Hiroshi Date

Kyoto University, Kioto, Kyoto, Japan

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Publications (602)1791.41 Total impact

  • No preview · Article · Jan 2016
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    ABSTRACT: Background: Lung perfusions after single lung transplantation (SLT) have not been fully clarified in patients with interstitial lung disease (ILD). The present study aimed to investigate temporal changes in native lung perfusion and their associated clinical factors in patients with ILD who have undergone SLT. Methods: Eleven patients were enrolled. Perfusion scintigraphy was serially performed up to 12 months after SLT. Correlations between the postoperative perfusion ratio in the native lung and clinical parameters, including preoperative perfusion ratio and computed tomography (CT) volumetric parameters, were evaluated. Results: On average, the perfusion ratio of the native lung was maintained at approximately 30% until 12 months after SLT. However, the ratio declined more significantly in idiopathic pulmonary fibrosis (IPF) than in other ILDs (p = 0.014). The perfusion ratio before SLT was significantly correlated with that at 3 months after SLT (ρ = 0.64, p = 0.048). The temporal change of the perfusion ratio in the native lung did not correlate with those of the CT parameters. Conclusion: The preoperative perfusion ratio may predict the postoperative perfusion ratio of the native lung shortly after SLT in ILD. Perfusion of the native lung may decline faster in IPF compared with other ILDs. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2016 · Clinical Transplantation
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    ABSTRACT: Background: Lung transplantation has been established as the definitive treatment option for patients with advanced lymphangioleiomyomatosis (LAM). However, the prognosis after registration and the circumstances of lung transplantation with sirolimus therapy have never been reported. Methods: In this national survey, we analyzed data from 98 LAM patients registered for lung transplantation in the Japan Organ Transplantation Network. Results: Transplantation was performed in 57 patients as of March 2014. Survival rate was 86.7% at 1 year, 82.5% at 3 years, 73.7% at 5 years, and 73.7% at 10 years. Of the 98 patients, 21 had an inactive status and received sirolimus more frequently than those with an active history (67% vs. 5%, p<0.001). Nine of twelve patients who remained inactive as of March 2014 initiated sirolimus before or while on a waiting list, and remained on sirolimus thereafter. Although the statistical analysis showed no statistically significant difference, the survival rate after registration tended to be better for lung transplant recipients than for those who awaited transplantation (p = 0.053). Conclusions: Lung transplantation is a satisfactory therapeutic option for advanced LAM, but the circumstances for pre-transplantation LAM patients are likely to alter with the use of sirolimus.
    Full-text · Article · Jan 2016 · PLoS ONE
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    ABSTRACT: OBJECTIVES Primary graft dysfunction (PGD) is a major cause of early morbidity and mortality after cadaveric lung transplantation (CLT). This study examined the incidence, time course and predictive value of PGD after living-donor lobar lung transplantation (LDLLT). METHODS We retrospectively investigated 75 patients (42 with LDLLT and 33 with CLT) who underwent lung transplantation from January 2008 to December 2013. Patients were assigned PGD grades at six time points, as defined by the International Society for Heart and Lung Transplantation: immediately after final reperfusion, upon arrival at the intensive care unit (ICU), and 12, 24, 48 and 72 h after ICU admission. RESULTS The incidence of severe (Grade 3) PGD at 48 or 72 h after ICU admission was similar for LDLLT and CLT patients (16.7 vs 12.1%; P = 0.581). The majority of the LDLLT patients having severe PGD first developed PGD immediately after reperfusion, whereas more than half of the CLT patients first developed severe PGD upon ICU arrival or later. In LDLLT patients, severe PGD immediately after reperfusion was significantly associated with fewer ventilator-free days during the first 28 postoperative days [median (interquartile range) of 0 (0–10) vs 21 (13–25) days, P = 0.001], prolonged postoperative ICU stay [median (interquartile range) of 20 (16–27) vs 12 (8–14) days, P = 0.005] and increased hospital mortality (27.3 vs 3.2%, P = 0.02). Severe PGD immediately after reperfusion was not associated with ventilator-free days during the first 28 postoperative days, time to discharge from ICU or hospital, or hospital mortality in CLT patients. CONCLUSIONS Postoperative incidence of severe PGD was not significantly different between LDLLT and CLT patients. In LDLLT patients, the onset of severe PGD tended to be earlier than that in CLT patients. Severe PGD immediately after reperfusion was a significant predictor of postoperative morbidity and mortality in LDLLT patients but not in CLT patients.
    Preview · Article · Dec 2015 · Interactive Cardiovascular and Thoracic Surgery
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    ABSTRACT: Reoperative pulmonary resection may be associated with a higher rate of postoperative complications secondary to postoperative adhesions. This review was designed to investigate the effect of a bioabsorbable material on postoperative intrapleural adhesions following thoracotomy. A search was performed in PubMed (United States National Library of Medicine) for original studies published in English and investigating a bioabsorbable material in preventing postoperative intrapleural adhesions, using the terms "pleural", "adhesion", and "surgery". Eight animal experimental studies (five rodents and three canines) were eligible for review. No human studies were identified. The type of bioabsorbable material was a sheet in five studies and a powder or spray in three studies. In five studies (62.5 %), a biomaterial included polymers. Six studies (75 %) suggested that a bioabsorbable material was effective in preventing intrapleural adhesions on the basis of statistical analysis. We conclude that a bioabsorbable material may prevent postoperative adhesions following thoracotomy and that available materials may reasonably be applied in clinical practice. Clinical trials on postoperative anti-adhesions are warranted in select patients.
    Full-text · Article · Dec 2015 · General Thoracic and Cardiovascular Surgery
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    Preview · Article · Dec 2015 · Journal of Cardiothoracic Surgery
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    ABSTRACT: Objective: Although bilateral lung transplantation is the procedure of choice internationally, single lung transplantation is preferred in Japan because of the severe donor shortage except in cases of contraindications to single lung transplantation. This study aimed to evaluate the clinical characteristics of single lung transplant recipients and outcomes of this procedure at one of the largest lung transplant centers in Japan. Methods: Between April 2002 and May 2015, 57 cadaveric lung transplantations (33 single and 24 bilateral) were performed in Kyoto University Hospital. The clinical characteristics of the lung transplant recipients and outcomes of these procedures, including overall survival and postoperative complications, were investigated. Results: Overall, the 1-, 3-, and 5-year survival rates were 86, 77, and 72 %, respectively, with a median follow-up period of 1.9 years. There was no significant difference in survival between patients who underwent single lung transplantations and those who underwent bilateral lung transplantations (p = 0.92). The median waiting time was significantly shorter for single lung transplant patients than for bilateral lung transplant patients (p = 0.02). Native lung complications were seen in 14 out of 33 patients (42 %) who underwent single lung transplantation. There was no significant difference in survival between patients with and without postoperative native lung complications. Conclusions: Single lung transplantation has been performed with acceptable outcomes in our institution. In the current situation of severe donor shortage in Japan, single lung transplantation can remain the first choice of treatment except in cases of contraindications to single lung transplantation.
    No preview · Article · Nov 2015 · General Thoracic and Cardiovascular Surgery
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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.
    No preview · Article · Nov 2015 · European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery

  • No preview · Article · Nov 2015 · The Annals of thoracic surgery
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    No preview · Article · Nov 2015 · The Annals of thoracic surgery

  • No preview · Article · Nov 2015
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    ABSTRACT: Lymphangioleiomyomatosis (LAM), a rare progressive disease that almost exclusively affects women, is characterized by pulmonary cysts and neoplastic proliferation of smooth muscle-like cells (LAM cells). Airflow obstruction is a physiologic consequence that is commonly observed in LAM and has been attributed to narrowing of peripheral airways. However, histopathologic examinations of the entire airway have been precluded by the limited availability of such specimens. Here, we utilized explanted lung tissues from 30 LAM patients for a thorough histological analysis with a special emphasis on the bronchi. We found bronchial involvement by LAM cells and lymphatics in all patients examined. Furthermore, a moderate to severe degree of chronic inflammation (73%), goblet cell hyperplasia (97%), squamous cell metaplasia (83%) of the epithelium, and thickening of basal lamina (93%) were identified in the bronchi. Because LAM cells are transformed by the functional loss of the TSC genes leading to a hyperactivated mTORC1 signaling pathway, we confirmed the expression of phospho-p70S6K, phospho-S6, phospho-4E-BP1, and VEGF-D in LAM cells from all of the patients examined. In contrast, no protein expression of HIF-1α, a downstream molecule indicative of mTORC1 activation and leading to VEGF production, was detected in any patient. Our study indicates that late-stage LAM patients commonly have bronchi involved by the proliferation of both LAM cells and lymphatics and that chronic inflammation complicated their disease. Furthermore, the upregulation of HIF-1α, a common event in mTORC1-driven tumor cells, does not occur in LAM cells and plays no role in VEGF-D expression in LAM cells.
    No preview · Article · Nov 2015 · Human pathology
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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.
    No preview · Article · Oct 2015 · Cancer Medicine
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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.
    No preview · Article · Sep 2015 · Journal of Cancer Research and Clinical Oncology
  • 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.
    No preview · Article · Sep 2015 · Current opinion in organ transplantation

  • No preview · Article · Sep 2015
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    Hiroshi Date · Ei Miyamoto · Masaaki Sato · Tetsu Yamada

    Preview · Article · Sep 2015 · Interactive Cardiovascular and Thoracic Surgery

  • No preview · Conference Paper · Sep 2015
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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.
    No preview · Article · Aug 2015 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer

  • No preview · Article · Aug 2015

Publication Stats

7k Citations
1,791.41 Total Impact Points


  • 2008-2016
    • Kyoto University
      • Department of Thoracic Surgery
      Kioto, Kyoto, 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