Updated on 2022/03/21

写真a

 
CHEN-YOSHIKAWA Toyofumi
 
Organization
Graduate School of Medicine Program in Integrated Medicine Musculoskeletal and Cutaneous Medicine Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Professor

Degree 1

  1. Doctor (Medicine) ( 2007.5   Kyoto University ) 

Research Interests 8

  1. 肺生理

  2. 手術シミュレーション

  3. 慢性呼吸不全

  4. 肺再生

  5. 肺移植

  6. 胸腺腫

  7. 中皮腫

  8. 肺癌

Research Areas 1

  1. Life Science / Respiratory surgery

Research History 10

  1. Graduate School of Medicine, Nagoya University   Thoracic Surgery   Professor

    2019.9

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    Country:Japan

  2. Graduate School of Medicine, Kyoto University   Thoracic Surgery   Associate professor

    2019.1 - 2019.8

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    Country:Japan

  3. Graduate School of Medicine, Kyoto University   Thoracic Surgery   Lecturer

    2014.1 - 2018.12

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    Country:Japan

  4. Graduate School of Medicine, Kyoto University   Thoracic Surgery   Assistant Professor

    2009.7 - 2013.12

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    Country:Japan

  5. Toronto Univeristy   Thoracic Surgery   Clinical fellow

    2008.7 - 2009.6

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    Country:Japan

  6. Graduate School of Medicine, Kyoto University   Organ Preservation Technology   Assistant Professor

    2007.2 - 2008.12

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    Country:Japan

  7. Kyoto University Hospital   Thoracic Surgery   Clinical fellow

    2003.4 - 2004.3

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    Country:Japan

  8. Shizuoka City Hospital   Thoracic and Cardiovascular Surgery   Staff Surgeon

    2000.10 - 2003.3

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    Country:Japan

  9. Kochi Municipal Hospital   Thoracic Surgery   Resident

    1998.4 - 2000.9

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    Country:Japan

  10. Kyoto University Chest Research Institute   Surgery   Resident

    1997.5 - 1998.3

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    Country:Japan

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Education 2

  1. Kyoto University   Graduate School, Division of Medicine   Thoracic Surgery

    2004.4 - 2007.1

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    Country: Japan

  2. Kyoto University   Faculty of Medicine

    1991.4 - 1997.3

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    Country: Japan

Professional Memberships 24

  1. AATS (American Association for Thoracic Surgery)   Member, Editorial Board

  2. 日本呼吸器外科学会   評議員、移植委員会委員、国際委員会委員、NCD委員会委員

  3. 日本移植学会   代議員、幹事、医療標準化委員会委員、トランスレーショナルリサーチ委員会委員、脳死・心停止移植環境整備委員会委員

  4. 日本呼吸器内視鏡学会   評議員、COI委員会副委員長、評議員資格審査委員会委員、広報委員会委員

  5. 日本胸部外科学会   評議員

  6. 日本呼吸器学会   代議員

    1997

  7. 日本癌治療学会   会員

  8. 日本癌学会   会員

  9. 近畿肺移植検討会   幹事、世話人

  10. The Transplantation Society   Member

  11. International Society of Heart and Lung Transplantation (ISHLT)   Member

  12. International Association for the Study of Lung Cancer   Member

  13. ESTS (European Society of Thoracic Surgeons)   Member

  14. 日本肺高血圧・肺循環学会   評議員

  15. 日本蛍光ガイド手術研究会   世話人

  16. 関西胸部外科学会   評議員

  17. 日本臓器保存生物医学会   評議員

  18. 日本肺癌学会   理事、評議員、気管支鏡委員会委員

  19. 組織適合性学会近畿地方会   幹事

  20. 日本外科学会   代議員、会員

  21. バイオフィジオロジー―研究会   幹事、世話人

  22. 日本内視鏡外科学会   会員

  23. 日本組織適合性学会   評議員、会員

  24. ESTS (European Society of Thoracic Surgeons)

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Awards 10

  1. Brompton Prize

    2019.6   ヨーロッパ呼吸器外科学会  

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    Award type:Award from international society, conference, symposium, etc.  Country:Ireland

  2. 第33回日本内視鏡外科学会総会 Surgical Forum Award

    2017   第33回日本内視鏡外科学会総会  

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  3. 第116回日本外科学会定期学術集会 優秀演題賞

    2016   第116回日本外科学会定期学術集会  

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  4. 第69回日本胸部外科学会定期学術集会 プレナリー発表賞

    2016   第69回日本胸部外科学会定期学術集会  

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  5. 第53回日本癌治療学会学術集会 優秀演題賞

    2015   第53回日本癌治療学会学術集会  

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  6. 日本臓器保存生物医学会 研究奨励賞

    2014   日本臓器保存生物医学会  

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  7. 第52回日本癌治療学会学術集会 優秀演題賞

    2014   第52回日本癌治療学会学術集会   肺移植における術前の悪性疾患の既往と術後の悪性疾患の発症

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  8. 第98回日本肺癌学会関西支部会 優秀演題賞

    2013   第98回日本肺癌学会関西支部会  

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  9. 呼吸器外科学会賞

    2012   日本呼吸器外科学会  

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  10. 第63回日本胸部外科学会定期学術集会 優秀演題賞

    2010   第63回日本胸部外科学会定期学術集会  

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    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

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Papers 164

  1. Radiologic evaluation of compensatory lung growth using computed tomography by comparison with histological data from a large animal model

    Ohata K., Chen-Yoshikawa T.F., Hamaji M., Kubo T., Nakamura T., Date H.

    Scientific Reports   Vol. 12 ( 1 )   2022.12

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    Language:Japanese   Publisher:Scientific Reports  

    Non-invasive analysis using computed tomography (CT) data may be a promising candidate to evaluate neo-alveolarization in adult lungs following lung resection. This study evaluates and compares the validity of CT analysis with histologic morphometry for compensatory lung growth in a large animal model. We calculated the radiologic tissue volume and the radiologic lung weight from CT data taken at 1, 3, and 6 months post-surgery on 15 male beagle dogs that had a right thoractotomy, bilobectomy, or pneumonectomy (n = 5 in each group). Results were analyzed using one-way ANOVA and were subsequently compared to histologic findings of tissue samples at 6 months post-surgery using Pearson’s correlation. An increase in radiologic tissue volume and radiologic lung weight was identified, which was positively correlated with histologic lung parenchymal amounts (correlation coefficient = 0.955 and 0.934, respectively, p < 0.001). Histology of lung specimens at 6 months post-surgery revealed an increase in the tissue amount in both Bilobectomy and Peumonectomy groups, which was consistent with compensatory lung growth. Radiologic tissue volume and radiologic lung weight reflected compensatory lung growth following lung resection. Radiologic assessment using CT data can be a promising clinical modality to evaluate postoperative lung growth.

    DOI: 10.1038/s41598-022-06398-y

    Scopus

  2. Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade

    Miyai Y., Sugiyama D., Hase T., Asai N., Taki T., Nishida K., Fukui T., Chen-Yoshikawa T.F., Kobayashi H., Mii S., Shiraki Y., Hasegawa Y., Nishikawa H., Ando Y., Takahashi M., Enomoto A.

    Life science alliance   Vol. 5 ( 6 )   2022.6

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    Language:Japanese   Publisher:Life science alliance  

    Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape the TME toward an immunosuppressive milieu and attenuate the efficacy of immune checkpoint blockade (ICB) therapy. However, the detailed mechanism of how heterogeneous CAFs regulate tumor response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by the expression of Meflin, a glycosylphosphatidylinositol-anchored protein marker of mesenchymal stromal/stem cells, is associated with survival and favorable therapeutic response to ICB monotherapy in patients with non-small cell lung cancer (NSCLC). The prevalence of Meflin-positive CAFs was positively correlated with CD4-positive T-cell infiltration and vascularization within non-small cell lung cancer tumors. Meflin deficiency and CAF-specific Meflin overexpression resulted in defective and enhanced ICB therapy responses in syngeneic tumors in mice, respectively. These findings suggest the presence of a CAF subset that promotes ICB therapy efficacy, which adds to our understanding of CAF functions and heterogeneity.

    DOI: 10.26508/lsa.202101230

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  3. Risk Assessment for Loss-of-Exercise Capacity After Lung Cancer Surgery: Current Advances in Surgery and Systemic Treatment

    Ozeki N., Kadomatsu Y., Mizuno Y., Inoue T., Nagaya M., Goto M., Nakamura S., Fukumoto K., Chen-Yoshikawa T.F.

    World Journal of Surgery   Vol. 46 ( 4 ) page: 933 - 941   2022.4

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    Language:Japanese   Publisher:World Journal of Surgery  

    Background: Considering advances in current post-recurrence treatment, we examined the prognostic significance of the number of risk factors for loss-of-exercise capacity (LEC) after lung cancer surgery, which were identified by our previous prospective observational study. Methods: Risk factors for LEC were defined as a short baseline 6-min walk distance (<400 m), older age (≥75 years), and low predicted postoperative diffusing capacity for carbon monoxide (<60%). Patients were classified as Risk 0/I/II/III according to the number of risk factors. The survival data were retrospectively analyzed. Results: Between 2014 and 2017, 564 patients (n = 307, 193, 57, 7; Risk 0/I/II/III) who underwent lung cancer surgery were included in the study. The number of risk factors was associated with smoking status, predicted postoperative forced expiratory volume in 1 s, histology, pathological stage, and adjuvant therapy. In a multivariate Cox regression analysis, compared to Risk 0, Risk I/II/III showed significant associations with overall survival (hazard ratios: 1.92, 3.35, 9.21; 95% confidence interval: 1.27–2.92, 2.01–5.58, 3.64–23.35; Risk I/II/III, respectively). In 141 patients with recurrence, molecular targeted therapies (MTTs) or immune checkpoint inhibitors (ICIs) were included in 58%, 47%, 32%, and 0% (Risk 0/I/II/III) during the course of treatment. In patients with MTT/ICI treatment, the estimated 1-year and 3-year post-recurrence survival rates were 88% and 58%, respectively. Conclusions: Risk classification for LEC was associated with survival after lung cancer surgery, as well as post-recurrence treatment. The concept of physical performance-preserving surgery may contribute to improving the outcomes of current lung cancer treatment.

    DOI: 10.1007/s00268-021-06427-3

    Scopus

  4. ASO Visual Abstract: Pleural Invasion Depth of Disseminated Nodules in Patients with Stage IVa or Recurrent Thymoma: Assessment, Curative Impact, and Surgical Outcomes

    Nakamura S., Tateyama H., Nakanishi K., Sugiyama T., Kadomatsu Y., Ueno H., Goto M., Ozeki N., Fukui T., Yokoi K., Chen-Yoshikawa T.F.

    Annals of surgical oncology   Vol. 29 ( 3 )   2022.3

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    Language:Japanese   Publisher:Annals of surgical oncology  

    DOI: 10.1245/s10434-021-10969-0

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  5. Clinical, radiological and pathological features of idiopathic and secondary interstitial pneumonia with pleuroparenchymal fibroelastosis in patients undergoing lung transplantation

    Ikegami N., Nakajima N., Yoshizawa A., Handa T., Chen-Yoshikawa T., Kubo T., Tanizawa K., Ohsumi A., Yamada Y., Hamaji M., Nakajima D., Yutaka Y., Tanaka S., Watanabe K., Nakatsuka Y., Murase Y., Nakanishi T., Niwamoto T., Chin K., Date H., Hirai T.

    Histopathology   Vol. 80 ( 4 ) page: 665 - 676   2022.3

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    Language:Japanese   Publisher:Histopathology  

    Aims: Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare type of idiopathic interstitial pneumonia, and pathological PPFE is also observed in patients with secondary interstitial pneumonia. This study aimed to evaluate the pathological findings associated with radiological PPFE-like lesions and the clinical and morphological features of patients with pathological PPFE. Methods and results: We retrospectively reviewed the pathology of the explanted lungs from 59 lung transplant recipients with radiological PPFE-like lesions. Pathological PPFE lesions were identified in 14 patients with idiopathic disease and in 12 patients with secondary disease. Pathological PPFE was associated with previous pneumothorax, volume loss in the upper lobes, and a flattened chest. Patients with idiopathic disease and those with secondary disease with pathological PPFE had similar clinical, radiological and pathological findings, whereas fibroblastic foci were more common in patients with idiopathic disease, and patients with secondary disease more frequently showed alveolar septal thickening with elastosis or fibrosis. Post-transplantation survival did not differ between patients with idiopathic and secondary disease with pathological PPFE (log-rank; P = 0.57) and was similar between patients with idiopathic disease with pathological PPFE and those with idiopathic pulmonary fibrosis (IPF) (log-rank; P = 0.62). Conclusions: Not all patients with interstitial pneumonia with radiological PPFE-like lesions have pathological PPFE. Characteristic clinical features can suggest the presence of pathological PPFE, and idiopathic and secondary cases with pathological PPFE are similar except for fibroblastic foci in idiopathic cases and alveolar septal thickening with elastosis or fibrosis in secondary cases. Patients with pathological PPFE have a similar prognosis to those with IPF after transplantation.

    DOI: 10.1111/his.14595

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  6. Pleural Invasion Depth of Disseminated Nodules in Patients with Stage IVa or Recurrent Thymoma: Assessment, Curative Impact, and Surgical Outcomes

    Nakamura S., Tateyama H., Nakanishi K., Sugiyama T., Kadomatsu Y., Ueno H., Goto M., Ozeki N., Fukui T., Yokoi K., Chen-Yoshikawa T.F.

    Annals of Surgical Oncology   Vol. 29 ( 3 ) page: 1829 - 1837   2022.3

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    Language:Japanese   Publisher:Annals of Surgical Oncology  

    Background: Thymoma patients with pleural dissemination are difficult to manage, and their treatment strategy remains undefined. This study aimed to investigate the clinicopathologic features of these patients, focusing on the association between the depth of pleural invasion and prognosis. Methods: Between 2003 and 2019, the study identified 120 disseminated lesions in 20 thymoma patients. Seven patients had de novo stage IVa thymoma and 13 were recurrent cases. Extrapleural pneumonectomy was performed for 8 patients and debulking surgery for 12 patients. Invasion depth of pleural tumors was classified into two groups: when the disseminated tumors invaded the pleura beneath the elastic layer, the tumor was diagnosed as Da, and when the disseminated tumors invaded the pleura beyond the elastic layer, the tumor was diagnosed as Db. Results: Of 120 nodules, 31 (26%), found in eight patients with recurrent malignancies, were classified as Db. The pathologic status of the surgical margin (PSM) was positive in eight patients, seven of whom had Db nodules. The 5-year overall survival (OS) rate was 100% in the Da group and 75% in the Db group (P = 0.02). The 5-year progression-free survival (PFS) rate was 66.7% in the Da group and 25% in the Db group (P = 0.02). Cox univariate analysis showed that PFS was significantly influenced by the depth of invasion (P = 0.04) and PSM (P = 0.03). Conclusion: Depth of pleural invasion may influence survival outcomes for thymoma patients with pleural dissemination. The patients in this study with Da-disseminated nodules had an increased probability of a longer OS and PFS and tended to achieve negative PSM compared with the patients with Db.

    DOI: 10.1245/s10434-021-10888-0

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  7. SRGN-Triggered Aggressive and Immunosuppressive Phenotype in a Subset of TTF-1-Negative Lung Adenocarcinomas

    Tanaka I., Dayde D., Tai M.C., Mori H., Solis L.M., Tripathi S.C., Fahrmann J.F., Unver N., Parhy G., Jain R., Parra E.R., Murakami Y., Aguilar-Bonavides C., Mino B., Celiktas M., Dhillon D., Casabar J.P., Nakatochi M., Stingo F., Baladandayuthapani V., Wang H., Katayama H., Dennison J.B., Lorenzi P.L., Do K.A., Fujimoto J., Behrens C., Ostrin E.J., Rodriguez-Canales J., Hase T., Fukui T., Kajino T., Kato S., Yatabe Y., Hosoda W., Kawaguchi K., Yokoi K., Chen-Yoshikawa T.F., Hasegawa Y., Gazdar A.F., Wistuba I.I., Hanash S., Taguchi A.

    Journal of the National Cancer Institute   Vol. 114 ( 2 ) page: 290 - 301   2022.2

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    Language:Japanese   Publisher:Journal of the National Cancer Institute  

    Background: Approximately 20% of lung adenocarcinoma (LUAD) is negative for the lineage-specific oncogene Thyroid transcription factor 1 (TTF-1) and exhibits worse clinical outcome with a low frequency of actionable genomic alterations. To identify molecular features associated with TTF-1-negative LUAD, we compared the transcriptomic and proteomic profiles of LUAD cell lines. SRGN, a chondroitin sulfate proteoglycan Serglycin, was identified as a markedly overexpressed gene in TTF-1-negative LUAD. We therefore investigated the roles and regulation of SRGN in TTF-1-negative LUAD. Methods: Proteomic and metabolomic analyses of 41 LUAD cell lines were done using mass spectrometry. The function of SRGN was investigated in 3 TTF-1-negative and 4 TTF-1-positive LUAD cell lines and in a syngeneic mouse model (n = 5 to 8 mice per group). Expression of SRGN was evaluated in 94 and 105 surgically resected LUAD tumor specimens using immunohistochemistry. All statistical tests were 2-sided. Results: SRGN was markedly overexpressed at mRNA and protein levels in TTF-1-negative LUAD cell lines (P <. 001 for both mRNA and protein levels). Expression of SRGN in LUAD tumor tissue was associated with poor outcome (hazard ratio = 4.22, 95% confidence interval = 1.12 to 15.86, likelihood ratio test, P =. 03), and with higher expression of Programmed cell death 1 ligand 1 (PD-L1) in tumor cells and higher infiltration of Programmed cell death protein 1-positive lymphocytes. SRGN regulated expression of PD-L1 as well as proinflammatory cytokines, including Interleukin-6, Interleukin-8, and C-X-C motif chemokine 1 in LUAD cell lines; increased migratory and invasive properties of LUAD cells and fibroblasts; and enhanced angiogenesis. SRGN was induced by DNA demethylation resulting from Nicotinamide N-methyltransferase-mediated impairment of methionine metabolism. Conclusions: Our findings suggest that SRGN plays a pivotal role in tumor-stromal interaction and reprogramming into an aggressive and immunosuppressive tumor microenvironment in TTF-1-negative LUAD.

    DOI: 10.1093/jnci/djab183

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  8. Changes in the health-related quality of life and social reintegration status after lung transplantation following hematopoietic stem cell transplantation

    Hamada R., Oshima Y., Sato S., Yoshioka Y., Nankaku M., Kondo T., Chen-Yoshikawa T.F., Ikeguchi R., Nakajima D., Date H., Matsuda S.

    Supportive Care in Cancer   Vol. 30 ( 2 ) page: 1831 - 1839   2022.2

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    Language:Japanese   Publisher:Supportive Care in Cancer  

    Purpose: Late-onset non-infectious pulmonary complications (LONIPCs) after allogeneic hematopoietic stem cell transplantation are fatal; however, lung transplantation might achieve good survival. Nevertheless, improving the health-related quality of life (HRQoL) is still a major concern. This study aimed to investigate, in detail, the recovery in HRQoL and social reintegration status after lung transplantation in patients with LONIPC after allo-HSCT. Methods: This prospective cohort study involving 18 patients examined changes in the health and social reintegration status after lung transplantation following LONIPC. Results: Physical function and HRQoL were lowest before lung transplantation. Two years after lung transplantation, the dyspnea scores and performance status improved. Most patients had made a successful return to society, and patients who achieved social reintegration were significantly younger and had a good performance status. However, their Physical Functioning score and Physical Component Summary did not show significant improvement after lung transplantation. Moreover, recipients who were unemployed before lung transplantation were likely to remain unemployed and continued to show poor HRQoL. Conclusions: These results showed poor recovery of HRQoL, especially in terms of physical function, and the likelihood of failure to reintegrate into society within 2 years after lung transplantation. It is necessary to consider long-term follow-up and physical training to improve social reintegration and HRQoL.

    DOI: 10.1007/s00520-021-06592-0

    Scopus

  9. Protective effect of necrosulfonamide on rat pulmonary ischemia-reperfusion injury via inhibition of necroptosis

    Ueda S., Chen-Yoshikawa T.F., Tanaka S., Yamada Y., Nakajima D., Ohsumi A., Date H.

    Journal of Thoracic and Cardiovascular Surgery   Vol. 163 ( 2 ) page: e113 - e122   2022.2

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    Language:Japanese   Publisher:Journal of Thoracic and Cardiovascular Surgery  

    Background: Necroptosis plays an important role in cell death during pulmonary ischemia-reperfusion injury (IRI). We hypothesized that therapy with necrosulfonamide (NSA), a mixed-lineage kinase domain-like protein inhibitor, would attenuate lung IRI. Methods: Rats were assigned at random into the sham operation group (n = 6), vehicle group (n = 8), or NSA group (n = 8). In the NSA and vehicle groups, the animals were heparinized and underwent left thoracotomy, and the left hilum was clamped for 90 minutes, followed by reperfusion for 120 minutes. NSA (0.5 mg/body) and a solvent were administered i.p. in the NSA group and the vehicle group, respectively. The sham group underwent 210 minutes of perfusion without ischemia. After reperfusion, arterial blood gas analysis, physiologic data, lung wet-to-dry weight ratio, histologic changes, and cytokine levels were assessed. Fluorescence double immunostaining was performed to evaluate necroptosis and apoptosis. Results: Arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) was better, dynamic compliance was higher, and mean airway pressure and lung edema were lower in the NSA group compared with the vehicle group. Moreover, in the NSA group, lung injury was significantly alleviated, and the mean number of necroptotic cells (55.3 ± 4.06 vs 78.2 ± 6.87; P =.024), but not of apoptotic cells (P =.084), was significantly reduced compared with the vehicle group. Interleukin (IL)-1β and IL-6 levels were significantly lower with NSA administration. Conclusions: In a rat model, our results suggest that NSA may have a potential protective role in lung IRI through the inhibition of necroptosis.

    DOI: 10.1016/j.jtcvs.2021.01.037

    Scopus

  10. Meclozine Attenuates the MARK Pathway in Mammalian Chondrocytes and Ameliorates FGF2-Induced Bone Hyperossification in Larval Zebrafish

    Takemoto G., Matsushita M., Okamoto T., Ito T., Matsuura Y., Takashima C., Chen-Yoshikawa T.F., Ebi H., Imagama S., Kitoh H., Ohno K., Hosono Y.

    Frontiers in Cell and Developmental Biology   Vol. 9   2022.1

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    Language:Japanese   Publisher:Frontiers in Cell and Developmental Biology  

    Meclozine has been developed as an inhibitor of fibroblast growth factor receptor 3 (FGFR3) to treat achondroplasia (ACH). Extracellular signal regulated kinase (ERK) phosphorylation was attenuated by meclozine in FGF2-treated chondrocyte cell line, but the site of its action has not been elucidated. Although orally administered meclozine promoted longitudinal bone growth in a mouse model of ACH, its effect on craniofacial bone development during the early stage remains unknown. Herein, RNA-sequencing analysis was performed using murine chondrocytes from FGF2-treated cultured tibiae, which was significantly elongated by meclozine treatment. Gene set enrichment analysis demonstrated that FGF2 significantly increased the enrichment score of mitogen-activated protein kinase (MAPK) family signaling cascades in chondrocytes; however, meclozine reduced this enrichment. Next, we administered meclozine to FGF2-treated larval zebrafish from 8 h post-fertilization (hpf). We observed that FGF2 significantly increased the number of ossified vertebrae in larval zebrafish at 7 days post-fertilization (dpf), while meclozine delayed vertebral ossification in FGF2-induced zebrafish. Meclozine also reversed the FGF2-induced upregulation of ossified craniofacial bone area, including ceratohyal, hyomandibular, and quadrate. The current study provided additional evidence regarding the inhibitory effect of meclozine on the FGF2-induced upregulation of MAPK signaling in chondrocytes and FGF2-induced development of craniofacial and vertebral bones.

    DOI: 10.3389/fcell.2021.694018

    Scopus

  11. Predictive value of EGFR mutation in non–small-cell lung cancer patients treated with platinum doublet postoperative chemotherapy

    Takahashi T., Sakai K., Kenmotsu H., Yoh K., Daga H., Ohira T., Ueno T., Aoki T., Hayashi H., Yamazaki K., Hosomi Y., Chen-Yoshikawa T.F., Okumura N., Takiguchi Y., Sekine A., Haruki T., Yamamoto H., Sato Y., Akamatsu H., Seto T., Saeki S., Sugio K., Nishio M., Inokawa H., Yamamoto N., Nishio K., Tsuboi M.

    Cancer Science   Vol. 113 ( 1 ) page: 287 - 296   2022.1

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    Language:Japanese   Publisher:Cancer Science  

    The mutation status of tumor tissue DNA (n = 389) of resected stage II-III non-squamous non–small-cell lung cancer (Ns-NSCLC) was analyzed using targeted deep sequencing as an exploratory biomarker study (JIPANG-TR) for the JIPANG study, a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) vs vinorelbine/cisplatin (Vnr/Cis). The TP53 mutation, common EGFR mutations (exon 19 deletion and L858R), and KRAS mutations were frequently detected. The frequency of the EGFR mutation was significant among female patients. Patients with an EGFR mutation-positive status had a significantly shorter recurrence-free survival (RFS) time (24 mo vs not reached) (HR, 1.64; 95% CI, 1.22-2.21; P =.0011 for EGFR mutation status). Multivariable analysis identified both the pathological stage and EGFR mutation status as independent prognostic factors for RFS (HR, 1.78; 95% CI, 1.30-2.44; P =.0003 for disease stage; and HR, 1.57; 95% CI, 1.15-2.16; P =.0050 for EGFR mutation status). This study demonstrated that the EGFR mutation has either a poor prognostic or predictive impact on a poor response to postoperative chemotherapy with platinum doublet chemotherapy for stage II-III Ns-NSCLC patients. This result supports a role for mandatory molecular diagnosis of early-stage Ns-NSCLC for precision oncology and signifies the importance of adjuvant for the 3rd generation tyrosine kinase inhibitor rather than platinum-based chemotherapy. This study is registered with the UMIN Clinical Trial Registry (UMIN 000012237).

    DOI: 10.1111/cas.15171

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  12. Multicentre, prospective, observational study investigating the most appropriate surgical option that can prevent the recurrence of primary spontaneous pneumothorax after surgery: The PATCH study, protocol

    Kadomatsu Y., Yoshioka H., Shigemitsu K., Nomata Y., Mori S., Hijiya K., Motoyama H., Ichikawa Y., Sueyoshi K., Okasaka T., Miyamoto E., Kobayashi M., Takahashi M., Fujinaga T., Takechi H., Yamagishi H., Takuwa T., Kobayashi J., Sakamoto J., Taniguchi T., Hanaoka N., Kubo Y., Chen-Yoshikawa T.F.

    BMJ Open   Vol. 11 ( 12 )   2021.12

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    Language:Japanese   Publisher:BMJ Open  

    Introduction Thoracoscopic surgery is performed for refractory or recurrent primary spontaneous pneumothorax (PSP). To reduce postoperative recurrence, additional treatment is occasionally adopted during surgery after bulla resection. However, the most effective method has not been fully elucidated. Furthermore, the preference for additional treatment varies among countries, and its efficacy in preventing recurrence must be evaluated based on settings tailored for the conditions of a specific country. The number of registries collecting detailed data about PSP surgery is limited. Therefore, to address this issue, a prospective multicentre observational study was performed. Methods and analysis This multicentre, prospective, observational study will enrol 450 participants aged between 16 and 40 years who initially underwent PSP surgery. Data about demographic characteristics, disease and family history, surgical details, and CT scan findings will be collected. Follow-up must be conducted until 3 years after surgery or in the event of recurrence, whichever came first. Patients without recurrence will undergo annual follow-up until 3 years after surgery. The primary outcome is the rate of recurrence within 2 years after surgery. A multivariate analysis will be performed to compare the efficacy of different surgical options. Then, adverse outcomes correlated with various treatments and the feasibility of treatment methods will be compared. Ethics and dissemination This study was approved by the local ethics committee of all participating centres. The findings will be available in 2025, and they can be used as a basis for clinical decision-making regarding appropriate options for the initial PSP surgery. Trial registration number NCT04758143.

    DOI: 10.1136/bmjopen-2021-052045

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  13. Updated long-term outcomes of salvage surgery after stereotactic body radiotherapy for early-stage non-small-cell lung cancer

    Yamanashi K.

    Interactive cardiovascular and thoracic surgery   Vol. 31 ( 6 ) page: 892 - 894   2021.12

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    DOI: 10.1093/icvts/ivaa194

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  14. Improved visualization of virtual-assisted lung mapping by indocyanine green

    Tokuno J., Chen-Yoshikawa T.F., Nakajima D., Aoyama A., Motoyama H., Sato M., Date H.

    JTCVS Techniques   Vol. 10   page: 542 - 549   2021.12

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    Objectives: Virtual-assisted lung mapping (VAL-MAP) is a bronchoscopic marking method of dye application on the surface of the lungs before resecting nonpalpable nodules. However, in some cases, it can be difficult to identify the markings of VAL-MAP on computed tomography and intraoperative thoracoscopy. We developed and assessed the feasibility of indocyanine green VAL-MAP (ICG-VAL-MAP). Methods: A historical control trial was conducted to investigate the effectiveness of ICG-VAL-MAP for marking visualization compared with that of VAL-MAP. In ICG-VAL-MAP, instead of indigo carmine, ICG and computed tomography contrast agents were used for dye marking, and near-infrared fluorescence endoscopy was employed to visualize the ICG markings. The other processes in VAL-MAP were carried out. The marking visibility was assessed in 3 grades of easy, faint, or not identifiable. We compared the visibility of the markings on computed tomography images and during thoracoscopic operations between VAL-MAP (567 markings in 147 cases) and ICG-VAL-MAP (142 markings in 63 cases). Results: On the preoperative computed tomography images, ICG-VAL-MAP provided significantly better marking visualization than VAL-MAP (easy/faint/not identifiable = 142/0/0 vs 427/100/30; P <.0001). ICG-VAL-MAP provided significantly better intraoperative markings than VAL-MAP (easy/faint/not identifiable = 141/0/1, respectively, vs 475/50/42, respectively; P <.0001). Regarding complications, pneumothorax occurred in 8 (5.4%) cases of VAL-MAP and zero cases (0%) of ICG-VAL-MAP (P =.12); fever was observed in 7 (5.0%) cases of VAL-MAP and 2 (3.2%) cases of ICG-VAL-MAP (P =.72). Conclusions: ICG-VAL-MAP provided significantly better visibility of markings than VAL-MAP. It might be useful in the resection of nonpalpable small lung lesions.

    DOI: 10.1016/j.xjtc.2021.07.019

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  15. Diagnostic utility of metabolic parameters on FDG PET/CT for lymph node metastasis in patients with cN2 non-small cell lung cancer

    Nakanishi K., Nakamura S., Sugiyama T., Kadomatsu Y., Ueno H., Goto M., Ozeki N., Fukui T., Iwano S., Chen-Yoshikawa T.F.

    BMC Cancer   Vol. 21 ( 1 )   2021.12

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    Background: The aim of this study was to assess the diagnostic utility of metabolic parameters on fluorine-18-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) for predicting lymph node (LN) metastasis in patients with cN2 non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed patients who underwent surgery for cN2 NSCLC between 2007 and 2020. Those who had clinically diagnosed positive hilar and mediastinal LNs by routine CT and PET/CT imaging were investigated. To measure the metabolic parameters of LNs, the data according to maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and LN-to-primary tumor ratio of SUVmax (LPR) were examined. The diagnosis of each retrieved LN was confirmed based on histopathological examination of surgical tissue specimens. Receiver operating characteristics (ROC) curves with area under the curve (AUC) calculations and multivariate analysis by logistic regression were performed. Results: Forty-five patients with 84 clinically diagnosed positive hilar or mediastinal LNs were enrolled in the present study. Of the 84 LNs, 63 LNs were pathologically proven as positive (75%). The SUVmax, MTV, TLG, and LPR of LN metastasis were significantly higher than those of benign nodes. In the ROC analysis, the AUC value of LPR [AUC, 0.776; 95% confidence interval (CI), 0.640–0.913] was higher than that of LN SUVmax (AUC, 0.753; 95% CI, 0.626–0.880) or LN TLG3.5 (AUC, 0.746; 95% CI, 0.607–0.885). Using the optimal LPR cutoff value of 0.47, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.1, 66.7, 88.3, 58.3, and 79.8%, respectively. Multivariate analysis by logistic regression showed that LPR was an independent predictor for LN metastasis (odds ratio, 6.45; 95% CI, 1.785–23.301; P = 0.004). In the subgroup analysis of adenocarcinoma patients (n = 18; 32 LNs), TLG3.5 was a better predictor (AUC, 0.816; 95% CI, 0.639–0.985) than LPR (AUC, 0.792; 95% CI, 0.599–0.986) or LN SUVmax (AUC, 0.792; 95% CI, 0.625–0.959). Conclusions: Our findings suggest that LPR on FDG-PET is a useful predictor for LN metastasis in patients with cN2 NSCLC. TLG can be a good predictor for LN metastasis in patients with adenocarcinoma.

    DOI: 10.1186/s12885-021-08688-6

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  16. Patient-reported dyspnea and health predict waitlist mortality in patients waiting for lung transplantation in Japan

    Ikeda M., Oga T., Chen-Yoshikawa T.F., Tokuno J., Oto T., Okawa T., Okada Y., Akiba M., Tanaka S., Yamada Y., Yutaka Y., Ohsumi A., Nakajima D., Hamaji M., Isomi M., Chin K., Date H.

    Respiratory Research   Vol. 22 ( 1 )   2021.12

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    Background: Waitlist mortality due to donor shortage for lung transplantation is a serious problem worldwide. Currently, the selection of recipients in Japan is mainly based on the registration order. Hence, scientific evidence for risk stratification regarding waitlist mortality is urgently needed. We hypothesized that patient-reported dyspnea and health would predict mortality in patients waitlisted for lung transplantation. Methods: We analyzed factors related to waitlist mortality using data of 203 patients who were registered as candidates for lung transplantation from deceased donors. Dyspnea was evaluated using the modified Medical Research Council (mMRC) dyspnea scale, and the health status was determined with St. George’s Respiratory Questionnaire (SGRQ). Results: Among 197 patients who met the inclusion criteria, the main underlying disease was interstitial lung disease (99 patients). During the median follow-up period of 572 days, 72 patients died and 96 received lung transplantation (69 from deceased donors). Univariable competing risk analyses revealed that both mMRC dyspnea and SGRQ Total score were significantly associated with waitlist mortality (p = 0.003 and p < 0.001, respectively) as well as age, interstitial lung disease, arterial partial pressure of carbon dioxide, and forced vital capacity. Multivariable competing risk analyses revealed that the mMRC and SGRQ score were associated with waitlist mortality in addition to age and interstitial lung disease. Conclusions: Both mMRC dyspnea and SGRQ score were significantly associated with waitlist mortality, in addition to other clinical variables such as patients’ background, underlying disease, and pulmonary function. Patient-reported dyspnea and health may be measured through multi-dimensional analysis (including subjective perceptions) and for risk stratification regarding waitlist mortality.

    DOI: 10.1186/s12931-021-01715-x

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  17. Polyglycolic acid sheet covering to prevent recurrence after surgery for spontaneous pneumothorax: a meta-analysis

    Kadomatsu Y., Fukui T., Mori S., Chen-Yoshikawa T.F., Wakai K.

    Scientific Reports   Vol. 11 ( 1 )   2021.12

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    The coverage technique using absorbable mesh was first described in a European guideline published in 2015 as a preventive method for the recurrence of spontaneous pneumothorax. We performed a meta-analysis based on a literature search of primary studies that compared the postoperative recurrence rate of primary spontaneous pneumothorax between the use and nonuse of polyglycolic acid sheet coverage. Two reviewers independently selected and evaluated the quality of the relevant studies. The risk ratio in each study was calculated in a random-effect meta-analysis. Statistical heterogeneity among the included studies was quantitatively evaluated using the I2 index, and publication bias was assessed using a funnel plot. A total of 19 retrospective cohort studies were analyzed: 1524 patients who underwent wedge resection alone (the control group) and 1579 who received additional sheet coverage. Polyglycolic acid sheet coverage was associated with a lower recurrence rate than that in the control group (risk ratio: 0.27, 95% confidence interval 0.20–0.37, P < 0.001; I2 0%). The funnel plot suggested possible publication bias. The covering technique reduced the recurrence rate of pneumothorax after thoracoscopic surgery to one-fourth.

    DOI: 10.1038/s41598-021-83103-5

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  18. Kernel-based framework to estimate deformations of pneumothorax lung using relative position of anatomical landmarks

    Yamamoto U., Nakao M., Ohzeki M., Tokuno J., Chen-Yoshikawa T.F., Matsuda T.

    Expert Systems with Applications   Vol. 183   2021.11

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    In video-assisted thoracoscopic surgeries, successful procedures of nodule resection are highly dependent on the precise estimation of lung deformation between the inflated lung in the computed tomography (CT) images during preoperative planning and the deflated lung in the treatment views during surgery. Lungs in the pneumothorax state during surgery have a large volume change from normal lungs, making it difficult to build a mechanical model.The purpose of this study is to develop a deformation estimation method of 3D surface of a deflated lung from a few partial observations. To estimate deformations for a largely deformed lung, a kernel regression-based solution was introduced. The proposed method used a few landmarks to capture the partial deformation between the 3D surface mesh obtained from preoperative CT and the intraoperative anatomical positions. The deformation for each vertex of the entire mesh model was estimated per-vertex as a relative position from the landmarks. The landmarks were placed in the anatomical position of the lung's outer contour. The method was applied on nine datasets of the left lungs of live beagle dogs. Contrast-enhanced CT images of the lungs were acquired.The proposed method achieved a local positional error of vertices of 2.74 mm, Hausdorff distance of 6.11 mm, and Dice similarity coefficient of 0.94. Moreover, the proposed method achieved the estimation lung deformations from a small number of training cases and a small observation area.This study contributes to data-driven modeling of pneumothorax deformation of the lung.

    DOI: 10.1016/j.eswa.2021.115288

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  19. Morphological and functional reserves of the right middle lobe: Radiological analysis of changes after right lower lobectomy in healthy individuals

    Yamagishi H.

    Journal of Thoracic and Cardiovascular Surgery   Vol. 162 ( 5 ) page: 1417 - 1423.e2   2021.11

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    DOI: 10.1016/j.jtcvs.2020.08.017

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  20. Impacts of single nucleotide polymorphisms in Fc gamma receptor IIA (rs1801274) on lung transplant outcomes among Japanese lung transplant recipients

    Kayawake H., Chen-Yoshikawa T.F., Tanaka S., Tanaka Y., Ohdan H., Yutaka Y., Yamada Y., Ohsumi A., Nakajima D., Hamaji M., Egawa H., Date H.

    Transplant International   Vol. 34 ( 11 ) page: 2192 - 2204   2021.11

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    This study aimed to analyze the influences of single nucleotide polymorphisms (SNPs) in Fc gamma receptor IIA (FCGR2A) on postoperative outcomes after lung transplantation (LTx). We enrolled 191 lung transplant recipients [80 undergoing living-donor lobar lung transplants (LDLLTs) and 111 undergoing deceased-donor lung transplants (DDLTs)] in this study. We identified SNPs in FCGR2A (131 histidine [H] or arginine [R]; rs1801274) and reviewed the infectious complication-free survival after ICU discharge. The SNPs in FCGR2A comprised H/H (n = 53), H/R (n = 24), and R/R (n = 3) in LDLLT and H/H (n = 67), H/R (n = 42), and R/R (n = 2) in DDLT. Recipients with H/H (H/H group) and those with H/R or R/R (R group) were compared in the analyses of infectious complications. In multivariate analyses, the R group of SNPs in FCGR2A was associated with pneumonia-free survival {HR: 2.52 [95% confidence interval (CI): 1.35–4.71], P = 0.004}, fungal infection-free survival [HR: 2.50 (95% CI: 1.07–5.84), P = 0.035], and cytomegalovirus infection-free survival [HR: 2.24 (95% CI: 1.07–4.69), P = 0.032] in LDLLT, but it was not associated with infectious complication-free survival in DDLT. Therefore, in LDLLT, more attention to infectious complications might need to be paid for LTx recipients with H/R or R/R than for those with H/H.

    DOI: 10.1111/tri.13974

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  21. Left Upper Lobe Trisegmentectomy After Pulmonary Endarterectomy

    Tsubouchi H., Goto M., Terazawa S., Adachi S., Suzuki Y., Usui A., Kondo T., Chen-Yoshikawa T.F.

    Annals of Thoracic Surgery   Vol. 112 ( 5 ) page: e361 - e363   2021.11

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    Major pulmonary resection has been successfully performed after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension in a few cases. A pulmonary nodule was detected in a 68-year-old man with a diagnosis of chronic thromboembolic pulmonary hypertension. After pulmonary hypertension was resolved with pulmonary endarterectomy, left upper lobe trisegmentectomy was performed for small lung cancer. Dissection of the pulmonary artery was carefully performed with a possibility of a fragile state on the arterial wall due to previous pulmonary endarterectomy. Pathologically, the arterial media with an uneven thickness was exposed to the vascular lumen in the resected pulmonary artery.

    DOI: 10.1016/j.athoracsur.2021.02.022

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  22. 綜説 小児肺移植の現状

    芳川 豊史

    小児科   Vol. 62 ( 11 ) page: 1364 - 1373   2021.10

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    Publisher:金原出版  

    DOI: 10.18888/sh.0000001943

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  23. Deformation analysis of surface and bronchial structures in intraoperative pneumothorax using deformable mesh registration

    Nakao M., Kobayashi K., Tokuno J., Chen-Yoshikawa T., Date H., Matsuda T.

    Medical Image Analysis   Vol. 73   2021.10

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    The positions of nodules can change because of intraoperative lung deflation, and the modeling of pneumothorax-associated deformation remains a challenging issue for intraoperative tumor localization. In this study, we introduce spatial and geometric analysis methods for inflated/deflated lungs and discuss heterogeneity in pneumothorax-associated lung deformation. Contrast-enhanced CT images simulating intraoperative conditions were acquired from live Beagle dogs. The images contain the overall shape of the lungs, including all lobes and internal bronchial structures, and were analyzed to provide a statistical deformation model that could be used as prior knowledge to predict pneumothorax. To address the difficulties of mapping pneumothorax CT images with topological changes and CT intensity shifts, we designed deformable mesh registration techniques for mixed data structures including the lobe surfaces and the bronchial centerlines. Three global-to-local registration steps were performed under the constraint that the deformation was spatially continuous and smooth, while matching visible bronchial tree structures as much as possible. The developed framework achieved stable registration with a Hausdorff distance of less than 1 mm and a target registration error of less than 5 mm, and visualized deformation fields that demonstrate per-lobe contractions and rotations with high variability between subjects. The deformation analysis results show that the strain of lung parenchyma was 35% higher than that of bronchi, and that deformation in the deflated lung is heterogeneous.

    DOI: 10.1016/j.media.2021.102181

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  24. Various techniques for anastomosis of pulmonary arteries with size mismatch during lung transplantation

    Yokoyama Y., Chen-Yoshikawa T.F., Nakajima D., Ohsumi A., Date H.

    JTCVS Techniques   Vol. 9   page: 192 - 194   2021.10

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    DOI: 10.1016/j.xjtc.2021.06.009

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  25. 特集 胸部外科領域における再手術up to date II. 呼吸器領域 7. 生体肺移植後の再移植

    芳川 豊史, 伊達 洋至

    胸部外科   Vol. 74 ( 10 ) page: 850 - 855   2021.9

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    Publisher:南江堂  

    DOI: 10.15106/j_kyobu74_850

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  26. Differential impacts of postoperative complications on patients’ survival in completely resected non-small-cell lung cancer

    Kadomatsu Y., Tsubouchi H., Nakanishi K., Sugiyama T., Ueno H., Goto M., Ozeki N., Nakamura S., Fukui T., Chen-Yoshikawa T.F.

    General Thoracic and Cardiovascular Surgery   Vol. 69 ( 9 ) page: 1283 - 1290   2021.9

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    Objective: The aim of this study was to investigate the effects of inflammatory respiratory complications on long-term survival in patients with resected non-small cell lung cancer. We defined inflammatory respiratory complications to include the following six conditions: pneumonia, empyema, bronchial fistula, respiratory dysfunction, acute interstitial pneumonia, and atelectasis. Methods: Part of the National Clinical Database was linked to our prospective database from 2014 to 2017. Linkage was achieved for 866 patients. The Kaplan–Meier method was used to evaluate the overall, relapse-free, and cancer-related survival. The Cox proportional hazard model was used to analyze the impact of each complication. Results: Of the 736 patients included in the study, 149 had complications. The 5-year overall and cancer-specific survival rates were significantly lower in patients with inflammatory respiratory complications. The Cox proportional hazard model showed that the inflammatory respiratory complications had a significant impact on overall survival (hazard ratio 2.48, 95% confidence interval 1.41–4.38) but not air leak (hazard ratio 1.38, 95% confidence interval 0.70–2.70). Conclusions: Our study shows the differential impact of each complication on the survival of patients with non-small cell lung cancer. The presence of inflammatory respiratory complications was the only predictor of poor overall survival.

    DOI: 10.1007/s11748-021-01619-z

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  27. Physical function after lung transplantation for late-onset noninfectious pulmonary complications after allogeneic hematopoietic stem cell transplantation

    Hamada R., Oshima Y., Sato S., Yoshioka Y., Sato T., Nankaku M., Kondo T., Chen-Yoshikawa T.F., Ikeguchi R., Nakajima D., Date H., Matsuda S.

    Supportive Care in Cancer   Vol. 29 ( 9 ) page: 5447 - 5454   2021.9

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    Purpose: Late-onset noninfectious pulmonary complications (LONIPCs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are fatal, and lung transplantation is the only curative treatment. Although lung transplantation for LONIPCs may confer good survival rates, it is unclear whether or how impaired physical functioning is restored. Thus, this study aimed to investigate the long-term course and associated changes in physical functions after lung transplantation in patients with LONIPCs after allo-HSCT. Methods: This prospective cohort study enrolled 15 patients who received lung transplantation for LONIPCs after allo-HSCT between 2012 and 2018. Dyspnea scores, performance status, physical function, and exercise tolerance were assessed before lung transplantation and up to 2 years after transplantation. Results: Two years after lung transplantation, the dyspnea scores and performance status improved, but did not recover completely. Physical function was assessed using the knee extensor strength (KES) and 6-min walk test (6MWT); the results were poor until 3 months after transplantation but improved over 2 years. The 6MWT distance showed improvement to a nearly healthy level (562.7 m). Recovery of exercise tolerance was associated with recovery in % vital capacity (%VC; r=0.5) and KES (r=0.4) from 3 months to 2 years after lung transplantation. Furthermore, a flat thorax, which is a characteristic of patients with LONIPCs, affected the %VC at 2 years after transplantation (r=0.8). Conclusion: Lung transplantation for LONIPCs may restore impaired physical function. A multifaceted rehabilitation program should be considered, especially to improve muscle weakness and pulmonary function.

    DOI: 10.1007/s00520-021-06118-8

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  28. Commentary: Constant dripping wears a stone away

    Ozeki N.

    Journal of Thoracic and Cardiovascular Surgery   Vol. 162 ( 2 ) page: e159 - e160   2021.8

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    DOI: 10.1016/j.jtcvs.2020.04.136

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  29. Outcomes of lung transplantation for idiopathic pleuroparenchymal fibroelastosis

    Shiiya H., Nakajima J., Date H., Chen-Yoshikawa T.F., Tanizawa K., Handa T., Oto T., Otani S., Shiotani T., Okada Y., Matsuda Y., Shiraishi T., Moroga T., Minami M., Funaki S., Chida M., Yoshino I., Hatachi G., Uemura Y., Sato M.

    Surgery Today   Vol. 51 ( 8 ) page: 1276 - 1284   2021.8

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    Purpose: This study was performed to compare the outcome of lung transplantation (LT) for idiopathic pleuroparenchymal fibroelastosis (IPPFE) with that of LT for idiopathic pulmonary fibrosis (IPF). Methods: We reviewed, retrospectively, all adult patients who underwent LT for IPPFE or IPF in Japan between 1998 and 2018. Results: There were 100 patients eligible for this study (31 with IPPFE and 69 with IPF). Patients with IPPFE tended to have a significantly lower body mass index (BMI) than those with IPF (median, 16.7 vs. 22.6 kg/m2, respectively; P < 0.01). However, Kaplan–Meier survival curves showed no significant difference in overall survival between the groups. The BMI did not increase in patients with IPPFE, even 1 year after LT (pretransplant, 16.5 ± 3.2 kg/m2 vs. 1 year post-transplant, 15.6 ± 2.5 kg/m2; P = 0.08). The percent predicted forced vital capacity (%FVC) 1 year after LT was significantly lower in the IPPFE group than in the IPF group (48.4% ± 19.5% vs. 68.6% ± 15.5%, respectively; P < 0.01). Conclusions: Despite extrapulmonary problems such as a flat chest, low BMI, and associated restrictive impairment persisting in patients with IPPFE, patient survival after LT for IPPFE or IPF was equivalent.

    DOI: 10.1007/s00595-021-02232-6

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  30. Thymic mucinous adenocarcinoma: A case report

    Tsubouchi Hideki, Ozeki Naoki, Suzuki Yuka, Kawaguchi Koji, Fukui Takayuki, F. Chen-Yoshikawa Toyofumi

    The Journal of the Japanese Association for Chest Surgery   Vol. 35 ( 5 ) page: 547 - 552   2021.7

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    <p>A 61-year-old woman presented with a 44-mm well-circumscribed tumor in the anterior mediastinum on chest computed tomography. <sup>18</sup>F-Fluorodeoxyglucose positron emission tomography showed a high-level accumulation of <sup>18</sup>F-Fluorodeoxyglucose (standardized uptake value: 12.07). She underwent thymectomy with combined resection of partial pericardium. Histopathological findings showed that the tumor was a thymic mucinous adenocarcinoma (pT2N0M0 Stage II, and Masaoka stage III). After receiving adjuvant radiotherapy, she was in good health without any tumor recurrence at 6 months after surgery.</p>

    DOI: 10.2995/jacsurg.35.547

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  31. Pulmonary benign metastasizing leiomyoma: A clinicopathological study of 10 cases

    Maeda Jun, Higashiyama Masahiko, Nishio Wataru, Yoshikawa Toyofumi, Kadota Yoshihisa, Iwasaki Teruo, Terada Yasuji, Okami Jiro

    The Journal of the Japanese Association for Chest Surgery   Vol. 35 ( 5 ) page: 537 - 546   2021.7

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    <p>Pulmonary benign metastasizing leiomyoma (BML) is a rare disease in which a benign uterine leiomyoma metastasizes to the lung. We herein report a clinicopathological study of 10 cases. The median interval between hysterectomy and lung resection for pulmonary nodules was 114 months (range: 15-240 months). The median tumor size was 11 mm (range: 5-16 mm). While nine patients with multiple nodules underwent wedge resection, one was treated with lobectomy. Hormonal treatment was administered to 3 patients with residual lesions and 1 patient as adjuvant therapy. During the follow-up periods (range: 26-192 months, median: 105 months), seven patients were alive with disease and two without evidence of disease. One patient died of systemic metastases due to atypical leiomyoma diagnosed by reviewing uterine and pulmonary specimens. Diagnostic, surgical, and therapeutic problems associated with this disease were discussed.</p>

    DOI: 10.2995/jacsurg.35.537

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  32. Multicellular modeling of ciliopathy by combining ips cells and microfluidic airway-on-a-chip technology

    Sone N., Konishi S., Igura K., Tamai K., Ikeo S., Korogi Y., Kanagaki S., Namba T., Yamamoto Y., Xu Y., Takeuchi K., Adachi Y., Chen-Yoshikawa T.F., Date H., Hagiwara M., Tsukita S., Hirai T., Torisawa Y.S., Gotoh S.

    Science Translational Medicine   Vol. 13 ( 601 )   2021.7

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    Mucociliary clearance is an essential lung function that facilitates the removal of inhaled pathogens and foreign matter unidirectionally from the airway tract and is innately achieved by coordinated ciliary beating of multiciliated cells. Should ciliary function become disturbed, mucus can accumulate in the airway causing subsequent obstruction and potentially recurrent pneumonia. However, it has been difficult to recapitulate unidirectional mucociliary flow using human-derived induced pluripotent stem cells (iPSCs) in vitro and the mechanism governing the flow has not yet been elucidated, hampering the proper humanized airway disease modeling. Here, we combine human iPSCs and airway-on-a-chip technology, to demonstrate the effectiveness of fluid shear stress (FSS) for regulating the global axis of multicellular planar cell polarity (PCP), as well as inducing ciliogenesis, thereby contributing to quantifiable unidirectional mucociliary flow. Furthermore, we applied the findings to disease modeling of primary ciliary dyskinesia (PCD), a genetic disease characterized by impaired mucociliary clearance. The application of an airway cell sheet derived from patient-derived iPSCs and their gene-edited counterparts, as well as genetic knockout iPSCs of PCD causative genes, made it possible to recapitulate the abnormal ciliary functions in organized PCP using the airway-on-a-chip. These findings suggest that the disease model of PCD developed here is a potential platform for making diagnoses and identifying therapeutic targets and that airway reconstruction therapy using mechanical stress to regulate PCP might have therapeutic value.

    DOI: 10.1126/scitranslmed.abb1298

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  33. CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation

    Shi H., Niimi A., Takeuchi T., Shiogama K., Mizutani Y., Kajino T., Inada K., Hase T., Hatta T., Shibata H., Fukui T., Chen-Yoshikawa T.F., Nagano K., Murate T., Kawamoto Y., Tomida S., Takahashi T., Suzuki M.

    Cancer Science   Vol. 112 ( 7 ) page: 2770 - 2780   2021.7

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    Ceramide synthase 6 (CERS6) promotes lung cancer metastasis by stimulating cancer cell migration. To examine the underlying mechanisms, we performed luciferase analysis of the CERS6 promoter region and identified the Y-box as a cis-acting element. As a parallel analysis of database records for 149 non–small-cell lung cancer (NSCLC) cancer patients, we screened for trans-acting factors with an expression level showing a correlation with CERS6 expression. Among the candidates noted, silencing of either CCAAT enhancer-binding protein γ (CEBPγ) or Y-box binding protein 1 (YBX1) reduced the CERS6 expression level. Following knockdown, CEBPγ and YBX1 were found to be independently associated with reductions in ceramide-dependent lamellipodia formation as well as migration activity, while only CEBPγ may have induced CERS6 expression through specific binding to the Y-box. The mRNA expression levels of CERS6, CEBPγ, and YBX1 were positively correlated with adenocarcinoma invasiveness. YBX1 expression was observed in all 20 examined clinical lung cancer specimens, while 6 of those showed a staining pattern similar to that of CERS6. The present findings suggest promotion of lung cancer migration by possible involvement of the transcription factors CEBPγ and YBX1.

    DOI: 10.1111/cas.14928

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  34. Comparison of de novo donor-specific antibodies between living and cadaveric lung transplantation

    Gochi F., Chen-Yoshikawa T.F., Kayawake H., Ohsumi A., Tanaka S., Yamada Y., Yutaka Y., Nakajima D., Hamaji M., Yurugi K., Hishida R., Date H.

    Journal of Heart and Lung Transplantation   Vol. 40 ( 7 ) page: 607 - 613   2021.7

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    Background: Despite growing interest in donor-specific antibodies (DSAs) and antibody-mediated rejection (AMR) in lung transplantation (LTx), no study evaluating the outcomes in recipients with de novo DSAs (dnDSAs) in living-donor lobar LTx (LDLLT) exists. We compared various characteristics of DSAs in LDLLT with those in cadaveric LTx (CLT) based on prospectively collected data. Methods: Between October 2009 and September 2019, 211 recipients underwent LTx (128 CLTs and 83 LDLLTs). We reviewed 108 CLTs and 74 LDLLTs to determine the characteristics and clinical impact of dnDSAs. Eighteen data-deficient cases, 7 cases with preformed DSAs, and 4 re-transplants were excluded. Results: There were significant differences between CLT and LDLLT patients in age, primary disease, ischemic time, and number of human leukocyte antigen mismatches per donor. The dnDSA incidence in LDLLT (6.8%) was significantly lower than that in CLT (19.4%, p = 0.02). The dnDSAs appeared later in LDLLT (mean 1,256 days) than in CLT (mean 196 days, p = 0.003). According to Cox models analyzed using dnDSA as a time-dependent covariate, dnDSA positivity was significantly associated with a poor overall survival (OS; hazard ratio [HR] 3.46, 95% confidence interval [CI] 1.59-7.57, p = 0.002) and poor CLAD-free survival in case of CLT (HR: 2.23, 95% CI: 1.08-4.63, p = 0.003). However, no such significant associations were noted in case of LDLLT. Conclusions: The dnDSA occurrence was significantly lower and later in LDLLT than in CLT. Furthermore, dnDSA-positivity was significantly associated with worse OS and CLAD-free survival after CLT but not after LDLLT.

    DOI: 10.1016/j.healun.2021.03.019

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  35. Mammalian enteral ventilation ameliorates respiratory failure

    Okabe R., Chen-Yoshikawa T.F., Yoneyama Y., Yokoyama Y., Tanaka S., Yoshizawa A., Thompson W.L., Kannan G., Kobayashi E., Date H., Takebe T.

    Med   Vol. 2 ( 6 ) page: 773 - 783.e5   2021.6

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    Background: Several aquatic organisms such as loaches have evolved unique intestinal breathing mechanisms to survive under extensive hypoxia. To date, it is highly controversial whether such capability can be adapted in mammalian species as another site for gas exchange. Here, we report the advent of the intestinal breathing phenomenon in mammalians by exploiting EVA (enteral ventilation via anus). Methods: Two different modes of EVA were investigated in an experimental model of respiratory failure: intra-rectal oxygen O2 gas ventilation (g-EVA) or liquid ventilation (l-EVA) with oxygenated perfluorocarbon. After induction of type 1 respiratory failure, we analyzed the effectiveness of g-EVA and I-EVA in mouse and pig, followed by preclinical safety analysis in rat. Findings: Both intra-rectal O2 gas and oxygenated liquid delivery were shown to provide vital rescue of experimental models of respiratory failure, improving survival, behavior, and systemic O2 level. A rodent and porcine model study confirmed the tolerable and repeatable features of an enema-like l-EVA procedure with no major signs of complications. Conclusions: EVA has proven effective in mammalians such that it oxygenated systemic circulation and ameliorated respiratory failure. Due to the proven safety of perfluorochemicals in clinics, EVA potentially provides an adjunctive means of oxygenation for patients under respiratory distress conditions. Funding: This work is funded by the Research Program on Emerging and Re-emerging Infectious Diseases, Research Projects on COVID-19 (JP20fk0108278, 20fk0108506h0001), from the Japan Agency for Medical Research and Development (AMED), to T.T.; Strategic Promotion for Practical Application of Innovative Medical Technology, Seeds A (A145), to T.T.; and KAKENHI 19K22657, to T.C.-Y. This research is partially supported by the AMED Translational Research Program; Strategic Promotion for Practical Application of Innovative Medical Technology (TR-SPRINT), to T.C.-Y.; and AMED JP18bm0704025h0001 (Program for Technological Innovation of Regenerative Medicine), to T.T.

    DOI: 10.1016/j.medj.2021.04.004

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  36. Association Between Pretransplant Serum Carcinoembryonic Antigen Levels and Immunohistochemical Staining of Explanted Native Lungs in Patients Who Underwent Lung Transplantation

    Okabe R.

    Seminars in Thoracic and Cardiovascular Surgery   Vol. 33 ( 2 ) page: 608 - 615   2021.6

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    DOI: 10.1053/j.semtcvs.2020.09.003

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  37. Combined surgical therapy for pulmonary sequestration and aberrant artery from the abdominal aorta

    Hakiri S., Fukui T., Chen-Yoshikawa T.F.

    General Thoracic and Cardiovascular Surgery   Vol. 69 ( 6 ) page: 1031 - 1034   2021.6

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    Pulmonary sequestration with feeding vessels from the abdominal aorta is relatively rare. A 56-year-old woman with chronic left thoracic pain was referred to our hospital. Computed tomography showed multiple pulmonary cysts in the left lung and an aberrant artery from the abdominal aorta. She was diagnosed with pulmonary sequestration. She underwent embolization of the aberrant artery and wedge resection of the sequestrated lung under indocyanine green guidance. The surgical treatment combining preoperative embolization of the artery and intraoperative indocyanine green-guided lung resection might be safe and minimally invasive for patients with lung sequestrations accompanied by feeding vessels from the abdominal aorta.

    DOI: 10.1007/s11748-021-01612-6

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  38. Ischemia–reperfusion injury in lung transplantation

    Chen-Yoshikawa T.F.

    Cells   Vol. 10 ( 6 )   2021.6

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    Lung transplantation has been established worldwide as the last treatment for end-stage respiratory failure. However, ischemia–reperfusion injury (IRI) inevitably occurs after lung transplantation. The most severe form of IRI leads to primary graft failure, which is an important cause of morbidity and mortality after lung transplantation. IRI may also induce rejection, which is the main cause of mortality in recipients. Despite advances in donor management and graft preservation, most donor grafts are still unsuitable for transplantation. Although the pulmonary endothelium is the primary target site of IRI, the pathophysiology of lung IRI remains incompletely understood. It is essential to understand the mechanism of pulmonary IRI to improve the outcomes of lung transplantation. Therefore, we reviewed the state-of-the-art in the management of pulmonary IRI after lung transplantation. Recently, the ex vivo lung perfusion (EVLP) system has been clinically introduced worldwide. Various promising therapeutic strategies for the protection of the endothelium against IRI, including EVLP, inhalation therapy with therapeutic gases and substances, fibrinolytic treatment, and mesenchymal stromal cell therapy, are awaiting clinical application. We herein review the latest advances in the field of pulmonary IRI in lung transplantation.

    DOI: 10.3390/cells10061333

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  39. Preoperative paraspinous muscle sarcopenia and physical performance as prognostic indicators in non-small-cell lung cancer

    Tanaka S., Ozeki N., Mizuno Y., Nakajima H., Hattori K., Inoue T., Nagaya M., Fukui T., Nakamura S., Goto M., Sugiyama T., Nishida Y., Chen-Yoshikawa T.F.

    Journal of Cachexia, Sarcopenia and Muscle   Vol. 12 ( 3 ) page: 646 - 656   2021.6

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    Background: Despite the associations of both preoperative sarcopenia and physical performance with post-operative mortality in non-small-cell lung cancer (NSCLC), there have been no comprehensive studies of the impact of physical status on prognosis. This study was performed to investigate the prognostic significance of preoperative sarcopenia and physical performance in NSCLC. Methods: This retrospective cohort study was performed in NSCLS patients undergoing curative lung resection at a university hospital between January 2014 and December 2017. The patients were divided into four groups according to the skeletal muscle index [sarcopenia (lowest sex-specific tertile) and non-sarcopenia] and 6 min walking distance (6MWD) [short distance (<400 m) and long distance (≥400 m)]. Sarcopenia was assessed by preoperative cross-sectional areas of right and left paraspinous muscles at the level of the 12th thoracic vertebra from computed tomography images, and physical performance was determined by preoperative 6MWD. The primary and secondary endpoints were post-operative overall survival (OS) and disease-free survival (DFS). Results: The 587 patients [mean age: 68.5 ± 8.8 years, 399 men (68%)] included in the study were divided into the non-sarcopenia/long-distance group (58%), sarcopenia/long-distance group (26%), non-sarcopenia/short-distance group (9%), and sarcopenia/short-distance group (7%). A total of 109 (18.6%) deaths and 209 (35.6%) combined endpoints were observed over a mean follow-up of 3.1 ± 1.3 years. After adjusting for other covariates, the sarcopenia/short-distance group showed significant associations with shorter OS (hazard ratio, 3.38; 95% confidence interval, 1.79–6.37; P < 0.001) and DFS (hazard ratio, 2.11; 95% confidence, 1.27–3.51; P = 0.004) compared with the non-sarcopenia/long-distance group on multivariate analyses. Although not significant, adding skeletal muscle index and 6MWD to the pre-existing risk model increased the area under the curve on time-dependent receiver operating characteristic curve analysis for OS and DFS, except within 2 years of surgery. Conclusions: The presence of both preoperative paraspinous muscle sarcopenia and short distance in 6MWD had an adverse effect on post-operative prognosis in patients with NSCLC, suggesting that preoperative assessment of thoracic sarcopenia and physical performance may be useful for risk stratification of surgical candidates with potential for targeted interventions.

    DOI: 10.1002/jcsm.12691

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  40. Native lung complications after living-donor lobar lung transplantation

    Mineura K., Chen-Yoshikawa T.F., Tanaka S., Yamada Y., Yutaka Y., Nakajima D., Ohsumi A., Hamaji M., Menju T., Date H.

    Journal of Heart and Lung Transplantation   Vol. 40 ( 5 ) page: 343 - 350   2021.5

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    Background: Living-donor lobar lung transplantation (LDLLT) is viable for critically ill patients in situations of donor shortage. Because it is sometimes difficult to find 2 ideal living donors with suitable graft sizes, we developed native lung-sparing procedures, including single LDLLT and native upper lobe-sparing LDLLT. This study aimed to investigate native lung complications (NLCs) in native lung-sparing LDLLT. Methods: Between April 2002 and March 2019, 92 LDLLTs and 124 cadaveric lung transplantations (CLTs) were performed at the Kyoto University Hospital. Our prospectively maintained database and clinical records were reviewed to compare NLCs among recipients who underwent native lung-sparing LDLLT (n = 21) with those among recipients who underwent single CLT (n = 61). Results: Among 21 recipients who underwent native lung-sparing LDLLT, 11 NLCs occurred in 8 recipients. No fatal NLC was noted; however, 2 required surgical intervention. Post-transplant survival was not significantly different between native lung-sparing LDLLT recipients with NLCs and those without NLCs. The incidence of NLCs was comparable between native lung-sparing LDLLT recipients and single CLT recipients (8/21 vs 26/61, p = 0.80); however, NLCs occurred significantly later in LDLLT recipients than in CLT recipients (median: 665 vs 181.5 days after transplantation, p = 0.014). Conclusions: NLCs after native lung-sparing LDLLT had favorable outcomes. Therefore, native lung-sparing LDLLT is a useful treatment option for severely ill patients who cannot wait for CLT. However, it is important to recognize that NLCs may occur later in LDLLT than in CLT.

    DOI: 10.1016/j.healun.2021.01.1562

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  41. Postoperative outcomes of lung transplant recipients with preformed donor-specific antibodies

    Kayawake H., Chen-Yoshikawa T.F., Gochi F., Tanaka S., Yurugi K., Hishida R., Yutaka Y., Yamada Y., Ohsumi A., Hamaji M., Nakajima D., Date H.

    Interactive cardiovascular and thoracic surgery   Vol. 32 ( 4 ) page: 616 - 624   2021.4

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    OBJECTIVES: Few studies have evaluated the outcomes of lung transplantation (LTx) in recipients with preformed donor-specific antibodies (DSAs). This study investigated the postoperative changes in preformed DSAs based on prospectively collected data of DSAs, and the influences of preformed DSAs on postoperative outcomes among LTx recipients. METHODS: Between July 2010 and December 2019, 216 recipients underwent LTx (81 living-donor lobar lung transplants and 135 deceased-donor lung transplants). We reviewed 8 cases with preformed DSAs to determine postoperative changes in DSAs and compared postoperative outcomes between recipients with and without DSAs. RESULTS: The preoperative mean fluorescence intensity of preformed DSAs ranged from 1141 to 14 695. Two recipients experienced antibody-mediated rejection within 2 weeks after LTx. DSAs disappeared in 7 recipients; however, 1 recipient experienced the relapse of DSAs and died from chronic lung allograft syndrome (CLAD), whereas 1 recipient had persisting DSAs within the study period and died from CLAD. Neither overall survival (OS) nor CLAD-free survival was significantly different between recipients with and without DSAs (P = 0.26 and P = 0.17, respectively). However, both OS and CLAD-free survival were significantly lower in recipients with DSAs against HLA class II than in those without these antibodies {5-year OS: 25.0% [95% confidence interval (CI): 0.9-66.5%] vs 72.1% (95% CI: 63.8-78.9%), P = 0.030 and 5-year CLAD-free survival: 26.7% (95% CI: 1.0-68.6%) vs 73.7% (95% CI: 66.5-79.5%), P = 0.002}. CONCLUSIONS: Prognosis in recipients experiencing the relapse of preformed DSAs and those with persisting DSAs may be poor. The recipients with anti-HLA class II preformed DSAs had a significantly worse prognosis.

    DOI: 10.1093/icvts/ivaa311

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  42. Left brachiocephalic vein aneurysm: a case report

    Ueno Harushi, Yazawa Mari, Tsubouchi Hideki, Nakanishi Keita, Sugiyama Tomoshi, Kadomatsu Yuka, Goto Masaki, Ozeki Naoki, Nakamura Shota, Fukui Takayuki, Mutsuga Masato, Yoshikawa Toyofumi Fengshi Chen

    SURGICAL CASE REPORTS   Vol. 7 ( 1 )   2021.3

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  43. Factors associated with changes in the 12-m stair-climbing time after lung lobectomy

    Ozeki N.

    General Thoracic and Cardiovascular Surgery   Vol. 69 ( 2 ) page: 282 - 289   2021.2

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    DOI: 10.1007/s11748-020-01458-4

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  44. Thymic lipofibroadenoma accompanied with largish calcifications

    Hakiri S.

    General Thoracic and Cardiovascular Surgery   Vol. 69 ( 2 ) page: 394 - 397   2021.2

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    DOI: 10.1007/s11748-020-01475-3

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  45. Protective Effects of a Hydrogen-Rich Preservation Solution in a Canine Lung Transplantation Model

    Kayawake H., Chen-Yoshikawa T.F., Saito M., Yamagishi H., Yoshizawa A., Hirano S.i., Kurokawa R., Date H.

    Annals of Thoracic Surgery   Vol. 111 ( 1 ) page: 246 - 252   2021.1

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    Background: Molecular hydrogen (H2) has protective effects against ischemia-reperfusion injury in various organs. Because they are easier to transport and safer to use than inhaled H2, H2-rich solutions are suitable for organ preservation. In this study, we examined the protective effects of an H2-rich solution for lung preservation in a canine left lung transplantation (LTx) model. Methods: Ten beagles underwent orthotopic left LTx after 23 hours of cold ischemia followed by reperfusion for 4 hours. Forty-five minutes after reperfusion, the right main pulmonary artery was clamped to evaluate the function of the implanted graft. The beagles were divided into two groups: control group (n = 5), and H2 group (n = 5). In the control group, the donor lungs were flushed and immersed during cold preservation at 4°C using ET-Kyoto solution, and in the H2 group, these were flushed and immersed using H2-rich ET-Kyoto solution. Physiologic assessments were performed during reperfusion. After reperfusion, the wet-to-dry ratios were determined, and histology examinations were performed. Results: Significantly higher partial pressure of arterial oxygen and significantly lower partial pressure of carbon dioxide were observed in the H2 group than in the control group (P =.045 and P <.001, respectively). The wet-to-dry ratio was significantly lower in the H2 group than in the control group (P =.032). Moreover, in histology examination, less lung injury and fewer apoptotic cells were observed in the H2 group (P <.001 and P <.001, respectively). Conclusions: Our results demonstrated that the H2-rich preservation solution attenuated ischemia-reperfusion injury in a canine left LTx model.

    DOI: 10.1016/j.athoracsur.2020.05.076

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  46. Kernel-based framework to estimate deformations of pneumothorax lung using anatomical landmarks

    Yamamoto Utako, Nakao Megumi, Ohzeki Masayuki, Tokuno Junko, Yoshikawa Toyofumi, Matsuda Tetsuya

    Transactions of Japanese Society for Medical and Biological Engineering   Vol. Annual59 ( Abstract ) page: 515 - 515   2021

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    <p>In video-assisted thoracoscopic surgeries, the precise estimation of lung deformation between the inflated lung in the computed tomography (CT) images during preoperative planning and the deflated lung in the treatment views during surgery is expected. The purpose of this study is to develop a deformation estimation method of the 3D surface of a deflated lung from a few partial observations. To estimate deformations for a largely deformed lung, a kernel regression-based solution was introduced. The proposed method used a few landmarks to capture the partial deformation between the 3D surface mesh obtained from preoperative CT and the intraoperative anatomical positions. The method was applied on nine datasets of the left lungs of live Beagle dogs. Contrast-enhanced CT images of the lungs were acquired. The proposed method achieved a local positional error of vertices of 2.74 mm, Hausdorff distance of 6.11 mm, and Dice similarity coefficient of 0.94. </p>

    DOI: 10.11239/jsmbe.annual59.515

    CiNii Research

  47. Rituximab for antibody-mediated rejection after lung transplantation

    CHEN-YOSHIKAWA Toyofumi F., DATE Hiroshi, SUGIMOTO Seiichiro, SHIRAISHI Takeshi, NAKAGAWA Ken, EGAWA Hiroto

    Japanese Journal of Transplantation   Vol. 56 ( 1 ) page: 53 - 68   2021

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    <p>【<b>Objective</b>】 We retrospectively surveyed the details of treatment with rituximab for antibody-mediated rejection (AMR) after lung transplantation.</p><p>【<b>Design</b>】 Case series.</p><p>【<b>Methods</b>】 This study was conducted to assess outcomes in patients who underwent lung transplantation in Japan from August 2001 to December 2016 and were treated with rituximab for AMR. A questionnaire was sent to medical institutions that had used rituximab for such treatment, and information on AMR treatment, including rituximab dosage, efficacy, and safety, was collected.</p><p>【<b>Results</b>】 Among the 525 patients undergoing lung transplantation during the study period in Japan, fourteen patients (2.7%; 1 child and 13 adults) were enrolled. Records showed definite clinical AMR in 3 patients, probable clinical AMR in 2 patients, possible clinical AMR in 8 patients and suspected AMR in 1 patient. All patients had allograft dysfunction, and 13 adult patients were positive for donor-specific antibodies (DSA). Two patients experienced rejection more than twice. Rituximab was administered to all patients. In one patient who experienced AMR twice, rituximab was administered for each AMR. The rituximab dose was 375 mg/m<sup>2</sup> in all but one patient, who received 348 mg/m<sup>2</sup>. Eight patients recovered from AMR. AMR treatments, including rituximab, were well tolerated. However, 11 patients developed graft loss due to rejection, and 10 patients died from chronic lung allograft syndrome or sepsis.</p><p>【<b>Conclusion</b>】 Based on these findings, treatment containing rituximab was considered effective for AMR, but careful monitoring is needed to prevent or reduce the number of adverse events such as infection.</p>

    DOI: 10.11386/jst.56.1_53

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  48. Commentary: Change the temperature before we have to

    Kadomatsu Y., Chen-Yoshikawa T.F.

    Journal of Thoracic and Cardiovascular Surgery     2021

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    DOI: 10.1016/j.jtcvs.2021.01.083

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  49. Kernel-based modeling of pneumothorax deformation using intraoperative cone-beam CT images

    Nakao M., Maekawa H., Mineura K., Chen-Yoshikawa T.F., Matsuda T.

    Progress in Biomedical Optics and Imaging - Proceedings of SPIE   Vol. 11598   2021

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    In this study, we introduce statistical modeling methods for pneumothorax deformation using paired cone-beam computed tomography (CT) images. We designed a deformable mesh registration framework for shape changes involving non-linear deformation and rotation of the lungs. The registered meshes with local correspondences are available for both surgical guidance in thoracoscopic surgery and building statistical deformation models with inter-patient variations. In addition, a kernel-based deformation learning framework is proposed to reconstruct intraoperative dfl ated states of the lung from the preoperative CT models. This paper reports the findings of pneumothorax deformation and evaluation results of the kernel-based deformation framework.

    DOI: 10.1117/12.2581388

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  50. Erector spinae muscle radiographic density is associated with survival after lung transplantation

    Oshima Y., Sato S., Chen-Yoshikawa T.F., Nakajima D., Nankaku M., Date H., Matsuda S.

    Journal of Thoracic and Cardiovascular Surgery     2021

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    Objective: The study objective was to verify whether low preoperative radiographic density of erector spinae muscles is associated with poor prognosis after lung transplantation. Methods: Preoperative chest computed tomography scans for patients who underwent deceased-donor lung transplantation between 2013 and 2019 at Kyoto University Hospital were retrospectively retrieved. The radiographic density of erector spinae muscles was quantitatively evaluated as the mean attenuation of erector spinae muscles, and low mean radiographic density of the erector spinae muscles was defined as a mean radiographic density of the erector spinae muscles value below the median value for all patients. Overall survival and chronic lung allograft dysfunction-free survival with high and low mean radiographic density of the erector spinae muscles were estimated using the Kaplan–Meier method and evaluated by the log-rank test, as well as by univariate and multivariate Cox proportional hazard analyses. Results: Of the 107 adult patients who underwent primary transplantation, 96 underwent at least 1 chest computed tomography scan within 24 hours before lung transplantation. The median mean radiographic density of the erector spinae muscles in these 96 patients was 49.2 Hounsfield units. A low mean radiographic density of the erector spinae muscles value was significantly associated with decreased overall survival (hazard ratio, 4.50; P =.030) and chronic lung allograft dysfunction–free survival (hazard ratio, 3.18; P =.028) in the multivariate analysis. Additionally, patients with preoperative steroid use and a low mean radiographic density of the erector spinae muscles value had a worse overall survival (P <.001) and chronic lung allograft dysfunction–free survival (P <.001) than patients with preoperative steroid use and a high mean radiographic density of the erector spinae muscles value and those without preoperative steroid use. Conclusions: Low mean radiographic density of the erector spinae muscles was closely associated with a poor prognosis after lung transplantation. The prognosis was particularly poor in patients with preoperative steroid use and a low mean radiographic density of the erector spinae muscles. These results may be useful when considering the indications for lung transplantation or preoperative interventions. Video Abstract:[Figure presented]

    DOI: 10.1016/j.jtcvs.2021.07.039

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  51. Electromagnetic navigation bronchoscopy versus virtual bronchoscopy navigation for improving the diagnosis of peripheral lung lesions: analysis of the predictors of successful diagnosis

    Yutaka Y., Sato T., Isowa M., Murata Y., Tanaka S., Yamada Y., Ohsumi A., Nakajima D., Hamaji M., Menju T., Chen-Yoshikawa T.F., Date H.

    Surgery Today     2021

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    Purpose: To investigate if electromagnetic navigation bronchoscopy (ENB) improves the diagnostic yield for peripheral lung lesions from that achieved by virtual bronchoscopy navigation (VBN). Methods: This retrospective study compared the results of 100 ENB-transbronchial lung biopsies (TBLBs) with those of 50 VBN-TBLBs at a single institution. Results: ENB improved the diagnostic yield significantly compared with VBN (64.0% for 19.4 ± 9.0 mm tumors vs. 46.0% for 27.6 ± 8.9 mm tumors; p < 0.0001). Irrespective of the bronchus sign, ENB was more favorable than VBN, with 81.0% (47/58) achieved by ENB vs. 60.0% (21/35) achieved by VBN in the presence of the positive bronchus sign (p = 0.0283), and 40.5% (17/42) achieved by ENB vs. 13.3% (2/15) achieved by VBN in the absence of the bronchus sign (p = 0.0431). Univariate analysis identified tumor size (p = 0.0048), amount of intravenous sedation (p = 0.0182), registration time (p = 0.0111), minimum distance to target (p = 0.0244), and the bronchus sign (p < 0.0001) as factors that affected the yield significantly for ENB. Multivariate analysis identified the bronchus sign (odds ratio 6.74; 95% CI 1.84–24.7) and the registration time (OR 1.01; 95% CI 1.00–1.02) as significant factors. Conclusions: Despite the bronchus sign being a significant factor, ENB improved the diagnostic yield of smaller lesions significantly, compared with VBN, regardless of the bronchus sign.

    DOI: 10.1007/s00595-021-02398-z

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  52. Commentary: To know yourself is to know your neighbor

    Nakanishi K., Chen-Yoshikawa T.F.

    Journal of Thoracic and Cardiovascular Surgery     2021

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    DOI: 10.1016/j.jtcvs.2021.01.030

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  53. Commentary: Look Before You Leap

    Fukumoto K., Chen-Yoshikawa T.F.

    Seminars in Thoracic and Cardiovascular Surgery     2021

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    DOI: 10.1053/j.semtcvs.2021.06.018

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  54. Learning curve of robotic lobectomy for lung malignancies by certified thoracic surgeons

    Fukui T., Kawaguchi K., Tsubouchi H., Ueno H., Sugiyama T., Mori S., Goto M., Ozeki N., Hakiri S., Nakamura S., Chen-Yoshikawa T.F.

    Nagoya Journal of Medical Science   Vol. 83 ( 2 ) page: 227 - 237   2021

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    Video-assisted thoracic surgery (VATS) has become widespread in the last 20 years, followed by robot-assisted thoracic surgery (RATS). Few studies compared the learning curve between RATS lobectomy and conventional VATS. This study included 79 RATS lobectomy cases performed in our hospital from November 2015 to October 2019. To estimate the required number for learning, the cumulative sum method, which is to plot a value obtained by sequentially accumulating a difference from a mean value was applied. As a result, the median total operative time and the median console time for all cases were 167 minutes and 138 minutes, respectively. Firstly, for our team, 28 cases were estimated to be required for learning curve for RATS lobectomy. For individual, each surgeon might be learned in only 5 to 6 cases. By contrast, the number of cases for learning VATS lobectomy which was underwent by a ‘single' surgeon from 2009 was estimated to be 35 cases. The time to dock from start operation (median 14 minutes) reached plateau in 18 cases, but the time after rollout was median of 18 minutes and there was no significant change from the beginning. In conclusion, RATS lobectomy might be a technique that could be learned in a small number of cases compared to VATS. The results of this study might be helpful for certified surgeons who tried to get started with RATS and for establishing a learning program.

    DOI: 10.18999/nagjms.83.2.227

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  55. Prognostic Value of Uncertain Resection for Overall Survival in Non-small Cell Lung Cancer

    Kadomatsu Y., Nakamura S., Ueno H., Goto M., Ozeki N., Fukumoto K., Fukui T., Suzuki Y., Chen-Yoshikawa T.F.

    Annals of Thoracic Surgery     2021

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    Background: In this study we evaluated the R(un) category proposed by the International Association for the Study of Lung Cancer (IASLC) for non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed the medical records of patients with NSCLC who underwent segmentectomy or lobectomy between 2014 and 2015 at our institution. Residual tumor (R) status was reclassified from the Union for International Cancer Control designation to the IASLC-proposed R classification of R0 and R(un). The underlying reasons for the R(un) reclassification were analyzed according to pathologic stage, lymph node status, and resected lobe. A Cox proportional hazard model was used to evaluate the impacts of R(un) categorization on overall survival. Results: Of 355 patients, 44.5% were reclassified as R(un). The most common reason for the reclassification was insufficient number of harvested lymph nodes or no station 7 lymph nodes. When stratified by tumor location, the absence of station 7 lymph nodes was especially prominent in both the right and left upper lung resections. In the multivariate Cox regression model, the IASLC R classification was associated with poor overall survival in node-positive patients (hazard ratio, 2.657; P =.016). Conclusions: Various factors resulted in reclassification to R(un) because the R(un) group was highly heterogeneous. Careful consideration is required to determine whether the R(un) classification can be used as an indicator of lymph node dissection quality. For advanced cases, the R(un) definition may be useful in predicting poor prognosis.

    DOI: 10.1016/j.athoracsur.2021.07.087

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  56. Development of an immuno-wall device for the rapid and sensitive detection of EGFR mutations in tumor tissues resected from lung cancer patients

    Yogo N.

    PLoS ONE   Vol. 15 ( 11 November )   2020.11

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    DOI: 10.1371/journal.pone.0241422

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  57. Impact of inspiratory muscle strength on exercise capacity after lung transplantation.-a longitudinal study in early stage

    Sato Tatsuya, Tabira Kazuyuki, Sato Susumu, Oshima Yohei, Yoshioka Yuji, Hamada Ryota, Tanimura Kazuya, Yoshikawa Toyofumi, Date Hiroshi, Matsuda Shuichi

    EUROPEAN RESPIRATORY JOURNAL   Vol. 56   2020.9

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  58. Orthotopic foetal lung tissue direct injection into lung showed a preventive effect against paraquat-induced acute lung injury in mice

    Okabe R.

    European Journal of Cardio-thoracic Surgery   Vol. 58 ( 3 ) page: 638 - 645   2020.9

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    DOI: 10.1093/ejcts/ezaa091

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  59. A case of right upper lobectomy for lung cancer with partial anomalous pulmonary venous connection and tracheal bronchus

    Ito Toshinari, Fukui Takayuki, Hakiri Shuhei, Nakamura Shota, Kawaguchi Koji, Chen-Yoshikawa Toyofumi

    The Journal of the Japanese Association for Chest Surgery   Vol. 34 ( 5 ) page: 321 - 326   2020.7

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    <p>A 76-year-old man presented with an abnormal shadow on a chest roentgenogram. After a comprehensive radiographic examination and transbronchial lung biopsy, the preoperative diagnosis was lung adenocarcinoma Stage IA2 (cT1bN0M0).</p><p>Chest computed tomography showed a partial anomalous pulmonary venous connection from the right upper and middle lobe and a right B1 bronchus branching from the trachea simultaneously. We attempted to perform complete video-assisted thoracic surgery (VATS) for right upper lobectomy. However, we required a small window incision to complete VATS lobectomy to improve our understanding of the intraoperative anatomy. In cases with uncommon anomalies such as the present patient, enlargement of the port incision to improve intraoperative understanding of the anatomy is important to perform a safe and minimally invasive procedure.</p>

    DOI: 10.2995/jacsurg.34.321

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  60. Tranilast inhibits TGF-β1-induced epithelial-mesenchymal transition and invasion/metastasis via the suppression of Smad4 in human lung cancer cell lines

    Takahashi K

    Anticancer Research   Vol. 40 ( 6 ) page: 3287-3296 - 3296   2020.6

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    Background/Aim: Transforming growth factor β1 (TGF-β1) is an important epithelial-mesenchymal transition (EMT) activator that regulates the expression of E-cadherin and vimentin through Smad signalling. Tranilast is an antiallergic drug that inhibits TGF-β1, and is used in the treatment of keloids and hypertrophic scars. We investigated whether tranilast inhibits TGF-β1-induced EMT and invasiveness in human non-small cell lung cancer cell lines. Materials and Methods: We examined the effects of tranilast treatment on EMT markers, TGF-β1/Smad signalling, and cell invasiveness in A549 and PC14 cells. Tumours from a mouse orthotopic lung cancer model with or without tranilast treatment were also immunohistochemically evaluated. Results: Tranilast increased E-cadherin expression via Smad4 suppression and inhibited cell invasion in TGF-β1-stimulated cells. Tranilast treatment of the in vivo mouse model reduced the pleural dissemination of cancer cells and suppressed vimentin and Smad4 expression. Conclusion: Tranilast inhibited TGF-β1- induced EMT and cellular invasion/metastasis by suppressing Smad4 expression in cancer cells.

    DOI: 10.2196/10.21873/anticanres.14311

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  61. Psoas muscle mass in patients undergoing lung cancer surgery: a prognostic difference between squamous cell carcinoma and adenocarcinoma

    Ozeki N

    International Journal of Clinical Oncology   Vol. 25 ( 5 ) page: 876-884 - 884   2020.5

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    DOI: 10.1007/s10147-020-01624-x

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  62. Current trends in thoracic surgery

    Chen-Yoshikawa T.F

    Nagoya Journal of Medical Science   Vol. 82 ( 2 ) page: 161-173 - 173   2020.5

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    DOI: 10.18999/nagjms.82.2.161

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  63. Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin International journal

    Nishinaga Y

    Cells   Vol. 9 ( 4 )   2020.4

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    Malignant pleural mesothelioma (MPM) has extremely limited treatment despite a poor prognosis. Moreover, molecular targeted therapy for MPM has not yet been implemented; thus, a new targeted therapy is highly desirable. Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer therapy that combines the specificity of antibodies for targeting tumors with toxicity induced by the photoabsorber after exposure to NIR-light. In this study, we developed a new phototherapy targeting podoplanin (PDPN) for MPM with the use of both NIR-PIT and an anti-PDPN antibody, NZ-1. An antibody-photosensitizer conjugate consisting of NZ-1 and phthalocyanine dye was synthesized. In vitro NIR-PIT-induced cytotoxicity was measured with both dead cell staining and luciferase activity on various MPM cell lines. In vivo NIR-PIT was examined in both the flank tumor and orthotopic mouse model with in vivo real-time imaging. In vitro NIR-PIT-induced cytotoxicity was NIR-light dose dependent. In vivo NIR-PIT led to significant reduction in both tumor volume and luciferase activity in a flank model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). The PDPN-targeted NIR-PIT resulted in a significant antitumor effect in an MPM orthotopic mouse model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). This study suggests that PDPN-targeted NIR-PIT could be a new promising treatment for MPM.

    DOI: 10.3390/cells9041019

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  64. Deformation Estimation of Deflated Lung using Kernel Method based on the Relative Position of Some Landmarks

    Yamamoto Utako, Nakao Megumi, Ohzeki Masayuki, Tokuno Junko, Yoshikawa Toyofumi, Matsuda Tetsuya

    Transactions of the Institute of Systems, Control and Information Engineers   Vol. 33 ( 4 ) page: 123 - 127   2020.4

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    <p>It is expected to grasp how the lung deform by the deaeration during surgery compared to the inflated lung. In this study we propose a method to estimate deformation of the deflated lung from the inflated one based on the relative position of some landmarks using dog lungs. The kernel method was employed for the estimation as a machine learning technique. We achieved mean local positional error of 2.96 mm for test data where the volume reduction by the deaeration was 40 %.</p>

    DOI: 10.5687/iscie.33.123

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  65. Protective Effects of Necrosulfonamide on Ischemia-Reperfusion Injury in Rat Lung

    Ueda S

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 39 ( 4 )   2020.4

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    DOI: 10.1016/j.healun.2020.01.414

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  66. Analysis of the Change in Sleep Quality in Lung Transplant Recipients

    Tokuno J

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 39 ( 4 )   2020.4

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    DOI: 10.1016/j.healun.2020.01.515

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  67. CD26/DPP4 Inhibitor: A Novel Prophylactic Drug for Chronic Allograft Dysfunction after Clinical Lung Transplantation

    Yamada Y

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 39 ( 4 )   2020.4

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    DOI: 10.1016/j.healun.2020.01.1269

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  68. Comparison of Characteristics of De Novo Donor-Specific Anti-HLA Antibodies (dnDSAs) in Living-Donor Lobar Lung Transplantation and Deceased-Donor Lung Transplantation

    Kayawake H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 39 ( 4 ) page: S307-S308   2020.4

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    DOI: 10.1016/j.healun.2020.01.690

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  69. Extrapulmonary Problems Limit the Outcome of Lung Transplantation in Idiopathic Pleuroparenchymal Fibroelastosis: A Multi-Center Study in Japan

    Shiiya H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 39 ( 4 ) page: S313-S314 - S314   2020.4

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    Copyright © 2020. Published by Elsevier Inc. PURPOSE: Idiopathic pleurparenchymal fibroelastosis (IPPFE) is a relatively new disease entity of interstitial pneumonia characterized by upper lobe dominant fibrosis and flat chest. The purpose of this study is to evaluate the outcome of lung transplantation for IPPFE in comparison with idiopathic pulmonary fibrosis (IPF). METHODS: We retrospectively reviewed patients with IPPFE and those with IPF aged 20 or over who underwent lung transplantation between 1998 and 2018. Data were collected from all nine lung transplant centers in Japan, under the support of Japanese Society of Lung and Heart-Lung Transplantation. RESULTS: One hundred patients were eligible, including 31 IPPFE and 69 IPF patients. Patients with IPPFE were more likely to be women (58% vs 28%; P < 0.01) and to have a significantly lower body mass index (BMI) (17.6±3.6 vs 22.6±4.2 kg/m2; P < 0.01) than those in the IPF group. Kaplan-Meier survival curves showed no significant difference in overall survival between groups (P = 0.66; Figure 1A). The stay in the intensive care unit (ICU) was significantly longer in the IPPFE group (22.8±19.15 vs 13.2±11.2 days; P < 0.01). In the IPPFE group, BMI did not improve even 1 year after transplant (pre-; 16.5±3.2 kg/m2 vs 2 years later; 15.6±2.5 kg/m2; P = 0.08). By two years after transplantation, percent predicted forced vital capacity in IPPFE group significantly improved (pre-; 36.9±17.2 vs 2 years later; 52.0±20.0 %; P = 0.03; Figure 1B). However, compared with the IPF group, the value was still significantly lower (52.0±20.0 vs 70.8±18.7 %; P < 0.01). CONCLUSION: The survival of patients with IPPFE after lung transplantation was comparable with those with IPF. However, patients with IPPFE showed longer ICU stay, limited improvement in pulmonary function, and no improvement in low BMI, suggesting systemic or extrapulmonary problems such as stiff chest wall in patients with IPPFE.

    DOI: 10.1016/j.healun.2020.01.706

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  70. Prognostic factors related to postoperative survival in the newly classified clinical T4 lung cancer. Reviewed International journal

    Keiji Yamanashi, Toshi Menju, Masatsugu Hamaji, Satona Tanaka, Yojiro Yutaka, Yoshito Yamada, Daisuke Nakajima, Akihiro Ohsumi, Akihiro Aoyama, Toshihiko Sato, Toyofumi Fengshi Chen-Yoshikawa, Makoto Sonobe, Hiroshi Date

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 57 ( 4 ) page: 754 - 761   2020.4

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    OBJECTIVES: T4 lung cancer has become a more heterogeneous group since the 8th edition of tumour, node, metastasis classification. The aim of this study was to identify predictive factors related to post-surgical survival in patients with clinical T4 non-small-cell lung cancer (NSCLC), based on the 8th edition of the classification. METHODS: We retrospectively reviewed consecutive patients with clinical T4 NSCLC who underwent resection between January 2006 and December 2016, to identify factors associated with overall survival. RESULTS: Ninety-three patients were identified. The criteria for clinical T4 disease included tumours larger than 7 cm (n = 54), great vessels or left atrial invasion (n = 22), mediastinal invasion (n = 11), vertebral invasion (n = 3), tracheal or carina invasion (n = 3), diaphragm invasion (n = 1) and ipsilateral different lobe pulmonary metastasis (n = 2). The postoperative nodal status was 0, 1, 2 and 3 in 59, 18, 15 and 1 patient, respectively. R0 resection was achieved in 80 patients, and the 30-day mortality was 0%. The median follow-up time was 37.6 months, and the 5-year overall survival rate was 56.3%. The multivariable analysis revealed that nodal status and R-status were significant prognostic factors for postoperative survival [hazard ratio (HR) 2.62, 95% confidence interval (CI) 1.20-5.72, P = 0.016 and HR 3.29, 95% CI 1.45-7.44, P = 0.004]. CONCLUSIONS: Surgery provided encouraging survival outcomes for clinical T4 NSCLC based on the 8th edition of classification. The nodal status and R-status were significant prognostic factors for postoperative survival.

    DOI: 10.1093/ejcts/ezz288

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  71. Commentary: Development of a new concept is achieved only step-by-step

    Chen-Yoshikawa T.F

    Journal of Thoracic and Cardiovascular Surgery   Vol. 159 ( 4 ) page: 1656-1657 - 1657   2020.4

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    DOI: 10.1016/j.jtcvs.2019.09.109

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  72. Characteristics of incomplete endobronchial ultrasound-guided transbronchial needle aspiration cases

    Kayawake H., Chen-Yoshikawa T.F., Takana S., Yamada Y., Yutaka Y., Nakajima D., Hamaji M., Menju T., Ohsumi A., Date H.

    Journal of Thoracic Disease   Vol. 12 ( 3 ) page: 573 - 580   2020.3

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    Backgrounds: The number of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) cases is increasing due to its less-invasiveness and usefulness. However, there are several unresolved issues, including the existence of incomplete cases and complications. This study aimed to investigate the frequency and diagnostic management of incomplete EBUS-TBNA cases. Methods: Between July 2009 and December 2017, 424 patients underwent EBUS-TBNA for the diagnosis of suspected malignancy. Among them, we retrospectively reviewed the frequency, characteristics and diagnostic managements of incomplete cases of EBUS-TBNA. Results: EBUS-TBNA was not completed in 16 patients (3.8%), all of whom underwent EBUS-TBNA cases under conscious sedation. The factors for incompleteness of EBUS-TBNA under conscious sedation were divided into two groups: impossibility to perform EBUS-TBNA under conscious sedation (n=8) and impossibility to perform safe needle biopsy (n=8). The former factor consisted of strong coughing reflex and insufficient sedation (n=5), frequent desaturation during EBUS-TBNA (n=2), and allergy to lidocaine (n=1), while the latter factor consisted of anatomical reasons (n=4), abundant blood flow in the target lesion (n=3), and invisibility of the target lesion due to airway deformation (n=1). Eventually, 10 out of 16 cases were histologically diagnosed as having malignancy by a surgical approach (n=5) and EBUS-TBNA under general anesthesia (n=5). Conclusions: Although the number was small, we did note some incomplete cases of EBUS-TBNA under conscious sedation. In incomplete cases under conscious sedation, EBUS-TBNA under general anesthesia and other surgical approaches can be considered as additional options.

    DOI: 10.21037/jtd.2019.12.133

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  73. Near infrared photoimmunotherapy targeting DLL3 for small cell lung cancer

    Isobe Y

    EBioMedicine   Vol. 52   2020.2

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    © 2020 The Authors Background: Small cell lung cancer (SCLC) has a poor prognosis, and its treatment options are limited. Delta-like protein 3 (DLL3) is expressed specifically in SCLC and is considered a promising therapeutic target for patients with this disease. Rovalpituzumab tesirine (Rova-T) was the first antibody-drug conjugate targeting DLL3. Although Rova-T development was unfortunately terminated, DLL3 remains an ideal target for SCLC. Near infrared photoimmunotherapy (NIR-PIT) is a new form of cancer treatment that employs an antibody-photosensitiser conjugate followed by NIR light exposure and damage target cells specifically. In this study, we demonstrate DLL3-targeted NIR-PIT to develop a novel molecularly targeted treatment for SCLC. Methods: The anti-DLL3 monoclonal antibody rovalpituzumab was conjugated to an IR700 photosensitiser (termed ‘rova-IR700’). SCLC cells overexpressing DLL3 as well as non-DLL3-expressing controls were incubated with rova-IR700 and then exposed to NIR-light. Next, mice with SCLC xenografts were injected with rova-IR700 and irradiated with NIR-light. Findings: DLL3-overexpressing cells underwent immediate destruction upon NIR-light exposure, whereas the control cells remained intact. The xenograft in mice treated with rova-IR700 and NIR-light shrank markedly, whereas neither rova-IR700 injection nor NIR-light irradiation alone affected tumour size. Interpretation: Our data suggest that targeting of DLL3 using NIR-PIT could be a novel and promising treatment for SCLC. Funding: Research supported by grants from the Program for Developing Next-generation Researchers (Japan Science and Technology Agency), KAKEN (18K15923, JSPS), Medical Research Encouragement Prize of The Japan Medical Association, The Nitto Foundation, Kanae Foundation for the Promotion of Medical Science.

    DOI: 10.1016/j.ebiom.2020.102632

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  74. Outcomes of combination therapy including rituximab for antibody-mediated rejection after lung transplantation. Reviewed

    Keiji Yamanashi, Toyofumi Fengshi Chen-Yoshikawa, Masatsugu Hamaji, Kimiko Yurugi, Satona Tanaka, Yojiro Yutaka, Yoshito Yamada, Daisuke Nakajima, Akihiro Ohsumi, Hiroshi Date

    General thoracic and cardiovascular surgery   Vol. 68 ( 2 ) page: 142 - 149   2020.2

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    OBJECTIVES: This study assessed the outcomes of combination therapy including rituximab for antibody-mediated rejection after lung transplantation. METHODS: Retrospective chart reviews were performed for all patients who received combination therapy including rituximab for post-lung transplantation antibody-mediated rejection between June 2008 and October 2018. RESULTS: Among the 196 consecutive patients undergoing lung transplantation during the study period, eight (4.1%) were eligible for this study. Two patients (25.0%) were classified as having clinically definite antibody-mediated rejection and six (75.0%) as having possible antibody-mediated rejection. Prior to treatment, four patients (50.0%) met the definition of chronic lung allograft dysfunction; seven of the eight patients (87.5%) remained alive at 6 months and four (50.0%) at 12 months after antibody-mediated rejection. All patients identified as having chronic lung allograft dysfunction, prior to the treatment, died of allograft failure, or underwent re-transplantation. Decreases in the mean fluorescence intensities of the major donor-specific antibodies were observed in three patients. One patient, diagnosed with clinical antibody-mediated rejection but without pre-treatment chronic lung allograft dysfunction, began treatment relatively soon after lung transplantation, and demonstrated improved respiratory function at the 3-year follow-up. CONCLUSIONS: Our experience suggests that multimodality therapy that includes rituximab is feasible and may prevent progression of antibody-mediated rejection after lung transplantation in selected patients.

    DOI: 10.1007/s11748-019-01189-1

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  75. A preliminary study on deformation analysis of collapsed lung using intraoperative CBCT images

    MAEKAWA Hinako, NAKAO Megumi, MINEURA Katsutaka, CHEN-YOSHIKAWA Toyofumi F, MATSUDA Tetsuya

      Vol. 119 ( 399 ) page: 31 - 36   2020.1

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  76. Variations and surgical management of pulmonary vein in living-donor lobectomy. Reviewed International journal

    Hidenao Kayawake, Toyofumi Fengshi Chen-Yoshikawa, Satona Tanaka, Yoshito Yamada, Yojiro Yutaka, Daisuke Nakajima, Akihiro Ohsumi, Masatsugu Hamaji, Hiroshi Date

    Interactive cardiovascular and thoracic surgery   Vol. 30 ( 1 ) page: 24 - 29   2020.1

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    OBJECTIVES: In a living-donor lobectomy, the donor undergoes a right or left lower lobectomy. The surgical procedures for living-donor lobectomy are sometimes influenced by the anatomical variations of the pulmonary vein (PV). The goal of this study was to analyse the PV variations in living donors and to review the influence of these variations on the surgical procedures used. METHODS: Between June 2008 and September 2018, 154 living donors underwent right or left lower lobectomy. The PV variations were analysed using 3-dimensional computed tomography (3D-CT), and the surgical management of these variations was reviewed. RESULTS: Among 154 donors, 21 PV variations that could influence the surgical procedure for a right lower lobectomy were found in 19 (12.3%) donors, whereas no such variations for a left lower lobectomy were found. Detected PV variations were dorsal branch of the right upper PV (n = 12), middle PV draining into the right lower PV (n = 6) and the superior segment branch of the right lower PV draining into the right upper PV (n = 3). Among 96 donors undergoing right lower lobectomy, 9 (9.4%) donors had PV variations that could influence the surgical procedure. In 2 donors, sparing of PV branches with multiple vascular clamps was required. Pulmonary venoplasty was not required in any donor, whereas pulmonary venoplasty in recipient surgery was required in 4 recipients. There were no complications related to the surgical procedures performed on the PV. CONCLUSIONS: Living-donor lobectomy was performed safely owing to the preoperative evaluation of PV on 3D-CT and the use of appropriate surgical approaches to PV.

    DOI: 10.1093/icvts/ivz238

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  77. Results of a nationwide survey in Japan on the status of antibody-mediated rejection treatment and the use of rituximab in that treatment

    NAKAGAWA Ken, SATOH Shigeru, EGAWA Hiroto, AKAMATSU Nobuhisa, ITO Taihei, UENO Takehisa, OKUMI Masayoshi, SAKAMOTO Seisuke, CHEN-YOSHIKAWA Toyofumi F, NAWATA Kan, FUKUSHIMA Norihide

    Japanese Journal of Transplantation   Vol. 55 ( 1 ) page: 51-59   2020

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    <p>We retrospectively surveyed the status of rituximab use in treatment for antibody-mediated rejection (AMR) in Japan between 2013 and 2016 for kidney transplantation and between 2001 and 2016 for transplantation of other organs, including the liver, pancreas, heart, lung, and intestine.</p><p>Two hundred twenty-seven institutions responded. AMR developed in 493 patients who underwent kidney transplantation; 288 of those patients were treated with rituximab. AMR developed in 81 patients for liver transplantation, 4 patients for pancreas transplantation, 16 patients for heart transplantation, 22 patients for lung transplantation, and 2 patients for small intestine transplantation; rituximab was used in 18, 4, 4, 14, and 1 of those patients, respectively.</p><p>We also report on treatment details and rituximab dosage.</p>

    DOI: 10.11386/jst.55.1_51

  78. Results of a nationwide survey in Japan on transplantation in patients with pre-formed anti-donor specific antibody against HLA antigen, and on the use of rituximab in this transplantation

    NAKAGAWA Ken, SATOH Shigeru, EGAWA Hiroto, AKAMATSU Nobuhisa, ITO Taihei, UENO Takehisa, OKUMI Masayoshi, SAKAMOTO Seisuke, CHEN-YOSHIKAWA Toyofumi F, NAWATA Kan, FUKUSHIMA Norihide

    Japanese Journal of Transplantation   Vol. 55 ( 1 ) page: 39-50   2020

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    <p>A retrospective survey was conducted to assess the status of organ transplantation in patients with pre-formed donor-specific anti-HLA antibodies and the implementation of desensitization with rituximab in Japan. We obtained the data from 227 institutions for procedures performed between 2013 and 2016 for kidney transplantation and between 2001 and 2016 for transplantation of other organs, including the liver, pancreas, heart, lung, and intestine.</p><p>Results showed pre-formed donor-specific antibodies (DSA) in recipients of 529 transplanted kidneys; rituximab was used in 462 of those transplantations. Rituximab was used in 48 of 135 liver transplantations in recipients with pre-formed DSA and in 1 of 1 small intestine transplantation involving pre-formed DSA. Such DSA was also reported in 5 heart transplants and 4 lung transplants. However, rituximab was not used for desensitization in any of those procedures.</p><p>We also report on detection and assay of anti-HLA antibodies and DSA, criteria for transplantation, dosage of rituximab, and concomitant immunosuppressive drugs used at the institutions.</p>

    DOI: 10.11386/jst.55.1_39

  79. Sleep quality and its association with health-related quality of life of patients on lung transplantation waitlist in Japan

    Tokuno J

    Sleep and Breathing   Vol. 25 ( 1 ) page: 219 - 225   2020

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    DOI: 10.1007/s11325-020-02092-3

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  80. Survival outcomes of resection for pulmonary malignancies including non-small cell lung cancer and pulmonary metastasis after esophagectomy for esophageal carcinoma

    Yamanashi K

    General Thoracic and Cardiovascular Surgery   Vol. 68 ( 10 ) page: 1179 - 1186   2020

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    OBJECTIVES: This study investigated survival outcomes of resection for pulmonary malignancies after esophagectomy for esophageal carcinoma, comparing non-small cell lung cancer and pulmonary metastases. METHODS: We retrospectively reviewed consecutive patients who underwent resection for pulmonary malignancies after esophagectomy for esophageal carcinoma between 2009 and 2018. The overall survival and relapse-free survival rate were assessed using Kaplan-Meier analysis. RESULTS: Eleven patients had non-small cell lung cancer and eight patients had pulmonary metastases from esophageal carcinoma. The 5-year overall survival rate was 92.9% in all patients with a median follow-up period of 50.4 (range: 9.1-130.2) months. While the 5-year overall survival rate was 100.0% in patients with non-small cell lung cancer, it was 85.7% in patients with pulmonary metastases from esophageal carcinoma. The 5-year relapse-free survival rate was 85.7% in patients with non-small cell lung cancer. CONCLUSIONS: Our data suggest that resection for pulmonary malignancies after esophagectomy for esophageal carcinoma is associated with favorable survival outcomes and should be considered in selected patients.

    DOI: 10.1007/s11748-020-01373-8

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  81. Prognostic factors of stage I thymic epithelial tumors

    Fukui T

    General Thoracic and Cardiovascular Surgery   Vol. 69 ( 1 ) page: 59 - 66   2020

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    Objective: According to the tumor-node-metastasis classification for thymic malignancies, the proportion of patients diagnosed with stage I is expected to increase significantly. However, whether those patients have homogenous clinicopathological features and survival has not been fully evaluated. Methods: We reviewed 153 consecutive patients with stage I thymic epithelial tumors (133 thymomas, 15 thymic carcinomas, and 5 neuroendocrine tumors) who underwent complete resection at our institution between 2001 and 2016 and evaluated the prognostic significance of their clinicopathological factors. Results: The stage I patients accounted for 78% of all thymic epithelial tumors. The 5-year overall survival and recurrence-free survival rates of the 153 patients were 94% and 80%, respectively. The patients with the histology of thymic carcinoma or neuroendocrine tumor and with a tumor larger than 5.0 cm showed significantly worse recurrence-free survival in multivariate analysis (p = 0.027 and 0.038, respectively). Only the tumor size was revealed as a significant prognostic factor for recurrence-free survival when limited in the 133 cases of thymoma (p = 0.048). Conclusions: Patients with large tumors showed significantly worse recurrence-free survival than those with small tumors both in stage I thymic epithelial tumors and thymomas.

    DOI: 10.1007/s11748-020-01427-x

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  82. Commentary: Infants Toddle Before They Ambulate. Where Are We Now?

    Okabe R

    Seminars in Thoracic and Cardiovascular Surgery   Vol. 33 ( 1 ) page: 274 - 275   2020

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    DOI: 10.1053/j.semtcvs.2020.06.004

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  83. Is left-side DaVinci™ procedure challenging? Initial experiences of a single institute.

    Toshihiko Sato, Akinori Iwasaki, Yojiro Yutaka, Yoshito Yamada, Daisuke Nakajima, Akihiro Ohsumi, Masatsugu Hamaji, Toshi Menju, Toyofumi Fengshi Chen-Yoshikawa, Hiroshi Date

    General thoracic and cardiovascular surgery   Vol. 68 ( 11 ) page: 1285 - 1289   2020

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    OBJECTIVE: Among the standard techniques for anatomical lung cancer resection, left upper lobectomy has been regarded as challenging by thoracic surgeons. Thus, this study aimed to examine whether laterality of robot-assisted thoracoscopic procedures has any influence on the incidence of conversion to thoracotomy, operation time, amount of bleeding, and postoperative complications in the introduction phase of this procedure. METHODS: The first consecutive 65 patients (right upper/middle/lower lobe with 31/3/15 cases, left upper/lower lobe with 10/6 cases) who underwent robot-assisted thoracoscopic lobectomy from December 2011 to April 2019 in Kyoto University were retrospectively reviewed. RESULTS: Five cases were converted to open thoracotomy, including four for the left upper lobectomy and one for the right lower lobectomy (p = 0.011). The mean operation time was 229.9 ± 53.9 min (n = 12) and 192.8 ± 53.1 min (n = 48) for the left-sided and right-sided procedures, respectively (p = 0.043, conversion cases were not included). The mean bleeding amount was 29.1 ± 75.7 g (n = 49) and 136.8 ± 330.9 g (n = 16) for the right side and left side, respectively (p = 0.036). The mean operation time (min) for each lobe was as follows: 253.5 ± 73.9 for the left upper lobe (n = 6), 206.3 ± 41.3 for the left lower lobe (n = 6), 189.7 ± 51.3 for the right upper lobe (n = 31), 192.3 ± 57.5 for the right middle lobe (n = 3), and 199.9 ± 61.8 for the right lower lobe (n = 14). CONCLUSION: Robot-assisted thoracoscopic surgery on the left side was associated with higher conversion rate, longer operation time, and more blood loss than that on the right side.

    DOI: 10.1007/s11748-020-01382-7

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  84. Commentary: Local chemotherapy with nanoparticles: A ray of light in the dark?

    Nakamura S

    Journal of Thoracic and Cardiovascular Surgery   Vol. 160 ( 3 ) page: e169 - e170   2020

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    DOI: 10.1016/j.jtcvs.2019.12.089

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  85. Analysis of Optimal Health-Related Quality of Life Measures in Patients Waitlisted for Lung Transplantation

    Tokuno J

    Canadian Respiratory Journal   Vol. 2020   2020

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    DOI: 10.1155/2020/4912920

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  86. 臓器別パネルディスカッション 「拡大基準ドナーに対するコンセンサス 肺」

    星川 康, 芳川 豊史, 渡辺 有為, 此枝 千尋, 田中 里奈

    移植   Vol. 55 ( 3 ) page: 145 - 153   2020

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    DOI: 10.11386/jst.55.3_145

    CiNii Research

  87. Expanded indications for lung transplantation for pulmonary complications after hematopoietic stem cell transplantation

    Noguchi M.

    Journal of Thoracic and Cardiovascular Surgery     2020

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    DOI: 10.1016/j.jtcvs.2020.10.065

    Scopus

  88. Commentary: Continuous steady development is made by taking 2 steps forward, 1 step back

    Mutsuga M.

    Journal of Thoracic and Cardiovascular Surgery     2020

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    DOI: 10.1016/j.jtcvs.2020.09.110

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  89. 移植医療とCOVID-19

    山永 成美, 江川 裕人, 蛭子 洋介, 大澤 良介, 小野 稔, 剣持 敬, 十川 博, 名取 洋一郎, 日比 泰造, 矢野 晴美, 芳川 豊史, 吉川 美喜子, 吉田 一成, 湯沢 賢治

    移植   Vol. 55 ( Supplement ) page: 194_1 - 194_1   2020

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    <p>2019年末からの中国武漢での報告後、瞬く間に世界中に拡散した新型コロナウイルス感染症 (COVID-19)は、現在も収束することなく、2020年8月31日時点で全世界で2500万人以上が感染していると報告されている。COVID-19は、移植医療の在り方に大きな影響をもたらし、世界中の多くの移植施設で、生命に関わる臓器の移植を除き、生体移植を中心とした待機可能な移植は一時停止を余儀なくされた。ドナーからの伝播の可能性、院内感染の可能性、移植患者への感染対応など、様々な状況を想定し、院内のコンセンサスを得ることで、現状では多くの施設が移植医療の提供を再開した。しかし、安心安全な移植医療を提供するためには、COVID-19以前とは異なる、新しい移植医療の様式を実践していく必要がある。また、移植患者は免疫抑制剤を服用しており、ウイルス感染症に脆弱である一方、COVID-19は、感染後期での免疫抑制剤使用による重症化抑制も知られている。相反する病態を理解し、免疫抑制剤調整を含めた移植患者の管理を適切に行うことも重要である。これまでに得られたCOVID-19と移植医療に関する文献的報告をレビューし、新しい移植医療の様式について提言したい。</p>

    DOI: 10.11386/jst.55.supplement_194_1

    CiNii Research

  90. Fcγ受容体IIAの一塩基多型と肺移植後の感染性合併症との相関

    栢分 秀直, 芳川 豊史, 田中 里奈, 田中 友加, 大段 秀樹, 豊 洋次郎, 山田 義人, 大角 明宏, 中島 大輔, 濱路 政嗣, 江川 裕人, 伊達 洋至

    移植   Vol. 55 ( Supplement ) page: 354_1 - 354_1   2020

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    <p>【背景】固形臓器移植後の術後成績にFcγ受容体の一塩基多型(SNP)が与えうる影響についての研究はいくつかあるが、肺移植に関する研究はほとんどない。本研究の目的はFcγ受容体IIA(FCGR2A)のSNPが肺移植後の術後成績に与える影響を検討することである。【対象と方法】2008年から2018年までに201例の肺移植が施行された。この中から再肺移植症例、残余DNAサンプルがない症例、ICU退室不可症例を除いた191例を対象とした。この191例に関してFCGR2AのSNP(131 histidine [H] or arginine [R])を解析し、術後成績とSNPとの関連について検討した。【結果】FCGR2AのSNPの内訳は、H/H(n=120)、H/R(n=66)、R/R(n=5)であった。H/H群(H/H)とR群(H/R or R/R)の2群で解析を行ったところ、ICU退室から術後1年以内の肺炎の頻度および真菌感染症の頻度は、R群で有意に高かった(p=0.004およびp=0.012)。全生存率に関しては2群間に有意差を認めなかった(p=0.67)。【結語】FCGR2AのSNPに関して、予後には2群間で有意な差を認めなかったが、R群では1年以内の肺炎および真菌感染症の頻度が有意に高かった。</p>

    DOI: 10.11386/jst.55.supplement_354_1

    CiNii Research

  91. Diameter of the dilated main pulmonary artery in patients with pulmonary hypertension decreases after lung transplantation.

    Kayawake H, Aoyama A, Kinoshita H, Yoneda T, Baba S, Teramoto Y, Miyagawa-Hayashino A, Yamazaki K, Motoyama H, Hamaji M, Nakajima D, Chen-Yoshikawa TF, Date H

    Surgery today   Vol. 50 ( 3 ) page: 275 - 283   2019.10

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    PURPOSE: The pulmonary artery (PA) in patients with pulmonary hypertension (PH) becomes dilated. We analyzed the postoperative changes of the main PA after lung transplantation (LuTx). METHODS: The subjects of this retrospective study were 68 LuTx recipients, divided into a PH group (n = 36) and a non-PH group (n = 32), based on preoperative right heart catheterization findings. The PA diameter was measured on chest computed tomography. We evaluated the correlation between the mean pulmonary arterial pressure (mPAP) and the main PA diameter and compared the main PA diameters before and 3 months after LuTx. RESULTS: The main PA diameter was significantly correlated with the mPAP (r = 0.423, P < 0.001). Preoperatively, the mean main PA diameter in the PH group was significantly greater than that in the non-PH group. However, by 3 months after LuTx, the main PA diameter in the PH group had decreased significantly from 32.4 ± 6.7 to 26.9 ± 4.8 mm (P < 0.001), while that in the non-PH group had decreased minimally from 28.3 ± 4.9 to 26.4 ± 4.6 mm (P < 0.001), resulting in no significant difference in postoperative main PA diameters between the two groups. CONCLUSIONS: The main PA diameter in recipients with PH was enlarged and correlated with the mPAP. The dilated main PA diameter in PH patients decreased shortly after LuTx.

    DOI: 10.1007/s00595-019-01887-6

    PubMed

  92. Resection Process Map: A novel dynamic simulation system for pulmonary resection.

    Tokuno J, Chen-Yoshikawa TF, Nakao M, Matsuda T, Date H

    The Journal of thoracic and cardiovascular surgery     2019.9

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    DOI: 10.1016/j.jtcvs.2019.07.136

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  93. Emergent surgical treatment for acute thrombosis caused by pulmonary artery kinking after left upper sleeve lobectomy.

    Nakajima D, Oda H, Chen-Yoshikawa TF, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 29 ( 3 ) page: 481-483   2019.9

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    DOI: 10.1093/icvts/ivz110

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  94. Completion pneumonectomy and auto-transplantation for bronchopleural fistula.

    Hamaji M, Chen-Yoshikawa TF, Date H

    The Journal of thoracic and cardiovascular surgery   Vol. 158 ( 3 ) page: e121-e123   2019.9

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    DOI: 10.1016/j.jtcvs.2019.04.093

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  95. Trametinib Attenuates Delayed Rejection and Preserves Thymic Function in Rat Lung Transplantation.

    Takahagi A, Shindo T, Chen-Yoshikawa TF, Yoshizawa A, Gochi F, Miyamoto E, Saito M, Tanaka S, Motoyama H, Aoyama A, Takaori-Kondo A, Date H

    American journal of respiratory cell and molecular biology   Vol. 61 ( 3 ) page: 355-366 - 366   2019.9

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    DOI: 10.1165/rcmb.2018-0188OC

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  96. Living-donor lobar lung transplants provide comparable pulmonary function to cadaveric lung transplants.

    Nakajima D, Chen-Yoshikawa TF, Ohsumi A, Date H

    The Journal of thoracic and cardiovascular surgery     2019.8

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    DOI: 10.1016/j.jtcvs.2019.07.099

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  97. Use of a three-dimensional model in lung transplantation for a patient with giant pulmonary aneurysm. International journal

    Oda H, Hamaji M, Motoyama H, Ikeda T, Minatoya K, Nakajima D, Chen-Yoshikawa TF, Date H

    The Annals of thoracic surgery   Vol. 109 ( 3 ) page: e183-e185   2019.8

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    Management of a giant pulmonary trunk aneurysm in lung transplantation is a challenge. Herein, we present a patient undergoing replacement of the giant pulmonary artery aneurysm with a donor's aorta in bilateral lung transplantation for idiopathic pulmonary arterial hypertension. A plastic three-dimensional model of the pulmonary artery aneurysm created accurately based on computed tomography data allowed us to simulate the procedure on the back table. Our intraoperative findings and management are discussed in this article.

    DOI: 10.1016/j.athoracsur.2019.06.092

    PubMed

  98. Salvage surgery after chemo- or chemoradiotherapy for initially unresectable lung carcinoma.

    Sonobe M, Yutaka Y, Nakajima D, Hamaji M, Menju T, Ohsumi A, Chen-Yoshikawa TF, Sato T, Date H

    The Annals of thoracic surgery     2019.8

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    DOI: 10.1016/j.athoracsur.2019.06.087

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  99. Surgery and stereotactic body radiotherapy for early stage non-small cell lung cancer: review of meta-analyses. Reviewed International journal

    Masatsugu Hamaji, Yukinori Matsuo, Toyofumi Fengshi Chen-Yoshikawa, Takashi Mizowaki, Hiroshi Date

    Journal of thoracic disease   Vol. 11 ( Suppl 13 ) page: S1646-S1652   2019.8

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    Observational or randomized studies on survival outcome following surgery versus stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) demonstrated various results, and several meta-analyses on this topic have been published. The PubMed database was queried for meta-analyses comparing surgery and SBRT for early stage NSCLC. Six meta-analyses on this comparison were identified and 4 (66.7%) suggested that surgery be associated with significantly more favorable overall survival than SBRT, using odds ratio or hazard ratio (HR) as measures of effect. Most of the included studies in the meta-analyses were observational studies and those meta-analyses should be interpreted with caution.

    DOI: 10.21037/jtd.2018.10.35

    PubMed

  100. Acquired recipient pulmonary function is better than lost donor pulmonary function in living-donor lobar lung transplantation. International journal

    Kayawake H, Chen-Yoshikawa TF, Hamaji M, Nakajima D, Ohsumi A, Aoyama A, Date H

    The Journal of thoracic and cardiovascular surgery   Vol. 158 ( 6 ) page: 1710 - 1716   2019.7

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    OBJECTIVE: In standard bilateral living-donor lobar lung transplantation (LDLLT), the right and left lower lobes from 2 healthy donors are implanted in the recipient in place of whole right and left lungs. In other words, total 10 lobes (5 lobes in each donor) are shared by the 2 donors (4 lobes in each donor) and the recipient (2 lobes) in this transplant procedure. This study aimed to compare pulmonary function between donors and recipients before and after LDLLT. METHODS: We performed 76 LDLLT procedures between June 2008 and March 2017. After excluding 12 single LDLLT and 11 native-lung-sparing LDLLT procedures, we identified 38 recipients of bilateral LDLLT who survived >1 year and underwent routine pulmonary function testing. Acquired recipient pulmonary function was compared with lost donor pulmonary function at 1 year post-LDLLT. RESULTS: The median age of the 38 recipients was 44 years (range, 8-62 years); 14 were men. The median age of the 76 donors was 41.5 years (range, 20-60 years); 50 were men. One year post-LDLLT, acquired recipient forced vital capacity was significantly greater than lost donor forced vital capacity (1889.5 ± 581.3 mL vs 1073.9 ± 661.6 mL; P < .001). Similarly, acquired recipient forced expiratory volume in 1 second at 1 year post-LDLLT was significantly greater than lost donor forced expiratory volume in 1 second (1646.8 ± 483.0 mL vs 1064.2 ± 534.5 mL; P < .001). CONCLUSIONS: These results indicated that acquired recipient pulmonary function was better than lost donor pulmonary function in bilateral LDLLT.

    DOI: 10.1016/j.jtcvs.2019.06.058

    PubMed

  101. In Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2 Using Human Induced Pluripotent Stem Cell-Derived Alveolar Organoids. International journal

    Yohei Korogi, Shimpei Gotoh, Satoshi Ikeo, Yuki Yamamoto, Naoyuki Sone, Koji Tamai, Satoshi Konishi, Tadao Nagasaki, Hisako Matsumoto, Isao Ito, Toyofumi F Chen-Yoshikawa, Hiroshi Date, Masatoshi Hagiwara, Isao Asaka, Akitsu Hotta, Michiaki Mishima, Toyohiro Hirai

    Stem cell reports   Vol. 13 ( 1 ) page: 235 - 235   2019.7

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    DOI: 10.1016/j.stemcr.2019.05.022

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  102. Living-donor lung transplantation after surgical repair of transposition of the great arteries.

    Yoshinaga D, Baba S, Hirata T, Fukushima H, Hamaji M, Aoyama A, Chen-Yoshikawa TF, Yamagishi H, Date H, Heike T

    General thoracic and cardiovascular surgery   Vol. 67 ( 7 ) page: 640-643   2019.7

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    DOI: 10.1007/s11748-018-1006-y

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  103. Pirfenidone alleviates lung ischemia-reperfusion injury in a rat model.

    Saito M, Chen-Yoshikawa TF, Suetsugu K, Okabe R, Takahagi A, Masuda S, Date H

    The Journal of thoracic and cardiovascular surgery   Vol. 158 ( 1 ) page: 289-296   2019.7

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    DOI: 10.1016/j.jtcvs.2018.08.098

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  104. Surface deformation analysis of collapsed lungs using model-based shape matching.

    Nakao M, Tokuno J, Chen-Yoshikawa T, Date H, Matsuda T

    International journal of computer assisted radiology and surgery   Vol. 14 ( 10 ) page: 1763 - 1774   2019.6

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    DOI: 10.1007/s11548-019-02013-0

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    Other Link: https://dblp.uni-trier.de/db/journals/cars/cars14.html#NakaoTCDM19

  105. Nutrition-related factors associated with waiting list mortality in patients with interstitial lung disease: A retrospective cohort study. Reviewed International journal

    Ayako Oshima, Akiko Nishimura, Toyofumi F Chen-Yoshikawa, Shin-Ichi Harashima, Teruya Komatsu, Tomohiro Handa, Akihiro Aoyama, Koji Takahashi, Masaki Ikeda, Yohei Oshima, Kohei Ikezoe, Susumu Sato, Maki Isomi, Kenichiro Shide, Hiroshi Date, Nobuya Inagaki

    Clinical transplantation   Vol. 33 ( 6 ) page: e13566   2019.6

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    Japanese patients with interstitial lung disease (ILD) sometimes die waiting for lung transplantation (LTx) because it takes about 2 years to receive it in Japan. We evaluated nutrition-related factors associated with waiting list mortality. Seventy-six ILD patients were hospitalized in Kyoto University Hospital at registration for LTx from 2013 to 2015. Among them, 40 patients were included and analyzed. Patient background was as follows: female, 30%; age, 50.3 ± 6.9 years; body mass index, 21.1 ± 4.0 kg/m2 ; 6-minute walk distance (6MWD), 356 ± 172 m; serum albumin, 3.8 ± 0.4 g/dL; serum transthyretin (TTR), 25.3 ± 7.5 mg/dL; and C-reactive protein, 0.5 ± 0.5 mg/dL. Median observational period was 497 (range 97-1015) days, and median survival time was 550 (95% CI 414-686) days. Survival rate was 47.5%, and mortality rate was 38.7/100 person-years. Cox analyses showed that TTR (HR 0.791, 95% CI 0.633-0.988) and 6MWD (HR 0.795, 95% CI 0.674-0.938) were independently correlated with mortality and were influenced by body fat mass and leg skeletal muscle mass, respectively. It is suggested that nutritional markers and exercise capacity are important prognostic markers in waitlisted patients, but further study is needed to determine whether nutritional intervention or exercise can change outcomes.

    DOI: 10.1111/ctr.13566

    PubMed

  106. Commentary: Promising future solution for unmet needs in lung transplantation.

    Chen-Yoshikawa TF

    The Journal of thoracic and cardiovascular surgery   Vol. 157 ( 5 ) page: 2107-2108   2019.5

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    DOI: 10.1016/j.jtcvs.2018.12.064

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  107. Ex Vivo Sleeve Lobectomy and Autotransplantation After Chemoradiation.

    Yamashita T, Hamaji M, Nakanobo R, Aoyama A, Chen-Yoshikawa TF, Sonobe M, Date H

    The Annals of thoracic surgery   Vol. 107 ( 5 ) page: e341-e343   2019.5

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    DOI: 10.1016/j.athoracsur.2018.09.013

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  108. Long agonal period deteriorates cardiac death donor lung function in a rat EVLP model.

    Hijiya K, Chen-Yoshikawa TF, Motoyama H, Ohsumi A, Nakajima D, Sakamoto J, Aoyama A, Date H

    General thoracic and cardiovascular surgery   Vol. 67 ( 5 ) page: 457-463   2019.5

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    DOI: 10.1007/s11748-018-1038-3

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  109. Survival outcomes after minimally invasive thymectomy for early-stage thymic carcinoma.

    Miyata R, Hamaji M, Omasa M, Nakagawa T, Sumitomo R, Huang CL, Ikeda M, Fujinaga T, Shoji T, Katakura H, Motoyama H, Nakajima D, Ohsumi A, Menju T, Aoyama A, Chen-Yoshikawa TF, Sato T, Sonobe M, Date H

    Surgery today   Vol. 49 ( 4 ) page: 357-360   2019.4

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    DOI: 10.1007/s00595-018-1740-x

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  110. In Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2 Using Human Induced Pluripotent Stem Cell-Derived Alveolar Organoids. Reviewed International journal

    Yohei Korogi, Shimpei Gotoh, Satoshi Ikeo, Yuki Yamamoto, Naoyuki Sone, Koji Tamai, Satoshi Konishi, Tadao Nagasaki, Hisako Matsumoto, Isao Ito, Toyofumi F Chen-Yoshikawa, Hiroshi Date, Masatoshi Hagiwara, Isao Asaka, Akitsu Hotta, Michiaki Mishima, Toyohiro Hirai

    Stem cell reports   Vol. 12 ( 3 ) page: 431 - 440   2019.3

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    It has been challenging to generate in vitro models of alveolar lung diseases, as the stable culture of alveolar type 2 (AT2) cells has been difficult. Methods of generating and expanding AT2 cells derived from induced pluripotent stem cells (iPSCs) have been established and are expected to be applicable to disease modeling. Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by dysfunction of lysosome-related organelles, such as lamellar bodies (LBs), in AT2 cells. From an HPS type 2 (HPS2) patient, we established disease-specific iPSCs (HPS2-iPSCs) and their gene-corrected counterparts. By live cell imaging, the LB dynamics were visualized and altered distribution, enlargement, and impaired secretion of LBs were demonstrated in HPS2-iPSC-derived AT2 cells. These findings provide insight into the AT2 dysfunction in HPS patients and support the potential use of human iPSC-derived AT2 cells for future research on alveolar lung diseases.

    DOI: 10.1016/j.stemcr.2019.01.014

    PubMed

  111. Low incidence of and mortality from a second malignancy after resection of thymic carcinoma†.

    Hamaji M, Kawaguchi A, Omasa M, Nakagawa T, Sumitomo R, Huang CL, Fujinaga T, Ikeda M, Shoji T, Katakura H, Motoyama H, Menju T, Aoyama A, Sato T, Chen-Yoshikawa TF, Sonobe M, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 28 ( 3 ) page: 375-379   2019.3

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    DOI: 10.1093/icvts/ivy260

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  112. Dual approach for large mediastinal tumors in the thoracic outlet: transmanubrial osteomuscular sparing approach and video-assisted thoracoscopic surgery. International journal

    Kayawake H, Chen-Yoshikawa TF, Date H

    Journal of cardiothoracic surgery   Vol. 14 ( 1 ) page: 42 - 42   2019.2

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    BACKGROUND: Selecting the proper surgical approach for mediastinal tumors in the thoracic outlet is difficult. Video-assisted thoracoscopic surgery is ideal because of the less invasiveness; however, it is often difficult to resect tumors only by video-assisted thoracoscopic surgery due to the poor visualization of the cranial side of tumors. We report two successfully treated cases by using a dual approach consisting of the transmanubrial osteomuscular sparing technique and video-assisted thoracoscopic surgery for aiming both the less invasiveness and the good visualization of the cranial side of tumors. CASE PRESENTATIONS: We present two resected cases of the mediastinal tumor in the thoracic outlet. The first case was a 28-year-old woman and the second case was a 37-year-old man. They had a mediastinal tumor in the thoracic outlet which was detected on the roentgenogram. A definitive preoperative diagnosis was unavailable. The surgical resection was started with video-assisted thoracoscopic surgery in the both cases. After the dissection of the caudal side of the tumor, the dissection of the cranial side was judged to be difficult and risky because the tumor was located adjacent to major vessels and the good visualization of this side couldn't be acquired. Therefore, the transmanubrial approach was sequentially performed and complete resection was safely achieved. Postoperatively, although transient Horner syndrome appeared in both cases, they recovered from this syndrome and were discharged. The final diagnosis was schwannoma for both cases. Neither of the cases had any functional restriction of the upper extremity. CONCLUSIONS: This dual approach for mediastinal tumors in the thoracic outlet is useful in terms of safety and lower invasiveness.

    DOI: 10.1186/s13019-019-0863-5

    PubMed

  113. Impact of flat chest on cadaveric lung transplantation: postoperative pulmonary function and survival.

    Miyahara S, Chen-Yoshikawa TF, Motoyama H, Nakajima D, Hamaji M, Aoyama A, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 55 ( 2 ) page: 316-322   2019.2

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    DOI: 10.1093/ejcts/ezy248

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  114. Prognostic impact of microscopic vessel invasion and visceral pleural invasion and their correlations with epithelial-mesenchymal transition, cancer stemness, and treatment failure in lung adenocarcinoma. Reviewed International journal

    Shinya Neri, Toshi Menju, Terumasa Sowa, Yojiro Yutaka, Daisuke Nakajima, Masatsugu Hamaji, Akihiro Ohsumi, Toyofumi F Chen-Yoshikawa, Toshihiko Sato, Makoto Sonobe, Akihiko Yoshizawa, Hironori Haga, Hiroshi Date

    Lung cancer (Amsterdam, Netherlands)   Vol. 128   page: 13 - 19   2019.2

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    OBJECTIVES: Microscopic vessel invasion (MVI) and visceral pleural invasion (VPI) have been recently reported as poor prognostic factors of non-small cell lung cancer. Epithelial-mesenchymal transition (EMT) and cancer stemness (CS) are known malignant phenotypes that induce resistance to cancer therapy. We aimed to assess the prognostic significance of MVI and the correlations among VPI/MVI, EMT, CS, and treatment failure for recurrent tumor. MATERIALS AND METHODS: From 2002 to 2013, 1034 consecutive patients with pathological T1-4N0-2M0 lung adenocarcinoma underwent complete resection. Moreover, we established 206 tissue microarray (TMA) samples from 2002 to 2007. We then evaluated the prognostic impact of MVI, including conventional clinicopathological factors, and analyzed the VPI/MVI, EMT, CS, and treatment failure by TMA immunohistochemical staining. RESULTS: Among the 1034 cases, the proportion of patients with a 5-year overall survival (OS) period was 63.9% and 88.2% (MVI: +/-; p < .001). Multivariate analysis revealed that both MVI and VPI were independent predictors of OS (HR 1.57 and 1.47, respectively). Significant separation of the OS rate curves was observed among the 3 groups [VPI/MVI: both positive (2), either positive (1), and both negative (0)]. Among the 206 TMA cases, these 3 groups of VPI/MVI were significantly correlated with EMT and CS. The median time to progression after recurrence were 3.8, 8.9, and 15.9 months, respectively (VPI/MVI: 2/1/0; p =  0.016). CONCLUSION: MVI and VPI are significant prognostic factors of lung cancer, and they are correlated with EMT, CS, and treatment failure for recurrent tumor.

    DOI: 10.1016/j.lungcan.2018.12.001

    PubMed

  115. Native upper lobe-sparing living-donor lobar lung transplantation maximizes respiratory function of the donor graft.

    Takahagi A, Chen-Yoshikawa TF, Saito M, Okabe R, Gochi F, Yamagishi H, Hamaji M, Motoyama H, Nakajima D, Ohsumi A, Aoyama A, Sonobe M, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 38 ( 1 ) page: 66-72   2019.1

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    DOI: 10.1016/j.healun.2018.09.012

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  116. Novel insights into lung regenerative medicine.

    Chen-Yoshikawa TF, Okabe R

    The Journal of thoracic and cardiovascular surgery   Vol. 157 ( 1 ) page: 421-422   2019.1

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    DOI: 10.1016/j.jtcvs.2018.09.062

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  117. Statins may have double-edged effects in patients with lung adenocarcinoma after lung resection. International journal

    Nishikawa S, Menju T, Takahashi K, Miyata R, Chen-Yoshikawa TF, Sonobe M, Yoshizawa A, Sabe H, Sato T, Date H

    Cancer management and research   Vol. 11   page: 3419-3432 - 3432   2019

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    Purpose: The epithelial to mesenchymal transition (EMT) is pivotal for driving metastasis and recurrence in lung cancer. Some in vitro reports have shown that statins suppress EMT by inactivating mutant p53 functions. Several clinical trials of conventional treatments with statins have been performed, but the effect of these drugs on prognosis is still uncertain. The purpose of this study is to examine the impact of statins on EMT and the prognosis of patients with lung adenocarcinoma. Materials and methods: Morphological changes were evaluated and EMT markers (E-cadherin, vimentin) were analyzed by Western blotting in p53-overexpressing H1650 and mutant p53-harboring H1975 lung adenocarcinoma cells, with and without simvastatin administration. The invasive ability of these cells was analyzed in a Matrigel chemoinvasion assay. A total of 250 lung adenocarcinoma specimens were also collected from patients who underwent surgery in our institute. EMT markers in these tumor specimens were evaluated by immunostaining and p53 mutation status was determined by direct sequencing. Associations among EMT status, p53 mutation status, and statin use were evaluated, and prognosis was analyzed using a marginal structural model. Results: Mutant p53 induced EMT and increased the invasive ability of H1650 cells. Simvastatin restored the epithelial phenotype and decreased the invasive ability of both H1650 and H1975 cells. Statin administration was associated with inactivation of EMT only in patients with mutant p53, which was consistent with the in vitro results. Moreover, in patients with mutant p53, statin users had significantly better survival than non-statin users. In contrast, statins significantly worsened the prognosis of patients with wild type p53 (HR 2.10, 95% CI 1.14-3.85). Conclusion: Statins suppress EMT and change the prognosis of patients with lung adenocarcinoma in a p53 mutation-dependent manner.

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  118. Near-Infrared Imaging Using Intravenous Indocyanine Green at a Conventional Dose to Locate Pulmonary Metastases: A Pilot Study.

    Hamaji M, Chen-Yoshikawa TF, Minami M, Date H

    The Thoracic and cardiovascular surgeon     2018.11

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    DOI: 10.1055/s-0038-1675346

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  119. Prognostic impact of preoperative comorbidities in geriatric patients with early-stage lung cancer: Significance of sublobar resection as a compromise procedure.

    Yutaka Y, Sonobe M, Kawaguchi A, Hamaji M, Nakajima D, Ohsumi A, Menju T, Chen-Yoshikawa TF, Sato T, Date H

    Lung cancer (Amsterdam, Netherlands)   Vol. 125   page: 192-197   2018.11

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    DOI: 10.1016/j.lungcan.2018.09.023

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  120. Unilateral Chronic Lung Allograft Dysfunction Assessed by Biphasic Computed Tomographic Volumetry in Bilateral Living-donor Lobar Lung Transplantation. International journal

    Saito M, Chen-Yoshikawa TF, Nakamoto Y, Kayawake H, Tokuno J, Ueda S, Yamagishi H, Gochi F, Okabe R, Takahagi A, Hamaji M, Motoyama H, Aoyama A, Date H

    Transplantation direct   Vol. 4 ( 11 ) page: e398   2018.11

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    Background: Early diagnosis of unilateral chronic lung allograft dysfunction (CLAD) is difficult because the unaffected contralateral lung functions as a reservoir in bilateral living-donor lobar lung transplantation (LDLLT). We previously reported the usefulness of 133Xe ventilation scintigraphy for detection of unilateral change, but the supply of 133Xe has been stopped globally. The present study aimed to examine the usefulness of inspiratory and expiratory computed tomography (I/E CT) volumetry for detection of unilateral change in CLAD patients. Methods: This was a retrospective single-center, observational study using prospectively collected data. A total of 58 patients who underwent bilateral LDLLT from August 2008 to February 2017 were analyzed. Respiratory function tests, I/E CT were prospectively conducted. ΔLung volume was defined as the value obtained by subtracting expiratory lung volume from inspiratory lung volume. Results: Fourteen (24%) cases were clinically diagnosed with CLAD, of which 10 (71%) were diagnosed as unilateral CLAD. ΔLung volume of bilateral lungs strongly correlated with forced vital capacity (r = 0.92, P < 0.01) and forced expiratory volume in 1 second (r = 0.80, P < 0.01). Regardless the phenotypes (bronchiolitis obliterans syndrome or restrictive allograft syndrome) of CLAD, Δlung volume onset/baseline significantly decreased compared with that in the non-CLAD group. Among the 10 unilateral CLAD patients, 3 with clinically suspected unilateral rejection yet did not show a 20% decline in forced expiratory volume in 1 second. In 2 of these, Δlung volume of unilateral lungs on the rejection side decreased by 20% or more. Conclusions: Our findings suggest that I/E CT volumetry may be useful for assessment and early diagnosis of unilateral CLAD after bilateral LDLLT.

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  121. Gastrointestinal complications after lung transplantation in Japanese patients.

    Kayawake H, Chen-Yoshikawa TF, Motoyama H, Hamaji M, Nakajima D, Aoyama A, Date H

    Surgery today   Vol. 48 ( 9 ) page: 883-890 - 890   2018.9

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    PURPOSE: Gastrointestinal complications after lung transplantation (LTx) are an important postoperative morbidity associated with malnutrition and the malabsorption of drugs. We reviewed our experience of managing gastrointestinal complications after LTx. METHODS: Between June, 2008 and April, 2017, 160 lung transplants were performed at our institution, as living-donor lobar lung transplants in 77 patients, and as deceased-donor lung transplants in 83. We reviewed, retrospectively, the incidence, type and management of gastrointestinal complications. RESULTS: Among the 160 LTx recipients, 58 (36.3%) suffered a collective 70 gastrointestinal complications, the most frequent being gastroparesis, followed by gastroesophageal reflux disease. Two complications were managed surgically, by Nissen fundoplication for gastroesophageal reflux disease in one recipient and Hartmann's operation for sigmoid colon perforation in one. The other 68 complications were managed medically. Two patients died of complications: one, of aspiration pneumonia caused by gastroparesis; and one, of panperitonitis caused by a gastric ulcer. There were no significant differences in overall survival or chronic lung allograft dysfunction-free survival between the patients with and those without gastrointestinal complications. CONCLUSIONS: Gastrointestinal complications are not uncommon in LTx recipients and may be serious; therefore, early detection and appropriate treatment are imperative. Surgical management is required for some complications, but most can be managed medically.

    DOI: 10.1007/s00595-018-1666-3

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  122. Clinical significance of radiological pleuroparenchymal fibroelastosis pattern in interstitial lung disease patients registered for lung transplantation: a retrospective cohort study. Reviewed International journal

    Kiminobu Tanizawa, Tomohiro Handa, Takeshi Kubo, Toyofumi F Chen-Yoshikawa, Akihiro Aoyama, Hideki Motoyama, Kyoko Hijiya, Akihiko Yoshizawa, Yohei Oshima, Kohei Ikezoe, Shinsaku Tokuda, Yoshinari Nakatsuka, Yuko Murase, Sonoko Nagai, Shigeo Muro, Toru Oga, Kazuo Chin, Toyohiro Hirai, Hiroshi Date

    Respiratory research   Vol. 19 ( 1 ) page: 162 - 162   2018.8

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    BACKGROUND: Radiological pleuroparenchymal fibroelastosis (PPFE) lesion is characterized by pleural thickening with associated signs of subpleural fibrosis on high-resolution computed tomography (HRCT). This study evaluated the clinical significance of radiological PPFE as an isolated finding or associated with other interstitial lung diseases (ILDs) in patients having fibrotic ILDs and registered for cadaveric lung transplantation (LT). METHODS: This retrospective study included 118 fibrotic ILD patients registered for LT. Radiological PPFE on HRCT was assessed. The impact of radiological PPFE on clinical features and transplantation-censored survival were evaluated. RESULTS: Radiological PPFE was observed in 30/118 cases (25%): definite PPFE (PPFE concentrated in the upper lobes, with involvement of lower lobes being less marked) in 12 (10%) and consistent PPFE (PPFE not concentrated in the upper lobes, or PPFE with features of coexistent disease present elsewhere) in 18 (15%). Of these, 12 had late-onset non-infectious pulmonary complications after hematopoietic stem-cell transplantation and/or chemotherapy (LONIPCs), 9 idiopathic PPFE, and 9 other fibrotic ILDs (idiopathic pulmonary fibrosis, IPF; other idiopathic interstitial pneumonias, other IIPs; connective tissue disease-associated ILD, CTD-ILD, and hypersensitivity pneumonia, HP). Radiological PPFE was associated with previous history of pneumothorax, lower body mass index, lower percentage of predicted forced vital capacity (%FVC), higher percentage of predicted diffusion capacity of carbon monoxide, less desaturation on six-minute walk test, and hypercapnia. The median survival time of all study cases was 449 days. Thirty-seven (28%) received LTs: cadaveric in 31 and living-donor lobar in six. Of 93 patients who did not receive LT, 66 (71%) died. Radiological PPFE was marginally associated with better survival after adjustment for age, sex, %FVC, and six-minute walk distance < 250 m (hazard ratio 0.51 [0.25-1.05], p = 0.07). After adjustment for covariates, idiopathic PPFE and LONIPC with radiological PPFE was associated with better survival than fibrotic ILDs without radiological PPFE (hazard ratio 0.38 [0.16-0.90], p = 0.03), and marginally better survival than other fibrotic ILDs with radiological PPFE (hazard ratio, 0.20 [0.04-1.11], p = 0.07). CONCLUSIONS: idiopathic PPFE and LONIPC with radiological PPFE has better survival on the wait list for LT than fibrotic ILDs without radiological PPFE, after adjustment for age, sex, %FVC, and six-minute walk distance.

    DOI: 10.1186/s12931-018-0860-6

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  123. Adjuvant vinorelbine and cisplatin after complete resection of stage II and III non-small cell lung cancer: long-term follow-up of our study of Japanese patients Reviewed

    Makoto Sonobe, Masatsugu Hamaji, Hideki Motoyama, Toshi Menju, Akihiro Aoyama, Toyofumi F. Chen-Yoshikawa, Toshihiko Sato, Hiroshi Date

    Surgery Today   Vol. 48 ( 7 ) page: 687 - 694   2018.7

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    Purpose: We reported previously a phase II study of adjuvant chemotherapy consisting of four cycles of vinorelbine (25 mg/m2) and cisplatin (40 mg/m2), given on days 1 and 8, every 4 weeks, to Japanese patients with completely resected stage II or III non-small cell lung cancer (NSCLC
    UMIN 000005055). However, the follow-up was too short for us to evaluate a definitive 5-year overall survival rate and after-effects. Methods: Between December 2006 and January 2011, 60 patients were enrolled in this study. We analyzed relapse-free and overall survival, long-lasting adverse effects, the influence of treatment on recurrent tumors, and the development of a second primary cancer, in relation with the regimen. Results: After a median follow-up period of 95.8 months, the 5-year relapse-free and overall survival rates were 51.7 and 76.7%, respectively. Neuralgia developed in one patient and this was the only case of a long-lasting adverse effect. Recurrence developed in 31 patients, 29 of whom received intensive treatment. Although 16 s (or more) primary neoplasms developed among 13 patients, these were common carcinomas in Japan and did not include sarcoma or hematologic malignancies. Conclusion: Adjuvant vinorelbine and cisplatin chemotherapy showed encouraging relapse-free and overall survival rates, and long-term safety in Japanese patients with resected NSCLC.

    DOI: 10.1007/s00595-018-1646-7

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  124. GATA6-positive lung adenocarcinomas are associated with invasive mucinous adenocarcinoma morphology, hepatocyte nuclear factor 4α expression, and KRAS mutations Reviewed

    Naoki Nakajima, Akihiko Yoshizawa, Tomoyuki Nakajima, Masahiro Hirata, Ayako Furuhata, Shinji Sumiyoshi, Mariyo Rokutan-Kurata, Makoto Sonobe, Toshi Menju, Ei Miyamoto, Toyofumi F. Chen-Yoshikawa, Hiroshi Date, Hironori Haga

    Histopathology   Vol. 73 ( 1 ) page: 38 - 48   2018.7

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    Aims: GATA6 is known to play a role in lung development. However, its role in the carcinogenesis of lung cancer is not well studied. The aim of this study was to analyse GATA6 expression in lung adenocarcinomas (LAs) by immunohistochemistry (IHC) in order to define its association with clinicopathological characteristics. Methods and results: IHC analysis of GATA6 was performed with tissue microarray slides containing 348 LAs. The association between GATA6 expression and clinicopathological parameters was evaluated. GATA6 expression in epithelial tumours other than lung cancer was also evaluated. GATA6 expression was found in 47 LAs (13.5%). This occurred more frequently in younger patients (P = 0.005), and was associated with the absence of lymph node metastasis (P =0.024), well-differentiated to moderately differentiated tumours (P &lt
    0.001), the absence of lymphatic invasion (P = 0.020), and the absence of vascular invasion (P = 0.011). GATA6 expression was associated with mucin production (P &lt
    0.001), the invasive mucinous adenocarcinoma subtype (P &lt
    0.001), KRAS mutations (P = 0.026), expression of MUC2 (P &lt
    0.001), CDX2 (P = 0.049), and MUC5AC (P &lt
    0.001), and absence of expression of TTF-1 (P = 0.002). GATA6 expression was also associated with hepatocyte nuclear factor 4α (HNF4α) expression (P &lt
    0.001). GATA6 expression tended to indicate better prognoses, whereas patients with HNF4α expression had significantly worse prognoses (P = 0.033). Of 270 tumours other than lung cancer, 110 expressed GATA6. Conclusions: These findings suggest that GATA6 might interact with HNF4α and contribute to the development of mucinous-type LAs.

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  125. Surgical management of bronchial stumps in lobar lung transplantation Reviewed

    Hidenao Kayawake, Toyofumi F. Chen-Yoshikawa, Akihiro Aoyama, Hideki Motoyama, Masatsugu Hamaji, Kyoko Hijiya, Hiroshi Date

    Journal of Thoracic and Cardiovascular Surgery   Vol. 156 ( 1 ) page: 451 - 460   2018.7

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    Background: The validity of lobar lung transplantation (LT) has been established in both living-donor lobar lung transplantation (LDLLT) and cadaveric-donor lung transplantation (CLT). However, bronchial stump management in lobar LT has not been precisely documented. Thus, we retrospectively analyzed our strategies for bronchial stump management in lobar LT. Methods: Between June 2008 and August 2016, 145 LTs (72 LDLLTs and 73 CLTs) were performed at our institution. Bronchial stumps were left in 14 LDLLTs. Eight patients underwent bilateral CLTs with downsizing lobectomy. We avoided leaving donor bronchial stumps by lobar-to-lobar bronchial anastomosis, and left recipient bronchial stumps if necessary. We retrospectively reviewed the bronchial stump management methods and outcomes in these 22 patients. Results: Among the 14 LDLLTs, right-to-left inverted lobar LT and right single-lobe LT with left pneumonectomy were performed in 12 and 2 patients, respectively. Among the 8 CLTs, 11 lobectomies were performed because of oversized grafts and/or localized pneumonia. Twenty-three lobar-to-lobar bronchial anastomoses were performed, and there were 21 recipient bronchial stumps in total. Three bronchial stumps were left in the donor graft, the middle bronchus in all cases. No complications related to lobar-to-lobar bronchial anastomoses were observed. All bronchial stumps healed well without developing a bronchopleural fistula. The 3-year overall survival rate was 88.1% (95% confidence interval, 58.8%-97.0%). Conclusions: We successfully avoided leaving bronchial stumps in the donor graft, except in the middle bronchus, by performing lobar-to-lobar bronchial anastomoses in lobar LTs. Excellent healing of lobar-to-lobar bronchial anastomoses and bronchial stumps was observed.

    DOI: 10.1016/j.jtcvs.2017.10.150

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  126. Anterior mediastinal tissue volume is correlated with antiacetylcholine receptor antibody level in myasthenia gravis Reviewed

    Akihiro Takahagi, Mitsugu Omasa, Toyofumi F. Chen-Yoshikawa, Masatsugu Hamaji, Akihiko Yoshizawa, Takashi Sozu, Makoto Sonobe, Hiroshi Date

    Journal of Thoracic and Cardiovascular Surgery   Vol. 155 ( 6 ) page: 2738 - 2744   2018.6

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    Objectives: Extended thymectomy is a treatment option for myasthenia gravis (MG), but the surgical indications are controversial. Pathologic features of the thymus can be used to predict surgical outcomes, but there is no reliable method for evaluating these characteristics preoperatively. The purpose of this study was to determine whether anterior mediastinal tissue volume, as measured via 3-dimensional computed tomography (3DCT) volumetry, correlates with serum anti-acetylcholine receptor antibody (AChRAb) levels in patients undergoing thymectomy for myasthenia gravis. Therefore, we investigated the relationships among anterior mediastinal tissue volume determined by 3DCT volumetry and AChRAb levels. Methods: The subjects were 28 patients who underwent extended thymectomy and were enrolled retrospectively. We measured volume of the anterior mediastinum and calculated the volumes of more than −30 Hounsfield units (V−30) by using 3DCT volumetry and compared them with perioperative AChRAb levels. The significance of their volumes in MG was examined by comparison with 53 patients without MG. Results: V−30 values were related to age and were significantly greater in patients with MG than in patients without MG (P &lt
    .001). V−30 values were correlated positively with preoperative AChRAb levels (ρ = 0.505, P =.006) and inversely with the post/preoperative AChRAb ratio (ρ = −0.453, P =.018). The histologic nonadipose tissue ratio was correlated with the V−30/volume of the anterior mediastinum (ρ = 0.700, P &lt
    .001). Conclusions: This method for evaluation of the anterior mediastinal tissue volume and AChRAb production may be helpful in establishing a treatment plan for MG.

    DOI: 10.1016/j.jtcvs.2017.10.082

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  127. Diagnostic yield of electromagnetic navigational bronchoscopy: Results of initial 35 cases in a Japanese institute Reviewed

    Toshihiko Sato, Yojiro Yutaka, Yuichiro Ueda, Masatsugu Hamaji, Hideki Motoyama, Toshi Menju, Akihiro Aoyama, Toyofumi Fengshi Chen-Yoshikawa, Makoto Sonobe, Hiroshi Date

    Journal of Thoracic Disease   Vol. 10 ( Suppl 14 ) page: S1615 - S1619   2018.6

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    Background: Electromagnetic navigational bronchoscopy (ENB) is a new bronchoscopic technique for navigational transbronchial lung biopsy (TBLB) that guides the sheath to the target lesion in real time. Herein, we report our experience with this navigational system, its diagnostic yields, and associated complications. Methods: A single-center, single-operator retrospective chart review was performed. We included 35 consecutive patients who underwent ENB with superDimension™ (Medtronic, MN, USA) for the diagnosis of pulmonary lesions from February 2016 to May 2017 in Kyoto University Hospital. The size of the target lesion varied from 8 to 25 mm (median, 15.28±5.48 mm). All ENB procedures were performed under conscious sedation using 2 to 10 mg midazolam and 1 to 10 mg morphine hydrochloride. No fluoroscopic guide was employed except in three cases. Results: A total of 25 patients were diagnosed via ENB, yielding a diagnostic rate of 71.4% (25/35). The average lesion size of the diagnosed group was 16.44±5.44 mm (range, 8-25 mm). Eighteen cases were diagnosed as primary lung cancer, 3 were metastatic lung cancer, and 4 were inflammatory diseases. The average lesion size of the 10 undiagnosed cases was 12.40±5.21 mm (range, 8-24 mm). The lesion size of the undiagnosed group was significantly smaller than that of the diagnosed group (P=0.02). The average time required for the procedure was 16.78±9.57 minutes (range, 3-46 minutes), independent of the diagnosis, the lesion size, and the tumor location. We encountered one pneumothorax which required chest drainage and one hemopneumothorax which required non-elective thoracotomy and wedge resection. One patient developed high fever over 38 ° for one day following the procedure. Conclusions: In our initial series of 35 cases, ENB-guided TBLB showed an acceptable diagnostic yield.

    DOI: 10.21037/jtd.2018.04.123

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  128. Lung transplantation after haematopoietic stem cell transplantation for Wiskott-Aldrich syndrome Reviewed

    Satoshi Ueda, Toyofumi F. Chen-Yoshikawa, Kyoko Hijiya, Hiroshi Date

    European Journal of Cardio-thoracic Surgery   Vol. 53 ( 6 ) page: 1286 - 1287   2018.6

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    The authors report the first case involving a patient with Wiskott-Aldrich syndrome who underwent single living-donor lobar lung transplantation after haematopoietic stem cell transplantation. Haematopoietic stem cell transplantation was performed at 1 year of age
    however, he developed severe pulmonary complications. Although lung transplantation is generally contraindicated in patients with immunodeficiency disease, the patient was able to undergo living-donor lobar lung transplantation because his immunodeficiency and thrombocytopenia were well controlled as a result of haematopoietic stem cell transplantation. Currently, the patient is doing well and is free from oxygen supplementation.

    DOI: 10.1093/ejcts/ezx461

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  129. Successful conservative management of an anastomotic airway dehiscence at the left main bronchus following bilateral cadaveric lung transplantation Reviewed

    Ryo Miyata, Toyofumi F. Chen-Yoshikawa, Masatsugu Hamaji, Fumiaki Gochi, Hideki Motoyama, Toshi Menju, Akihiro Aoyama, Toshihiko Sato, Makoto Sonobe, Hiroshi Date

    General Thoracic and Cardiovascular Surgery   Vol. 66 ( 6 ) page: 368 - 371   2018.6

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    There is a dearth of data on management of anastomotic airway dehiscence following lung transplantation. Herein we report a case of successful conservative management of an anastomotic airway dehiscence after cadaveric donor lung transplantation. A 41-year-old woman with primary ciliary dyskinesia underwent cadaveric bilateral lung transplantation without cardiopulmonary bypass. On the postoperative day 25, left pneumothorax developed and bronchoscopy demonstrated a localized anastomotic dehiscence at the left main bronchus. The dehiscence was managed with 2 weeks of pleural drainage and was completely covered with regenerated bronchial epithelium at 4 months after transplantation. There is no finding suggestive of significant stenosis at 4 years of follow-up. Our case suggested asymptomatic and localized anastomotic dehiscence does not always require endobronchial stent placement or re-operation. Multiple factors that may contribute to the successful conservative management were discussed in this article.

    DOI: 10.1007/s11748-017-0826-5

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  130. Transition of the programmed death 1 pathway from the primary colorectal cancer to its corresponding pulmonary metastasis.

    Miyamoto E, Chen-Yoshikawa TF, Ueshima C, Yoshizawa A, Hamaji M, Yamamoto T, Kawada K, Haga H, Sakai Y, Date H

    Journal of surgical oncology   Vol. 117 ( 7 ) page: 1405-1412   2018.6

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  131. Effect of early tracheostomy on clinical outcomes in critically ill lung transplant recipients Reviewed

    Ryo Miyoshi, Toyofumi F. Chen-Yoshikawa, Masatsugu Hamaji, Atsushi Kawaguchi, Hidenao Kayawake, Kyoko Hijiya, Hideki Motoyama, Akihiro Aoyama, Hiroshi Date

    General Thoracic and Cardiovascular Surgery   Vol. 66 ( 9 ) page: 1 - 8   2018.5

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    Objectives: The purpose of this study was to evaluate the effect of early tracheostomy in patients following lung transplantation and to determine its optimal timing and influence on clinical outcomes. Methods: We retrospectively reviewed records of 96 adult patients who underwent lung transplantation at our institution between August 2008 and January 2016. Time-to-tracheostomy was defined based on timing of the procedure: “early” if less than 3 days or “late” if 3 or more days after lung transplantation. Results: Forty-nine patients (51%) underwent tracheostomy 3.2 ± 1.8 days after lung transplantation. Among these patients, 21 patients (42.9%) underwent early tracheostomy and 28 patients (57.1%) underwent late tracheostomy. Multivariable logistic regression analysis indicated that preoperative performance status was a significant predictor for tracheostomy (p = 0.006, odds ratio 2.72). Patients in the early tracheostomy group began walking (p = 0.003) and oral feeding (p = 0.0006) earlier and had a shorter duration of mechanical ventilation (p = 0.04) and shorter length of intensive care unit (p = 0.01) and hospital stay (p = 0.04) than patients in the late tracheostomy group. No significant differences in postoperative walking (p = 0.06), oral feeding (p = 0.17), or length of hospital stay (p = 0.37) were observed between patients who underwent early tracheostomy and those who did not undergo tracheostomy. Conclusions: Early tracheostomy following lung transplantation decreased both intensive care and hospital stay, due to improved postoperative recovery, even in patients with poor preoperative conditions. Furthermore, length of hospital stay in patients with early tracheostomy was similar to that of patients without tracheostomy after lung transplantation.

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  132. Nontuberculous mycobacterial and Aspergillus infections among cadaveric lung transplant recipients in Japan Reviewed

    Kazunobu Tachibana, Yoshinori Okada, Yasushi Matsuda, Kentaroh Miyoshi, Takahiro Oto, Toyofumi F. Chen-Yoshikawa, Hiroshi Date, Masato Minami, Meinoshin Okumura, Akinori Iwasaki, Takeshi Shiraishi, Sumiko Maeda, Yuji Matsumura, Takahiro Nakajima, Ichiro Yoshino, Seiji Hayashi

    Respiratory Investigation   Vol. 56 ( 3 ) page: 243 - 248   2018.5

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    Background: Lung transplantation is an effective treatment modality for respiratory failure. Chronic lung infections, including infections caused by nontuberculous mycobacteria (NTM) and Aspergillus, are difficult to control, and uncontrolled infections are relative contraindications for lung transplantation. However, few reports have documented the incidence and outcome of these infections in lung transplant recipients. Methods: To quantify the incidence and outcomes of colonization and disease caused by NTM and aspergillosis in recipients before and after lung transplantation, we reviewed the medical records and microbiology data from 240 consecutive cadaveric lung transplant recipients between 2000 and 2014. Results: Before lung transplantation, NTM and Aspergillus species were isolated from five (2.1%) and six (2.5%) patients, respectively, out of the total 240 recipients. All patients with NTM infection received treatment, resulting in culture conversion. They had no recurrence after lung transplantation. All patients with aspergillosis received treatment, one of whom had recurrence after lung transplantation. Over a median follow-up period of 3.3 years, NTM species were isolated after transplantation from eight of 240 patients (3.3%). Five of these patients met the criteria for NTM disease, and four of them received treatment. Four patients survived without a worsening of NTM disease. Over the same median follow-up period, Aspergillus species were isolated from seven of 240 patients (2.9%), six of whom received treatment. Conclusions: Isolation of NTM or Aspergillus species from lung transplant recipients is uncommon. Adequate pre-transplant control and post-transplant management of NTM and Aspergillus infections allows for safe lung transplantation.

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  133. Inverted Lobes Have Satisfactory Functions Compared With Noninverted Lobes in Lung Transplantation Reviewed

    Hidenao Kayawake, Toyofumi F. Chen-Yoshikawa, Hideki Motoyama, Masatsugu Hamaji, Kyoko Hijiya, Akihiro Aoyama, Yasufumi Goda, Hiromi Oda, Satoshi Ueda, Hiroshi Date

    Annals of Thoracic Surgery   Vol. 105 ( 4 ) page: 1044 - 1049   2018.4

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    Background: To overcome the problem of small-for-size grafts in standard living-donor lobar lung transplantation (LDLLT), we developed inverted LDLLT, in which a right lower lobe from 1 donor is implanted as a right graft and another right lower lobe from another donor is implanted as a left graft. We retrospectively analyzed the functions of inverted grafts vs noninverted grafts. Methods: Between 2008 and 2015, 64 LDLLTs were performed. Included were 35 LDLLTs whose recipients were adults and monitored for more than 6 months without developing chronic lung allograft dysfunction. Among them, 65 implanted lobes were eligible for this analysis. There were 31 right lower lobes implanted as right grafts (right-to-right group), 7 right lower lobes as inverted left grafts (right-to-left group), and 27 left lower lobes as left grafts (left-to-left group). We evaluated the graft forced vital capacity (G-FVC) and graft volume of the 65 lobes before and 6 months after LDLLT and compared them among the three groups. Results: Preoperatively, G-FVC in the right-to-left group (1,050 mL) was comparable to that in the right-to-right group (1,177 mL) and better than that in the left-to-left group (791 mL, p &lt
    0.01). Six months after LDLLT, G-FVC in the right-to-left group (1,015 mL) remained comparable to that in the right-to-right group (1,001 mL) and better than that in the left-to-left group (713 mL, p = 0.047). The ratio of graft volume 6 months after LDLLT to the preoperative value was comparable. Conclusions: The functions of inverted grafts in inverted LDLLTs were satisfactory compared with those of noninverted grafts.

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  134. Surgery for metachronous second primary lung cancer versus surgery for primary lung cancer: A propensity score-matched comparison of postoperative complications and survival outcomes Reviewed

    Yusuke Muranishi, Makoto Sonobe, Masatsugu Hamaji, Atsushi Kawaguchi, Kyoko Hijiya, Hideki Motoyama, Toshi Menju, Akihiro Aoyama, Toyofumi F Chen-Yoshikawa, Toshihiko Sato, Hiroshi Date

    Interactive Cardiovascular and Thoracic Surgery   Vol. 26 ( 4 ) page: 631 - 637   2018.4

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    OBJECTIVES: Surgical treatments for metachronous second primary lung cancer (MSPLC) may be increasing. It was thought that surgery for MSPLC is associated with high mortality and morbidity. However, recent diffusion of minimally invasive surgical procedures may improve the safety of surgery for MSPLC. The aim of this study was to clarify the safety and prognosis of surgery for MSPLC compared with that for primary lung cancer (PLC). METHODS: We reviewed medical records of 1340 patients who underwent pulmonary resection for non-small-cell lung cancer between 2006 and 2013. We identified patients with PLC and those with MSPLC, and surgical parameters and survival outcome were compared. To eliminate selection bias between the MSPLC group and the PLC group, propensity score-matched analysis on the basis of clinicopathological factors was performed. RESULTS: Fifty-three patients underwent resection for MSPLC. Propensity score matching identified 50 patients from each treatment group. Of the 50 MSPLC patients, 41 (82.0%) underwent segmentectomy or wedge resection, 44 (82.0%) had clinical Stage I tumour and 36 (72.0%) received resection via video-assisted thoracoscopic surgery approach. Postoperative complications with a severity of Grade II or more occurred in 11 (22.0%) patients. The incidence of postoperative complications in the MSPLC group was not different from that of the PLC group (P = 0.4894). The 5-year overall survival rates were 68.7% and 83.0% in the PLC and the MSPLC groups, respectively. There was no significant difference between the PLC and the MSPLC groups in terms of overall survival (P = 0.2018, log-rank test). CONCLUSIONS: Pulmonary resection for MSPLC was safely performed with low short-term morbidity similar to that of PLC, and its longterm overall survival was acceptable.

    DOI: 10.1093/icvts/ivx389

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  135. Late-onset chest wall abscess due to a biodegradable rib pin infection after lung transplantation Reviewed

    Yasufumi Goda, Toyofumi F. Chen-Yoshikawa, Masaaki Kusunose, Masatsugu Hamaji, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hiroshi Date

    General Thoracic and Cardiovascular Surgery   Vol. 66 ( 3 ) page: 175 - 178   2018.3

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    A 55-year-old man with end-stage emphysema underwent a right single-lung transplantation through a posterolateral thoracotomy. The fifth rib was divided and fused back using a biodegradable pin made of polylactide acid and hydroxyapatite. Two weeks postoperatively, he suffered from central vein catheter-related sepsis due to methicillin-sensitive Staphylococcus aureus. After being successfully treated for sepsis, he was discharged. However, 3 months later, computed tomography revealed multiple loculated abscesses in the chest wall and the right pleural space. Reoperative thoracotomy revealed abscesses mainly located around the fifth rib, where the pin was inserted. Both cultures of the abscess and the fifth rib were positive for methicillin-sensitive S. aureus, which suggested that the rib pin was the cause of the secondary infection. This case suggests the rib pins, even if they are biodegradable, could have a risk of infections side effect especially for the immunosuppressed patients.

    DOI: 10.1007/s11748-017-0768-y

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  136. Radiologic and Functional Analysis of Compensatory Lung Growth After Living-Donor Lobectomy. Reviewed International journal

    Kei Shikuma, Toyofumi F Chen-Yoshikawa, Tsuyoshi Oguma, Takeshi Kubo, Keiji Ohata, Masatsugu Hamaji, Atsushi Kawaguchi, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hisako Matsumoto, Shigeo Muro, Hiroshi Date

    The Annals of thoracic surgery   Vol. 105 ( 3 ) page: 909 - 914   2018.3

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    BACKGROUND: Whether compensatory lung growth occurs in adult humans is controversial. The aim of this study was to confirm compensatory lung growth by analyzing ipsilateral residual lung after lower lobectomy in living lung transplant donors with quantitative and qualitative computed tomography assessments. METHODS: Chest computed tomography and pulmonary function tests were performed in 31 eligible donors before and 1 year after donor lobectomy. Ipsilateral residual lung volume was measured with three-dimensional computed tomography volumetry. The computed tomography-estimated volumes of low, middle, and high attenuations in the lung were calculated. Assessment of the D value, a coefficient of the cumulative size distribution of low-density area clusters, was performed to evaluate the structural quality of the residual lung. RESULTS: Postoperative pulmonary function test values were significantly larger than preoperative estimated values. Although postoperative total volume, low attenuation volume, middle attenuation volume, and high attenuation volume of the ipsilateral residual lung were significantly larger than the preoperative volumes, with 50.2%, 50.0%, 41.5%, and 43.1% increase in the median values, respectively (all p < 0.0001), the differences in D values before and after donor lobectomy were not significant (p = 0.848). The total volume of ipsilateral residual lung was increased by more than 600 mL (50%). CONCLUSIONS: The volume of ipsilateral residual lung increased, but its structural quality did not change before and after donor lobectomy. The existence of compensatory lung growth in adult humans was suggested by quantitative and qualitative computed tomography assessments.

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  137. Wise surgeons learn from others' experiences.

    Chen-Yoshikawa TF

    The Journal of thoracic and cardiovascular surgery   Vol. 155 ( 3 ) page: e115   2018.3

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    DOI: 10.1016/j.jtcvs.2017.11.047

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  138. The synergistic role of ATP-dependent drug efflux pump and focal adhesion signaling pathways in vinorelbine resistance in lung cancer Reviewed

    Takao Nakanishi, Toshi Menju, Shigeto Nishikawa, Koji Takahashi, Ryo Miyata, Kei Shikuma, Terumasa Sowa, Naoto Imamura, Masatsugu Hamaji, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Toshihiko Sato, Toyofumi F. Chen-Yoshikawa, Makoto Sonobe, Hiroshi Date

    Cancer Medicine   Vol. 7 ( 2 ) page: 408 - 419   2018.2

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    The vinorelbine (VRB) plus cisplatin regimen is widely used to treat non–small cell lung cancer (NSCLC), but its cure rate is poor. Drug resistance is the primary driver of chemotherapeutic failure, and the causes of resistance remain unclear. By focusing on the focal adhesion (FA) pathway, we have highlighted a signaling pathway that promotes VRB resistance in lung cancer cells. First, we established VRB-resistant (VR) lung cancer cells (NCI-H1299 and A549) and examined its transcriptional changes, protein expressions, and activations. We treated VR cells by Src Family Kinase (SFK) inhibitors or gene silencing and examined cell viabilities. ATP-binding Cassette Sub-family B Member 1 (ABCB1) was highly expressed in VR cells. A pathway analysis and western blot analysis revealed the high expression of integrins β1 and β3 and the activation of FA pathway components, including Src family kinase (SFK) and AKT, in VR cells. SFK involvement in VRB resistance was confirmed by the recovery of VRB sensitivity in FYN knockdown A549 VR cells. Saracatinib, a dual inhibitor of SFK and ABCB1, had a synergistic effect with VRB in VR cells. In conclusion, ABCB1 is the primary cause of VRB resistance. Additionally, the FA pathway, particularly integrin, and SFK, are promising targets for VRB-resistant lung cancer. Further studies are needed to identify clinically applicable target drugs and biomarkers that will improve disease prognoses and predict therapeutic efficacies.

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  139. Prognostic Factors in Lung Transplantation after Hematopoietic Stem Cell Transplantation Reviewed

    Toyofumi F. Chen-Yoshikawa, Seiichiro Sugimoto, Takeshi Shiraishi, Masato Minami, Yasushi Matsuda, Masayuki Chida, Sumiko Maeda, Akihiro Aoyama, Yoshinori Okada, Meinoshin Okumura, Akinori Iwasaki, Shinichiro Miyoshi, Takahiro Oto, Hiroshi Date

    Transplantation   Vol. 102 ( 1 ) page: 154 - 161   2018.1

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    Background Lung transplantation is the final lifesaving option for patients with pulmonary complications after hematopoietic stem cell transplantation (HSCT). Patients undergoing HSCT for hematologic diseases are thought to be high-risk candidates for lung transplantation
    therefore, few lung transplants are performed for these patients, and few studies have been reported. This study aimed to describe the characteristics and outcomes of lung transplantation in patients with pulmonary complications after HSCT. Methods We retrospectively investigated 62 patients who underwent lung transplantation after HSCT. All data were collected from 6 lung transplant centers in Japan. Results Seventeen patients underwent cadaveric lung transplantation, whereas 45 underwent living-donor lobar lung transplantation (LDLLT). In the LDLLT group, 18 patients underwent LDLLT after HSCT in which one of the donors had also served as a donor for HSCT. Seven patients underwent single LDLLT for which the donor was the same as the patient from whom stem cells were obtained for HSCT. Preoperative hypercapnia was observed in 52 patients (84%). Thirteen patients (21%) required mechanical ventilation preoperatively. Fifty-five patients underwent HSCT for hematologic malignancies, and 4 (7%) relapsed after lung transplantation. The 5-year survival rate was 64.2%. In a multivariable analysis, patients younger than 45 years and those with the same donor for both procedures exhibited significantly better survival (P = 0.012 and 0.041, respectively). Conclusions Lung transplantation for pulmonary complications after HSCT was performed safely and yielded better survival, especially in younger recipients for whom both lung transplantation and HSCT involved the same donor.

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  140. Pulmonary endothelial chimerism after hematopoietic stem cell transplantation Reviewed

    Kyoko Hijiya, Toyofumi Fengshi Chen-Yoshikawa, Aya Miyagawa-Hayashino, Tadakazu Kondo, Akihiro Aoyama, Hironori Haga, Akifumi Takaori-Kondo, Hiroshi Date

    Surgery Today   Vol. 48 ( 1 ) page: 101 - 109   2018.1

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    Purpose: Few studies have investigated pulmonary endothelial chimerism after hematopoietic stem cell transplantation. In the present study, we investigated pulmonary endothelial chimerism using the ABH histo-blood group antigen as an identifying marker in cases of ABO-incompatible hematopoietic stem cell transplantation. Methods: Sixteen lung samples were analyzed. Of these, seven were explanted lungs from lung transplant recipients with severe pulmonary chronic graft-versus-host disease (GVHD). The remaining nine were autopsy samples from patients who died from various causes, and six of these nine cases had a diagnosis of pulmonary chronic GVHD. The ABH histo-blood group antigen was used to differentiate donor cells from recipient cells immunohistochemically. We estimated the percentage of vessels positive for donor blood group antigens in comparison with the total number of vessels. Results: Donor blood group antigens were expressed in the endothelium of 13 samples, all of which were pathologically diagnosed with pulmonary chronic GVHD. The proportion of vessels with donor group antigens ranged from 0.1 to 17.5%. In contrast, no chimeric vessels were observed in the three samples without pulmonary chronic GVHD. Conclusions: Our results demonstrate that circulating stem cells engraft into the endothelium to a considerable extent in pulmonary chronic GVHD.

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  141. Three-dimensional image in lung transplantation Reviewed

    Toyofumi F. Chen-Yoshikawa, Hiroshi Date

    General Thoracic and Cardiovascular Surgery   Vol. 66 ( 1 ) page: 19 - 26   2018.1

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    Three-dimensional computed tomography (3D-CT) technologies have been developed and, recently, high-speed and high-quality 3D-CT technologies have been introduced to the field of thoracic surgery. The purpose of this manuscript is to demonstrate the clinical application of 3D-CT technologies in lung transplantation. In Japan, because of the severe donor shortage, living-donor lobar lung transplantation (LDLLT) is essential, in addition to cadaveric lung transplantation. In LDLLT, size matching is a grave issue, since ideal size matching between donor and recipient is usually difficult because of the limited population of potential donor. Size matching using pulmonary function test results has been widely used as a gold standard, but anatomical size matching using 3D-CT volumetry data has also been utilized in LDLLT. In donor lobectomy, 3D-CT images provided a variety of information regarding anatomical variation of pulmonary vessels and bronchial trees preoperatively. These images ensure surgical quality and safety, and they also affect surgical procedures for the recipient. 3D-CT images are also utilized in various aspects of postoperative care, such as detection of chronic lung allograft dysfunction and clarification of its subtypes. Furthermore, preoperative 3D-CT simulation is useful in developing and performing a special surgical procedure, such as right-to-left inverted LDLLT. In conclusion, following the introduction of 3D-CT to the field of thoracic surgery, various 3D-CT images and their application to preoperative simulations have been introduced in lung transplantation. In the near future, this technique will become more prevalent, and frequent use by thoracic surgeons will be seen worldwide in daily practice.

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  142. Clinical application of projection mapping technology for surgical resection of lung metastasis Reviewed

    Toyofumi F. Chen-Yoshikawa, Etsuro Hatano, Atsushi Yoshizawa, Hiroshi Date

    INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY   Vol. 25 ( 6 ) page: 1010 - 1011   2017.12

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    Indocyanine green fluorescent image-guided surgery was developed to identify primary and metastatic nodules of various malignancies. However, currently, surgeons need to identify the fluorescent image on a monitor, which impedes surgical procedures. Herein, we developed a novel projection mapping device that can cast the real-time fluorescent image onto the surface of the targeted organ. We performed surgical resection of a lung metastasis of hepatoblastoma using this technique. The projection mapping technique clearly detected the pulmonary lesion, and no other lesions were identified in the ipsilateral thorax. The patient is well and free of recurrence 2 years after surgery.

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  143. Physical activity level significantly affects the survival of patients with end-stage lung disease on a waiting list for lung transplantation Reviewed

    Teruya Komatsu, Ayako Oshima, Toyofumi F. Chen-Yoshikawa, Shin-ichi Harashima, Akihiro Aoyama, Nobuya Inagaki, Hiroshi Date

    SURGERY TODAY   Vol. 47 ( 12 ) page: 1526 - 1532   2017.12

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    Purpose Our objective was to investigate the factors predicting the survival of patients on the waiting list for lung transplantation (LT) during the waiting period, with a special emphasis on the physical activity level.
    Methods The study included 70 patients with end-stage pulmonary disease who were on the waiting list for LT at Kyoto University Hospital. We examined the association between the baseline characteristics, including the body mass index and body composition, serum albumin, serum C-reactive protein (CRP), steroid administration, physical activity level (calculated by the food frequency questionnaire) and survival during the waiting period using Kaplan-Meier curves and Cox proportional hazard regression models.
    Results A physical activity level of &lt;= 1.2 was correlated with significantly decreased survival (1-year survival: 68 vs. 90.9%, p = 0.0089), with a hazard ratio (HR) of 2.24 (95% confidence interval (CI) 1.22-4.19, p = 0.0001). Hypo-albumin (HR 2.024, 95% CI 1.339-6.009, p = 0.004), a high level of CRP (HR 2.551, CI 1.229-4.892, p = 0.02), and the administration of steroids (HR 2.258, CI 1.907-5.032, p = 0.024) were also significant predictors of survival.
    Conclusions Low levels of physical activity during the waiting period for LT led to decreased survival times among LT candidates.

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  144. Clamping improves your judgment Reviewed

    Toyofumi F. Chen-Yoshikawa

    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY   Vol. 154 ( 5 ) page: E93 - E93   2017.11

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  145. Complications of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Reviewed

    Hidenao Kayawake, Toyofumi F. Chen-Yoshikawa, Hiromi Oda, Hideki Motoyama, Masatsugu Hamaji, Toshi Menju, Akihiro Aoyama, Toshihiko Sato, Makoto Sonobe, Hiroshi Date

    ANNALS OF THORACIC SURGERY   Vol. 104 ( 5 ) page: E363 - E365   2017.11

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    Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is considered useful for the staging and diagnosis of lung cancer or thoracic lymph node enlargement; however, little is known about its complications. Between July 2009 and November 2016, 413 patients underwent EBUS-TBNA, and four complications (0.97%) occurred. Here we report four cases involving complications of EBUS-TBNA, including mediastinitis (n = 2), obstructive pneumonia (n = 1), and airway obstruction requiring admission to the intensive care unit (n = 1). All patients recovered with appropriate medical treatment. Despite their low incidence, the complications associated with EBUS-TBNA can be serious. (C) 2017 by The Society of Thoracic Surgeons

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  146. Cytomegalovirus infection in living-donor and cadaveric lung transplantations Reviewed

    Keiji Ohata, Toyofumi F. Chen-Yoshikawa, Koji Takahashi, Akihiro Aoyama, Hideki Motoyama, Kyoko Hijiya, Masatsugu Hamaji, Toshi Menju, Toshihiko Sato, Makoto Sonobe, Shunji Takakura, Hiroshi Date

    INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY   Vol. 25 ( 5 ) page: 710 - 715   2017.11

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    OBJECTIVES: Cytomegalovirus (CMV) infection remains a major cause of morbidity after lung transplantation. Some studies have reported prognostic factors for the postoperative development of CMV infection in cadaveric lung transplantation (CLT), but no research has been performed in living-donor lobar lung transplantation (LDLLT). Therefore, we analysed the possible risk factors of post-transplant CMV infection and the differences between LDLLT and CLT.
    METHODS: The development of CMV disease and viraemia in 110 patients undergoing lung transplantation at Kyoto University Hospital in 2008-2015 were retrospectively assessed. The prognostic factors in the development of CMV infection and the differences between LDLLT and CLT were analysed.
    RESULTS: Among 110 patients, 58 LDLLTs and 52 CLTs were performed. The 3-year freedom rates from CMV disease and viraemia were 92.0% and 58.5%, respectively. There was no difference in the development of CMV infection between LDLLT and CLT (disease: 94.6% vs 91.0%, P = 0.58 and viraemia: 59.3% vs 57.2%, P = 0.76). In preoperative anti-CMV immunoglobulin status, R-D+ recipients (recipient: negative, donor: positive) and R-D-recipients (recipient: negative, donor: negative) tended to have higher and lower cumulative incidences, respectively, of CMV infection (disease: P = 0.34 and viraemia: P = 0.24) than that with R+ recipients (recipient: seropositive). Significantly lower cumulative incidence of CMV viraemia was observed in patients receiving 12-month prophylactic medication (70.6% vs 36.8%, P &lt; 0.001). Twenty-eight patients (25.5%) had early cessation of anti-CMV prophylaxis due to toxicity; however, the extended prophylaxis duration did not increase the incidence of early cessation (P = 0.88). These trends were seen in both LDLLT and CLT.
    CONCLUSIONS: We found that there was no difference in the development of CMV infection between LDLLT and CLT. Twelve-month prophylaxis protocol provides beneficial effect without increased toxicity also in LDLLT.

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  147. Pulmonary Function and Exercise Capacity in Patients With Flat Chests After Lung Transplantation Reviewed

    Ryo Miyoshi, Toyofumi F. Chen-Yoshikawa, Akihiro Takahagi, Yohei Oshima, Kyoko Hijiya, Hideki Motoyama, Akihiro Aoyama, Hiroshi Date

    ANNALS OF THORACIC SURGERY   Vol. 104 ( 5 ) page: 1695 - 1701   2017.11

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    Background. Severe chest wall deformation is generally a contraindication for lung transplantation; however, it is not known whether patients with flat chests have reduced postoperative exercise capacity and pulmonary function. This study's purpose was to investigate the relationship between preoperative thoracic shape and postoperative exercise capacity and pulmonary function in patients undergoing lung transplantation.& para;& para;Methods. Twenty recipients who underwent successful bilateral living-donor lobar lung transplantation were evaluated. To analyze postoperative graft function in relation to preoperative thoracic shape, 40 donor grafts implanted into 20 recipients were divided into two groups: flat chest group and normal chest group. Flat chest is diagnosed when the thoracic anteroposterior diameter to transverse diameter ratio is 1:3 or less.& para;& para;Results. The ratio of the postoperative forced vital capacity to the preoperatively estimated forced vital capacity was significantly lower in the flat chest group than in the normal chest group 1 year after lung transplantation (p = 0.002). However, there were no significant differences in postoperative 6-minute walk distances between the two groups. Furthermore, the thoracic anteroposterior diameter to transverse diameter ratio in the flat chest group significantly increased after lung transplantation (p = 0.02).& para;& para;Conclusions. Although postoperative pulmonary function was significantly poorer for patients with flat chests than for patients with normal chests, their postoperative exercise capacity was equivalent. We also found that flat chest severity significantly improved after lung transplantation. Our study, the first investigating post operative functional status in patients with flat chests, clearly shows that it is possible to perform lung transplantation in such patients with acceptable outcomes. (C) 2017 by The Society of Thoracic Surgeons

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  148. Superior mesenteric artery syndrome after lung transplantation: a rare early gastrointestinal complication of lung transplantation Reviewed

    Hidenao Kayawake, Toyofumi F. Chen-Yoshikawa, Akihiro Aoyama, Jitian Zhang, Hiroshi Date

    SURGERY TODAY   Vol. 47 ( 11 ) page: 1415 - 1418   2017.11

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    Gastrointestinal complications sometimes occur after lung transplantation and remain a cause of postoperative morbidity. Superior mesenteric artery syndrome is caused by the compression of the duodenum by the superior mesenteric artery, but few reports have described superior mesenteric artery syndrome after lung transplantation. We herein report two cases of superior mesenteric artery syndrome as an early complication after lung transplantation. Both patients were emaciated and had lost weight before transplantation. They also lost an additional 2-4 kg early after transplantation. They were medically treated with enteral nutrition and recovered without recurrence of the syndrome. Since critically ill patients with pulmonary disease usually lose weight both before and early after lung transplantation, superior mesenteric artery syndrome is important to consider in the differential diagnosis of gastrointestinal complications after transplantation.

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  149. Pulmonary venoplasty with a pericardial conduit in living-donor lobar lung retransplantation Reviewed

    Hidenao Kayawake, Toyofumi F. Chen-Yoshikawa, Hideki Motoyama, Hiroshi Date

    INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY   Vol. 25 ( 5 ) page: 830 - 831   2017.11

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    In living-donor lobar lung transplantation, donor lobectomies must be performed carefully for both donors and recipients. Furthermore, the recipients undergo pneumonectomies rather than lobectomies. Occasionally, anastomosis of the pulmonary vessels is difficult in living-donor lobar lung transplantation because of the limited length of the pulmonary vessels in the graft. This report describes a successful case of pulmonary venoplasty using an autologous pericardial conduit, which was interposed between the superior pulmonary vein of the recipient and the inferior pulmonary vein of the donor in living-donor lobar lung retransplantation. This technique may be required for the success of living-donor lobar lung retransplantation.

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  150. Basiliximab for posterior reversible encephalopathy syndrome after lung transplantation Reviewed

    Hiroya Yamagishi, Toyofumi F. Chen-Yoshikawa, Hiroshi Date

    EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY   Vol. 52 ( 4 ) page: 823 - 824   2017.10

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    Posterior reversible encephalopathy syndrome is a neurological complication associated with calcineurin inhibitors. There is no consensus regarding the continuation of calcineurin inhibitors in the event of posterior reversible encephalopathy syndrome. We report 3 cases of posterior reversible encephalopathy syndrome among 155 lung transplant recipients (1.9%). The calcineurin inhibitor trough level exceeded the therapeutic range in only 1 case. Our findings demonstrate that temporary cessation of calcineurin inhibitors and administration of basiliximab may be effective strategies for managing posterior reversible encephalopathy syndrome.

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  151. Severe underweight decreases the survival rate in adult lung transplantation Reviewed

    Teruya Komatsu, Toyofumi F. Chen-Yoshikawa, Ayako Oshima, Shin-ichi Harashima, Akihiro Aoyama, Nobuya Inagaki, Hiroshi Date

    SURGERY TODAY   Vol. 47 ( 10 ) page: 1243 - 1248   2017.10

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    The body mass index (BMI) before lung transplantation (LT) is a benchmark of the post-LT survival. The aim of the study is to determine the BMI inadequate for the post-LT survival.
    We examined the survival after LT in patients grouped into the following BMI categories: &lt; 18.5 kg/m(2) (underweight), 18.5-24.9 kg/m(2) (normal weight), 25-29.9 kg/m(2) (overweight), and 30.0 kg/m(2) (obese) according to the World Health Organization (WHO) criteria. A more detailed categorization was made for further evaluation of the underweight group: mild (17.0 BMI &lt; 18.5 kg/m(2)) and severely underweight (BMI &lt; 17.0 kg/m(2)).
    There was no statistically significant difference in the post-LT survival between underweight and normal-weight patients (5-year survival: 78.7 vs. 76.1%). Patients with BMI &lt; 17.0 kg/m(2) had a worse prognosis than those with 17.0 BMI &lt; 18.5 kg/m(2) (5-year survival: 70.3 vs. 90.0%).
    Standard BMI categorization per the WHO criteria is inadequate for determining the post-LT survival, especially in underweight patients. For the nutritional evaluation of underweight pre-LT patients, BMI &lt; 17.0 kg/m(2) should be used instead of BMI &lt; 18.5 kg/m(2).

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  152. Prognostic factors and outcomes in Japanese lung transplant candidates with interstitial lung disease Reviewed

    Kohei Ikezoe, Tomohiro Handa, Kiminobu Tanizawa, Toyofumi F. Chen-Yoshikawa, Takeshi Kubo, Akihiro Aoyama, Hideki Motoyama, Kyoko Hijiya, Shinsaku Tokuda, Yoshinari Nakatsuka, Yuko Yamamoto, Ayako Oshima, Shin-ichi Harashima, Sonoko Nagai, Toyohiro Hirai, Hiroshi Date, Kazuo Chin

    PLOS ONE   Vol. 12 ( 8 ) page: e0183171   2017.8

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    Objective
    Young patients with advanced interstitial lung disease (ILD) are potential candidates for cadaveric lung transplantation. This study aimed to examine clinical features, outcomes, and prognostic factors in Japanese ILD patients awaiting lung transplantation.
    Methods
    We investigated the clinical features and outcomes of 77 consecutive candidates with ILD who were referred to Kyoto University Hospital and subsequently actively listed for lung transplant in the Japan Organ Transplant Network between 2010 and 2014.
    Results
    Of the 77 candidates, 33 had idiopathic pulmonary fibrosis (IPF) and 15 had unclassifiable ILD. During the observational period, 23 patients (30%) received lung transplantations and 49 patients (64%) died before transplantation. Of the 33 patients with IPF, 13 (39%) had a family history of ILD and 13 (39%) had an inconsistent with usual interstitial pneumonia pattern on high-resolution computed tomography (HRCT). The median survival time from registration was 16.7 months, and mortality was similar among patients with IPF, unclassifiable ILD, and other ILDs. Using a multivariate stepwise Cox proportional hazards model, 6-min walking distance was shown to be an independent prognostic factor in candidates with ILD (per 10 m, hazard ratio (HR): 0.97; 95% confidence interval (CI): 0.95-0.99, p &lt; 0.01), while lower body mass index (HR: 0.83; 95% CI: 0.72-0.95, p &lt; 0.01) independently contributed to mortality in patients with IPF.
    Conclusions
    Japanese patients with ILD awaiting transplantation had very poor outcomes regardless of their specific diagnosis. A substantial percentage of IPF patients had an atypical HRCT pattern. 6-min walking distance in ILD patients and body mass index in IPF patients were independent predictors of mortality.

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  153. Immune function monitoring in lung transplantation using adenosine triphosphate production: time trends and relationship to postoperative infection Reviewed

    Mamoru Takahashi, Akihiro Ohsumi, Keiji Ohata, Takeshi Kondo, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hiroshi Date, Toyofumi F. Chen-Yoshikawa

    SURGERY TODAY   Vol. 47 ( 6 ) page: 762 - 769   2017.6

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    Purpose The ImmuKnow (IK) assay is a comprehensive immune function test that involves measuring adenosine triphosphate produced by the cluster of differentiation 4+ T lymphocytes in peripheral blood. The aim of this study was to analyze the time trends of IK values and assess the relationship between IK values and infections in lung transplants.
    Methods We prospectively collected 178 blood samples from 22 deceased-donor lung transplant (DDLT) recipients and 17 living-donor lobar lung transplant (LDLLT) recipients. A surveillance IK assay was performed postoperatively, then after 1 week and 1, 3, 6, and 12 months.
    Results Time trends of IK values in stable recipients peaked 1 week after DDLT (477 +/- 247 ATP ng/ml), and 1 month after LDLLT (433 +/- 134 ng/ml), followed by a gradual decline over 1 year. The mean IK values in infections were significantly lower than those in the stable state (119 vs 312 ATP ng/ml, p = 0.0002).
    Conclusions IK values increased sharply after lung transplantation and then decreased gradually over time in the first year, suggesting a natural history of immune function. IK values were also significantly reduced during infections. These results may provide new insights into the utility of immune monitoring after lung transplantation.

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  154. Association of Local Intrapulmonary Production of Antibodies Specific to Donor Major Histocompatibility Complex Class I With the Progression of Chronic Rejection of Lung Allografts Reviewed

    Ei Miyamoto, Hideki Motoyama, Masaaki Sato, Akihiro Aoyama, Toshi Menju, Kei Shikuma, Terumasa Sowa, Akihiko Yoshizawa, Masao Saito, Akihiro Takahagi, Satona Tanaka, Mamoru Takahashi, Keiji Ohata, Takeshi Kondo, Kyoko Hijiya, Toyofumi F. Chen-Yoshikawa, Hiroshi Date

    TRANSPLANTATION   Vol. 101 ( 5 ) page: e156 - e165   2017.5

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    Background Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA.
    Methods Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats. Rats that underwent allogeneic lung transplantation were subsequently administered cyclosporine until day 14 (short immunosuppression) or day 35 (long immunosuppression). The lung grafts and spleens of recipient animals were tissue cultured for 4 days, and the titer of antibody against donor major histocompatibility complex molecules was assayed by flow cytometry. Explanted lung grafts were also evaluated pathologically.
    Results By day 98, DSA titers in supernatants of lung graft (P = 0.0074) and spleen (P = 0.0167) cultures, but not serum, from the short immunosuppression group were significantly higher than titers in syngeneic controls. Cultures and sera from the long immunosuppression group showed no production of DSA. Microscopically, the lung grafts from the short immunosuppression group showed severe bronchiole obliteration and parenchymal fibrosis, along with lymphoid aggregates containing T and B cells, accompanying plasma cells. These findings suggestive of local humoral immune response were not observed by days 28 and 63.
    Conclusions DSA can be locally produced in chronically rejected lung allografts, along with intragraft immunocompetent cells. Clinical testing of DSA in serum samples alone may underestimate lung allograft dysfunction.

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  155. Right-to-left inverted living-donor lobar lung transplantation combined with sparing of native right upper lobe Reviewed

    Yasufumi Goda, Hideki Motoyama, Akihiro Aoyama, Masatsugu Hamaji, Kyoko Hijiya, Toyofumi F. Chen-Yoshikawa, Hiroshi Date

    JOURNAL OF HEART AND LUNG TRANSPLANTATION   Vol. 36 ( 5 ) page: 483 - 485   2017.5

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    DOI: 10.1016/j.healun.2016.12.003

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  156. Gastric motility and emptying assessment by magnetic resonance imaging after lung transplantation: correlation with gastric emptying scintigraphy Reviewed

    Nobuyuki Hayakawa, Yuji Nakamoto, Toyofumi F. Chen-Yoshikawa, Aki Kido, Takayoshi Ishimori, Koji Fujimoto, Tetsu Yamada, Masaaki Sato, Akihiro Aoyama, Hiroshi Date, Kaori Togashi

    ABDOMINAL RADIOLOGY   Vol. 42 ( 3 ) page: 818 - 824   2017.3

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    Purpose: Gastroparesis is a frequent gastrointestinal complication after lung transplantation. Although gastric emptying scintigraphy (GES) is the standard technique to evaluate gastroparesis, magnetic resonance imaging (MRI) can also assess gastric motility and emptying. This study compared the results obtained by these two modalities.
    Methods: Twenty-two lung transplant recipients underwent MRI and GES after ingesting a small pancake as a test meal. Parameters assessed on MRI included antral peristaltic wave velocity and frequency, and the ratios of gastric content volume at 15 and 35 min. GES parameters included retention rates (RR) in the stomach at 30, 60, and 120 min (RR30, RR60, and RR120) and half-time of emptying (T1/2) calculated by exponential curve fitting. Correlations between MRI and GES results were evaluated.
    Results: Peristaltic wave velocity showed significant moderate negative correlations with RR120 (r = - 0.58, p &lt; 0.05) and T1/2 (r = - 0.60, p &lt; 0.05), indicating an association between reduced velocity and prolonged gastric emptying. Gastric content volume ratios on MRI showed significant moderate positive correlations with RR30 (r = 0.46, p &lt; 0.05), RR60 (r = 0.60, p &lt; 0.01), and T1/2 (r = 0.60, p &lt; 0.01). There were no significant correlations between peristaltic wave frequency and GES parameters. MRI and GES parameters did not differ significantly between the six patients with and the 16 without upper gastrointestinal symptoms.
    Conclusions: MRI-based determinations of gastric motility and gastric emptying correlate with GES-based gastric emptying in lung transplant recipients, suggesting that MRI is useful for evaluating patients with gastroparesis.

    DOI: 10.1007/s00261-016-0959-5

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  157. Immersing lungs in hydrogen-rich saline attenuates lung ischaemia-reperfusion injury Reviewed

    Mamoru Takahashi, Toyofumi F. Chen-Yoshikawa, Masao Saito, Satona Tanaka, Ei Miyamoto, Keiji Ohata, Takeshi Kondo, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hiroshi Date

    EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY   Vol. 51 ( 3 ) page: 442 - 448   2017.3

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    OBJECTIVES: Anti-oxidant effects of hydrogen have been reported in studies examining ischaemia-reperfusion injury (IRI). In this study, we evaluated the therapeutic efficacy of immersing lungs in hydrogen-rich saline on lung IRI.
    METHODS: Lewis rats were divided into three groups: (i) sham, (ii) normal saline and (iii) hydrogen-rich saline. In the first experiment, the left thoracic cavity was filled with either normal saline or hydrogen-rich saline for 1 h. Then, we measured the hydrogen concentration in the left lung using a sensor gas chromatograph (N = 3 per group). In the second experiment, lung IRI was induced by occlusion of the left pulmonary hilum for 1 h, followed by reperfusion for 3 h. During the ischaemic period, the left thoracic cavity was filled with either normal saline or hydrogen-rich saline. After reperfusion, we assessed lung function, histological changes and cytokine production (N = 5-7 per group).
    RESULTS: Immersing lungs in hydrogen-rich saline resulted in an elevated hydrogen concentration in the lung (6.9 +/- 2.9 mu mol/1 g lung). After IRI, pulmonary function (pulmonary compliance and oxygenation levels) was significantly higher in the hydrogen-rich saline group than in the normal saline group (P &lt; 0.05). Similarly, pro-inflammatory cytokine levels (interleukin-1 beta and interleukin-6) in the left lung were significantly lower in the hydrogen-rich saline group than in the normal saline group (P &lt; 0.05).
    CONCLUSIONS: Immersing lungs in hydrogen-rich saline delivered hydrogen into the lung and consequently attenuated lung IRI. Hydrogen-rich solution appears to be a promising approach to managing lung IRI.

    DOI: 10.1093/ejcts/ezw342

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  158. Living-Donor Lung Transplantation After Bone Marrow Transplantation for Chediak-Higashi Syndrome Reviewed

    Tetsu Yamada, Toyofumi F. Chen-Yoshikawa, Shigeharu Oh, Rieko Ito-Taniguchi, Fumiaki Gochi, Masaaki Sato, Akihiro Aoyama, Hiroshi Date

    ANNALS OF THORACIC SURGERY   Vol. 103 ( 3 ) page: E281 - E283   2017.3

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    An 8-year-old girl with Chediak-Higashi syndrome (CHS) had pulmonary complications after hematopoietic stem cell transplantation (HSCT) for hemophagocytic lymphohistiocytosis (HLH) and eventually underwent single living-donor lobar lung transplantation (LDLLT). Electron micrographic findings showed vagus nerve tissue in extracted lung having granular inclusions, which are pathognomonic for CHS. Because her mother was the donor for both hematopoietic stem cell and lung transplantations, she was weaned from immunosuppression and is doing well 3 years after lung transplantation. Furthermore, an induced pluripotent stem (iPS) cell line was established from her skin fibroblasts for investigation and potential future treatment for CHS. (C) 2017 by The Society of Thoracic Surgeons

    DOI: 10.1016/j.athoracsur.2016.08.049

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  159. Bronchodilator Inhalation During Ex Vivo Lung Perfusion Improves Posttransplant Graft Function After Warm Ischemia Reviewed

    Kyoko Hijiya, Toyofumi F. Chen-Yoshikawa, Takeshi Kondo, Hideki Motoyama, Akihiro Ohsumi, Daisuke Nakajima, Jin Sakamoto, Keiji Ohata, Mamoru Takahashi, Satona Tanaka, Ei Miyamoto, Akihiro Aoyama, Hiroshi Date

    ANNALS OF THORACIC SURGERY   Vol. 103 ( 2 ) page: 447 - 453   2017.2

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    Background. We hypothesized that an injured lung graft from donation after cardiac death donors could be reconditioned before transplantation using an ex vivo lung perfusion (EVLP) system and ventilation with highdose short-acting beta(2)-adrenergic receptor agonists.
    Methods. Cardiac arrest was induced in a canine model by intravenous potassium chloride injection. Lungs were randomly assigned to two groups after 150 minutes of warm ischemia: inhalation of 1,400 mu g of procaterol (BETA group, n = 5) or control group receiving solvent (CON group, n = 5) during EVLP. Left lungs were transplanted after 120 minutes of EVLP. Functional variables, tissue adenosine 5 '-triphosphate levels, and tissue cyclic adenosine monophosphate levels were measured 240 minutes after transplantation.
    Results. Physiologic pulmonary function was similar at the end of EVLP in both groups. However, significantly better graft oxygenation, dynamic pulmonary compliance, and reduced pulmonary vascular resistance were observed in the BETA group than in the CON group 240 minutes after transplantation. No severe adverse effects were observed after lung transplantation in the BETA group. Lung tissue adenosine 5 '-triphosphate levels and cyclic adenosine monophosphate levels were significantly higher in the BETA group than in the CON group at the end of EVLP and at 240 minutes after transplantation.
    Conclusions. High-dose nebulized procaterol during EVLP ameliorated lung graft dysfunction at the early posttransplantation period without severe adverse effects. These data suggest that lung reconditioning with procaterol ventilation during EVLP improves lung graft function after transplantation. (C) 2017 by The Society of Thoracic Surgeons

    DOI: 10.1016/j.athoracsur.2016.07.066

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  160. Excellent outcome of donor lobectomy with various surgical techniques for the interlobar artery Reviewed

    Hidenao Kayawake, Toyofumi F. Chen-Yoshikawa, Akihiro Aoyama, Hideki Motoyama, Kyoko Hijiya, Toshi Menju, Toshihiko Sato, Makoto Sonobe, Hiroshi Date

    EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY   Vol. 51 ( 2 ) page: 279 - 283   2017.2

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    OBJECTIVES: Donor lobectomies in living-donor lobar lung transplantation sometimes require additional surgical procedures on the interlobar pulmonary artery. We retrospectively reviewed the surgical techniques and outcomes of living-donor lobectomy.
    METHODS: Between 2008 and 2015, 116 living-donor lobectomies were performed in 64 consecutive living-donor lobar lung transplantations (52 bilateral, 12 single). The surgical techniques and outcomes were reviewed retrospectively.
    RESULTS: Right lower lobectomies were performed in 69 donors, left lower lobectomies in 45 and middle lobectomies in 2. In 61 living donors (52.6%), small branches of the pulmonary artery were sacrificed for anatomical reasons. Pulmonary arterioplasties to preserve the pulmonary artery branches were performed in 13 donors (11.2%). Thirteen left lower lobectomies with pulmonary arterioplasty were performed to preserve lingular branches, as the lingular branch originated far distal to the superior segmental branch of the left lower lobe. Pulmonary arterioplasty with an autologous pericardial patch in 10 donors and with an end-to-end anastomosis in three donors was performed. All surgical procedures had no complications. Three months after lobectomy, the ratio of the pulmonary function test results to the preoperative values and the complication rate showed no significant differences between donors with and without pulmonary arterioplasties, and donors with and without sacrifice of small branches. All living donors resumed their previous lifestyles without restriction.
    CONCLUSIONS: Although additional surgical procedures were often required in living-donor lobectomies, the donor outcomes were satisfactory. Arterioplasty to close the interlobar artery in the donor was needed in left-sided cases only.

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  161. Loss of SMAD4 Promotes Lung Metastasis of Colorectal Cancer by Accumulation of CCR1(+) Tumor-Associated Neutrophils through CCL15-CCR1 Axis Reviewed

    Takamasa Yamamoto, Kenji Kawada, Yoshiro Itatani, Susumu Inamoto, Ryosuke Okamura, Masayoshi Iwamoto, Ei Miyamoto, Toyofumi F. Chen-Yoshikawa, Hideyo Hirai, Suguru Hasegawa, Hiroshi Date, Makoto M. Taketo, Yoshiharu Sakai

    CLINICAL CANCER RESEARCH   Vol. 23 ( 3 ) page: 833 - 844   2017.2

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    Purpose: We have reported loss of SMAD4 promotes expression of CCL15 from colorectal cancer to recruit CCR1(+) myeloid cells through the CCL15-CCR1 axis, which contributes to invasion and liver metastasis. However, the molecular mechanism of lung metastasis is yet to be elucidated. Our purpose is to determine whether similar mechanism is involved in the lung metastasis of colorectal cancer.
    Experimental Design: In a mouse model, we examined whether SMAD4 could affect the metastatic activity of colorectal cancer cells to the lung through the CCL15-CCR1 axis. We immunohistochemically analyzed expression of SMAD4, CCL15, and CCR1 with 107 clinical specimens of colorectal cancer lung metastases. We also characterized the CCR1(+) myeloid cells using several cell-type-specific markers.
    Results: In a mouse model, CCL15 secreted from SMAD4-deficient colorectal cancer cells recruited CCR1(+) cells, promoting their metastatic activities to the lung. Immunohistochemical analysis of lung metastases from colorectal cancer patients revealed that CCL15 expression was significantly correlated with loss of SMAD4, and that CCL15-positive metastases recruited approximately 1.9 times more numbers of CCR1(+) cells than CCL15-negative metastases. Importantly, patients with CCL15-positive metastases showed a significantly shorter relapse-free survival (RFS) than those with CCL15-negative metastases, and multivariate analysis indicated that CCL15 expression was an independent predictor of shorter RFS. Immunofluorescent staining showed that most CCR1(+) cells around lung metastases were tumor-associated neutrophil, although a minor fraction was granulocytic myeloid-derived suppressor cell.
    Conclusions: CCL15-CCR1 axis may be a therapeutic target to prevent colorectal cancer lung metastasis. CCL15 can be a bio-marker indicating poor prognosis of colorectal cancer patients with lung metastases. (C) 2016 AACR.

    DOI: 10.1158/1078-0432.CCR-16-0520

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  162. Protective Effect of Inhaled Rho-Kinase Inhibitor on Lung Ischemia- Reperfusion Injury Reviewed

    Keiji Ohata, Toyofumi F. Chen-Yoshikawa, Toshi Menju, Ei Miyamoto, Satona Tanaka, Mamoru Takahashi, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Hiroshi Date

    ANNALS OF THORACIC SURGERY   Vol. 103 ( 2 ) page: 476 - 483   2017.2

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    Background. Rho-kinase, an intracellular serine/threonine kinase, is a key regulator of cytoskeletal dynamics. Recent studies have demonstrated that Rho-kinase is involved in the ischemia-reperfusion injury (IRI) pathogenesis of many organs; however, its involvement with lung IRI remains unclear. This study assessed the association of Rho-kinase with lung IRI and evaluated the protective effect of inhaled Rho-kinase inhibitors in lung IRI.
    Methods. The study included isolated rat lung perfusion models, divided into three groups: sham, Rho-kinase inhibitor, and warm ischemia (n = 6 each). The lungs were exposed to 60 minutes of warm ischemia by perfusion cessation. At the onset of ischemia, nebulized fasudil, a novel Rho-kinase inhibitor, and saline were inhaled in the Rho-kinase inhibitor and warm ischemia groups, respectively. Perfusion was restarted after the ischemic period, and physiologic data were collected for 90 minutes. Lungs in the sham group were continuously perfused without ischemia or drug administrations. Protein expression in tissue specimens related to the Rho-kinase pathway was evaluated by Western blotting.
    Results. Warm ischemia and subsequent reperfusion enhanced Rho-kinase activity, and this was suppressed by fasudil inhalation. Fasudil inhalation significantly attenuated IRI pathophysiology, including pulmonary vascular contraction, dynamic compliance, lung edema, and oxygenation. Molecular analysis showed that Rho-kinase suppressed myosin phosphatase and endothelial nitric oxide synthase activities, suggesting these are downstream targets of Rho-kinase during lung IRI pathogenesis.
    Conclusions. The present study suggests that Rho-kinase activation is involved in lung IRI pathogenesis and that inhaled Rho-kinase inhibitors may attenuate this pathogenesis. (Ann Thorac Surg 2017; 103: 476-83) (C) 2017 by The Society of Thoracic Surgeons

    DOI: 10.1016/j.athoracsur.2016.07.067

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  163. Outcomes of various transplant procedures (single, sparing, inverted) in living-donor lobar lung transplantation Reviewed

    Hiroshi Date, Akihiro Aoyama, Kyoko Hijiya, Hideki Motoyama, Tomohiro Handa, Hideyuki Kinoshita, Shiro Baba, Toshiyuki Mizota, Kenji Minakata, Toyofumi F. Chen-Yoshikawa

    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY   Vol. 153 ( 2 ) page: 479 - 486   2017.2

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    Objectives: In standard living-donor lobar lung transplantation (LDLLT), the right and left lower lobes from 2 healthy donors are implanted. Because of the difficulty encountered in finding 2 donors with ideal size matching, various transplant procedures have been developed in our institution. The purpose of this retrospective study was to compare outcomes of nonstandard LDLLT with standard LDLLT.
    Methods: Between June 2008 and January 2016, we performed 65 LDLLTs for critically ill patients. Functional size matching was performed by estimating graft forced vital capacity based on the donor's measured forced vital capacity and the number of pulmonary segments implanted. For anatomical size matching, 3dimensional computed tomography volumetry was performed. In cases of oversize mismatch, single-lobe transplant or downsizing transplant was performed. In cases of undersize mismatch, native upper lobe sparing transplant or rightleft inverted transplant was performed. In right-left inverted transplants, the donor's right lower lobe was inverted and implanted into the recipient's left chest cavity.
    Results: Twenty-nine patients (44.6%) received nonstandard LDLLT, including 12 single-lobe transplants, 7 native upper lobe sparing transplants, 6 right-left inverted transplants, 2 sparing + inverted transplants, and 2 others. Thirty-six patients (57.4%) received standard LDLLT. Three-and five-year survival rates were similar between the 2 groups (89.1% and 76.6% after nonstandard LDLLT vs 78.0% and 71.1% after standard LDLLT, P = .712).
    Conclusions: Various transplant procedures such as single, sparing and inverted transplants are valuable options when 2 donors with ideal size matching are not available for LDLLT.

    DOI: 10.1016/j.jtcvs.2016.10.017

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  164. Hypoxia-inducible factor 1 promotes chemoresistance of lung cancer by inducing carbonic anhydrase IX expression Reviewed

    Terumasa Sowa, Toshi Menju, Toyofumi F. Chen-Yoshikawa, Koji Takahashi, Shigeto Nishikawa, Takao Nakanishi, Kei Shikuma, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Toshihiko Sato, Makoto Sonobe, Hiroshi Harada, Hiroshi Date

    CANCER MEDICINE   Vol. 6 ( 1 ) page: 288 - 297   2017.1

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    Lung cancer treatment is difficult owing to chemoresistance. Hypoxia-inducible factor 1 (HIF-1) and HIF-1-induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF-1 and carbonic anhydrase IX (CAIX), a transmembrane protein neutralizing intracellular acidosis, on chemoresistance and prognosis of lung cancer patients after induction chemoradiotherapy. Associations of HIF-1, glucose transporter 1 (GLUT1), and CAIX with chemoresistance of lung cancer were investigated using A549 lung cancer cells under normoxia or hypoxia in vitro. HIF-1-induced reprogramming of glucose metabolic pathway in A549 cells and the effects of HIF-1 and CAIX on the cytotoxicity of vinorelbine were investigated. Immunohistochemical analyses were performed to determine HIF-1, GLUT1, and CAIX expression levels in cancer specimens from lung cancer patients after induction chemoradiotherapy. Hypoxia induced HIF-1 expression in A549 cells. Moreover, hypoxia induced GLUT1 and CAIX expression in A549 cells in a HIF-1-dependent manner. Glucose metabolic pathway was shifted from oxidative phosphorylation to glycolysis by inducing HIF-1 in A549 cells. HIF-1 and CAIX induced chemoresistance under hypoxia, and their inhibition restored the chemosensitivity of A549 cells. The expression levels of HIF-1, GLUT1, and CAIX were associated with poor overall survival of lung cancer patients after induction chemoradiotherapy. HIF-1 and CAIX affected the chemosensitivity of A549 cells and prognosis of lung cancer patients. Therefore, inhibition of HIF-1 and CAIX might improve prognosis of lung cancer patients after induction chemoradiotherapy. Further analysis might be helpful in developing therapies for lung cancer.

    DOI: 10.1002/cam4.991

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MISC 206

  1. In Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2 Using Human Induced Pluripotent Stem Cell-Derived Alveolar Organoids. Reviewed

      Vol. 13 ( 1 ) page: 235   2019.7

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    DOI: 10.1016/j.stemcr.2019.05.022

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  2. In Vitro Disease Modeling of Hermansky-Pudlak Syndrome Type 2 Using Human Induced Pluripotent Stem Cell-Derived Alveolar Organoids. Reviewed

      Vol. 12 ( 3 ) page: 431-440   2019.3

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    DOI: 10.1016/j.stemcr.2019.01.014

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  3. Dual approach for large mediastinal tumors in the thoracic outlet: transmanubrial osteomuscular sparing approach and video-assisted thoracoscopic surgery. Reviewed

    Kayawake H, Chen-Yoshikawa TF, Date H

    Journal of cardiothoracic surgery   Vol. 14 ( 1 ) page: 42   2019.2

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    DOI: 10.1186/s13019-019-0863-5

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  4. Statins may have double-edged effects in patients with lung adenocarcinoma after lung resection. Reviewed

    Nishikawa S, Menju T, Takahashi K, Miyata R, Chen-Yoshikawa TF, Sonobe M, Yoshizawa A, Sabe H, Sato T, Date H

    Cancer management and research   Vol. 11   page: 3419-3432   2019

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    DOI: 10.2147/CMAR.S200819

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  5. Near-Infrared Imaging Using Intravenous Indocyanine Green at a Conventional Dose to Locate Pulmonary Metastases: A Pilot Study. Reviewed

    Hamaji M, Chen-Yoshikawa TF, Minami M, Date H

    The Thoracic and cardiovascular surgeon     2018.11

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    DOI: 10.1055/s-0038-1675346

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  6. Unilateral Chronic Lung Allograft Dysfunction Assessed by Biphasic Computed Tomographic Volumetry in Bilateral Living-donor Lobar Lung Transplantation. Reviewed

    Saito M, Chen-Yoshikawa TF, Nakamoto Y, Kayawake H, Tokuno J, Ueda S, Yamagishi H, Gochi F, Okabe R, Takahagi A, Hamaji M, Motoyama H, Aoyama A, Date H

    Transplantation direct   Vol. 4 ( 11 ) page: e398   2018.11

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    DOI: 10.1097/TXD.0000000000000839

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  7. Prognostic impact of preoperative comorbidities in geriatric patients with early-stage lung cancer: Significance of sublobar resection as a compromise procedure. Reviewed

    Yutaka Y, Sonobe M, Kawaguchi A, Hamaji M, Nakajima D, Ohsumi A, Menju T, Chen-Yoshikawa TF, Sato T, Date H

    Lung cancer (Amsterdam, Netherlands)   Vol. 125   page: 192-197   2018.11

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    DOI: 10.1016/j.lungcan.2018.09.023

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  8. Effect of early tracheostomy on clinical outcomes in critically ill lung transplant recipients. Reviewed

    Miyoshi R, Chen-Yoshikawa TF, Hamaji M, Kawaguchi A, Kayawake H, Hijiya K, Motoyama H, Aoyama A, Date H

    General thoracic and cardiovascular surgery   Vol. 66 ( 9 ) page: 529-536   2018.9

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    DOI: 10.1007/s11748-018-0949-3

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  9. Gastrointestinal complications after lung transplantation in Japanese patients. Reviewed

    Kayawake H, Chen-Yoshikawa TF, Motoyama H, Hamaji M, Nakajima D, Aoyama A, Date H

    Surgery today   Vol. 48 ( 9 ) page: 883-890   2018.9

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    DOI: 10.1007/s00595-018-1666-3

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  10. Clinical significance of radiological pleuroparenchymal fibroelastosis pattern in interstitial lung disease patients registered for lung transplantation: a retrospective cohort study. Reviewed

    Tanizawa K, Handa T, Kubo T, Chen-Yoshikawa TF, Aoyama A, Motoyama H, Hijiya K, Yoshizawa A, Oshima Y, Ikezoe K, Tokuda S, Nakatsuka Y, Murase Y, Nagai S, Muro S, Oga T, Chin K, Hirai T, Date H

    Respiratory research   Vol. 19 ( 1 ) page: 162   2018.8

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    DOI: 10.1186/s12931-018-0860-6

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  11. GATA6-positive lung adenocarcinomas are associated with invasive mucinous adenocarcinoma morphology, hepatocyte nuclear factor 4α expression, and KRAS mutations. Reviewed

      Vol. 73 ( 1 ) page: 38-48   2018.7

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    DOI: 10.1111/his.13500

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  12. Adjuvant vinorelbine and cisplatin after complete resection of stage II and III non-small cell lung cancer: long-term follow-up of our study of Japanese patients. Reviewed

    Sonobe M, Hamaji M, Motoyama H, Menju T, Aoyama A, Chen-Yoshikawa TF, Sato T, Date H

    Surgery today   Vol. 48 ( 7 ) page: 687-694   2018.7

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    DOI: 10.1007/s00595-018-1646-7

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  13. Surgical management of bronchial stumps in lobar lung transplantation. Reviewed

    Kayawake H, Chen-Yoshikawa TF, Aoyama A, Motoyama H, Hamaji M, Hijiya K, Date H

    The Journal of thoracic and cardiovascular surgery   Vol. 156 ( 1 ) page: 451-460   2018.7

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    DOI: 10.1016/j.jtcvs.2017.10.150

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  14. Lung transplantation after haematopoietic stem cell transplantation for Wiskott-Aldrich syndrome. Reviewed

    Ueda S, Chen-Yoshikawa TF, Hijiya K, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 53 ( 6 ) page: 1286-1287   2018.6

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    DOI: 10.1093/ejcts/ezx461

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  15. Anterior mediastinal tissue volume is correlated with antiacetylcholine receptor antibody level in myasthenia gravis. Reviewed

    Takahagi A, Omasa M, Chen-Yoshikawa TF, Hamaji M, Yoshizawa A, Sozu T, Sonobe M, Date H

    The Journal of thoracic and cardiovascular surgery   Vol. 155 ( 6 ) page: 2738-2744   2018.6

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    DOI: 10.1016/j.jtcvs.2017.10.082

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  16. Transition of the programmed death 1 pathway from the primary colorectal cancer to its corresponding pulmonary metastasis. Reviewed

    Miyamoto E, Chen-Yoshikawa TF, Ueshima C, Yoshizawa A, Hamaji M, Yamamoto T, Kawada K, Haga H, Sakai Y, Date H

    Journal of surgical oncology   Vol. 117 ( 7 ) page: 1405-1412   2018.6

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    DOI: 10.1002/jso.25045

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  17. Diagnostic yield of electromagnetic navigational bronchoscopy: results of initial 35 cases in a Japanese institute. Reviewed

    Sato T, Yutaka Y, Ueda Y, Hamaji M, Motoyama H, Menju T, Aoyama A, Chen-Yoshikawa TF, Sonobe M, Date H

    Journal of thoracic disease   Vol. 10 ( Suppl 14 ) page: S1615-S1619   2018.6

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    DOI: 10.21037/jtd.2018.04.123

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  18. Successful conservative management of an anastomotic airway dehiscence at the left main bronchus following bilateral cadaveric lung transplantation. Reviewed

    Miyata R, Chen-Yoshikawa TF, Hamaji M, Gochi F, Motoyama H, Menju T, Aoyama A, Sato T, Sonobe M, Date H

    General thoracic and cardiovascular surgery   Vol. 66 ( 6 ) page: 368-371   2018.6

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    DOI: 10.1007/s11748-017-0826-5

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  19. Nontuberculous mycobacterial and Aspergillus infections among cadaveric lung transplant recipients in Japan. Reviewed

    Tachibana K, Okada Y, Matsuda Y, Miyoshi K, Oto T, Chen-Yoshikawa TF, Date H, Minami M, Okumura M, Iwasaki A, Shiraishi T, Maeda S, Matsumura Y, Nakajima T, Yoshino I, Hayashi S

    Respiratory investigation   Vol. 56 ( 3 ) page: 243-248   2018.5

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    DOI: 10.1016/j.resinv.2017.12.010

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  20. Surgery for metachronous second primary lung cancer versus surgery for primary lung cancer: a propensity score-matched comparison of postoperative complications and survival outcomes. Reviewed

    Muranishi Y, Sonobe M, Hamaji M, Kawaguchi A, Hijiya K, Motoyama H, Menju T, Aoyama A, Chen-Yoshikawa TF, Sato T, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 26 ( 4 ) page: 631-637   2018.4

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    DOI: 10.1093/icvts/ivx389

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  21. Inverted Lobes Have Satisfactory Functions Compared With Noninverted Lobes in Lung Transplantation. Reviewed

    Kayawake H, Chen-Yoshikawa TF, Motoyama H, Hamaji M, Hijiya K, Aoyama A, Goda Y, Oda H, Ueda S, Date H

    The Annals of thoracic surgery   Vol. 105 ( 4 ) page: 1044-1049   2018.4

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    DOI: 10.1016/j.athoracsur.2017.11.034

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  22. Radiologic and Functional Analysis of Compensatory Lung Growth After Living-Donor Lobectomy. Reviewed

    Shikuma K, Chen-Yoshikawa TF, Oguma T, Kubo T, Ohata K, Hamaji M, Kawaguchi A, Motoyama H, Hijiya K, Aoyama A, Matsumoto H, Muro S, Date H

    The Annals of thoracic surgery   Vol. 105 ( 3 ) page: 909-914   2018.3

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    DOI: 10.1016/j.athoracsur.2017.09.060

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  23. Wise surgeons learn from others' experiences. Reviewed

    Chen-Yoshikawa TF

    The Journal of thoracic and cardiovascular surgery   Vol. 155 ( 3 ) page: e115   2018.3

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    DOI: 10.1016/j.jtcvs.2017.11.047

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  24. Late-onset chest wall abscess due to a biodegradable rib pin infection after lung transplantation. Reviewed

    Goda Y, Chen-Yoshikawa TF, Kusunose M, Hamaji M, Motoyama H, Hijiya K, Aoyama A, Date H

    General thoracic and cardiovascular surgery   Vol. 66 ( 3 ) page: 175-178   2018.3

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    DOI: 10.1007/s11748-017-0768-y

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  25. The synergistic role of ATP-dependent drug efflux pump and focal adhesion signaling pathways in vinorelbine resistance in lung cancer. Reviewed

    Nakanishi T, Menju T, Nishikawa S, Takahashi K, Miyata R, Shikuma K, Sowa T, Imamura N, Hamaji M, Motoyama H, Hijiya K, Aoyama A, Sato T, Chen-Yoshikawa TF, Sonobe M, Date H

    Cancer medicine   Vol. 7 ( 2 ) page: 408-419   2018.2

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    DOI: 10.1002/cam4.1282

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  26. Three-dimensional image in lung transplantation. Reviewed

    Chen-Yoshikawa TF, Date H

    General thoracic and cardiovascular surgery   Vol. 66 ( 1 ) page: 19-26   2018.1

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    DOI: 10.1007/s11748-017-0849-y

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  27. Pulmonary endothelial chimerism after hematopoietic stem cell transplantation. Reviewed

    Hijiya K, Chen-Yoshikawa TF, Miyagawa-Hayashino A, Kondo T, Aoyama A, Haga H, Takaori-Kondo A, Date H

    Surgery today   Vol. 48 ( 1 ) page: 101-109   2018.1

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    DOI: 10.1007/s00595-017-1562-2

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  28. Prognostic Factors in Lung Transplantation After Hematopoietic Stem Cell Transplantation. Reviewed

    Chen-Yoshikawa TF, Sugimoto S, Shiraishi T, Minami M, Matsuda Y, Chida M, Maeda S, Aoyama A, Okada Y, Okumura M, Iwasaki A, Miyoshi S, Oto T, Date H

    Transplantation   Vol. 102 ( 1 ) page: 154-161   2018.1

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    DOI: 10.1097/TP.0000000000001886

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  29. Clinical application of projection mapping technology for surgical resection of lung metastasis. Reviewed

    Chen-Yoshikawa TF, Hatano E, Yoshizawa A, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 25 ( 6 ) page: 1010-1011   2017.12

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    DOI: 10.1093/icvts/ivx247

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  30. Physical activity level significantly affects the survival of patients with end-stage lung disease on a waiting list for lung transplantation. Reviewed

    Komatsu T, Oshima A, Chen-Yoshikawa TF, Harashima SI, Aoyama A, Inagaki N, Date H

    Surgery today   Vol. 47 ( 12 ) page: 1526-1532   2017.12

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    DOI: 10.1007/s00595-017-1542-6

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  31. Cytomegalovirus infection in living-donor and cadaveric lung transplantations. Reviewed

    Ohata K, Chen-Yoshikawa TF, Takahashi K, Aoyama A, Motoyama H, Hijiya K, Hamaji M, Menju T, Sato T, Sonobe M, Takakura S, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 25 ( 5 ) page: 710-715   2017.11

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    DOI: 10.1093/icvts/ivx226

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  32. Pulmonary venoplasty with a pericardial conduit in living-donor lobar lung retransplantation. Reviewed

    Kayawake H, Chen-Yoshikawa TF, Motoyama H, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 25 ( 5 ) page: 830-831   2017.11

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    DOI: 10.1093/icvts/ivx122

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  33. Complications of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration. Reviewed

    Kayawake H, Chen-Yoshikawa TF, Oda H, Motoyama H, Hamaji M, Menju T, Aoyama A, Sato T, Sonobe M, Date H

    The Annals of thoracic surgery   Vol. 104 ( 5 ) page: e363-e365   2017.11

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    DOI: 10.1016/j.athoracsur.2017.06.015

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  34. Pulmonary Function and Exercise Capacity in Patients With Flat Chests After Lung Transplantation. Reviewed

    Miyoshi R, Chen-Yoshikawa TF, Takahagi A, Oshima Y, Hijiya K, Motoyama H, Aoyama A, Date H

    The Annals of thoracic surgery   Vol. 104 ( 5 ) page: 1695-1701   2017.11

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    DOI: 10.1016/j.athoracsur.2017.06.023

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  35. Superior mesenteric artery syndrome after lung transplantation: a rare early gastrointestinal complication of lung transplantation. Reviewed

    Kayawake H, Chen-Yoshikawa TF, Aoyama A, Zhang J, Date H

    Surgery today   Vol. 47 ( 11 ) page: 1415-1418   2017.11

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    DOI: 10.1007/s00595-017-1513-y

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  36. Clamping improves your judgment. Reviewed

    Chen-Yoshikawa TF

    The Journal of thoracic and cardiovascular surgery   Vol. 154 ( 5 ) page: e93   2017.11

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    DOI: 10.1016/j.jtcvs.2017.07.041

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  37. Basiliximab for posterior reversible encephalopathy syndrome after lung transplantation. Reviewed

    Yamagishi H, Chen-Yoshikawa TF, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 52 ( 4 ) page: 823-824   2017.10

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    DOI: 10.1093/ejcts/ezx151

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  38. Severe underweight decreases the survival rate in adult lung transplantation. Reviewed

    Komatsu T, Chen-Yoshikawa TF, Oshima A, Harashima SI, Aoyama A, Inagaki N, Date H

    Surgery today   Vol. 47 ( 10 ) page: 1243-1248   2017.10

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    DOI: 10.1007/s00595-017-1508-8

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  39. Immune function monitoring in lung transplantation using adenosine triphosphate production: time trends and relationship to postoperative infection. Reviewed

    Takahashi M, Ohsumi A, Ohata K, Kondo T, Motoyama H, Hijiya K, Aoyama A, Date H, Chen-Yoshikawa TF

    Surgery today   Vol. 47 ( 6 ) page: 762-769   2017.6

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    DOI: 10.1007/s00595-016-1440-3

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  40. Association of Local Intrapulmonary Production of Antibodies Specific to Donor Major Histocompatibility Complex Class I With the Progression of Chronic Rejection of Lung Allografts. Reviewed

    Miyamoto E, Motoyama H, Sato M, Aoyama A, Menju T, Shikuma K, Sowa T, Yoshizawa A, Saito M, Takahagi A, Tanaka S, Takahashi M, Ohata K, Kondo T, Hijiya K, Chen-Yoshikawa TF, Date H

    Transplantation   Vol. 101 ( 5 ) page: e156-e165   2017.5

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    DOI: 10.1097/TP.0000000000001665

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  41. Right-to-left inverted living-donor lobar lung transplantation combined with sparing of native right upper lobe. Reviewed

    Goda Y, Motoyama H, Aoyama A, Hamaji M, Hijiya K, Chen-Yoshikawa TF, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 36 ( 5 ) page: 483-485   2017.5

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    DOI: 10.1016/j.healun.2016.12.003

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  42. Immersing lungs in hydrogen-rich saline attenuates lung ischaemia-reperfusion injury. Reviewed

    Takahashi M, Chen-Yoshikawa TF, Saito M, Tanaka S, Miyamoto E, Ohata K, Kondo T, Motoyama H, Hijiya K, Aoyama A, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 51 ( 3 ) page: 442-448   2017.3

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    DOI: 10.1093/ejcts/ezw342

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  43. Living-Donor Lung Transplantation After Bone Marrow Transplantation for Chediak-Higashi Syndrome. Reviewed

    Yamada T, Chen-Yoshikawa TF, Oh S, Ito-Taniguchi R, Gochi F, Sato M, Aoyama A, Date H

    The Annals of thoracic surgery   Vol. 103 ( 3 ) page: e281-e283   2017.3

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    DOI: 10.1016/j.athoracsur.2016.08.049

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  44. Gastric motility and emptying assessment by magnetic resonance imaging after lung transplantation: correlation with gastric emptying scintigraphy. Reviewed

    Hayakawa N, Nakamoto Y, Chen-Yoshikawa TF, Kido A, Ishimori T, Fujimoto K, Yamada T, Sato M, Aoyama A, Date H, Togashi K

    Abdominal radiology (New York)   Vol. 42 ( 3 ) page: 818-824   2017.3

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    DOI: 10.1007/s00261-016-0959-5

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  45. Excellent outcome of donor lobectomy with various surgical techniques for the interlobar artery. Reviewed

    Kayawake H, Chen-Yoshikawa TF, Aoyama A, Motoyama H, Hijiya K, Menju T, Sato T, Sonobe M, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 51 ( 2 ) page: 279-283   2017.2

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    DOI: 10.1093/ejcts/ezw298

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  46. Loss of SMAD4 Promotes Lung Metastasis of Colorectal Cancer by Accumulation of CCR1+ Tumor-Associated Neutrophils through CCL15-CCR1 Axis. Reviewed

    Yamamoto T, Kawada K, Itatani Y, Inamoto S, Okamura R, Iwamoto M, Miyamoto E, Chen-Yoshikawa TF, Hirai H, Hasegawa S, Date H, Taketo MM, Sakai Y

    Clinical cancer research : an official journal of the American Association for Cancer Research   Vol. 23 ( 3 ) page: 833-844   2017.2

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    DOI: 10.1158/1078-0432.CCR-16-0520

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  47. Outcomes of various transplant procedures (single, sparing, inverted) in living-donor lobar lung transplantation. Reviewed

    Date H, Aoyama A, Hijiya K, Motoyama H, Handa T, Kinoshita H, Baba S, Mizota T, Minakata K, Chen-Yoshikawa TF

    The Journal of thoracic and cardiovascular surgery   Vol. 153 ( 2 ) page: 479-486   2017.2

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    DOI: 10.1016/j.jtcvs.2016.10.017

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  48. Bronchodilator Inhalation During Ex Vivo Lung Perfusion Improves Posttransplant Graft Function After Warm Ischemia. Reviewed

      Vol. 103 ( 2 ) page: 447-453   2017.2

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    DOI: 10.1016/j.athoracsur.2016.07.066

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  49. Protective Effect of Inhaled Rho-Kinase Inhibitor on Lung Ischemia-Reperfusion Injury. Reviewed

    Ohata K, Chen-Yoshikawa TF, Menju T, Miyamoto E, Tanaka S, Takahashi M, Motoyama H, Hijiya K, Aoyama A, Date H

    The Annals of thoracic surgery   Vol. 103 ( 2 ) page: 476-483   2017.2

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    DOI: 10.1016/j.athoracsur.2016.07.067

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  50. Hypoxia-inducible factor 1 promotes chemoresistance of lung cancer by inducing carbonic anhydrase IX expression. Reviewed

    Sowa T, Menju T, Chen-Yoshikawa TF, Takahashi K, Nishikawa S, Nakanishi T, Shikuma K, Motoyama H, Hijiya K, Aoyama A, Sato T, Sonobe M, Harada H, Date H

    Cancer medicine   Vol. 6 ( 1 ) page: 288-297   2017.1

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    DOI: 10.1002/cam4.991

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  51. Prognostic factors and outcomes in Japanese lung transplant candidates with interstitial lung disease. Reviewed

    Ikezoe K, Handa T, Tanizawa K, Chen-Yoshikawa TF, Kubo T, Aoyama A, Motoyama H, Hijiya K, Tokuda S, Nakatsuka Y, Yamamoto Y, Oshima A, Harashima SI, Nagai S, Hirai T, Date H, Chin K

    PloS one   Vol. 12 ( 8 ) page: e0183171   2017

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    DOI: 10.1371/journal.pone.0183171

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  52. Erratum to: Malignancies after living-donor and cadaveric lung transplantations in Japanese patients. Reviewed

    Tanaka S, Chen-Yoshikawa TF, Yamada T, Hijiya K, Motoyama H, Aoyama A, Date H

    Surgery today   Vol. 46 ( 12 ) page: 1420   2016.12

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    DOI: 10.1007/s00595-016-1400-y

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  53. Malignancies after living-donor and cadaveric lung transplantations in Japanese patients. Reviewed

    Tanaka S, Chen-Yoshikawa TF, Yamada T, Hijiya K, Motoyama H, Aoyama A, Date H

    Surgery today   Vol. 46 ( 12 ) page: 1415-1419   2016.12

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    DOI: 10.1007/s00595-016-1327-3

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  54. Protective Effects of Imatinib on Ischemia/Reperfusion Injury in Rat Lung. Reviewed

    Tanaka S, Chen-Yoshikawa TF, Kajiwara M, Menju T, Ohata K, Takahashi M, Kondo T, Hijiya K, Motoyama H, Aoyama A, Masuda S, Date H

    The Annals of thoracic surgery   Vol. 102 ( 5 ) page: 1717-1724   2016.11

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    DOI: 10.1016/j.athoracsur.2016.05.037

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  55. Surgical and non-surgical management of repeat pulmonary metastasis from sarcoma following first pulmonary metastasectomy. Reviewed

    Hamaji M, Chen F, Miyamoto E, Kondo T, Ohata K, Motoyama H, Hijiya K, Menju T, Aoyama A, Sato T, Sonobe M, Date H

    Surgery today   Vol. 46 ( 11 ) page: 1296-300   2016.11

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    DOI: 10.1007/s00595-016-1312-x

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  56. [Characteristics of Postoperative Malignancies after Lung Transplantation]. Reviewed

    Tanaka S, Chen-Yoshikawa TF, Hijiya K, Hamaji M, Motoyama H, Aoyama A, Date H

    Kyobu geka. The Japanese journal of thoracic surgery   Vol. 69 ( 11 ) page: 935-939   2016.10

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  57. Pulmonary Arterioplasty With End-to-End Anastomosis of the Lingular Branch to the Interlobar Pulmonary Artery in Living-Donor Lobectomy. Reviewed

      Vol. 102 ( 4 ) page: e351-2   2016.10

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    DOI: 10.1016/j.athoracsur.2016.03.052

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  58. Off-Pump Bilateral Cadaveric Lung Transplantation Is Associated With Profound Intraoperative Hypothermia. Reviewed

    Dong L, Mizota T, Tanaka T, Chen-Yoshikawa TF, Date H, Fukuda K

    Journal of cardiothoracic and vascular anesthesia   Vol. 30 ( 4 ) page: 924-9   2016.8

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    DOI: 10.1053/j.jvca.2016.03.014

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  59. Reply. Reviewed

    Kondo T, Chen-Yoshikawa TF, Date H

    The Annals of thoracic surgery   Vol. 102 ( 1 ) page: 347   2016.7

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    DOI: 10.1016/j.athoracsur.2016.02.028

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  60. Separate pulmonary venous anastomoses using a left atrial appendage in a left single lung transplantation. Reviewed

    Chen-Yoshikawa TF, Goda Y, Dong L, Date H

    The Journal of thoracic and cardiovascular surgery   Vol. 152 ( 1 ) page: e11-2   2016.7

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    DOI: 10.1016/j.jtcvs.2016.01.046

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  61. Vascular Endothelial-Cadherin Expression After Reperfusion Correlates With Lung Injury in Rat Lung Transplantation. Reviewed

    Tanaka S, Chen-Yoshikawa TF, Miyamoto E, Takahashi M, Ohata K, Kondo T, Hijiya K, Motoyama H, Aoyama A, Date H

    The Annals of thoracic surgery   Vol. 101 ( 6 ) page: 2161-7   2016.6

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    DOI: 10.1016/j.athoracsur.2016.01.040

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  62. Is volumetric 3-dimensional computed tomography useful to predict histological tumour invasiveness? Analysis of 211 lesions of cT1N0M0 lung adenocarcinoma. Reviewed

    Shikuma K, Menju T, Chen F, Kubo T, Muro S, Sumiyoshi S, Ohata K, Sowa T, Nakanishi T, Cho H, Neri S, Aoyama A, Sato T, Sonobe M, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 22 ( 6 ) page: 831-8   2016.6

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    DOI: 10.1093/icvts/ivw037

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  63. Inhibition of Toll-like receptor 4 signaling ameliorates lung ischemia-reperfusion injury in acute hyperglycemic conditions. Reviewed

    Takahashi M, Chen-Yoshikawa TF, Menju T, Ohata K, Kondo T, Motoyama H, Hijiya K, Aoyama A, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 35 ( 6 ) page: 815-22   2016.6

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    DOI: 10.1016/j.healun.2015.12.032

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  64. Bronchial involvement in advanced stage lymphangioleiomyomatosis: histopathologic and molecular analyses. Reviewed

    Hayashi T, Kumasaka T, Mitani K, Okada Y, Kondo T, Date H, Chen F, Oto T, Miyoshi S, Shiraishi T, Iwasaki A, Hara K, Saito T, Ando K, Kobayashi E, Gunji-Niitsu Y, Kunogi M, Takahashi K, Yao T, Seyama K

    Human pathology   Vol. 50   page: 34-42   2016.4

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    DOI: 10.1016/j.humpath.2015.11.002

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  65. Serial perfusion in native lungs in patients with idiopathic pulmonary fibrosis and other interstitial lung diseases after single lung transplantation. Reviewed

    Sokai A, Handa T, Chen F, Tanizawa K, Aoyama A, Kubo T, Ikezoe K, Nakatsuka Y, Oguma T, Hirai T, Nagai S, Chin K, Date H, Mishima M

    Clinical transplantation   Vol. 30 ( 4 ) page: 407-14   2016.4

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    DOI: 10.1111/ctr.12701

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  66. Update on three-dimensional image reconstruction for preoperative simulation in thoracic surgery. Reviewed

    Chen-Yoshikawa TF, Date H

    Journal of thoracic disease   Vol. 8 ( Suppl 3 ) page: S295-301   2016.3

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  67. Graft dysfunction immediately after reperfusion predicts short-term outcomes in living-donor lobar lung transplantation but not in cadaveric lung transplantation. Reviewed

    Mizota T, Miyao M, Yamada T, Sato M, Aoyama A, Chen F, Date H, Fukuda K

    Interactive cardiovascular and thoracic surgery   Vol. 22 ( 3 ) page: 314-20   2016.3

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    DOI: 10.1093/icvts/ivv357

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  68. Stenosis of the segmental bronchus is a characteristic airway complication in living-donor lobar lung transplantation. Reviewed

    Miyamoto E, Chen-Yoshikawa TF, Higuchi H, Aoyama A, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 35 ( 3 ) page: 389-392   2016.3

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    DOI: 10.1016/j.healun.2015.11.001

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  69. Diagnostic and Therapeutic Assist Using 3D Images and Printers in the Respiratory Field. Reviewed

    Chen-Yoshikawa TF

    Nihon Hoshasen Gijutsu Gakkai zasshi   Vol. 72 ( 2 ) page: 167-70   2016.2

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    DOI: 10.6009/jjrt.2016_JSRT_72.2.167

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  70. Significance of single lung transplantation in the current situation of severe donor shortage in Japan. Reviewed

    Miyoshi R, Chen-Yoshikawa TF, Hijiya K, Motoyama H, Aoyama A, Menju T, Sato T, Sonobe M, Date H

    General thoracic and cardiovascular surgery   Vol. 64 ( 2 ) page: 93-7   2016.2

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    DOI: 10.1007/s11748-015-0610-3

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  71. Reply. Reviewed

    Kondo T, Chen F, Date H

    The Annals of thoracic surgery   Vol. 101 ( 1 ) page: 412   2016.1

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    DOI: 10.1016/j.athoracsur.2015.08.072

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  72. Thymic cancer mimicking a metastasis of testicular seminoma. Reviewed

    Fukui T, Terada N, Takeda M, Inoue T, Kamba T, Yoshimura K, Chen F, Ogawa O

    International cancer conference journal   Vol. 5 ( 1 ) page: 45-47   2016.1

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    DOI: 10.1007/s13691-015-0223-9

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  73. Lung Transplantation for Lymphangioleiomyomatosis in Japan. Reviewed

    Ando K, Okada Y, Akiba M, Kondo T, Kawamura T, Okumura M, Chen F, Date H, Shiraishi T, Iwasaki A, Yamasaki N, Nagayasu T, Chida M, Inoue Y, Hirai T, Seyama K, Mishima M, Respiratory Failure Research Group of the Japanese Ministry of Health Labour and Welfare.

    PloS one   Vol. 11 ( 1 ) page: e0146749   2016

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    DOI: 10.1371/journal.pone.0146749

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  74. Association between epithelial-mesenchymal transition and cancer stemness and their effect on the prognosis of lung adenocarcinoma. Reviewed

    Sowa T, Menju T, Sonobe M, Nakanishi T, Shikuma K, Imamura N, Motoyama H, Hijiya K, Aoyama A, Chen F, Sato T, Kobayashi M, Yoshizawa A, Haga H, Sozu T, Date H

    Cancer medicine   Vol. 4 ( 12 ) page: 1853-62   2015.12

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    DOI: 10.1002/cam4.556

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  75. Gefitinib treatment in patients with postoperative recurrent non-small-cell lung cancer harboring epidermal growth factor receptor gene mutations. Reviewed

    Yokoyama Y, Sonobe M, Yamada T, Sato M, Menju T, Aoyama A, Sato T, Chen F, Omasa M, Date H

    International journal of clinical oncology   Vol. 20 ( 6 ) page: 1122-9   2015.12

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    DOI: 10.1007/s10147-015-0838-z

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  76. Reply: To PMID 25661580. Reviewed

    Hamaji M, Chen F, Kawaguchi A, Morita S, Date H

    The Annals of thoracic surgery   Vol. 100 ( 5 ) page: 1968-9   2015.11

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    DOI: 10.1016/j.athoracsur.2015.05.082

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  77. Treatment and Prognosis of Isolated Local Relapse after Stereotactic Body Radiotherapy for Clinical Stage I Non-Small-Cell Lung Cancer: Importance of Salvage Surgery. Reviewed

    Hamaji M, Chen F, Matsuo Y, Ueki N, Hiraoka M, Date H

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer   Vol. 10 ( 11 ) page: 1616-24   2015.11

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    DOI: 10.1097/JTO.0000000000000662

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  78. Predictive factors of myasthenic crisis after extended thymectomy for patients with myasthenia gravis. Reviewed

    Ando T, Omasa M, Kondo T, Yamada T, Sato M, Menju T, Aoyama A, Sato T, Chen F, Sonobe M, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 48 ( 5 ) page: 705-9; discussion 709   2015.11

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    DOI: 10.1093/ejcts/ezu530

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  79. Update on ischemia-reperfusion injury in lung transplantation. Reviewed

    Chen F, Date H

    Current opinion in organ transplantation   Vol. 20 ( 5 ) page: 515-20   2015.10

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    DOI: 10.1097/MOT.0000000000000234

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  80. Lung autotransplantation technique for postpneumonectomy-like syndrome. Reviewed

    Chen F, Takahagi A, Sakamoto K, Date H

    The Journal of thoracic and cardiovascular surgery   Vol. 150 ( 3 ) page: e45-7   2015.9

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    DOI: 10.1016/j.jtcvs.2015.06.048

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  81. Relationship Between 18F-FDG PET/CT Scans and KRAS Mutations in Metastatic Colorectal Cancer. Reviewed

    Kawada K, Toda K, Nakamoto Y, Iwamoto M, Hatano E, Chen F, Hasegawa S, Togashi K, Date H, Uemoto S, Sakai Y

    Journal of nuclear medicine : official publication, Society of Nuclear Medicine   Vol. 56 ( 9 ) page: 1322-7   2015.9

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    DOI: 10.2967/jnumed.115.160614

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  82. Unilateral chronic lung allograft dysfunction is a characteristic of bilateral living-donor lobar lung transplantation. Reviewed

    Miyamoto E, Chen F, Aoyama A, Sato M, Yamada T, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 48 ( 3 ) page: 463-9   2015.9

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    DOI: 10.1093/ejcts/ezu463

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  83. β2-Adrenoreceptor Agonist Inhalation During Ex Vivo Lung Perfusion Attenuates Lung Injury. Reviewed

      Vol. 100 ( 2 ) page: 480-6   2015.8

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    DOI: 10.1016/j.athoracsur.2015.02.136

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  84. The clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation. Reviewed

    Mizota T, Matsukawa S, Fukagawa H, Daijo H, Tanaka T, Chen F, Date H, Fukuda K

    Journal of anesthesia   Vol. 29 ( 4 ) page: 562-9   2015.8

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    DOI: 10.1007/s00540-015-1986-z

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  85. Postoperative pulmonary function and complications in living-donor lobectomy. Reviewed

    Chen F, Yamada T, Sato M, Aoyama A, Takahagi A, Menju T, Sato T, Sonobe M, Omasa M, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 34 ( 8 ) page: 1089-94   2015.8

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    DOI: 10.1016/j.healun.2015.03.016

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  86. Imatinib for sclerodermatous graft-versus-host disease in lung transplantation. Reviewed

    Zhang J, Chen F, Ueki T, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 21 ( 2 ) page: 260-2   2015.8

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    DOI: 10.1093/icvts/ivv122

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  87. Preoperative Hypercapnia as a Predictor of Hypotension During Anesthetic Induction in Lung Transplant Recipients. Reviewed

    Mizota T, Matsukawa S, Fukagawa H, Daijo H, Tanaka T, Chen F, Date H, Fukuda K

    Journal of cardiothoracic and vascular anesthesia   Vol. 29 ( 4 ) page: 967-71   2015.8

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    DOI: 10.1053/j.jvca.2014.10.027

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  88. Lung allocation score and health-related quality of life in Japanese candidates for lung transplantation. Reviewed

    Chen F, Oga T, Yamada T, Sato M, Aoyama A, Chin K, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 21 ( 1 ) page: 28-33   2015.7

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    DOI: 10.1093/icvts/ivv101

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  89. Factors affecting the preoperative diagnosis of anterior mediastinal cysts. Reviewed

    Gochi F, Omasa M, Yamada T, Sato M, Menju T, Aoyama A, Sato T, Chen F, Sonobe M, Date H

    General thoracic and cardiovascular surgery   Vol. 63 ( 6 ) page: 349-53   2015.6

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    DOI: 10.1007/s11748-015-0530-2

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  90. Living-donor lobar lung transplantation provides similar survival to cadaveric lung transplantation even for very ill patients†. Reviewed

      Vol. 47 ( 6 ) page: 967-72; discussion 972-3   2015.6

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    DOI: 10.1093/ejcts/ezu350

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  91. Impact of the cardiac arrest mode on cardiac death donor lungs. Reviewed

    Yamada T, Chen F, Sakamoto J, Nakajima D, Ohsumi A, Bando T, Date H

    The Journal of surgical research   Vol. 195 ( 2 ) page: 596-603   2015.5

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    DOI: 10.1016/j.jss.2015.02.029

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  92. Video-assisted thoracoscopic lobectomy versus stereotactic radiotherapy for stage I lung cancer. Reviewed

    Hamaji M, Chen F, Matsuo Y, Kawaguchi A, Morita S, Ueki N, Sonobe M, Nagata Y, Hiraoka M, Date H

    The Annals of thoracic surgery   Vol. 99 ( 4 ) page: 1122-9   2015.4

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    DOI: 10.1016/j.athoracsur.2014.11.009

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  93. Clinical application of ET-Kyoto solution for lung transplantation. Reviewed

    Ikeda M, Bando T, Yamada T, Sato M, Menjyu T, Aoyama A, Sato T, Chen F, Sonobe M, Omasa M, Date H

    Surgery today   Vol. 45 ( 4 ) page: 439-43   2015.4

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    DOI: 10.1007/s00595-014-0918-0

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  94. A meta-analysis of debulking surgery versus surgical biopsy for unresectable thymoma. Reviewed

    Hamaji M, Kojima F, Omasa M, Sozu T, Sato T, Chen F, Sonobe M, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 47 ( 4 ) page: 602-7   2015.4

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    DOI: 10.1093/ejcts/ezu277

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  95. Virtual-assisted lung mapping: outcome of 100 consecutive cases in a single institute. Reviewed

    Sato M, Yamada T, Menju T, Aoyama A, Sato T, Chen F, Sonobe M, Omasa M, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 47 ( 4 ) page: e131-9   2015.4

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    DOI: 10.1093/ejcts/ezu490

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  96. Complete resection of a giant mediastinal leiomyosarcoma. Reviewed

    Chen F, Muranishi Y, Minakata K, Taura K, Okabe H, Mizota T, Sonobe M, Date H

    The Annals of thoracic surgery   Vol. 99 ( 3 ) page: e69-71   2015.3

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    DOI: 10.1016/j.athoracsur.2014.12.024

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  97. Pleuroparenchymal fibroelastosis and non-specific interstitial pneumonia: frequent pulmonary sequelae of haematopoietic stem cell transplantation. Reviewed

    Takeuchi Y, Miyagawa-Hayashino A, Chen F, Kubo T, Handa T, Date H, Haga H

    Histopathology   Vol. 66 ( 4 ) page: 536-44   2015.3

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    DOI: 10.1111/his.12553

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  98. Gastroparesis after living-donor lobar lung transplantation: report of five cases. Reviewed

    Chen F, Nakamoto Y, Kondo T, Yamada T, Sato M, Aoyama A, Bando T, Date H

    Surgery today   Vol. 45 ( 3 ) page: 378-82   2015.3

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    DOI: 10.1007/s00595-013-0817-9

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  99. Novel thermographic detection of regional malperfusion caused by a thrombosis during ex vivo lung perfusion. Reviewed

    Motoyama H, Chen F, Hijiya K, Kondo T, Ohata K, Takahashi M, Yamada T, Sato M, Aoyama A, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 20 ( 2 ) page: 242-7   2015.2

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    DOI: 10.1093/icvts/ivu386

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  100. Thoracoscopic wedge lung resection using virtual-assisted lung mapping. Reviewed

    Sato M, Aoyama A, Yamada T, Menjyu T, Chen F, Sato T, Sonobe M, Omasa M, Date H

    Asian cardiovascular & thoracic annals   Vol. 23 ( 1 ) page: 46-54   2015.1

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    DOI: 10.1177/0218492314539332

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  101. Noninvasive assessment for acute allograft rejection in a rat lung transplantation model. Reviewed

    Takahashi A, Hamakawa H, Sakai H, Zhao X, Chen F, Fujinaga T, Shoji T, Bando T, Wada H, Date H

    Physiological reports   Vol. 2 ( 12 )   2014.12

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    DOI: 10.14814/phy2.12244

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  102. Phase II study of adjuvant vinorelbine and cisplatin in Japanese patients with completely resected stage II and III non-small cell lung cancer. Reviewed

    Sonobe M, Okubo K, Teramukai S, Yanagihara K, Sato M, Sato T, Chen F, Sato K, Fujinaga T, Shoji T, Omasa M, Sakai H, Miyahara R, Bando T, Date H

    Cancer chemotherapy and pharmacology   Vol. 74 ( 6 ) page: 1199-206   2014.12

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    DOI: 10.1007/s00280-014-2595-5

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  103. Lung transplantation for pleuroparenchymal fibroelastosis after chemotherapy. Reviewed

    Chen F, Matsubara K, Miyagawa-Hayashino A, Tada K, Handa T, Yamada T, Sato M, Aoyama A, Date H

    The Annals of thoracic surgery   Vol. 98 ( 5 ) page: e115-7   2014.11

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    DOI: 10.1016/j.athoracsur.2014.07.045

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  104. Combined operative technique with anterior surgical approach and video-assisted thoracoscopic surgical lobectomy for anterior superior sulcus tumours. Reviewed

    Yokoyama Y, Chen F, Aoyama A, Sato T, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 19 ( 5 ) page: 864-6   2014.11

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    DOI: 10.1093/icvts/ivu231

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  105. Comparison of long-term survival outcomes between stereotactic body radiotherapy and sublobar resection for stage I non-small-cell lung cancer in patients at high risk for lobectomy: A propensity score matching analysis. Reviewed

    Matsuo Y, Chen F, Hamaji M, Kawaguchi A, Ueki N, Nagata Y, Sonobe M, Morita S, Date H, Hiraoka M

    European journal of cancer (Oxford, England : 1990)   Vol. 50 ( 17 ) page: 2932-8   2014.11

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    DOI: 10.1016/j.ejca.2014.09.006

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  106. Plasmin administration during ex vivo lung perfusion ameliorates lung ischemia-reperfusion injury. Reviewed

    Motoyama H, Chen F, Hijiya K, Kondo T, Ohsumi A, Yamada T, Sato M, Aoyama A, Bando T, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 33 ( 10 ) page: 1093-9   2014.10

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    DOI: 10.1016/j.healun.2014.06.004

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  107. Successful single-lung transplantation for multicentric Castleman disease. Reviewed

    Morimura Y, Chen F, Kinjo T, Miyagawa-Hayashino A, Kubo T, Yamada T, Sato M, Aoyama A, Date H

    The Annals of thoracic surgery   Vol. 98 ( 3 ) page: e63-5   2014.9

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    DOI: 10.1016/j.athoracsur.2014.06.074

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  108. Continuous carbon dioxide partial pressure monitoring in lung transplant recipients. Reviewed

    Chen F, Chin K, Ishii H, Kubo H, Miwa S, Ikeda T, Bando T, Date H

    Annals of transplantation   Vol. 19   page: 382-8   2014.8

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    DOI: 10.12659/AOT.890898

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  109. Identification of subsets of patients with favorable prognosis after recurrence in completely resected non-small cell lung cancer. Reviewed

    Sonobe M, Yamada T, Sato M, Menju T, Aoyama A, Sato T, Chen F, Omasa M, Bando T, Date H

    Annals of surgical oncology   Vol. 21 ( 8 ) page: 2546-54   2014.8

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    DOI: 10.1245/s10434-014-3630-9

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  110. Survival and treatments in patients with incompletely resected thymoma. Reviewed

    Hamaji M, Omasa M, Chen F, Yamada T, Sato M, Menju T, Sato T, Aoyama A, Sonobe M, Bando T, Date H

    Asian cardiovascular & thoracic annals   Vol. 22 ( 6 ) page: 712-8   2014.7

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    DOI: 10.1177/0218492313516116

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  111. Once-daily oral administration of cyclosporine in a lung transplant patient with a history of renal toxicity of calcineurin inhibitors. Reviewed

    Matsuda Y, Chen F, Miyata H, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 19 ( 1 ) page: 171-3   2014.7

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    DOI: 10.1093/icvts/ivu081

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  112. Videothoracoscopy-assisted surgical lung biopsy for interstitial lung diseases. Reviewed

    Sonobe M, Handa T, Tanizawa K, Sato M, Sato T, Chen F, Omasa M, Bando T, Date H, Mishima M

    General thoracic and cardiovascular surgery   Vol. 62 ( 6 ) page: 376-82   2014.6

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    DOI: 10.1007/s11748-014-0383-0

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  113. Use of virtual assisted lung mapping (VAL-MAP), a bronchoscopic multispot dye-marking technique using virtual images, for precise navigation of thoracoscopic sublobar lung resection. Reviewed

    Sato M, Omasa M, Chen F, Sato T, Sonobe M, Bando T, Date H

    The Journal of thoracic and cardiovascular surgery   Vol. 147 ( 6 ) page: 1813-9   2014.6

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    DOI: 10.1016/j.jtcvs.2013.11.046

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  114. Living-donor lobar lung transplantation for treatment of idiopathic pulmonary arterial hypertension with severe pulmonary arterial dilation. Reviewed

    Yokoyama Y, Chen F, Minakata K, Yamada T, Aoyama A, Sato M, Date H

    The Annals of thoracic surgery   Vol. 97 ( 5 ) page: e149   2014.5

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    DOI: 10.1016/j.athoracsur.2014.02.071

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  115. Surgical resection of a giant mediastinal teratoma occupying the entire left hemithorax. Reviewed

    Yokoyama Y, Chen F, Date H

    General thoracic and cardiovascular surgery   Vol. 62 ( 4 ) page: 255-7   2014.4

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    DOI: 10.1007/s11748-013-0239-z

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  116. Effect of hypogammaglobulinemia after lung transplantation: a single-institution study. Reviewed

    Ohsumi A, Chen F, Yamada T, Sato M, Aoyama A, Bando T, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 45 ( 3 ) page: e61-7   2014.3

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    DOI: 10.1093/ejcts/ezt583

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  117. Redo living-donor lobar lung transplantation for bronchiolitis obliterans associated with antibody-mediated rejection. Reviewed

    Chen F, Miyagawa-Hayashino A, Yurugi K, Chibana N, Yamada T, Sato M, Aoyama A, Takakura S, Bando T, Date H

    Transplant international : official journal of the European Society for Organ Transplantation   Vol. 27 ( 2 ) page: e8-12   2014.2

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    DOI: 10.1111/tri.12224

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  118. Prognostic factors for patients in postoperative brain metastases from surgically resected non-small cell lung cancer. Reviewed

    Sakamoto J, Sonobe M, Kobayashi M, Ishikawa M, Kikuchi R, Nakajima D, Yamada T, Nakayama E, Takahashi T, Sato T, Chen F, Bando T, Date H

    International journal of clinical oncology   Vol. 19 ( 1 ) page: 50-6   2014.2

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    DOI: 10.1007/s10147-012-0503-8

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  119. Severe pulmonary hypertension in adult pulmonary Langerhans cell histiocytosis: the effect of sildenafil as a bridge to lung transplantation. Reviewed

    Yoshida T, Konno S, Tsujino I, Sato T, Ohira H, Chen F, Date H, Ishizu A, Haga H, Tanino M, Nishimura M

    Internal medicine (Tokyo, Japan)   Vol. 53 ( 17 ) page: 1985-90   2014

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    DOI: 10.2169/internalmedicine.53.1772

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  120. Radiologic evaluation for volume and weight of remnant lung in living lung donors. Reviewed

    Mizobuchi T, Chen F, Yoshino I, Iwata T, Yoshida S, Bando T, Date H

    The Journal of thoracic and cardiovascular surgery   Vol. 146 ( 5 ) page: 1253-8   2013.11

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    DOI: 10.1016/j.jtcvs.2013.05.038

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  121. Incidence and pattern of hemolytic anemia after minor ABO-mismatched living-donor lobar lung transplantation. Reviewed

    Ohsumi A, Chen F, Yurugi K, Maekawa T, Shoji T, Sato M, Aoyama A, Bando T, Date H

    Surgery today   Vol. 43 ( 11 ) page: 1250-3   2013.11

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    DOI: 10.1007/s00595-012-0422-3

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  122. Virtual endobronchial ultrasound for transbronchial needle aspiration. Reviewed

    Sato M, Chen F, Aoyama A, Yamada T, Ikeda M, Bando T, Date H

    The Journal of thoracic and cardiovascular surgery   Vol. 146 ( 5 ) page: 1204-12   2013.11

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    DOI: 10.1016/j.jtcvs.2013.01.019

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  123. Mediastinal infectious complication after endobronchial ultrasound-guided transbronchial needle aspiration. Reviewed

    Gochi F, Chen F, Aoyama A, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 17 ( 4 ) page: 751-2   2013.10

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    DOI: 10.1093/icvts/ivt273

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  124. Postoperative respiratory management in living donor lobar lung transplantation. Reviewed

    Chen F, Chin K, Sato M, Aoyama A, Murase K, Azuma M, Bando T, Date H

    Clinical transplantation   Vol. 27 ( 4 ) page: E383-90   2013.7

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    DOI: 10.1111/ctr.12148

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  125. Inspiratory and expiratory computed tomographic volumetry for lung volume reduction surgery. Reviewed

    Morimura Y, Chen F, Sonobe M, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 16 ( 6 ) page: 926-8   2013.6

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    DOI: 10.1093/icvts/ivt059

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  126. Protective effect of plasmin in marginal donor lungs in an ex vivo lung perfusion model. Reviewed

    Motoyama H, Chen F, Ohsumi A, Hijiya K, Okita K, Nakajima D, Sakamoto J, Yamada T, Sato M, Aoyama A, Bando T, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 32 ( 5 ) page: 505-10   2013.5

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    DOI: 10.1016/j.healun.2013.02.007

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  127. Surgical resection of a giant emphysematous bulla occupying the entire hemithorax. Reviewed

    Kayawake H, Chen F, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 43 ( 5 ) page: e136-8   2013.5

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    DOI: 10.1093/ejcts/ezs699

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  128. Single-lobe lung transplantation for rapidly deteriorating pulmonary venoocclusive disease. Reviewed

    Takahashi K, Chen F, Ikeda T, Doi H, Nakamura H, Yanagi S, Sato M, Aoyama A, Bando T, Date H

    The Annals of thoracic surgery   Vol. 95 ( 2 ) page: 689-91   2013.2

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    DOI: 10.1016/j.athoracsur.2012.06.031

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  129. Living-donor lobar lung transplantation for rapidly progressive interstitial pneumonia associated with clinically amyopathic dermatomyositis: report of a case. Reviewed

    Shoji T, Bando T, Fujinaga T, Chen F, Sasano H, Yukawa N, Mimori T, Date H

    General thoracic and cardiovascular surgery   Vol. 61 ( 1 ) page: 32-4   2013.1

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    DOI: 10.1007/s11748-012-0106-3

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  130. Protective effect of surfactant inhalation against warm ischemic injury in an isolated rat lung ventilation model. Reviewed

    Ohsumi A, Chen F, Sakamoto J, Nakajima D, Kobayashi M, Bando T, Date H

    PloS one   Vol. 8 ( 8 ) page: e72574   2013

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    DOI: 10.1371/journal.pone.0072574

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  131. Pulmonary function of individual lung lobes after complex living-donor lobar lung transplantation using inspiratory and expiratory three-dimensional computed tomographic volumetry. Reviewed

    Chen F, Fujinaga T, Bando T, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 15 ( 6 ) page: 1077-9   2012.12

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    DOI: 10.1093/icvts/ivs386

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  132. Hyperfractionated irradiation with 3 cycles of induction chemotherapy in stage IIIA-N2 lung cancer. Reviewed

    Chen F, Okubo K, Sonobe M, Shibuya K, Matsuo Y, Kim YH, Yanagihara K, Bando T, Date H

    World journal of surgery   Vol. 36 ( 12 ) page: 2858-64   2012.12

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    DOI: 10.1007/s00268-012-1747-1

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  133. Reconditioning lungs donated after cardiac death using short-term hypothermic machine perfusion. Reviewed

    Nakajima D, Chen F, Okita K, Motoyama H, Hijiya K, Ohsumi A, Sakamoto J, Yamada T, Sato M, Aoyama A, Bando T, Date H

    Transplantation   Vol. 94 ( 10 ) page: 999-1004   2012.11

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    DOI: 10.1097/TP.0b013e31826f632e

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  134. Pulmonary arterioplasty for the remaining arterial stump of the donor and the arterial cuff of the donor graft in living-donor lobar lung transplantation. Reviewed

    Chen F, Miwa S, Bando T, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 42 ( 5 ) page: e138-9   2012.11

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    DOI: 10.1093/ejcts/ezs460

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  135. Protective effect of pre-recovery surfactant inhalation on lungs donated after cardiac death in a canine lung transplantation model. Reviewed

    Ohsumi A, Chen F, Sakamoto J, Nakajima D, Hijiya K, Motoyama H, Okita K, Horita K, Kikuchi R, Yamada T, Bando T, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 31 ( 10 ) page: 1136-42   2012.10

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    DOI: 10.1016/j.healun.2012.07.006

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  136. Therapeutic effect of surfactant inhalation during warm ischemia in an isolated rat lung perfusion model. Reviewed

    Ohsumi A, Chen F, Nakajima D, Sakamoto J, Yamada T, Fujinaga T, Shoji T, Sakai H, Bando T, Date H

    Transplant international : official journal of the European Society for Organ Transplantation   Vol. 25 ( 10 ) page: 1096-105   2012.10

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    DOI: 10.1111/j.1432-2277.2012.01532.x

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  137. Outcome of living-donor lobar lung transplantation using a single donor. Reviewed

    Date H, Shiraishi T, Sugimoto S, Shoji T, Chen F, Hiratsuka M, Aoyama A, Sato M, Yamane M, Iwasaki A, Miyoshi S, Bando T, Oto T

    The Journal of thoracic and cardiovascular surgery   Vol. 144 ( 3 ) page: 710-5   2012.9

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    DOI: 10.1016/j.jtcvs.2012.05.054

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  138. Posterior reversible encephalopathy syndrome due to immunosuppressant after living-donor lobar lung transplantation: report of a case. Reviewed

    Shoji T, Bando T, Fujinaga T, Chen F, Kohno M, Yabe M, Yabe H, Date H

    General thoracic and cardiovascular surgery   Vol. 60 ( 8 ) page: 514-7   2012.8

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    DOI: 10.1007/s11748-012-0030-6

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  139. Antibody-mediated rejection of a unilateral donor lung in bilateral living-donor lobar lung transplantation: report of a case. Reviewed

    Chen F, Chibana N, Kanematsu A, Takakura S, Yurugi K, Hishida R, Fukatsu A, Kubo T, Shoji T, Fujinaga T, Bando T, Date H

    Surgery today   Vol. 42 ( 8 ) page: 808-11   2012.8

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    DOI: 10.1007/s00595-012-0151-7

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  140. The effect of β-2 adrenoreceptor agonist inhalation on lungs donated after cardiac death in a canine lung transplantation model. Reviewed

      Vol. 31 ( 7 ) page: 773-9   2012.7

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    DOI: 10.1016/j.healun.2012.03.012

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  141. Short-term outcome in living donors for lung transplantation: the role of preoperative computer tomographic evaluations of fissures and vascular anatomy. Reviewed

    Chen F, Fujinaga T, Shoji T, Kubo T, Sonobe M, Sato M, Aoyama A, Sato T, Sakai H, Bando T, Date H

    Transplant international : official journal of the European Society for Organ Transplantation   Vol. 25 ( 7 ) page: 732-8   2012.7

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    DOI: 10.1111/j.1432-2277.2012.01444.x

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  142. Pharmacokinetic study of weekly (days 1-5) low-dose S-1 in patients with non-small-cell lung cancer. Reviewed

    Shoji T, Sonobe M, Sakai H, Fujinaga T, Sato T, Chen F, Miyahara R, Bando T, Wada H, Date H

    Reviews on recent clinical trials   Vol. 7 ( 2 ) page: 167-72   2012.5

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  143. Clinicopathological characteristics of surgically resected pulmonary pleomorphic carcinoma. Reviewed

    Chen F, Sonobe M, Sato T, Sakai H, Huang CL, Bando T, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 41 ( 5 ) page: 1037-42   2012.5

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    DOI: 10.1093/ejcts/ezr136

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  144. Pulmonary lymphoepithelioma-like carcinoma with rapid progression. Reviewed

    Tanaka S, Chen F, Date H

    General thoracic and cardiovascular surgery   Vol. 60 ( 3 ) page: 164-7   2012.3

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    DOI: 10.1007/s11748-011-0789-x

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  145. Reconditioning of lungs donated after circulatory death with normothermic ex vivo lung perfusion. Reviewed

    Nakajima D, Chen F, Yamada T, Sakamoto J, Ohsumi A, Bando T, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 31 ( 2 ) page: 187-93   2012.2

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    DOI: 10.1016/j.healun.2011.11.007

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  146. Outcomes and pulmonary function in living lobar lung transplant donors. Reviewed

    Chen F, Fujinaga T, Shoji T, Sonobe M, Sato T, Sakai H, Bando T, Date H

    Transplant international : official journal of the European Society for Organ Transplantation   Vol. 25 ( 2 ) page: 153-7   2012.2

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    DOI: 10.1111/j.1432-2277.2011.01401.x

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  147. Usefulness of endobronchial ultrasound in patients with previously treated thoracic malignancy. Reviewed

    Chen F, Miyahara R, Sato T, Sonobe M, Sakai H, Bando T, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 14 ( 1 ) page: 34-7   2012.1

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    DOI: 10.1093/icvts/ivr043

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  148. Delayed chest closure assessed by transesophageal echocardiogram in single-lobe lung transplantation. Reviewed

    Chen F, Matsukawa S, Ishii H, Ikeda T, Shoji T, Fujinaga T, Bando T, Date H

    The Annals of thoracic surgery   Vol. 92 ( 6 ) page: 2254-7   2011.12

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    DOI: 10.1016/j.athoracsur.2011.05.102

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  149. Stent angioplasty for a kink in the pulmonary artery anastomosis soon after living-donor lobar lung transplantation. Reviewed

    Chen F, Tazaki J, Shibata T, Miwa S, Yamazaki K, Ishii H, Shoji T, Fujinaga T, Bando T, Date H

    The Annals of thoracic surgery   Vol. 92 ( 5 ) page: e105-6   2011.11

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    DOI: 10.1016/j.athoracsur.2011.05.049

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  150. Effect of preprocurement ventilation on lungs donated after cardiac death in a canine lung transplantation model. Reviewed

    Sakamoto J, Chen F, Yamada T, Nakajima D, Ohsumi A, Kikuchi R, Zhao X, Fujinaga T, Shoji T, Sakai H, Bando T, Date H

    Transplantation   Vol. 92 ( 8 ) page: 864-70   2011.10

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    DOI: 10.1097/TP.0b013e31822d87c6

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  151. Hypothermic machine perfusion ameliorates ischemia-reperfusion injury in rat lungs from non-heart-beating donors. Reviewed

    Nakajima D, Chen F, Yamada T, Sakamoto J, Osumi A, Fujinaga T, Shoji T, Sakai H, Bando T, Date H

    Transplantation   Vol. 92 ( 8 ) page: 858-63   2011.10

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    DOI: 10.1097/TP.0b013e31822d8778

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  152. Management of patients with coronary stents in elective thoracic surgery. Reviewed

    Sonobe M, Sato T, Chen F, Fujinaga T, Shoji T, Sakai H, Miyahara R, Bando T, Huang CL, Date H

    General thoracic and cardiovascular surgery   Vol. 59 ( 7 ) page: 477-82   2011.7

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    DOI: 10.1007/s11748-011-0775-3

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  153. Postoperative pleural effusion in living lobar lung transplant donors. Reviewed

    Toyazaki T, Chen F, Shoji T, Sonobe M, Fujinaga T, Bando T, Date H

    General thoracic and cardiovascular surgery   Vol. 59 ( 6 ) page: 440-2   2011.6

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    DOI: 10.1007/s11748-010-0683-y

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  154. Tumor extension along chest wall tract after diagnostic intervention in malignant pleural mesothelioma. Reviewed

    Chen F, Yoshizawa A, Okubo K, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 12 ( 6 ) page: 1060-2   2011.6

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    DOI: 10.1510/icvts.2010.256214

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  155. Rib chondrosarcoma with intramedullary progression completely resected by magnetic resonance imaging: useful short inversion time inversion recovery sequence. Reviewed

    Ohata K, Chen F, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 12 ( 5 ) page: 853-4   2011.5

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    DOI: 10.1510/icvts.2010.262212

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  156. Comparison of pulmonary function test and computed tomography volumetry in living lung donors. Reviewed

    Chen F, Kubo T, Shoji T, Fujinaga T, Bando T, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 30 ( 5 ) page: 572-5   2011.5

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    DOI: 10.1016/j.healun.2010.11.019

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  157. Normothermic ex vivo lung perfusion in clinical lung transplantation. Reviewed

    Cypel M, Yeung JC, Liu M, Anraku M, Chen F, Karolak W, Sato M, Laratta J, Azad S, Madonik M, Chow CW, Chaparro C, Hutcheon M, Singer LG, Slutsky AS, Yasufuku K, de Perrot M, Pierre AF, Waddell TK, Keshavjee S

    The New England journal of medicine   Vol. 364 ( 15 ) page: 1431-40   2011.4

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    Language:English  

    DOI: 10.1056/NEJMoa1014597

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  158. ABO-incompatible living-donor lobar lung transplantation. Reviewed

    Shoji T, Bando T, Fujinaga T, Chen F, Yurugi K, Maekawa T, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 30 ( 4 ) page: 479-80   2011.4

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    DOI: 10.1016/j.healun.2010.10.015

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  159. Living-donor, single-lobe lung transplantation and simultaneous contralateral pneumonectomy in a child. Reviewed

    Sonobe M, Bando T, Kusuki S, Fujinaga T, Shoji T, Chen F, Sakai H, Ishii H, Ikeda T, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 30 ( 4 ) page: 471-4   2011.4

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    DOI: 10.1016/j.healun.2010.10.008

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  160. Living-donor lobar lung transplantation with sparing of bilateral native upper lobes: a novel strategy. Reviewed

    Fujinaga T, Bando T, Nakajima D, Sakamoto J, Chen F, Shoji T, Sakai H, Ishii H, Miwa S, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 30 ( 3 ) page: 351-3   2011.3

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    DOI: 10.1016/j.healun.2010.10.006

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  161. Lung metastasectomy for colorectal carcinoma in patients with a history of hepatic metastasis. Reviewed

    Chen F, Shoji T, Sakai H, Miyahara R, Bando T, Okubo K, Date H

    Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia   Vol. 17 ( 1 ) page: 13-8   2011

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    DOI: 10.5761/atcs.oa.09.01520

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  162. Salvage lung resection for non-small cell lung cancer after stereotactic body radiotherapy in initially operable patients. Reviewed

    Chen F, Matsuo Y, Yoshizawa A, Sato T, Sakai H, Bando T, Okubo K, Shibuya K, Date H

    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer   Vol. 5 ( 12 ) page: 1999-2002   2010.12

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    DOI: 10.1097/JTO.0b013e3181f260f9

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  163. Surgical management of bronchopulmonary typical carcinoid tumors: an institutional experience. Reviewed

    Chen F, Sato T, Fujinaga T, Sakai H, Miyahara R, Bando T, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 11 ( 6 ) page: 737-9   2010.12

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    DOI: 10.1510/icvts.2010.247361

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  164. Repeat resection of pulmonary metastasis is beneficial for patients with colorectal carcinoma. Reviewed

    Chen F, Sakai H, Miyahara R, Bando T, Okubo K, Date H

    World journal of surgery   Vol. 34 ( 10 ) page: 2373-8   2010.10

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    DOI: 10.1007/s00268-010-0695-x

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  165. Characteristic endobronchial ultrasound image of hemangiopericytoma/solitary fibrous tumor. Reviewed

    Chen F, Yoshizawa A, Okubo K, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 11 ( 3 ) page: 331-2   2010.9

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    DOI: 10.1510/icvts.2010.244459

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  166. Perioperative assessment of oversized lobar graft downsizing in living-donor lobar lung transplantation using three-dimensional computed tomographic volumetry. Reviewed

    Chen F, Fujinaga T, Shoji T, Yamada T, Nakajima D, Sakamoto J, Sakai H, Bando T, Date H

    Transplant international : official journal of the European Society for Organ Transplantation   Vol. 23 ( 9 ) page: e41-4   2010.9

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    DOI: 10.1111/j.1432-2277.2010.01123.x

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  167. Post-transplant lymphoproliferative disorder following cytomegalovirus reactivation in a lung recipient. Reviewed

    Aoyama A, Omasa M, Kondo N, Chen F, Date H, Bando T

    General thoracic and cardiovascular surgery   Vol. 58 ( 5 ) page: 251-4   2010.5

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    DOI: 10.1007/s11748-009-0526-x

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  168. Constrictive pericarditis after lung transplantation: an under-recognized complication. Reviewed

    Karolak W, Cypel M, Chen F, Daniel L, Chaparro C, Keshavjee S

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 29 ( 5 ) page: 578-81   2010.5

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    DOI: 10.1016/j.healun.2009.11.606

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  169. Forced oscillation technique as a non-invasive assessment for lung transplant recipients. Reviewed

    Hamakawa H, Sakai H, Takahashi A, Zhang J, Okamoto T, Satoda N, Aoyama A, Chen F, Fujinaga T, Shoji T, Bando T, Mishima M, Wada H, Date H

    Advances in experimental medicine and biology   Vol. 662   page: 293-8   2010

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    DOI: 10.1007/978-1-4419-1241-1_42

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  170. Age-related changes in the trachea in healthy adults. Reviewed

    Sakai H, Nakano Y, Muro S, Hirai T, Takubo Y, Oku Y, Hamakawa H, Takahashi A, Sato T, Chen F, Sahara H, Fujinaga T, Sato K, Sonobe M, Shoji T, Miyahara R, Okubo K, Bando T, Hirata T, Date H, Mishima M

    Advances in experimental medicine and biology   Vol. 662   page: 115-20   2010

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    DOI: 10.1007/978-1-4419-1241-1_16

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  171. Intermediate-term outcome in lung transplantation from a donor with glioblastoma multiforme. Reviewed

    Chen F, Karolak W, Cypel M, Keshavjee S, Pierre A

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 28 ( 10 ) page: 1116-8   2009.10

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    DOI: 10.1016/j.healun.2009.06.022

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  172. Repeat resection of pulmonary metastasis is beneficial for patients with osteosarcoma of the extremities. Reviewed

    Chen F, Miyahara R, Bando T, Okubo K, Watanabe K, Nakayama T, Toguchida J, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 9 ( 4 ) page: 649-53   2009.10

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    DOI: 10.1510/icvts.2009.212498

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  173. Initial experience with lung donation after cardiocirculatory death in Canada. Reviewed

    Cypel M, Sato M, Yildirim E, Karolak W, Chen F, Yeung J, Boasquevisque C, Leist V, Singer LG, Yasufuku K, Deperrot M, Waddell TK, Keshavjee S, Pierre A

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 28 ( 8 ) page: 753-8   2009.8

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    DOI: 10.1016/j.healun.2009.05.009

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  174. Use of totally implantable central venous access port via the basilic vein in patients with thoracic malignancies. Reviewed

    Sonobe M, Chen F, Fujinaga T, Sato K, Shoji T, Sakai H, Miyahara R, Bando T, Okubo K, Hirata T, Date H

    International journal of clinical oncology   Vol. 14 ( 3 ) page: 208-12   2009.6

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    DOI: 10.1007/s10147-008-0835-6

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  175. Post-ischemic infusion of atrial natriuretic peptide attenuates warm ischemia-reperfusion injury in rat lung. Reviewed

    Aoyama A, Chen F, Fujinaga T, Sato A, Tsuruyama T, Zhang J, Shoji T, Sakai H, Nakamura T, Date H, Wada H, Bando T

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 28 ( 6 ) page: 628-34   2009.6

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    DOI: 10.1016/j.healun.2009.03.015

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  176. Prognostic factors of pulmonary metastasectomy for colorectal carcinomas. Reviewed

    Chen F, Hanaoka N, Sato K, Fujinaga T, Sonobe M, Shoji T, Sakai H, Miyahara R, Bando T, Okubo K, Hirata T, Date H

    World journal of surgery   Vol. 33 ( 3 ) page: 505-11   2009.3

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    DOI: 10.1007/s00268-008-9875-3

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  177. Nebulized phosphodiesterase III inhibitor during warm ischemia attenuates pulmonary ischemia-reperfusion injury. Reviewed

    Zhang J, Chen F, Zhao X, Aoyama A, Okamoto T, Fujinaga T, Shoji T, Sakai H, Cui Y, Bando T, Date H

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 28 ( 1 ) page: 79-84   2009.1

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    DOI: 10.1016/j.healun.2008.10.012

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  178. A follow-up report on a new method of segmental resection for small-sized early lung cancer. Reviewed

    Bando T, Miyahara R, Sakai H, Shoji T, Sonobe M, Sato K, Fujinaga T, Chen F, Okubo K, Hirata T, Wada H

    Lung cancer (Amsterdam, Netherlands)   Vol. 63 ( 1 ) page: 58-62   2009.1

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    DOI: 10.1016/j.lungcan.2008.04.012

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  179. Sirolimus treatment for recurrent lymphangioleiomyomatosis after lung transplantation. Reviewed

    Chen F, Omasa M, Kondo N, Fujinaga T, Shoji T, Sakai H, Bando T

    The Annals of thoracic surgery   Vol. 87 ( 1 ) page: e6-7   2009.1

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    DOI: 10.1016/j.athoracsur.2008.07.107

    PubMed

  180. Protective effect of thioredoxin perfusion but not inhalation in warm ischemic-reperfused rat lungs. Reviewed

    Zhang J, Chen F, Nakamura T, Fujinaga T, Aoyama A, Hamakawa H, Sakai H, Hoshino Y, Yodoi J, Wada H, Bando T, Nakamura H

    Redox report : communications in free radical research   Vol. 14 ( 2 ) page: 75-81   2009

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    DOI: 10.1179/135100009X392511

    PubMed

  181. Value of FOXP3 expression in peripheral blood as rejection marker after miniature swine lung transplantation. Reviewed

    Satoda N, Shoji T, Wu Y, Fujinaga T, Chen F, Aoyama A, Zhang JT, Takahashi A, Okamoto T, Matsumoto I, Sakai H, Li Y, Zhao X, Manabe T, Kobayashi E, Sakaguchi S, Wada H, Ohe H, Uemoto S, Tottori J, Bando T, Date H, Koshiba T

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 27 ( 12 ) page: 1293-301   2008.12

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    DOI: 10.1016/j.healun.2008.08.006

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  182. Prognostic factors of pulmonary metastasectomy for osteosarcomas of the extremities. Reviewed

    Chen F, Miyahara R, Bando T, Okubo K, Watanabe K, Nakayama T, Toguchida J, Date H

    European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery   Vol. 34 ( 6 ) page: 1235-9   2008.12

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    DOI: 10.1016/j.ejcts.2008.07.032

    PubMed

  183. Schwannoma of the brachial plexus presenting as an enlarging cystic mass: report of a case. Reviewed

    Chen F, Miyahara R, Matsunaga Y, Koyama T

    Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia   Vol. 14 ( 5 ) page: 311-3   2008.10

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  184. Pulmonary resection for metastasis from esophageal carcinoma. Reviewed

    Chen F, Sato K, Sakai H, Miyahara R, Bando T, Okubo K, Hirata T, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 7 ( 5 ) page: 809-12   2008.10

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    DOI: 10.1510/icvts.2008.180778

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  185. Pulmonary resection for metastasis from renal cell carcinoma. Reviewed

    Chen F, Fujinaga T, Shoji T, Miyahara R, Bando T, Okubo K, Hirata T, Date H

    Interactive cardiovascular and thoracic surgery   Vol. 7 ( 5 ) page: 825-8   2008.10

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    DOI: 10.1510/icvts.2008.181065

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  186. Pulmonary resection for metastases from hepatocellular carcinoma. Reviewed

    Chen F, Sato K, Fujinaga T, Sonobe M, Shoji T, Sakai H, Miyahara R, Bando T, Okubo K, Hirata T, Date H

    World journal of surgery   Vol. 32 ( 10 ) page: 2213-7   2008.10

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    DOI: 10.1007/s00268-008-9684-8

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  187. Successful sub-zero non-freezing preservation of rat lungs at -2 degrees C utilizing a new supercooling technology. Reviewed

    Okamoto T, Nakamura T, Zhang J, Aoyama A, Chen F, Fujinaga T, Shoji T, Hamakawa H, Sakai H, Manabe T, Wada H, Date H, Bando T

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation   Vol. 27 ( 10 ) page: 1150-7   2008.10

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    DOI: 10.1016/j.healun.2008.07.008

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  188. Intrathoracic multiple schwannomas of a single intercostal nerve. Reviewed

    Chen F, Nakayama E, Okubo K, Date H

    The Annals of thoracic surgery   Vol. 86 ( 2 ) page: 660-1   2008.8

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    DOI: 10.1016/j.athoracsur.2008.02.004

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  189. Pulmonary resection for metastatic head and neck cancer. Reviewed

    Chen F, Sonobe M, Sato K, Fujinaga T, Shoji T, Sakai H, Miyahara R, Bando T, Okubo K, Hirata T, Date H

    World journal of surgery   Vol. 32 ( 8 ) page: 1657-62   2008.8

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    DOI: 10.1007/s00268-008-9631-8

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  190. En bloc total vertebrectomy for lung cancer invading the spine. Reviewed

    Chen F, Takahashi A, Omasa M, Neo M, Fujibayashi S, Wada H, Bando T

    Lung cancer (Amsterdam, Netherlands)   Vol. 61 ( 1 ) page: 137-9   2008.7

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    DOI: 10.1016/j.lungcan.2007.12.004

    PubMed

  191. Expression of endothelial cell-specific adhesion molecules in lungs after cardiac arrest. Reviewed

    Chen F, Kondo N, Sonobe M, Fujinaga T, Wada H, Bando T

    Interactive cardiovascular and thoracic surgery   Vol. 7 ( 3 ) page: 437-40   2008.5

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    DOI: 10.1510/icvts.2007.166355

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  192. Sternal wound dehiscence after transverse thoracosternotomy for bilateral lung transplantation: report of a case. Reviewed

    Chen F, Aoyama A, Kondo N, Fujinaga T, Shoji T, Omasa M, Sakai H, Bando T

    Surgery today   Vol. 38 ( 10 ) page: 942-4   2008

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    DOI: 10.1007/s00595-007-3735-x

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  193. [Viral infection after lung transplantation]. Reviewed

    Chen F, Aoyama A, Okamoto T, Takahashi A, Satoda N, Fujinaga T, Shoji T, Sakai H, Matsumoto I, Wada H, Bando T

    Kyobu geka. The Japanese journal of thoracic surgery   Vol. 60 ( 11 ) page: 982-7   2007.10

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    Language:Japanese  

    PubMed

  194. The ratio of membrane-bound form Flt-1 mRNA to VEGF mRNA correlates with tumor angiogenesis and prognosis in non-small cell lung cancer. Reviewed

    Takenaka K, Katakura H, Chen F, Ogawa E, Adachi M, Wada H, Tanaka F

    Cancer letters   Vol. 246 ( 1-2 ) page: 34-40   2007.2

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    DOI: 10.1016/j.canlet.2006.01.022

    PubMed

  195. Isoflurane inhalation after circulatory arrest protects against warm ischemia reperfusion injury of the lungs. Reviewed

    Fujinaga T, Nakamura T, Fukuse T, Chen F, Zhang J, Ueda S, Hamakawa H, Omasa M, Sakai H, Hanaoka N, Wada H, Bando T

    Transplantation   Vol. 82 ( 9 ) page: 1168-74   2006.11

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  196. Limited surgery and radiofrequency ablation for recurrent lung cancer. Reviewed

    Fukuse T, Ogawa E, Chen F, Sakai H, Wada H

    The Annals of thoracic surgery   Vol. 82 ( 4 ) page: 1506-8   2006.10

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    DOI: 10.1016/j.athoracsur.2005.12.066

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  197. Recurrence of bilateral diffuse bronchiectasis after bilateral lung transplantation. Reviewed

    Chen F, Hasegawa S, Bando T, Kitaichi M, Hiratsuka T, Kawashima M, Hanaoka N, Yoshimura T, Tanaka F, Trulock EP, Wada H

    Respirology (Carlton, Vic.)   Vol. 11 ( 5 ) page: 666-8   2006.9

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    DOI: 10.1111/j.1440-1843.2006.00904.x

    PubMed

  198. Protective effect of a nebulized beta2-adrenoreceptor agonist in warm ischemic-reperfused rat lungs. Reviewed

    Chen F, Nakamura T, Fujinaga T, Zhang J, Hamakawa H, Omasa M, Sakai H, Hanaoka N, Bando T, Wada H, Fukuse T

    The Annals of thoracic surgery   Vol. 82 ( 2 ) page: 465-71   2006.8

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    DOI: 10.1016/j.athoracsur.2006.01.010

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  199. Position of a chest tube at video-assisted thoracoscopic surgery for spontaneous pneumothorax. Reviewed

    Chen F, Yamada T, Aoyama A, Isowa N, Chihara K

    Respiration; international review of thoracic diseases   Vol. 73 ( 3 ) page: 329-33   2006

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    DOI: 10.1159/000088679

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  200. Early onset of ganciclovir-resistant cytomegalovirus infection in a lung-transplant recipient. Reviewed

    Chen F, Bando T, Hanaoka N, Fukuse T, Hasegawa S, Wada H

    The Japanese journal of thoracic and cardiovascular surgery : official publication of the Japanese Association for Thoracic Surgery = Nihon Kyobu Geka Gakkai zasshi   Vol. 53 ( 10 ) page: 562-4   2005.10

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    DOI: 10.1007/s11748-005-0068-9

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  201. Development of new organ preservation solutions in Kyoto University. Reviewed

    Chen F, Nakamura T, Wada H

    Yonsei medical journal   Vol. 45 ( 6 ) page: 1107-14   2004.12

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    DOI: 10.3349/ymj.2004.45.6.1107

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  202. Flt-4-positive endothelial cell density and its clinical significance in non-small cell lung cancer. Reviewed

    Chen F, Takenaka K, Ogawa E, Yanagihara K, Otake Y, Wada H, Tanaka F

    Clinical cancer research : an official journal of the American Association for Cancer Research   Vol. 10 ( 24 ) page: 8548-53   2004.12

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    DOI: 10.1158/1078-0432.CCR-04-0950

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  203. Rapid occurrence of pulmonary aspergillosis after pulmonary wedge resection. Reviewed

    Chen F, Itoi S, Hirata T, Chihara K

    The Japanese journal of thoracic and cardiovascular surgery : official publication of the Japanese Association for Thoracic Surgery = Nihon Kyobu Geka Gakkai zasshi   Vol. 52 ( 12 ) page: 577-9   2004.12

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    DOI: 10.1007/s11748-004-0027-x

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  204. Diaphragmatic elevation of a patient with chronic obstructive pulmonary disease after left upper lobectomy. Reviewed

    Chen F, Nakai M, Aoyama A, Isowa N, Chihara K

    Interactive cardiovascular and thoracic surgery   Vol. 2 ( 4 ) page: 688-91   2003.12

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    DOI: 10.1016/S1569-9293(03)00206-8

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  205. Right ventricular infarction during a lung lobectomy in a patient with chronic obstructive pulmonary disease: report of a case. Reviewed

    Chen F, Itoi S, Yoshimura T, Ueno T, Nakai M, Chihara K

    Surgery today   Vol. 33 ( 10 ) page: 758-60   2003

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    DOI: 10.1007/s00595-003-2588-1

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  206. Surgical treatment for cardiovascular lesions of patients with Marfan syndrome. Reviewed

    Yamazaki F, Shimamoto M, Fujita S, Nakai M, Kono T, Aoyama A, Chen F, Nakata T

    The Japanese journal of thoracic and cardiovascular surgery : official publication of the Japanese Association for Thoracic Surgery = Nihon Kyobu Geka Gakkai zasshi   Vol. 50 ( 9 ) page: 366-70   2002.9

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Presentations 3

  1. Protective Effects of a Hydrogen-Rich Preservation Solution in a Canine Lung Transplantation Model

    Kayawake H.

    Annals of Thoracic Surgery 

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    Event date: 2021.1

    Language:English   Presentation type:Oral presentation (general)  

    DOI: 10.1016/j.athoracsur.2020.05.076

    Scopus

  2. Characteristics of incomplete endobronchial ultrasound-guided transbronchial needle aspiration cases

    Kayawake H.

    Journal of Thoracic Disease 

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    Event date: 2020.3

    Language:English   Presentation type:Oral presentation (general)  

    DOI: 10.21037/jtd.2019.12.133

    Scopus

  3. Characteristics of incomplete endobronchial ultrasound-guided transbronchial needle aspiration cases International conference

    Kayawake H

    Journal of Thoracic Disease  2020.3.1 

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    Language:English   Presentation type:Oral presentation (general)  

Research Project for Joint Research, Competitive Funding, etc. 23

  1. 可変形3次元画像による大規模バーチャル手術手技アトラスの構築と呼吸器外科手術ガイドシステムの創出

    2020.9 - 2022.3

    AMED メディカル・アーツ 

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    Grant type:Competitive

  2. Intestinal ventilation-based therapeutics development for COVID-19 related severe respiratory complications

    2020.9 - 2021.3

    AMED 

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    Grant type:Competitive

  3. 臓器移植を革新する免疫プロファイリングによる個別化医療の開発

    2019.4 - 2022.3

    免疫アレルギー等疾患実用化研究事業(移植医療技術開発研究分野 課題管理番号19ek0510029h0001) 

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    Grant type:Competitive

  4. 肺及び腸オルガノイドと新規呼吸システムを用いた慢性呼吸不全に対する革新的治療法の創出

    2019.4 - 2020.3

    日本医療研究開発機構(AMED) 医療研究開発推進事業費補助金(橋渡し研究加速ネットワークプログラム) 研究開発委託費(シーズA) 

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    Grant type:Competitive

  5. 肺移植における体外肺灌流保存(EVLP)を用いたマージナルドナー肺の治療

    2018.4 - 2021.3

    日本医療研究開発機構(AMED)H30年度 免疫アレルギー等疾患実用化研究事業(移植医療技術開発研究分野) 

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    Grant type:Competitive

  6. 慢性呼吸不全患者における健康に関連した生活の質(Health-Related Quality of life)に関する研究

    2018.4 - 2019.3

    公益財団法人健康科学財団 平成29年度研究助成 

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    Grant type:Competitive

  7. 臓器移植における抗体関連拒絶反応の新規治療法の開発に関する研究

    2017.4 - 2020.3

    日本医療研究開発機構(AMED)H29年度 免疫アレルギー等疾患実用化研究事業(移植医療技術開発研究分野) 

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    Grant type:Competitive

  8. 脱気変形肺に対応した微小結節の術中同定法

    2017.4 - 2020.3

    日本医療研究開発機構(AMED)H29年度 医療分野研究成果展開事業 産学連携医療イノベーション創出プログラム(ACT-M) 

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    Grant type:Competitive

  9. MEK 阻害剤トラメチニブを用いた肺移植における新しい免疫抑制療法の開発

    2017.4 - 2018.3

    日本医療研究開発機構(AMED) 医療研究開発推進事業費補助金(橋渡し研究加速ネットワークプログラム) 研究開発委託費(シーズA)  H29年度探索医療研究助成 

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    Grant type:Competitive

  10. 3D模型や臓器切除プロセスマップを用いた呼吸器外科手術シミュレーション

    2016.4 - 2018.3

    日本医療研究開発機構(AMED) 医療研究開発推進事業費補助金(橋渡し研究加速ネットワークプログラム) 研究開発委託費(シーズA)   

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    Grant type:Competitive

  11. 肺移植後の慢性拒絶に対する新規治療法の開発

    2016.4 - 2017.3

    上原記念生命科学財団 研究助成金 

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    Grant type:Competitive

  12. 染料マーカーと3D画像技術を融合させた術前気管支鏡下マーキングを用いた、微小肺病変に対する胸腔鏡手術ナビゲーション法の開発

    2016.4 - 2017.3

    内視鏡医学研究振興財団 平成28年度研究助成金 

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    Grant type:Competitive

  13. 造血幹細胞移植後の肺GVHDに対する肺移植について

    2016.4 - 2017.3

    学内共同研究 

  14. プロジェクションマッピングによる近赤外画像の可視化とリアルタイムナビゲーションによる手術システムの開発

    2015.4 - 2018.3

    日本医療研究開発機構(AMED)医療分野研究成果展開事業 産学連携医療イノベーション創出プログラム(ACT-M) 

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    Grant type:Competitive

  15. 最適な体外潅流技術によるドナー肺の「評価、保存、治療」と「局所機能評価

    2015.4 - 2016.3

    平成27年度京都大学研究開発プログラム:京都大学研究支援制度「いしずえ」 

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    Grant type:Competitive

  16. ドナー肺の「評価」、「保存」、「治療」のための最適な体外潅流技術開発への挑戦

    2014.4 - 2015.3

    平成26年度 京都大学コアステージバックアップ研究費 

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    Grant type:Competitive

  17. ドナー肺の体外潅流における新技術の開発:薬剤吸入による治療と赤外線サーモグラフィーによる障害部位の同定

    2014.4 - 2015.3

    公益信託 外科学研究助成基金 

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    Grant type:Competitive

  18. コンピュータ支援デザイン(CAD)を用いた呼吸器外科手術~複雑な肺癌手術の術前シュミレーションから新規の肺移植手技の開発に至るまで~

    2014.4 - 2015.3

    公益信託 第106回日本外科学会定期学術集会記念・外科手術研究助成基金 

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    Grant type:Competitive

  19. 代償性肺成長に基づく術後呼吸予備能の正確な評価を目指す、生体肺移植ドナーにおける調査研究

    2014.4 - 2015.3

    大和証券ヘルス財団 平成26年度(第41回)調査研究助成 

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    Grant type:Competitive

  20. ドナー肺の体外潅流における新技術 :薬剤投与と赤外線サーモグラフィー

    2014.4 - 2015.3

    文部科学省 橋渡し研究加速ネットワークプログラム 京都大学 H26年度探索医療研究助成 

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    Grant type:Competitive

  21. 心臓支配移植における肺保護

    2007.4 - 2008.3

    藤原記念財団 研究奨励金 

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    Grant type:Competitive

  22. Evaluation and protection of the donor lung for the lung transplantation from non-heart-beating donors

    2006.4 - 2007.1

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    Grant type:Competitive

  23. 温虚血におけるサルメテロールの効果

    2006

    京都大学COEプログラム トラベルグラント 

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    Grant type:Competitive

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KAKENHI (Grants-in-Aid for Scientific Research) 55

  1. 間質性肺炎急性増悪病態における新規病的微小環境因子・ミトコンドリアDNAの役割

    Grant number:21K08202  2021.4 - 2024.3

    科学研究費助成事業  基盤研究(C)

    阪本 考司, 芳川 豊史, 若原 恵子, 橋本 直純, 猪股 弥生

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    特発性肺線維症(IPF)は中高年に発症する進行性難治性の肺疾患である。急性増悪はIPF患者の約4割に突然発症する死亡率の高い合併症であるが、原因が分かっておらず発症の予測や治療法の開発が進んでいない。我々は最近、IPF患者さんの体液中のミトコンドリアDNAの増加が急性増悪の発症を予測しうることを発見した。これにヒントを得た本研究は、急性増悪発症のメカニズムとして肺に存在するマクロファージの異常活性化とミトコンドリアの代謝異常が関与していると仮定して、新たに急性増悪の動物モデルを作成し治療標的と診断法の開発を目指します。

  2. 脱気変形アルゴリズムとバードビュー機能を用いた肺表面位置情報ガイドの開発への挑戦

    Grant number:21H03020  2021.4 - 2024.3

    科学研究費助成事業  基盤研究(B)

    芳川 豊史, 中村 彰太, 中尾 恵, 北坂 孝幸, 後藤 真輝, 門松 由佳

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    Authorship:Principal investigator 

    Grant amount:\17680000 ( Direct Cost: \13600000 、 Indirect Cost:\4080000 )

    肺は、術前CT画像は含気状態であるが、手術は脱気状態で行われるため、術前と術中の形態が大きく異なる。
    画像技術の進歩により、微小な肺結節の検出が増え、その切除には、術前マーキングが必須である。また、区域切除において、現在行われている区域間面の同定法も確実とはいえず、現在の内視鏡カメラでは視野に限界がある。
    本研究では, 侵襲的な処置をすることなく、真に低侵襲に微小肺結節を切除するために、微小結節の位置や区域間面の同定が正確に可能となるシステムを情報学的手法により構築する。また、バードビューカメラシステムを用い、肺表面の位置情報を術中にリアルタイムで、わかりやすく、正確にガイドすることを目指す。

  3. ドライバー癌遺伝子誘導性の細胞老化を作用機序とする変異KRAS肺癌の創薬研究

    Grant number:21H02924  2021.4 - 2024.3

    科学研究費助成事業  基盤研究(B)

    佐藤 光夫, 芳川 豊史, 長谷 哲成, 湯川 博, 田中 一大, 松井 佑介

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    変異KRAS癌の創薬を目的とする。代表者は自身開発の正常気管支上皮細胞モデルHBECにおいて、変異KRASの導入が細胞の悪性度を増強する一方で、細胞の増殖を停止させる癌遺伝子誘導細胞老化(oncogene-induced senescence; OIS)という現象に着目した。HBECモデルを用いたOIS回避機能に基づくプールshRNAライブラリースクリーニングを実施し、遺伝子Xを有望な治療標的候補として特定した。本課題では世界初のOIS誘導機序による肺癌治療薬の開発を目標とする。

  4. 生体肺移植におけるドナー、レシピエントの末梢血テロメア長と慢性移植肺機能不全

    Grant number:20K08925  2020.4 - 2023.3

    科学研究費助成事業  基盤研究(C)

    半田 知宏, 芳川 豊史, 松田 文彦, 伊達 洋至

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    脳死肺移植において、ドナーの末梢血テロメア長が移植後のCLAD発症や生命予後と関連する事、レシピエントのテロメア長が移植後の骨髄機能不全と関連する事が報告されているが、本邦で頻度が高い生体肺移植におけるドナー、レジピエントのテロメア長の臨床的意義については報告がない。本研究では、生体肺移植におけるドナー、レシピエントの末梢血テロメア長の臨床的意義を明らかにする事を目的とする。単施設の後ろ向き+前向き研究によって末梢血テロメア長と慢性拒絶の関連を中心に検討を行う。
    2002年1月1日から2019年7月31日までの間に京都大学医学部附属病院で生体肺移植が施行された患者とそのドナー257名(レシピエント89名、ドナー168名)を対象とした。DNA純度不適(A260/280比<1.7)やカルテ情報の不備、検体量不足などで85例を除外し、172例で末梢血テロメア長の測定を行う予定である。現在までにドナー116例の末梢血テロメア長解析を終了している。観察期間中、CLADの発症は11例であった。CLADを認めた症例の肺移植の術式は、両肺8例、片肺3例であった。CLADの発症は両肺で認めた症例が1例で、他は片肺の発症であった。テロメア長の測定は、qPCRを用いて行った。ドナーテロメア長と年齢には弱い負の相関関係が認められた(n=116, r=-0.222, P値<0.05)。また、男性(n=66)は女性(n=50)と比較してテロメア長が長かった(P値<0.0001Mann-Whitney U test)。DNAの保存期間とテロメア長に相関は認めなかった。左右のCLADは別々に評価し、それぞれのドナーの末梢血テロメア長とCLADの関連について検討した。T/S ratioとCLAD(P=0.195, Mann-Whitney U test)、T/S percentileとCLAD(P=0.325, Mann-Whitney U test)のいずれも有意な関連を認めなかった。
    保存DNA検体を用いたドナーのテロメア長の測定と臨床情報の収集、慢性拒絶の評価を完了しており、概ね予定通りの進捗と考えている。
    過去検体を用いた検討ではドナーの末梢血テロメア長と慢性拒絶の間に有意な関連は認めなかった。さらに症例を蓄積し、フォローアップ期間を延長して検討を行っていく。CLADとの関連が予想される遺伝子変異(多型)とCLADの関連についても検討を加えていく予定である。

  5. Innovative therapy for chronic respiratory failure using organoid technique

    Grant number:19K22657  2019.6 - 2021.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

    Yoshikawa Toyofumi

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    Grant amount:\6500000 ( Direct Cost: \5000000 、 Indirect Cost:\1500000 )

    Lung transplantation has been established as one of the last treatments for end-stage lung diseases, but the donor shortage is a great issue. A new treatment option which ca be an alternative for lung transplantation can be expected. In this study, we focused on to create the concept of new treatment option for end-stage lung diseases, which ca be an alternative for lung transplantation. We also aimed to use organoid technique for this strategy. First of all, we performed a study using a mouse fetal allogenic transplantation model, looking at morphological and functional aspects. We found that fetal tissues could alleviate the functions of injured lungs.

  6. ドナーグラフト内の白血球を標的とした肺移植における新規治療法の開発

    2019.4 - 2022.3

    科学研究費補助金  基盤研究(C)

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  7. 機能性極細気泡を用いた革新的臓器保存液の開発

    2019.4 - 2022.3

    科学研究費補助金  基盤研究(C)

    豊洋次郎

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  8. 臓器移植を革新する免疫プロファイリングによる個別化医療の開発

    2019.4 - 2022.3

    AMED  免疫アレルギー等疾患実用化研究事業(移植医療技術開発研究分野 課題管理番号19ek0510029h0001) 

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    Grant type:Competitive

  9. 機能性極細気泡を用いた革新的臓器保存液の開発

    2019.4 - 2022.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    豊洋次郎

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    Grant type:Competitive

  10. ドナーグラフト内の白血球を標的とした肺移植における新規治療法の開発

    2019.4 - 2022.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

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    Grant type:Competitive

  11. ドナーグラフト内の白血球を標的とした肺移植における新規治療法の開発

    Grant number:19K09302  2019.4 - 2022.3

    科学研究費助成事業  基盤研究(C)

    大角 明宏, 芳川 豊史, 伊達 洋至

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    ドナーの方から御提供頂き摘出した肺を、体内にある状態を模倣して換気・灌流することにより肺の機能を評価することが、欧米では一般的となっています。本研究では、小動物の体外肺灌流のシステムを用いて、ドナー肺内の白血球の動きに着目して、移植前に肺の機能を向上させる研究です。移植後は、主に白血球が主役となり傷害を起こすため、さまざまなタイプの白血球の動きに着目して、効果的な治療を行います。
    移植おけるドナー臓器不足は日本と同様、諸外国でも課題である。欧米では、近年ドナーの摘出肺を移植に用い得るか、体外肺灌流システムを用いて評価されている。このシステムは、肺動脈幹・左房・気管にカニューレを装着し、特殊な灌流液で循環させ、かつ人工呼吸器を用いて換気させながら、ドナー摘出肺の機能を評価するものである。本研究では、ラット肺の体外肺灌流および肺移植モデルを用いて、体外肺灌流中及び移植後のドナー由来の白血球分画(単球及び顆粒球)の変動をフローサイトメトリーによって解析する。また、これらの分画を薬剤処置等によって除去することにより肺移植後の機能が改善されるかを検証する。本研究の結果は、肺移植後の虚血再灌流傷害や慢性拒絶の予防に有用で、画期的な肺移植治療につながり得ると考える。
    2019年8月より、ラット肺の体外肺灌流モデルの練習を開始した。同年9月に無虚血ラット肺を用いた体外肺灌流モデルが確立したが、体外肺灌流装置を購入したのは約20年前であり同年10月には老朽化のためか装置が故障し、修理のために海外へ装置を輸送した。
    2019年11月よりラット肺移植モデルの練習を開始し、虚血ラット肺を用いたラット肺移植モデルを確立した。また、2020年3月よりフローサイトメトリーによる白血球分画の解析を開始し、血液や肺内の白血球分画の測定方法を確立した。
    2020年10月に体外肺灌流装置の修理が完了し、虚血ラット肺を用いた体外肺灌流モデルが確立した。
    2021年4月の時点で、薬剤を用い体外肺灌流中に白血球分画の除去を行う実験を終了した。今後は体外肺灌流中に白血球分画の除去を行うことで、肺移植後の虚血再灌流傷害を予防できるか検証する予定である。

  12. 機能性極細気泡を用いた革新的臓器保存液の開発

    Grant number:19K09283  2019.4 - 2022.3

    科学研究費助成事業  基盤研究(C)

    豊 洋次郎, 陳 豊史, 伊達 洋至

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    Authorship:Coinvestigator(s) 

    肺移植において移植肺(グラフト)機能不全は,早期死亡の主因であり、その成績は未だ満足すべきものではない。ドナー臓器摘出後の保存状態は肺移植後早期に生じるグラフト機能不全を引き起こす虚血再灌流傷害に直接影響する因子であり、周術期死亡の要因となる他、慢性拒絶のリスク因子とされる。現在臨床で使用されている単純冷却保存に、近年生鮮の長期保存を可能とした日本初の革新的技術であるウルトラファインバブル技術(生理活性作用を有した1μm以下の機能的微細気泡を液体に溶存させる技術)を導入することで、肺保存時間の延長、虚血再潅流肺障害に対する新たな治療選択肢になり得るかどうかを検討する計画を立案した。

  13. オルガノイドを用いた慢性呼吸不全に対する革新的治療法の開発

    2019.4 - 2021.3

    科学研究費補助金 

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    Authorship:Principal investigator 

  14. オルガノイドを用いた慢性呼吸不全に対する革新的治療法の開発

    2019.4 - 2021.3

    日本学術振興会  科学研究費助成事業  萌芽研究

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    Grant type:Competitive

  15. 肺及び腸オルガノイドと新規呼吸システムを用いた慢性呼吸不全に対する革新的治療法の創出

    2019.4 - 2020.3

    日本医療研究開発機構(AMED)  日本医療研究開発機構(AMED) 医療研究開発推進事業費補助金(橋渡し研究加速ネットワークプログラム) 研究開発委託費(シーズA) 

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    Grant type:Competitive

  16. 肺移植後の慢性拒絶撲滅を目指す、自然免疫を温存した選択的免疫抑制療法の創出

    2018.4 - 2021.3

    科学研究費補助金  基盤研究(B)

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    Authorship:Principal investigator 

  17. Development of selective immunosuppressive therapy preserving natural immunity for treating chronic rejection after lung transplantation

    Grant number:18H02893  2018.4 - 2021.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Yoshikawa Toyofumi

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    Grant amount:\16770000 ( Direct Cost: \12900000 、 Indirect Cost:\3870000 )

    The greatest cause to prevent long-term survival after lung transplantation is chronic allograft dysfunction (CLAD), which is mainly due to chronic rejection. The etiology of CLAD remains unknown and there is no proper therapy for progressive CLAD. Since lungs communicate with the outer world, immunity in lungs is developed, while lungs are susceptible to infection. Thus, in lung transplantation, it is crucial to develop a selective immune suppression which does not decrease immunity against infection. Herein, we focused on a MEK inhibitor (trametinib), which has a new mechanism for immunosuppression, as an immunosuppressant which does not decrease immunity against infection. We performed several studies to prove that a MEK inhibitor alleviated chronic rejection in a rat lung transplantation model.

  18. 肺移植後の慢性拒絶撲滅を目指す、自然免疫を温存した選択的免疫抑制療法の創出

    2018.4 - 2021.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

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    Grant type:Competitive

  19. 肺移植における体外肺灌流保存(EVLP)を用いたマージナルドナー肺の治療

    2018.4 - 2021.3

    日本医療研究開発機構(AMED)  日本医療研究開発機構(AMED)H30年度 免疫アレルギー等疾患実用化研究事業(移植医療技術開発研究分野) 

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    Grant type:Competitive

  20. ドライバー癌遺伝子により誘導される細胞老化 (OIS) を利用した肺癌治療の開発

    Grant number:18H02819  2018.4 - 2021.3

    科学研究費助成事業  基盤研究(B)

    佐藤 光夫, 長谷 哲成, 湯川 博, 田中 一大, 芳川 豊史, 川口 晃司, 川井 久美, 横井 香平

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    【本課題の目的】肺癌のドライバー癌遺伝子の一つ変異KRASは腺癌の20%程度に認められるが、その標的治療の開発は未成功である。これは変異KRASの癌化シグナルの薬物的な遮断が困難なためである。応募者は正常気管支モデルであるHBEC実験系を確立し(Sato, Cancer Res 2006)、さらに、変異KRASをHBECに導入すると悪性度の増強にもかかわらず細胞分裂を停止する現象を発見した(Sato, Mol Cancer Res 2013)。これは正常細胞が癌化を防御する機構の一つ癌遺伝子誘導細胞老化(oncogene-induced senescence; OIS)である。以上より、応募者は変異KRAS肺癌の新たな治療として変異KRASシグナルの遮断ではなく、OISを活用する治療を着想した。その実現のために、まず、HBECを用いて、OIS抑制作用を表現型とする機能的なプールshRNAスクリーニングを実施し、複数の標的候補を特定した。特に、肺癌細胞株が高発現する遺伝子Xは小分子化合物による治療標的となる可能性があるため、学内創薬産学協同研究センター(ラクオリア創薬株式会社)化合物スクリーニングを予定した(機密保持契約締結済み)。本研究はこれらの研究を発展させ、変異KRASならびに変異EGFRやALK遺伝子によるOIS誘導治療の開発を目的とする。
    <BR>
    【2019年度の成果】
    これまでに、複数の化合物ライブラリーを使用したハイスループットスクリーニング(HTS)を実施した。初期に同定したヒット化合物の活性が再現できなかったため、化合物選択基準の見直しを行い、ヒット化合物を選び直した。ヒット化合物の再現性、選択性、構造活性相関(Structure-Activity Relationship: SAR)解析の結果に基づき、数個のシーズ化合物に絞り込んだ。
    これまでに、複数の化合物ライブラリーを使用したハイスループットスクリーニング(HTS)を実施した。初期に同定したヒット化合物の活性が再現できなかったため、化合物選択基準の見直しを行い、ヒット化合物を選び直した。ヒット化合物の再現性、選択性、構造活性相関(Structure-Activity Relationship: SAR)解析の結果に基づき、数個のシーズ化合物に絞り込んだ。ヒット化合物の再現性ができなかったことなどにより当初の計画よりやや遅れている。
    これまでの研究成果に基づいて2020年度は以下を計画する。①SARの結果に基づいて新規化合物(リード化合物)を合成する。②リード化合物および遺伝子X産物との結晶構造解析を外部委託に実施する。③新規化合物に対して評価・解析およびデザイン・合成のステップを繰り返し実施し、さらに薬効の優れるリード化合物を合成する。④前記と併行して、遺伝子Xノックアウト肺癌細胞クローンを用いて、遺伝子X阻害の癌細胞の増殖抑制機序の解明を継続して実施する。⑤2020年度までに合成されるリード化合物に対して、各種非臨床試験(薬理、毒性、薬物動態試験など)に必要な予備的試験を実施する。具体的には、複数の化合物の薬効(XenograftやPDXモデル)、薬物動態(経口吸収率、血中半減期、代謝・排出経路、代謝物)、短期毒性(心血管作用、中枢作用、病理)、物性(溶解性、固体安定性)を評価する。以上の結果に基づいて、2020年度末までにリード化合物の基本特許申請を目標とする。

  21. 慢性呼吸不全患者における健康に関連した生活の質(Health-Related Quality of life)に関する研究

    2018.4 - 2019.3

    公益財団法人健康科学財団  公益財団法人健康科学財団 平成29年度研究助成 

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    Grant type:Competitive

  22. 水素水の拡散能を利用した心停止ドナー肺障害の修復と肺移植実現を目指した大動物実験

    2017.4 - 2020.3

    科学研究費補助金  基盤研究(B)

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    Authorship:Coinvestigator(s) 

  23. 臓器移植における抗体関連拒絶反応の新規治療法の開発に関する研究

    2017.4 - 2020.3

    日本医療研究開発機構(AMED)  日本医療研究開発機構(AMED)H29年度 免疫アレルギー等疾患実用化研究事業(移植医療技術開発研究分野) 

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    Grant type:Competitive

  24. 脱気変形肺に対応した微小結節の術中同定法

    2017.4 - 2020.3

    日本医療研究開発機構(AMED)  日本医療研究開発機構(AMED)H29年度 医療分野研究成果展開事業 産学連携医療イノベーション創出プログラム(ACT-M) 

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    Grant type:Competitive

  25. 水素水の拡散能を利用した心停止ドナー肺障害の修復と肺移植実現を目指した大動物実験

    2017.4 - 2020.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

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    Grant type:Competitive

  26. Large animal experimental study on lung repair by hydrogen diffusion for lung transplantation from donation after cardiac death

    Grant number:17H04295  2017.4 - 2020.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Date Hiroshi

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    Molecular hydrogen (H2) has protective effects against ischemia-reperfusion (I/R) injury in various organs. They are easier to transport and safer to use than inhaled H2. In this study, we examined the protective effects of an H2-rich solution for lung preservation in a canine left lung transplantation (LTx) model. Ten beagles underwent orthotopic left LTx after 23 h of cold ischemia followed by reperfusion for 4 h. The beagles were divided into two groups: control (CON group, n=5) and hydrogen (H2 group, n=5). Significantly higher partial pressure of arterial oxygen and significantly lower partial pressure of carbon dioxide were observed in the H2 group than in the CON group. The W/D ratio was significantly lower in the H2 group. Moreover, in histological examination, less lung injury and fewer apoptotic cells were observed in the H2 group.
    Our results indicated that the H2-rich preservation solution attenuated I/R injury in a canine left LTx model.

  27. MEK 阻害剤トラメチニブを用いた肺移植における新しい免疫抑制療法の開発

    2017.4 - 2018.3

    日本医療研究開発機構(AMED)  日本医療研究開発機構(AMED) 医療研究開発推進事業費補助金(橋渡し研究加速ネットワークプログラム) 研究開発委託費(シーズA) H29年度探索医療研究助成 

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    Grant type:Competitive

  28. 3D模型や臓器切除プロセスマップを用いた呼吸器外科手術シミュレーション

    2016.4 - 2018.3

    日本医療研究開発機構(AMED)  日本医療研究開発機構(AMED) 医療研究開発推進事業費補助金(橋渡し研究加速ネットワークプログラム) 研究開発委託費(シーズA) 

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    Grant type:Competitive

  29. チロシンキナーゼ阻害剤を用いた新たな臓器保存・虚血再灌流肺障害治療戦略

    2016.4 - 2017.3

    科学研究費補助金  基盤研究(C)

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    Authorship:Coinvestigator(s) 

  30. 造血幹細胞移植後の肺GVHDに対する肺移植について

    2016.4 - 2017.3

    JB奨学寄附金  学内共同研究 

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    Grant type:Competitive

  31. 肺移植後の慢性拒絶に対する新規治療法の開発

    2016.4 - 2017.3

    上原記念生命科学財団  上原記念生命科学財団 研究助成金 

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    Grant type:Competitive

  32. 染料マーカーと3D画像技術を融合させた術前気管支鏡下マーキングを用いた、微小肺病変に対する胸腔鏡手術ナビゲーション法の開発

    2016.4 - 2017.3

    内視鏡医学研究振興財団  内視鏡医学研究振興財団 平成28年度研究助成金 

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    Grant type:Competitive

  33. チロシンキナーゼ阻害剤を用いた新たな臓器保存・虚血再灌流肺障害治療戦略

    2016.4 - 2017.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

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    Grant type:Competitive

  34. 細胞外マトリックスの3次元的定量による肺の成長・過膨張・気腫形成の病態解明

    2015.4 - 2018.3

    科学研究費補助金  基盤研究(C)

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  35. 肺移植における抗体性拒絶の早期診断法と低用量IL-2を用いた新規治療法の開発

    2015.4 - 2018.3

    科学研究費補助金  基盤研究(C)

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  36. Early diagnosis and novel treatment with low-dose IL-2 of humoral rejection in lung transplantation.

    Grant number:15K10253  2015.4 - 2018.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Aoyama Akihiro, Kawai Tatsuo

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    Study 1: 193 lung transplantations (LuTx) was performed and 146 patients were alive s of March 2018. Anti-donor antibody was detected in peripheral blood in 20 cases. During the study period, nine patients developed obstructive bronchiolitis, and except one autopsy and one retransplantation, pulmonary biopsy was impossible due to poor status of the patients.
    Study 2: Rat orthotopic LuTx model was established, which is closer to clinical lung transplant than tracheal transplantation. Using this model, administration of 14-day cyclosporine resulted in anti-donor antibody in lung tissue and histologically obstructive bronchiolitis. It was confirmed that antibody production in lung allograft was produced in rat lung transplantation model.

  37. 肺移植における抗体性拒絶の早期診断法と低用量IL-2を用いた新規治療法の開発

    2015.4 - 2018.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

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    Grant type:Competitive

  38. 細胞外マトリックスの3次元的定量による肺の成長・過膨張・気腫形成の病態解明

    2015.4 - 2018.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

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    Grant type:Competitive

  39. Quantitative assessment of extra-cellar matrix in diseased lung, during regeneration, hyperinflation, and development of emphysema

    Grant number:15K09172  2015.4 - 2018.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Sato Susumu

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    Elastase induced lung injury (emphysematous lesion) in model mouse represent significant relationship with respiratory mechanical property measured by forced oscillation technique. In addition, cranial-caudal heterogeneity of emphysema showed significant and independent association with heterogeneity of elastane (SD of H). These associations were preserved in acute model (3 weeks after injury) and chronic model (13 weeks after injury). However, in chronic model, airway resistance (Raw) also showed significant association and may suggest difference of structure-function relationship in development of emphysema.
    Dose dependent effect of elastane in development of emphysema showed ceiling-effect in chronic model.

  40. プロジェクションマッピングによる近赤外画像の可視化とリアルタイムナビゲーションによる手術システムの開発

    2015.4 - 2018.3

    日本医療研究開発機構(AMED  日本医療研究開発機構(AMED)医療分野研究成果展開事業 産学連携医療イノベーション創出プログラム(ACT-M) 

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    Grant type:Competitive

  41. 血液型不適合やクロスマッチ陽性肺移植の実現を目指す、各種抗体に関する多角的研究

    2015.4 - 2017.3

    科学研究費補助金 

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    Authorship:Principal investigator 

  42. 血液型不適合やクロスマッチ陽性肺移植の実現を目指す、各種抗体に関する多角的研究

    2015.4 - 2017.3

    日本学術振興会  科学研究費助成事業  萌芽研究

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    Grant type:Competitive

  43. 心停止ドナーからの肺移植実現をめざした体外循環装置中吸入療法による肺傷害修復実験

    2014.4 - 2017.3

    科学研究費補助金  基盤研究(B)

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  44. 心停止ドナーからの肺移植実現をめざした体外循環装置中吸入療法による肺傷害修復実験

    2014.4 - 2017.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

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    Grant type:Competitive

  45. 抗体陽性・血液型不適合肺移植を目指すための、抗体関連拒絶に対する研究

    2013.4 - 2015.3

    科学研究費補助金 

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    Authorship:Principal investigator 

  46. 生体・脳死肺移植におけるメモリー細胞と制御性T細胞/ThTh17バランスの解析

    2012.4 - 2015.3

    科学研究費補助金  基盤研究(C)

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  47. 肺移植臨床応用をめざした心停止ドナー肺の体外循環装置による肺傷害修

    2011.4 - 2014.3

    科学研究費補助金  基盤研究(B)

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  48. 体外肺潅流技術を用いた、傷害のあるドナー肺の評価とその治療への挑戦

    2011.4 - 2014.3

    科学研究費補助金  若手研究(A)

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    Authorship:Principal investigator 

  49. マージナルドナー肺、心臓死ドナー肺の新しい評価法と治療法の開発

    2009.4 - 2011.3

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator 

  50. 心停止ドナーからの肺移植臨床応用をめざした大動物実験

    2008.4 - 2011.3

    科学研究費補助金  基盤研究(B)

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    Authorship:Coinvestigator(s) 

  51. 薬剤吸入による心停止後移植肺グラフト保護に関する前臨床研究

    2008.4 - 2011.3

    科学研究費補助金  基盤研究(C)

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  52. ET-Kyoto液による胸腹部多臓器同時ハーベスト法の開発

    2008.4 - 2011.3

    科学研究費補助金  基盤研究(C)

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  53. ナノ粒子キャリアを用いた吸入による新規DDSに関する研究

    2007.4 - 2009.3

    科学研究費補助金  基盤研究(C)

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  54. Evaluation and protection of the donor lungs from donation after cardiac death

    2007.4 - 2008.3

    Grant-in-Aid for Scientific Research 

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  55. 温虚血におけるサルメテロールの効果

    2006

    京都大学COEプログラム  京都大学COEプログラム トラベルグラント 

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    Grant type:Competitive

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