Hiroshi Date

Kyoto University, Kioto, Kyōto, Japan

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Publications (472)1073.16 Total impact

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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.
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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: 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.
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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 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;
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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; · 2.80 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.
    The Journal of thoracic and cardiovascular surgery. 09/2014;
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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; · 0.96 Impact Factor
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    ABSTRACT: Living-donor lobar lung transplantation (LDLLT) has been performed as a life-saving procedure for critically ill patients who are unlikely to survive the long wait for cadaveric lungs. The purpose of this study was to compare the preoperative condition and outcome of LDLLT patients with those of conventional cadaveric lung transplantation (CLT) patients.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 09/2014; · 2.40 Impact Factor
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    ABSTRACT: Intrapleural adhesions following thoracotomy may be associated with prolonged operating time or a higher complication rate at reoperation. The aim of this experimental study was to investigate the anti-adhesion property of a bioabsorbable sheet following thoracotomy in a canine model.
    Interactive Cardiovascular and Thoracic Surgery 09/2014; · 1.11 Impact Factor
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    ABSTRACT: Objectives While novel anti-human epidermal growth factor receptor 2 (HER2) agents have recently been developed, no definite criteria have been proposed as indications for the use of these agents in patients with lung cancer. Here, we tested HER2 alterations by using four methods and explored the concordance of these methods to improve our understanding of the accuracy of HER2 testing methods. Materials and Methods We analyzed HER2 protein expression by immunohistochemistry (IHC) and HER2 amplification by fluorescence in situ hybridization (FISH) and dual in situ hybridization (DISH) by using a tissue microarray comprising lung adenocarcinoma specimens from 243 consecutive patients. The presence of mutations in the EGFR, KRAS, and HER2 genes were also determined. Results Positive IHC (score 3 + ) was observed in six cases (2.5%). Amplification of HER2 was observed in five cases (2.1%) by FISH and in nine cases (3.7%) by DISH. HER2 expression by IHC and gene amplification by FISH were significantly associated (P < 0.001). The overall concordance between FISH and DISH by amplification status was 96.7% (P < 0.001). One hundred nine tumors (49.9%) had EGFR mutations, 25 (11.2%) had KRAS mutations, and six (2.7%) had HER2 mutations. All of these mutations were mutually exclusive. Cases having HER2 mutations were positively correlated with cases having HER2 amplification (P < 0.001). Two of six cases with HER2 mutations showed amplifications by FISH and DISH tests. Conclusion HER2 protein overexpression, gene amplification, and gene mutations appeared to be uncommon in lung adenocarcinoma. Cases with HER2 mutations tended to show HER2 gene amplification. The results indicated that HER2 gene amplification and mutations should be tested to determine whether patients are eligible for administration of new anti-HER2 agents. In addition, DISH was better than FISH for detection of cases with HER2 amplification.
    Lung Cancer 09/2014; · 3.39 Impact Factor
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    ABSTRACT: We report a rare case of multicentric Castleman disease treated successfully with single-lung transplantation. A 12-year-old patient developed increasing dyspnea. Elevated serum interleukin-6 (177.0 pg/mL) and immunoglobulin G (IgG; 13,900 mg/dL) levels were observed. Steroid therapy was effective but the respiratory condition gradually deteriorated. He underwent single-lung transplantation at 36 years of age. Preoperative interleukin-6 and IgG levels were 0.3 pg/mL and 5,260 mg/dL, respectively. After 6 months he is alive without symptoms. Postoperative IgG levels were restored to normal limits (1,624 mg/dL) and interleukin-6 levels remained within normal limits (1.4 pg/mL). Overinflation of the native left lung also improved.
    The Annals of thoracic surgery. 09/2014; 98(3):e63-5.
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    ABSTRACT: AimsPulmonary sequelae, reported as chronic graft-versus-host disease (cGVHD), of hematopoietic stem cell transplantation (HSCT) include constrictive bronchiolitis obliterans (CBO), lymphocytic bronchiolitis (LB), and veno-occlusive disease (VOD); and, recently, pleuroparenchymal fibroelastosis (PPFE) has been described in bone marrow transplant recipients. Histological features of pulmonary HSCT sequelae have not been described systematically.Methods and resultsA retrospective review of 20 patients who underwent lung transplantation for pulmonary disease following HSCT between 2004 and 2013 was conducted. The patient age at transplantation ranged from 8-57 (median, 27.5) years. Fifteen patients had cGVHD in other organs (skin, 9; liver, 6; salivary gland, 6). Lung transplantation was performed at a median of 4.6 (range, 1.2-14.8) years post-HSCT. Histologically, all cases had CBO, with concurrent LB in 10, and VOD in 3. PPFE was identified in 15 cases (75%), with subpleural (15), paraseptal (11), and centrilobular (13) distributions; and non-specific interstitial pneumonia (NSIP) in 15 cases (75%), with fibrotic (9) and cellular (6) patterns. PPFE was distributed in all lobes with upper lobe predominant. NSIP was mostly focal, with 2 cases having diffuse involvement.ConclusionsPPFE and NSIP were frequently seen in HSCT patients. Possible causes may include reactions to drugs or radiation, or cGVHD.This article is protected by copyright. All rights reserved.
    Histopathology 09/2014; · 2.86 Impact Factor
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    ABSTRACT: The hedgehog (Hh) signaling pathway is aberrantly activated in various cancers. Expression of the GLI family of genes, which encode for transcriptional factors of the Hh pathway, has not been fully assessed in clinical samples of advanced lung adenocarcinoma. In this study, we retrospectively evaluated the expression of the GLI family of genes in advanced stage lung adenocarcinoma samples and determined their relation to patient survival.
    World Journal of Surgical Oncology 08/2014; 12(1):253. · 1.09 Impact Factor
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    ABSTRACT: Indications for surgical resection for small cell lung cancer (SCLC) have been very limited. Because early-stage SCLC is a rare presentation of lung cancer, studies comparing surgical resection among a large number of patients are unlikely to be conducted. This study reports the most recent surgical outcomes of a large number of SCLC patients who underwent surgery in 2004. Methods: In 2010, the Japanese Joint Committee of Lung Cancer Registry performed a nationwide retrospective registry study regarding the prognosis and clinicopathologic profiles of 11,663 patients who underwent resection for primary lung cancer in 2004. Of the 11,663 patients, 243 patients with SCLC (2.1%) were included in this study. The registry data of the patients with SCLC were analyzed, and the clinicopathologic profiles and surgical outcomes of the patients were evaluated. Results: The 5-year survival rate for all cases (n = 243, 213 males, mean age 68.2 years) was 52.6%. The 5-year survival rates by c-stage and p-stage were as follows: IA, 64.3% (n = 132) and 72.3% (n = 93); IB, 45.7% (n = 36) and 61.1% (n = 51); IIA, 50.5% (n =25); and 44.8% (n = 27); IIB, 33.3% (n = 10) and 40.3% (n = 17); IIIA, 30.5% (n = 30) and 23.4% (n = 45); and IV, 0% (n = 7) and 0% (n = 9), respectively. A multivariate analysis showed that the significant prognostic factors were age, gender, c-stage, and surgical curability. A kappa value was moderate conformity between c-stage and p-stage in all cases. Conclusions: Surgical resection in selected patients with early-stage SCLC, especially stage I, had favorable results.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2014; 9(8):1140-1145. · 4.55 Impact Factor

Publication Stats

4k Citations
1,073.16 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