Hiroshi Date

Kyoto University, Kioto, Kyōto, Japan

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Publications (489)1279.78 Total impact

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    ABSTRACT: BACKGROUND The efficacy of postoperative radiotherapy (PORT) for thymic epithelial tumors is still controversial. Using the Japanese Association for Research on the Thymus (JART) database, this study was aimed at clarifying the efficacy of PORT for Masaoka stage II and III thymic carcinoma and thymoma.METHODS The JART database registered the records of 2835 patients collected from 32 Japanese institutions from 1991 to 2010. Thymic carcinoma and thymoma at stage II or III were extracted. The efficacy of PORT with respect to relapse-free survival (RFS) and overall survival (OS) was evaluated with the Kaplan-Meier method and Cox regression analysis.RESULTSThere were 1265 patients in all: 155 thymic carcinoma cases (12.3%) and 1110 thymoma cases (87.7%). Eight hundred ninety-five (70.8%) were at stage II, and 370 (29.2%) were at stage III. Four hundred three cases (31.9%) underwent PORT. PORT for stage II and III thymic carcinoma was associated with increasing RFS (hazard ratio, 0.48; 95% confidence interval, 0.30-0.78; P = .003) but was not associated with OS (hazard ratio, 0.94; 95% confidence interval, 0.51-1.75; P = .536). PORT for stage II and III thymoma was not associated with RFS or OS (P = .350). A subgroup analysis of stage III thymoma showed no factor associated with the efficacy of PORT.CONCLUSIONS In this study, PORT did not increase RFS or OS for stage II or III thymoma but increased RFS for stage II and III thymic carcinoma. Cancer 2015. © 2015 American Cancer Society.
    Cancer 01/2015; · 5.20 Impact Factor
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    ABSTRACT: We developed virtual-assisted lung mapping (VAL-MAP), a bronchoscopic multispot dye-marking technique using three dimensional (3D) virtual imaging, for precise thoracoscopic sublobar lung resection with safe surgical margins. We herein review the results of 100 consecutive cases of VAL-MAP in our institute to identify types of tumours or resections that benefit from VAL-MAP. Markings were bronchoscopically made within 2 days preoperatively using virtual 3D images. Post-VAL-MAP computer tomography (CT) scans localizing the actual markings were reconstructed into 3D images for intraoperative navigation. All data on patients, markings and outcomes were prospectively collected, and the contribution of VAL-MAP to the operation was graded by the surgeon. Resections of 156 lung lesions in 100 consecutive patients were planned from July 2012 to March 2014. The lesion diameter was 8.3 ± 4.9 (range, 2-24) mm. The total number of actually conducted markings was 380 (3.83 ± 1.07 markings/patient). Eighty-four lesions were resected by 71 wedge resections using 158 markings (2.1 ± 0.1/resection; range, 1-3). Seventy lesions were resected by 63 segmentectomies using 224 markings (3.6 ± 0.1/resection; range, 2-6). Markings were identifiable on post-VAL-MAP CT mostly as ground-glass opacities (87.7%) and/or bronchial dilatation (56.1%). During the operation, 357 of 380 markings (93.9%) were visible on the pleural surface and significantly associated with marking visibility on CT. Multiple markings that were complementary to one another appeared to have contributed to the high rate of successful resection (99.3%) with satisfactory resection margins. The contribution of VAL-MAP to the operation as graded by surgeons demonstrated that VAL-MAP is most effective during wedge resection or complex segmentectomy for hardly palpable, small tumours, while VAL-MAP still plays an important role in simple segmentectomy or resection of palpable tumours by providing higher confidence levels to surgeons during the operation. Minor pneumothoraces were found on post-VAL-MAP CT images in 4 patients without symptoms or a need for treatment. The present study further demonstrated the efficacy and safety of VAL-MAP. VAL-MAP is likely to benefit a broader range of patients than are conventional marking techniques by assisting with both accurate tumour identification and precise determination of resection lines. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 12/2014; · 2.40 Impact Factor
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    ABSTRACT: We report the case of a 64-year-old woman with recurrent mediastinal dedifferentiated liposarcoma. She had undergone surgical resection twice. Subsequently, on regular follow-up visits, chest computed tomography demonstrated a third local recurrence of the tumor with invasion into adjacent intrathoracic organs. Adhesion of the heart to the anterior chest wall through a pericardial defect that had been inadvertently created at the second operation was suspected. We decided to use a thoracoabdominal approach with four-dimensional computed tomography (4DCT) for preoperative guidance. The patient had also undergone MRI; however, the result was equivocal regarding adhesion of intrathoracic organs. The use of 4DCT enabled successful en bloc resection of the tumor. Results of the pathology examination showed complete resection of a dedifferentiated liposarcoma. The patient’s postoperative course was uneventful, and she was discharged on postoperative day 19.
    General Thoracic and Cardiovascular Surgery 12/2014;
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    ABSTRACT: OBJECTIVES: The optimal material for anterior chest wall reconstruction following chest wall resection remains controversial. The aim of this experimental study was to evaluate short-term, morphological and histological outcomes of anterior chest wall reconstruction with a rigid and bioabsorbable material in a canine model. METHODS: Twenty adult beagle dogs underwent anterior chest wall resection. In the experimental group (n = 10), the anterior chest wall was reconstructed with a rigid and bioabsorbable material composed of poly-L-lactide acid matrix (60wt%) and uncalcined and unsintered hydroxyapatite particles (40wt%), whereas in the control group it was (n = 10) reconstructed with dual polypropylene mesh sheets. Short-term complication rates were compared with a χ 2 test. Postoperative sternal deviations were evaluated with sternal alignment angles using computed tomography and multiplanar reconstruction and were compared with Mann–Whitney U-test immediately after reconstruction, and at 1, 3, 6, 9 and 12 months postoperatively. Histological findings of the regenerated chest wall tissue were obtained after staining with haematoxylin and eosin and Elastica van Gieson (EVG) and compared at 3, 6, 9 and 12 months. RESULTS: There was not a significant difference in the short-term postoperative complication rate (P = 0.53) and the complication rate was 20% (wound infection, n = 1 and lethal mediastinitis, n = 1) in the control group and 10% (wound infection, n = 1) in the experimental group. The postoperative sternal deviation was significantly less remarkable at 1 month (123.3 ± 32.2°vs 159.4 ± 19.7°, P = 0.027), 3 months (109.8 ± 34.7° vs 150.9 ± 34.2°, P = 0.039) and 12 months (61 ± 15.6° vs 170.3 ± 6.6°, P = 0.046) in the experimental group than in the control group, whereas no significant difference was noted immediately after reconstruction (165.7 ± 6.4° vs 168.4 ± 9.1°, P = 0.50). Histological findings showed dense connective tissue in the regenerated chest wall in both groups and showed chondroblasts in the regen-erated chest wall tissue at 3 and 6 months only in the experimental group. CONCLUSIONS: Our results suggest that anterior chest wall reconstruction with a rigid and bioabsorbable material is feasible and may be a valuable alternative to reconstruction with a non-rigid and non-absorbable material.
    Interactive Cardiovascular and Thoracic Surgery 12/2014; · 1.11 Impact Factor
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    ABSTRACT: DNA methylation is associated with aberrant gene expression in cancer, and has been shown to correlate with therapeutic response and disease prognosis in some types of cancer. We sought to investigate the biological significance of DNA methylation in lung cancer. We integrated the gene expression profiles and data of gene promoter methylation for a large panel of non-small cell lung cancer cell lines, and identified 578 candidate genes with expression levels that were inversely correlated to the degree of DNA methylation. We found these candidate genes to be differentially methylated in normal lung tissue versus non-small cell lung cancer tumors, and segregated by histologic and tumor subtypes. We used gene set enrichment analysis of the genes ranked by the degree of correlation between gene expression and DNA methylation to identify gene sets involved in cellular migration and metastasis. Our unsupervised hierarchical clustering of the candidate genes segregated cell lines according to the epithelial-to-mesenchymal transition phenotype. Genes related to the epithelial-to-mesenchymal transition, such as AXL, ESRP1, HoxB4, and SPINT1/2, were among the nearly 20% of the candidate genes that were differentially methylated between epithelial and mesenchymal cells. Greater numbers of genes were methylated in the mesenchymal cells and their expressions were upregulated by 5-azacytidine treatment. Methylation of the candidate genes was associated with erlotinib resistance in wild-type EGFR cell lines. The expression profiles of the candidate genes were associated with 8-week disease control in patients with wild-type EGFR who had unresectable non-small cell lung cancer treated with erlotinib, but not in patients treated with sorafenib. Our results demonstrate that the underlying biology of genes regulated by DNA methylation may have predictive value in lung cancer that can be exploited therapeutically.
    BMC Genomics 12/2014; 15(1):1079. · 4.04 Impact Factor
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    ABSTRACT: Living-donor lobar lung transplantation (LDLLT) has been established as a life-saving procedure for critically ill patients who cannot wait for cadaveric lung transplantation. Chronic lung allograft dysfunction (CLAD) is the main cause of late morbidity and mortality in lung transplantation. Studies on CLAD in cadaveric lung transplantation have been extensively reported, but few reports have been reported concerning CLAD after LDLLT. The aim of this study was to determine the prevalence, characteristics and prognosis of CLAD after LDLLT. Among 38 patients who survived more than 3 months after LDLLT at Kyoto University Hospital between June 2008 and December 2013, 8 patients (21%) were diagnosed with CLAD. The mean follow-up period after LDLLT was 33 months. Clinical course, pulmonary function and radiological findings were reviewed retrospectively in all the 38 patients as of May 2014. Six patients were female and 2 were male. The median age at LDLLT was 31 years, and the median interval between LDLLT and the initial diagnosis of CLAD was 23 months. Among 8 patients who developed CLAD, 2 patients underwent right single LDLLT and 6 patients underwent bilateral LDLLT. The former 2 patients survived 44 and 47 months after the treatment. Five out of 6 patients with bilateral LDLLT developed unilateral CLAD at the time of initial diagnosis according to ventilation scintigraphy. In 3 of these 5 patients, the progression of CLAD was halted by treatment, and the median follow-up period of 33 months after treatment. In the remaining 2 of 5 patients, CLAD progressed to the contralateral lung metachronously; 1 patient survived without oxygen supplement, but the other patient required reperformance of LDLLT 3 years after the first one. One patient with bilateral CLAD at the time of detection died of disease progression 4 years after LDLLT. Despite a relatively short observation time, CLAD developed in approximately one-fifth of the patients who survived more than 3 months after LDLLT. In bilateral LDLLT, CLAD developed unilaterally in most cases, which might be beneficial in the long term because the unaffected contralateral lung may function as a reservoir. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 12/2014; · 2.40 Impact Factor
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    ABSTRACT: As surgical robots have become increasingly used, verification of their usefulness in the general thoracic surgery field is required. Initial results of robot-assisted thoracoscopic surgery in Japan were investigated. A questionnaire survey was performed to retrospectively examine the current status of robotic surgery for general thoracic disease in Japan. The subjects were 112 cases performed by the end of September 2012 at 9 institutions. There were 60 cases of primary lung cancer, 38 cases of anterior-middle mediastinal disease, and 14 cases of posterior mediastinal disease. In lung cancer cases, the operative time was 284.7 min, the blood loss was 129 mL, the drainage period was 3.3 days, and the conversion rate was 3.3 %. The incidence of postoperative complications was 6.7 %. The postoperative hospital stay was 8.2 days. In cases of anterior-middle mediastinal disease, the operative time was 184.3 min, the blood loss was 43.8 mL, the drainage period was 2.3 days, and there was no conversion. The incidence of postoperative complications was 7.9 %. The postoperative hospital stay was 7.1 days. In cases of posterior mediastinal disease, the operative time was 142.6 min, the blood loss was 61.4 mL, the drainage period was 1.6 days, and there was no conversion. No postoperative complication developed in any case. The postoperative hospital stay was 5 days. In all cases underwent robotic surgery, there was no operation related mortality. Robotic surgery was safely introduced, and the incidence of postoperative complications tended to be low, although the operative time was long. Preparations for its employment in advanced medical care and coverage by national health insurance are urgent issue.
    General Thoracic and Cardiovascular Surgery 12/2014; 62(12):720-5.
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    ABSTRACT: After lung transplantation, early detection of acute allograft rejection is important not only for timely and optimal treatment, but also for the prediction of chronic rejection which is a major cause of late death. Many biological and immunological approaches have been developed to detect acute rejection; however, it is not well known whether lung mechanics correlate with disease severity, especially with pathological rejection grade. In this study, we examined the relationship between lung mechanics and rejection grade development in a rat acute rejection model using the forced oscillation technique, which provides noninvasive assessment of lung function. To this end, we assessed lung resistance and elastance (RL and EL) from implanted left lung of these animals. The perivascular/interstitial component of rejection severity grade (A-grade) was also quantified from histological images using tissue fraction (TF; tissue + cell infiltration area/total area). We found that TF, RL, and EL increased according to A-grade. There was a strong positive correlation between EL at the lowest frequency (Elow; EL at 0.5 Hz) and TF (r2 = 0.930). Furthermore, the absolute difference between maximum value of EL (Emax) and Elow (Ehet; Emax − Elow) showed the strong relationship with standard deviation of TF (r2 = 0.709), and A-grade (Spearman's correlation coefficients; rs = 0.964, P < 0.0001). Our results suggest that the dynamic elastance as well as its frequency dependence have the ability to predict A-grade. These indexes should prove useful for noninvasive detection and monitoring the progression of disease in acute rejection.
    Physiological Reports. 12/2014; 2(12).
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    ABSTRACT: Although ex vivo lung perfusion (EVLP) has been clinically applied as a novel rig to evaluate marginal donor lungs, no parameters have been reported to objectively detect regional lung damage during EVLP. The aim of this study was to investigate whether regional donor lung malperfusion-related damage caused by a thrombus could be detected by thermography during EVLP. Lewis rats were divided into two groups: the Thrombosis group and the Control group (n = 6 in each group). All rats were heparinized and the lungs were flushed with 20 ml of Steen solution. In the Thrombosis group, a 30-mg artificial thrombus was inserted into the left main pulmonary artery. All the lungs were perfused and ventilated using the EVLP system. Perfusion flow was increased every 2 min up to 10 ml/min. The lungs were evaluated by collecting thermographical and physiological data during EVLP. Pulmonary artery pressure was higher and lung compliance was lower in the Thrombosis group compared with those in the Control group (P = 0.0005 and <0.0001, respectively). Macroscopically, no differences were seen between the perfused area and the malperfused area, whereas significant differences were detected between them by thermography. The surface temperature of both lungs in the Control group and the right lungs in the Thrombosis group rose with increasing perfusion flow, whereas the surface temperature of the left lungs in the Thrombosis group did not rise (P < 0.0001). Although physiological data could possibly imply the existence of thrombi in the Thrombosis group, it could not reveal which area was obstructed by thrombi; however, thermography could detect a malperfused region. Thermographical evaluation may become a promising strategy to detect regional damage in donor lungs. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
    Interactive Cardiovascular and Thoracic Surgery 11/2014; · 1.11 Impact Factor
  • International Journal of Radiation Oncology*Biology*Physics; 11/2014
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    ABSTRACT: We report the youngest patient ever reported in the literature to exhibit pleuroparenchymal fibroelastosis (PPFE) as a late-onset pulmonary toxicity after treatment with anticancer chemotherapy. The patient was diagnosed with mature B-cell leukemia at age 14. He was successfully treated with intensive chemotherapy; however, 7 years later, he experienced recurrent pneumothoraces. He was clinically diagnosed with upper lobe pulmonary fibrosis. At age 28, he underwent single left lung transplantation. Histologic examination of the resected lung revealed PPFE in the upper lobe and constrictive bronchiolitis obliterans in the lower lobe, which implied a close relationship between PPFE and constrictive bronchiolitis obliterans. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    The Annals of Thoracic Surgery 11/2014; 98(5):e115-7. · 3.63 Impact Factor
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    ABSTRACT: Swyer-James syndrome was first described in 1953 as unilateral pulmonary emphysema in a 6-year-old boy. The characteristic feature of this syndrome is unilateral pulmonary hyperlucency on a chest X-ray film. Typical symptoms include recurrent chest infections, chronic cough, wheezing, and exertional dyspnea. Although there have been a few reports of pneumothorax in patients with Swyer-James syndrome, there have been no reports about an association with giant bullae. Here, we report a case of Swyer-James syndrome associated with a giant bulla and asthma, in which surgery achieved marked improvement of dyspnea.
    Respirology Case Reports. 11/2014;
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    ABSTRACT: Lung cancer patients with interstitial lung diseases (ILDs) who have undergone pulmonary resection often develop acute exacerbation of interstitial pneumonia (AE) in the post-operative period. To predict who is at high risk of AE, we propose a scoring system that evaluates the risk of AE in lung cancer patients with ILDs.
    General Thoracic and Cardiovascular Surgery 10/2014;
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    ABSTRACT: Background Donor lung thrombus are considered a significant etiology for primary graft dysfunction. We hypothesized that thrombolysis in an ex vivo lung perfusion (EVLP) before lung transplantation could alleviate ischemia–reperfusion injury (IRI), resulting in the reduction of primary graft dysfunction. Methods Rats were divided into control (n = 5), non-plasmin (n = 7), and plasmin (n = 7) groups. In the non-plasmin and plasmin groups, cardiac arrest was induced by withdrawal of ventilation without heparinization. After 120 min of warm ischemia, the lungs were ventilated and flushed. Heart and lungs were excised en bloc. The lungs were perfused and ventilated in the EVLP for 30 min, and plasmin or placebo was administered upon EVLP initiation. Then the lungs were stored at 4°C for 90 min and finally, perfused with rat blood for 80 min. The physiological and histological findings during reperfusion and the correlation between physiological data during EVLP and that after reperfusion were investigated. Results The plasmin group showed better findings in physiological data compared with the non-plasmin group. The lungs in the plasmin group showed fewer signs of histological injury. Caspase 3/7 activity in the plasmin group was lower than that in the non-plasmin group. Of note is that PVR during EVLP was correlated with that at the end of reperfusion. Conclusions We confirmed that plasmin administration during EVLP could protect the donor lungs after reperfusion. We also found that several physiological values in EVLP might be predictive markers for the lung function after reperfusion.
    The Journal of Heart and Lung Transplantation 10/2014; · 5.61 Impact Factor
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    ABSTRACT: Background The aim of this study was to perform a survival comparison between stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) in patients with stage I non-small-cell lung cancer (NSCLC) at high risk for lobectomy. Methods All patients who underwent SBRT or SLR because of medical comorbidities for clinical stage I NSCLC were reviewed retrospectively. Propensity score matching (PSM) was performed to reduce selection bias between SLR and SBRT patients based on age, gender, performance status, tumour diameter, forced expiratory volume in 1 second (FEV1) and Charlson comorbidity index (CCI). Results One hundred and fifteen patients who underwent SBRT and 65 SLR were enrolled. The median potential follow-up periods for SBRT and SLR were 6.7 and 5.3 years, respectively. No treatment-related deaths were observed. Before PSM, the 5-year overall survival (OS) was 40.3% and 60.5% for SBRT and SLR, respectively (P = 0.008). PSM identified 53 patients from each treatment group with similar characteristics: a median age of 76 years, a performance status of 0–1, a median tumour diameter of ∼20 mm, a median FEV1 of ∼1.8 L and a median CCI of 1. The difference in OS became insignificant between the matched pairs (40.4% and 55.6% at 5 years with SBRT and SLR; P = 0.124). The cumulative incidence of cause-specific death was comparable between groups (35.3% and 30.3% at 5 years, P = 0.427). Conclusion SBRT can be an alternative treatment option to SLR for patients who cannot tolerate lobectomy because of medical comorbidities.
    European Journal of Cancer 09/2014; · 4.82 Impact Factor
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    ABSTRACT: Adjuvant vinorelbine and cisplatin chemotherapy is recognized as a standard regimen for patients with completely resected stage II and III non-small cell lung cancer (NSCLC). However, efficacy of adjuvant chemotherapy in Japanese phase III trials with cisplatin-containing regimen has been controversial, and data are limited on the long-term outcome of adjuvant vinorelbine and cisplatin chemotherapy for NSCLC patients.
    Cancer Chemotherapy and Pharmacology 09/2014; · 2.57 Impact Factor
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    ABSTRACT: Patients with interstitial lung diseases have a poor prognosis and are at increased risk of developing lung cancer. We evaluated the survival and predictors of survival after surgical resection in lung cancers in patients with interstitial lung diseases. We retrospectively analyzed data from 1763 patients with non-small cell lung cancer with a clinical diagnosis of interstitial lung disease who underwent pulmonary resection between 2000 and 2009 at 61 Japanese institutions. Male patients (90.4%) and smokers (93.8%) were in the majority. The overall 5-year survival was 40%. The 5-year survivals were 59%, 42%, 43%, 29%, 25%, 17%, and 16% for patients with stage Ia, Ib, IIa, IIb, IIIa, IIIb, and IV, respectively. Patients with stage IA had a 5-year survival of 33.2%, 61.0%, and 68.4% in the wedge resection, segmentectomy, and lobectomy groups, respectively (log-rank test, P = .0038). The leading cause of death was cancer recurrence (50.2%), followed by respiratory failure (26.8%). Wedge resection reduced mortality due to respiratory failure when compared with that of lobectomy (P = .022). Multivariable analysis revealed that the type of surgical procedure, predicted percent vital capacity, and tumor locations were independent predictors for survival. The 5-year survival was 20% for patients with stage Ia with a predicted percent vital capacity of 80% or less, and 64.3% for patients with a predicted percent vital capacity greater than 80% (log-rank test, P < .0001). In these patients, there are competing risks of death. Wedge resection reduced death caused by respiratory failure but resulted in poorer long-term prognosis than lobectomy. For patients with poor predictors of survival, such as predicted percent vital capacity of 80% or less, surgical resection should be limited. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
    Journal of Thoracic and Cardiovascular Surgery 09/2014; · 3.99 Impact Factor
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    ABSTRACT: Intraoperative fine-needle aspiration biopsy (FNA) is one of the most important diagnostic tools for undiagnosed lung nodules suspected of being lung cancer; however, the sensitivity and safety of FNA, including the risk of intrapleural dissemination of cancer cells, have not been established.
    Surgery Today 09/2014; · 1.21 Impact Factor

Publication Stats

4k Citations
1,279.78 Total Impact Points


  • 2008–2014
    • Kyoto University
      • Department of Thoracic Surgery
      Kioto, Kyōto, Japan
    • Okayama Kyokuto Hospital
      Okayama, Okayama, Japan
  • 2013
    • Kobe City Medical Center General Hospital
      Kōbe, Hyōgo, Japan
    • Chiba University
      Tiba, Chiba, Japan
  • 1993–2013
    • Okayama University
      • • Department of Cancer and Thoracic Surgery
      • • Department of Cardiovascular Medicine
      • • Department of Molecular Genetics
      • • Department of Hematology, Oncology and Respiratory Medicine
      • • Medical School
      Okayama, Okayama, Japan
  • 2012
    • Shikoku Cancer Center
      Matuyama, Ehime, Japan
    • Hyogo Prefectural Amagasaki Hospital
      Amagasaki, Hyōgo, Japan
    • Shinshu University
      • Department of Internal Medicine I
      Shonai, Nagano, Japan
  • 2011
    • Tohoku University
      • Institute of Development, Aging and Cancer
      Sendai-shi, Miyagi-ken, Japan
  • 2010
    • Osaka City University
      • Department of Cardiovascular Surgery
      Ōsaka, Ōsaka, Japan
  • 2005–2009
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan
  • 1998–2008
    • Minami Okayama Medical Center
      Okayama, Okayama, Japan
    • Barnes Jewish Hospital
      San Luis, Missouri, United States
  • 2007
    • National Hospital Organization Sagamihara Hospital
      Sagamihara, Kanagawa, Japan
    • Kagawa Prefectural Central Hospital
      Takamatu, Kagawa, Japan
  • 1991–1996
    • University of Washington Seattle
      • • Division of Cardiothoracic Surgery
      • • Department of Surgery
      Seattle, WA, United States