KPC), and p53-inducible protein with RING-H2 domain (Pirh2) as well. We investigated the correlation among expression of these 3 ligases and p27 status in surgical specimens of human lung carcinomas by immunohistochemical analysis. Among 93 cases, expressions of p27, Skp2, KPC, and Pirh2 were found in 89.2%, 59.1%, 59.1%, and 67.7%, respectively. Down-regulation of p27 in cancer cells was frequently observed in adenocarcinoma (AC) and squamous cell carcinoma (SCC), but not in small cell carcinoma (SmCC). Overexpression of ubiquitin ligases was variously observed among histological types: Skp2 was more frequently observed in SCC and SmCC, KPC in SCC and Pirh2 in AC, followed by SCC. Several novel findings were obtained: (i) cytoplasmic p27 was observed in 8.6%, most frequently in SCC (13.3%), and correlated with nodal metastasis (P=.0044), (ii) significant inverse correlation between nuclear p27 and Pirh2 expression was observed by statistical analysis and at the cellular level, and (iii) cytoplasmic Pirh2 and total (cytoplasmic and/or nuclear) Pirh2 were significantly correlated with the nodal status (P=.0225, 0.0314), the pathological stage (P=.0213, 0.0475) and recurrence-free survival (P=.0194, 0.0482, respectively) in AC. Altogether, our data suggests that p27 and its cognate ubiquitin ligases are specifically involved in the clinical profiles, and thus, molecular targeting of these ubiquitin ligases, in particular, Pirh2, may have therapeutic value for human lung carcinomas.

Objectives Video-assisted thoracic surgery is widely applied for resection of mediastinal tumors. The mediastinal mature teratoma, however, is usually operated on via an open approach because it is generally large, making it difficult to dissect under a thoracoscopic view and remove it from the thoracic cavity. We attempted to extract intracystic material during video-assisted thoracic surgery to facilitate dissection and removal of the tumor from the thoracic cavity. Methods From January 1998 to April 2013, 13 patients (9 women, 4 men; mean age 33 years, range 17–54 years) with mediastinal mature teratomas were operated on via video-assisted thoracic surgery. Intracystic contents of the tumor were aspirated before dissection or after the teratoma was dissected and placed in the retrieval pouch. Results None of the patients required conversion to an open procedure. Operating time was 95–184 min (mean 132 min). Blood loss during the operation amounted to 10–300 mL (mean 78 mL). The tumor size ranged from 5 to 12 cm (mean 8 cm). In all cases, the tumors were confirmed pathologically to be mature cystic teratomas with no malignant components. During and after follow-up, all patients continue to do well without recurrence. Conclusion Extraction of intracystic contents enabled thoracoscopic resection of large mature mediastinal teratomas.

Nowadays, a diaphragmatic lesion is sometimes resected with use of an automatic stapling device, especially through video-assisted thoracoscopic procedure. We herein report 2 patients with a diaphragmatic hernia after diaphragmatic resection by automatic stapling devices. Etiology and cause of postoperative diaphragmatic hernia are discussed. Diaphragmatic resection by mechanical stapler was performed for thymic epithelial tumor recurring at the diaphragmatic pleura in both patients: 48-year-old man and 72-year-old woman. The former patient underwent a right diaphragmatic resection (3×4 cm in size) with a cartridge of mechanical stapler. Computed tomography (CT) and magnetic resonance imaging showed asymptomatic right diaphragmatic hernia 2 months after surgery. No symptom and progression occurred 8 years later. The latter patient underwent a right diaphragmatic resection (6×7 cm in size) with 2 cartridges of mechanical stapler. Diaphragmatic hernia advanced 7 months after surgery and required surgical intervention. Diaphragmatic repair was successful with the use of 8×6 cm expanded polytetrafluoroethylene patch. Surgical stump after diaphragmatic resection with automatic stapling device is easy to rupture during diaphragmatic movement synchronized with respiratory movement. Diaphragmatic resection with use of stapling device, which is a simple procedure, should be contraindicated.

Interposition with a vascular prosthesis or patch closure using autologous pericardium has been applied for superior vena cava (SVC) reconstruction during surgery for thoracic malignancies such as thymic epithelial tumors or lymphadenopathy that invade the SVC. We herein report a novel and simple method for repair of the SVC using a left brachiocephalic vein flap. This procedure is useful to repair the anterior wall of the distal portion of the SVC, which is a common site of invasion of thoracic malignancies.