Hiroshi Date

Kyoto University, Kioto, Kyōto, Japan

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Publications (579)1767.73 Total impact

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    ABSTRACT: Objectives: Myasthenia gravis (MG) has been reported to correlate with earlier stage and Type B thymomas by the World Health Organization classification. We analysed a large database of clinical characteristics of patients with MG and thymic epithelial tumours to elucidate whether the severity of MG affected postoperative survival of those with thymic epithelial neoplasms. Methods: We conducted a multi-institutional study on the patients who had undergone surgical treatment for thymic epithelial tumours between 1991 and 2010. We examined Masaoka stage, pathological type, serum titre of antiacetylcholine receptor antigen, severity of MG and postoperative prognosis of the patients with or without MG. Results: Of the 2835 registered patients at 32 institutes belonging to the Japanese Association for Research on the Thymus, 2638 were eligible for the study. MG was present in 598 patients (23%). Patients with MG had thymic epithelial tumours with significantly earlier stage (P = 0.0082) and significantly smaller tumours (P = 0.000) than those without. Type A, Type AB thymomas and thymic carcinomas were less frequently observed in patients with MG. Three of 304 patients (1%) with thymic carcinomas had MG preoperatively. Serum titres of antiacetylcholine receptor antibodies were positive in 98% of patients with MG, and 23% of those without. Patients with generalized MG had significantly higher titres of antiacetylcholine receptor antibodies than those with ocular MG (P = 0.000). The postoperative 30-day mortality rate was 0.3%. Postoperative 5- and 10-year survival rates of thymoma patients with MG and those without MG were 94 and 96, and 89 and 89%, respectively. We found no statistical difference in the postoperative survival rate or recurrence-free rate between the two groups. We found no significant statistical differences of these rates by MGFA classification or surgical approach. Conclusions: We conclude that earlier stage, smaller size or Type B thymomas are more frequently associated with MG, and MG may have no impact on the overall survival of patients with thymoma. We suggest that postoperative survival time of the patients with MG and thymic epithelial tumours may be mainly affected by the tumours, not by MG.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 11/2015; DOI:10.1093/ejcts/ezv380 · 3.30 Impact Factor
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    The Annals of thoracic surgery 11/2015; 100(5):1968-9. · 3.85 Impact Factor

  • Human pathology 11/2015; DOI:10.1016/j.humpath.2015.11.002 · 2.77 Impact Factor
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    ABSTRACT: The epithelial-mesenchymal transition (EMT) and cancer stemness (CS) are reported to be pivotal phenomena involved in metastasis, recurrence, and drug-resistance in lung cancer; however, their effects on tumor malignancy in clinical settings are not completely understood. The mutual association between these factors also remains elusive and are worthy of investigation. The purpose of this study was to elucidate the association between EMT and CS, and their effect on the prognosis of patients with lung adenocarcinoma. A total of 239 lung adenocarcinoma specimens were collected from patients who had undergone surgery at Kyoto University Hospital from January 2001 to December 2007. Both EMT (E-cadherin,vimentin) and CS (CD133, CD44, aldehyde dehydrogenase) markers were analyzed through immunostaining of tumor specimens. The association between EMT and CS as well as the patients' clinical information was integrated and statistically analyzed. The molecular expression of E-cadherin, vimentin, and CD133 were significantly correlated with prognosis (P = 0.003, P = 0.005, and P < 0.001). A negative correlation was found between E-cadherin and vimentin expression (P < 0.001), whereas, a positive correlation was found between vimentin and CD133 expression (P = 0.020). CD133 was a stronger prognostic factor than an EMT marker. Elevated CD133 expression is the signature marker of EMT and CS association in lung adenocarcinoma. EMT and CS are associated in lung adenocarcinoma. Importantly, CD133 is suggested to be the key factor that links EMT and CS, thereby exacerbating tumor progression.
    Cancer Medicine 10/2015; DOI:10.1002/cam4.556 · 2.50 Impact Factor
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    ABSTRACT: Purpose: As one form of tumor invasion, cancer cells can invade the extracellular matrix (ECM) through tracks that have been physically remodeled by cancer-associated fibroblasts (CAFs). However, CAFs are a heterogeneous population with diverse matrix-remodeling capacities. The purpose of this study was to investigate how CAFs with various matrix-remodeling capacities influence cancer cell invasion. Methods: We established single-cell-derived clones from three primary cultures of CAFs from lung adenocarcinoma patients (Case 1, 5 clones; Case 2, 5 clones; and Case 3, 7 clones). Using a co-culture model, we evaluated the correlations between the number of invaded cancer cells and the remodeling areas generated by CAF clones in each case. Results: When A549 lung adenocarcinoma cells and CAF clones were co-cultured, both the numbers of invaded cancer cells and the remodeling areas generated by the CAF clones varied greatly. The number of invaded cancer cells was moderately and strongly correlated with the remodeling areas generated by each CAF clone originating from Cases 1 and 2 (R (2) value = 0.53 and 0.68, respectively), suggesting that the remodeling areas in the ECM may determine the number of invaded cancer cells. In contrast, the number of invaded cancer cells was not correlated with the remodeling areas generated by CAF clones originating from Case 3, suggesting that factors other than the remodeling areas might determine the number of invading cancer cells. Conclusions: These findings showed two types of fibroblast-dependent cancer cell invasion that are dependent on and independent of the remodeling areas generated by CAFs.
    Journal of Cancer Research and Clinical Oncology 09/2015; DOI:10.1007/s00432-015-2046-7 · 3.08 Impact Factor
  • Fengshi Chen · Hiroshi Date ·
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    ABSTRACT: Purpose of review: Primary graft failure, which represents one of the most frequent causes of early mortality, is mostly caused by ischemia-reperfusion injury (IRI). IRI may also induce rejection, which is the principal cause of mortality after transplantation. It is essential to understand the mechanism of pulmonary IRI for improving the outcomes of lung transplantation, and therefore we reviewed the state of the art concerning pulmonary IRI in lung transplantation. Recent findings: Numerous strategies have been conducted to reduce IRI after lung transplantation both from the experimental and clinical aspects. The greatest efforts have been done in the method of lung preservation and reperfusion. Recently, ex-vivo lung perfusion system was developed and has been clinically introduced. Furthermore, more experimental studies to understand the pathophysiology of IRI and to alleviate lung IRI have been performed worldwide, and various new treatment modalities including inhalation therapy with therapeutic gases and substances, fibrinolytic treatment, subzero preservation, and mesenchymal stromal cell therapy are going to be applied to the clinical practice. Summary: IRI, whose pathophysiology remains incompletely understood, is one of the most critical phenomena in lung transplantation, and therefore more studies to control pulmonary IRI are required for improving the outcomes of lung transplantation.
    Current opinion in organ transplantation 09/2015; 20(5):515-520. DOI:10.1097/MOT.0000000000000234 · 2.88 Impact Factor
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    Hiroshi Date · Ei Miyamoto · Masaaki Sato · Tetsu Yamada ·

    Interactive Cardiovascular and Thoracic Surgery 09/2015; 21(3):398. DOI:10.1093/icvts/ivv208 · 1.16 Impact Factor
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    ABSTRACT: Many efforts have been made to detect local relapse (LR) in the follow-up after stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC), while limited data is available on its treatment and prognosis. We aimed to characterize treatment options and clarify long-term outcomes of isolated LR after SBRT for patients with clinical stage I NSCLC. We reviewed our institutional dababase in search of patients with isolated LR after SBRT for clinical stage I NSCLC at our institution between 1999 and 2013. Patient characteristics were compared with Mann-Whitney U test, chi-square test, or Fisher's exact test as appropriate. Survival outcomes were estimated with Kaplan-Meier method. Potential prognostic factors were investigated using Cox proportional hazard model. Of 308 patients undergoing SBRT for clinical stage I NSCLC, 49 patients were identified to have isolated LR. Twelve patients underwent salvage surgery, none underwent radiotherapy, and 8 patients received chemotherapy while 29 patients received best supportive care. No patient characteristic except operability was significantly related with patient selection for LR treatments. Five-year overall survival (OS) rate of the whole cohort was 47.9% from SBRT and 25.7% from LR. Salvage surgery was associated with improved OS following LR (p=0.014) and 5-year OS for patients undergoing salvage surgery was 79.5% from LR. It was confirmed that our patient selection for salvage surgery for isolated LR was associated with favorable survival outcomes. Operability based on multidisciplinary conferences, rather than measurable patient characteristics, is essential for appropriate patient selection for salvage surgery.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2015; DOI:10.1097/JTO.0000000000000662 · 5.28 Impact Factor
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    Hiroshi Date · A. Aoyama · T. Yamada · M. Sato · F. Chen ·

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  • Cancer Research 08/2015; 75(15 Supplement):2581-2581. DOI:10.1158/1538-7445.AM2015-2581 · 9.33 Impact Factor
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    ABSTRACT: Attenuation of ischemia reperfusion injury (IRI) is important in lung transplantation. Our group previously reported that β2-adrenoreceptor agonist inhalation during the period before procurement successfully attenuated IRI in donated lungs after cardiac death. We therefore hypothesized that β2-adrenoreceptor agonist inhalation during ex vivo lung perfusion (EVLP) after procurement might also have a protective effect. Cardiac-dead beagles were left at room temperature for 210 minutes, and all lungs were subsequently procured and subjected to EVLP for 240 minutes. The beagles were allocated to 2 groups: the β2 group (receiving an aerosolized β2-adrenoreceptor agonist 20 minutes after initiation of EVLP; n = 7) and the control group (receiving an aerosolized control solvent at the same time point; n = 6). Physiologic data, including lung function, were evaluated during EVLP. The β2 group showed significantly lower peak airway pressure and pulmonary artery pressure than the control group. Dynamic pulmonary compliance was higher, pulmonary vascular resistance (PVR) was lower, and the wet-to-dry lung weight ratio was lower in the β2 group than in the control group. Cyclic adenosine monophosphate (cAMP) and total adenosine nucleotide (TAN) levels in lung tissue after EVLP were higher in the β2 group than in the control group. The β2 group also showed more cystic fibrosis transmembrane conductance regulator (CFTR) gene expression. After procurement, β2-adrenoreceptor agonist inhalation during EVLP attenuates lung injury in a canine model of organ donation after cardiac death. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    The Annals of thoracic surgery 07/2015; 100(2). DOI:10.1016/j.athoracsur.2015.02.136 · 3.85 Impact Factor
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    ABSTRACT: A subset of non-small-cell lung cancer (NSCLC) patients with malignant pleural effusion and/or malignant pleural nodules is now classified as stage IV and is generally considered a contraindication to surgery. However, several reports have demonstrated that the prognosis of patients with pleural carcinomatosis first detected at thoracotomy is relatively favorable. The aim of this study was to describe the results of surgical intervention in NSCLC patients with pleural carcinomatosis in Japan. In 2010, the Japanese Joint Committee of Lung Cancer Registry conducted a nationwide registration of lung cancer patients who underwent surgery in 2004. Using this database, we performed a retrospective study focused on pleural carcinomatosis. We examined the clinicopathological features, the current status of therapy, and surgical outcomes in patients with pleural carcinomatosis. Among the 11,420 registered NSCLC patients, 329 (2.9%) patients had pleural carcinomatosis. The median survival time and 5-year survival rate of 313 patients without other metastatic disease were 34.0 months and 29.3%, respectively. Primary tumor resection was performed in 256 (81.8%) patients, and macroscopic complete resection was achieved in 152 (48.6%) patients, with 5-year survival rates of 33.1% and 37.1%, respectively. Multivariate analysis revealed that Eastern Cooperative Oncology Group performance status (p < 0.001), best stage nodal status (p = 0.002), and the presence or absence of gross residual tumor (p = 0.013) were independent predictors of survival. In our surgical registry for NSCLC, patients with pleural carcinomatosis accounted for 2.9%, and macroscopic complete resection for them was associated with better survival.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2015; 10(7):1076-82. DOI:10.1097/JTO.0000000000000554 · 5.28 Impact Factor
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    ABSTRACT: A number of studies have shown that KRAS mutations in colorectal cancer (CRC) result in the lack of response to anti-epidermal growth factor receptor (EGFR)-based therapy; thus, KRAS mutational testing has been incorporated into routine clinical practice. However, one limitation of this test is the heterogeneity of KRAS status, which can either be intratumoral heterogeneity within an individual primary CRC, or discordant KRAS status between a primary CRC and its corresponding metastases. We previously reported that fluorodeoxyglucose (FDG) accumulation was significantly higher in primary CRCs with mutated KRAS than in those with wild-type KRAS. However, the clinical utility of the previous report has been limited because endoscopic biopsy for testing KRAS status is safe and feasible only in primary CRC. The purpose of this study was to investigate whether KRAS status is associated with FDG accumulation in metastatic CRC, and whether FDG-Positron emission tomography/computed tomography (PET/CT) scans can be used to predict the KRAS status of metastatic CRC. A retrospective analysis was performed on 55 metastatic CRC tumors that were identified by FDG-PET/CT before surgical resection. Maximum standardized uptake value (SUVmax) of the respective metastatic tumor was calculated from FDG accumulation. From the analysis with the 55 tumors, no significant correlation was found between SUVmax and KRAS status. We next analyzed only tumors larger than 10mm to minimize the bias of partial volume effect, and found that SUVmax was significantly higher in the KRAS mutated group than in the wild-type group (8.3 ± 4.1 vs. 5.7 ± 2.4, respectively; P = 0.03). Multivariate analysis indicated that SUVmax remained significantly associated with KRAS mutations (P = 0.04). KRAS status could be predicted with an accuracy of 71.4% when SUVmax cutoff value of 6.0 was used. FDG accumulation into metastatic CRC was associated with KRAS status. FDG-PET/CT scans may be useful for predicting the KRAS status of metastatic CRC, and help in determining the therapeutic strategies against metastatic CRC. Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 07/2015; 56(9). DOI:10.2967/jnumed.115.160614 · 6.16 Impact Factor

  • The Journal of thoracic and cardiovascular surgery 06/2015; 150(3). DOI:10.1016/j.jtcvs.2015.06.048 · 4.17 Impact Factor
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    ABSTRACT: Thymic carcinoma is a rare thymic malignancy. The purpose of this study was to evaluate the prognostic impact of clinicopathological variables and perioperative therapy for surgically treated thymic carcinoma using a nationwide database. Of 2835 patients with surgically treated thymic epithelial tumours collected from 32 Japanese institutions, a total of 306 patients with thymic carcinomas, excluding neuroendocrine tumours, were enrolled in this retrospective study. Multivariable Cox regression analyses were performed for overall (OS) and recurrence-free survival (RFS) after R0 resection. Of 306 patients, 228 (75%) patients presented with Masaoka stage III-IV. Squamous cell carcinoma was the most common histological type (n = 216, 71%). R0 resection was performed in 181 (61%) patients, R1 in 46 (16%), R2 sub-total (≥80% tumour resection) in 43 (14%) and R2 non-resection in 27 (9%). The 5-year OS rate was 61%. Prognostic factors for OS were Masaoka stage and resection status. R0 resection was associated with most improved OS; however, both R1 and R2 sub-total resection resulted in superior OS compared with R2 non-resection [hazard ratio (95% confidence interval) for R0, R1 and R2 sub-total, 0.27 (0.15-0.48), 0.40 (0.22-0.74) and 0.38 (0.20-0.72), respectively]. Histological type and perioperative therapy did not affect OS, whereas tumour size and postoperative radiotherapy were associated with improved RFS after R0 resection. R0 resection is essential for prolonged OS for surgically treated thymic carcinoma, but maximal debulking surgery might be beneficial and worth evaluating for advanced disease deemed difficult for R0 resection. The benefit of postoperative radiotherapy after R0 resection should also be evaluated prospectively. © The Author 2015. 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 06/2015; DOI:10.1093/ejcts/ezv239 · 3.30 Impact Factor
  • A Aoyama · F Chen · K Minakata · K Yamazaki · T Yamada · M Sato · H Date ·
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    ABSTRACT: Living-donor lobar lung transplantation (LDLLT) is indicated for rapidly deteriorating patients, and the total volume of two lower lobe grafts must be sufficient for the recipient. To rescue patients with small lobar grafts, we performed five LDLLTs sparing native upper lobes. This strategy was used when upper lobes or segments were preoperatively less impaired. There were no hospital deaths. Extracorporeal circulation time and operative time were similar to those of conventional LDLLTs. The length of intensive care unit stay was also similar. Late complications attributed to the spared lungs were airway infection in one recipient and pneumothorax in two but they were successfully managed. All recipients were discharged without supplemental oxygen. The spared lung volumes measured by volumetry did not change after LDLLT. Lung perfusion scintigraphy performed at 1 year showed remaining perfusion in the spared lungs, although much less than in the grafts. These results suggested that the spared lobes kept adequate space in the thoracic cavity and kept functioning to a limited extent. The new lobar-sparing strategy appears feasible and effective in LDLLT using small grafts for selected patients when the upper lobes or segments are less impaired. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    American Journal of Transplantation 06/2015; DOI:10.1111/ajt.13357 · 5.68 Impact Factor
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    Ei Miyamoto · Msasaaki Sato · Tetsu Yamada · Hiroshi Date ·
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    ABSTRACT: Major tracheobronchial trauma may lead to underestimation of the potential for lung donation due to insufficient alveolar ventilation and resulting poor oxygenation, bronchoscopic findings and radiographic findings (e.g. atelectasis). Here, we report a case of successful bilateral lung transplantation from a deceased donor whose right bronchus was ruptured by a trauma from the main bronchus to the bronchus intermedius. Although poor oxygenation and a collapsed right lung detected by computed tomography scanning precluded the use of the donor lungs by multiple transplant centres, careful bronchoscopic evaluation and intraoperative assessment convinced us that the parenchyma of the donor lungs was preserved sufficiently well for transplantation. Upon transplantation, the donor right bronchus was anastomosed at two levels, the upper lobe bronchus and the bronchus intermedius, and the lacerated portion was removed. The recipient's postoperative course was uneventful and the bronchial anastomoses healed excellently. Careful preoperative evaluation and appropriate surgical techniques might enable successful lung transplantation, using seemingly suboptimal donor lungs with major airway trauma. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
    Interactive Cardiovascular and Thoracic Surgery 06/2015; 21(3). DOI:10.1093/icvts/ivv161 · 1.16 Impact Factor
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    ABSTRACT: Nevoid basal cell carcinoma syndrome (NBCCS) manifests multiple defects involving the skin, endocrine and nervous systems, eyes and bones. Mutations in the patched homologue 1 (PTCH1) gene are the underlying causes of NBCCS, leading to aberrant cell proliferation through constitutive activation of the hedgehog signaling pathway. We identified a novel frameshift mutation (c.1207dupT) of PTCH1 in a NBCCS patient, which might explain multiple cystic lesions and neoplastic growth in the patient.
    06/2015; 2:15014. DOI:10.1038/hgv.2015.14

Publication Stats

6k Citations
1,767.73 Total Impact Points


  • 2008-2015
    • Kyoto University
      • Department of Thoracic Surgery
      Kioto, Kyōto, Japan
  • 1988-2012
    • Okayama University
      • • Department of Cancer and Thoracic Surgery
      • • Medical School
      Okayama, Okayama, Japan
  • 2007
    • Kagawa Prefectural Central Hospital
      Takamatu, Kagawa, Japan
  • 2006-2007
    • Osaka City University
      • Graduate School of Medicine
      Ōsaka, Ōsaka, Japan
  • 1998-2006
    • Minami Okayama Medical Center
      Okayama, Okayama, Japan
  • 2003
    • St. Vincent's Hospital Sydney
      Sydney, New South Wales, Australia
  • 1993-1998
    • Washington University in St. Louis
      • • Division of Pulmonary and Critical Care
      • • Division of Cardiothoracic Surgery
      San Luis, Missouri, United States