Hiroshi Date

Kyoto University, Kioto, Kyōto, Japan

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Publications (533)1446.79 Total impact

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    ABSTRACT: Primary mediastinal leiomyosarcoma is an extremely rare malignancy, and the only opportunity for a cure lies with an aggressive surgical approach. We report a 66-year-old woman who underwent complete resection of a giant mediastinal leiomyosarcoma located on the bilateral diaphragm. The tumor encased the inferior vena cava and compressed the adjacent structures. Using cardiopulmonary bypass with 20 minutes of hepatic ischemia, the tumor was completely resected with combined resection and reconstruction of the surrounding structures. Because of the tumor size and location in the boundary area between thoracic and abdominal surgeries, the procedure necessitated the cooperation of many expert surgeons. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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    ABSTRACT: Although some interstitial pneumonia (IP) cases are not detected on computed tomography (CT) before surgery, they are confirmed by pathological diagnosis after pulmonary resection. In the present study, we aimed to investigate patients who underwent pulmonary resection for non-small-cell lung cancer (NSCLC) and subsequently showed pathological findings of IP but no apparent interstitial changes on CT. We retrospectively analysed 1688 patients with NSCLC who underwent pulmonary resection and presented with a radiological or pathological diagnosis of IP in 64 institutions between January 2000 and December 2009. We compared 135 patients without radiological findings but with pathological findings of IP (Group A) with 1553 patients with radiological findings of IP (Group B). The percent vital capacity and predicted diffusing capacity for carbon monoxide were higher in Group A than in Group B. Although there was no significant difference in the occurrence of acute exacerbation (AE) between both groups, the mortality after AE in Group A was significantly lower than that in Group B. The overall survival rates of patients in Groups A and B at 5 years were 59.1 and 40.9%, respectively (P = 0.0031). The mortality after AE in patients with only pathological findings of IP was significantly lower than in those with radiological findings of IP. Moreover, the patients with only pathological findings of IP had a better prognosis than those with radiological findings of IP. Thus, our findings suggest that patients with pathological findings of IP and without radiological abnormality had early-stage IP. © 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 02/2015; DOI:10.1093/icvts/ivv021 · 1.11 Impact Factor
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    ABSTRACT: We examined the clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation (post-HSCT), focusing on ventilatory management. We aimed to determine the incidence of oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction in post-HSCT lung transplant recipients, and to explore factors associated with their development. Nineteen consecutive patients who underwent lung transplantation post-HSCT at Kyoto University Hospital (Japan) were retrospectively studied. Data regarding patient characteristics, preoperative examination, and clinical course during anesthetic induction were analyzed. The incidence of oxygen desaturation (SpO2 < 90 %) during anesthetic induction and severe respiratory acidosis (pH < 7.2) after anesthetic induction were 21.1 and 26.3 %, respectively. Reduced dynamic compliance (Cdyn) during mechanical ventilation was significantly associated with oxygen desaturation during anesthetic induction (p = 0.01), as well as severe respiratory acidosis after anesthetic induction (p = 0.01). The preoperative partial pressure of carbon dioxide in arterial blood (PaCO2; r = -0.743, p = 0.002) and body mass index (BMI; r = 0.61, p = 0.021) significantly correlated with Cdyn, and multivariate analysis revealed that both PaCO2 and BMI were independently associated with Cdyn. Oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction frequently occur in post-HSCT lung transplant recipients. Low Cdyn may, at least partially, explain oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction. Moreover, preoperative hypercapnia and low BMI were predictive of low Cdyn.
    Journal of Anesthesia 02/2015; DOI:10.1007/s00540-015-1986-z · 1.12 Impact Factor
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    ABSTRACT: Donation after cardiac death (DCD) organs could alleviate the shortage of donor lungs. This study aimed to assess the influence on lung injuries of the way in which cardiac arrest was induced and to investigate the mechanisms leading to any differences. Male rats were allocated into three groups as follows: sham (no warm ischemia), ventricular fibrillation (VF), and asphyxia group. Cardiac arrest was induced by either VF by way of a fibrillator or asphyxia caused by withdrawal of ventilation, which reflected uncontrolled and controlled DCD situations, respectively. The impact on lung flushing after 60 min of warm ischemia time was evaluated (n = 5, in each group). The physiological functions of the lungs in an isolated lung perfusion circuit were also evaluated with warm ischemia time prolonged to 150 min (n = 8, in each group). Messenger RNA expression levels of surfactant proteins (SPs) and inflammatory cytokines, pathologic findings, and high-energy phosphates of the lung tissues were investigated. In the asphyxia group, flushing and physiological functions in the isolated lung perfusion circuit were the most severely affected. Reverse transcription-polymerase chain reaction and pathologic findings revealed depletion of surfactant protein (SP)-C in lung tissues of the asphyxia group after reperfusion. The VF group was characteristic with elevated pulmonary vascular resistance. Lung injuries were mainly attributed to alveolar wall damage and depletion of SP in the asphyxia group, and perivascular area prominent edema in the VF group. DCD donor lungs were affected differently by the way in which cardiac arrest was induced. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of Surgical Research 02/2015; DOI:10.1016/j.jss.2015.02.029 · 2.12 Impact Factor
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    ABSTRACT: Although anterior mediastinal cysts are generally benign diseases, the preoperative diagnosis of these lesions is not necessarily accurate. This study aimed to investigate the factors affecting the preoperative diagnosis of anterior mediastinal cysts. We conducted a retrospective analysis of 35 patients with pathologically diagnosed anterior mediastinal cysts (20 thymic cysts, 7 bronchogenic cysts, 5 pericardial cysts, and 3 others) that were resected at our hospital and evaluated their preoperative diagnosis, cyst size, and fluid content. Eighteen, 15, 1, and 1 patient(s) were preoperatively diagnosed with cystic disease, thymoma, thymic cancer, and teratoma, respectively. Cysts were significantly larger in the correct diagnosis group (40.2 ± 18.8 mm) than in the incorrect diagnosis group (21.1 ± 10.4 mm) (p = 0.0011). The cut-off value of the cyst size which separates these groups, as indicated by the receiver operating characteristic curve, was 28 mm, with a sensitivity and specificity of 0.722 and 0.823, respectively. The diagnostic accuracy for mucinous cysts was significantly lower (p < 0.001) than that for serous cysts. The presence of cysts smaller than 28 mm and mucinous fluid content was possible factors resulting in inaccurate preoperative diagnosis.
    General Thoracic and Cardiovascular Surgery 02/2015; DOI:10.1007/s11748-015-0530-2
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    Molecular and Clinical Oncology 02/2015; DOI:10.3892/mco.2015.509
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    ABSTRACT: Activation-induced cytidine deaminase (AID) is an enzyme required for antibody diversification, and it causes DNA mutations and strand breaks. Constitutive AID expression in mice invariably caused lung lesions morphologically similar to human atypical adenomatous hyperplasia (AAH), which can be a precursor of bronchioloalveolar carcinoma. Similar to AAH, mouse AAH-like lesion (MALL) exhibited signs of alveolar differentiation, judging from the expression of alveolar type II (AT2) cell marker surfactant protein C (SP-C). However, electron microscopy indicated that MALL, which possessed certain features of a mucous cell, is distinct from an AAH or AT2 cell. Although MALL developed in all individuals within 30 weeks after birth, lung tumors occurred in only 10%; this suggests that the vast majority of MALLs fail to grow into visible tumors. MALL expressed several recently described markers of lung alveolar regeneration such as p63, keratin 5, keratin 14, leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), and Lgr6. Increased cell death was observed in the lungs of AID transgenic mice compared with wild-type mice. Based on these observations, we speculate that MALL is a regenerating tissue compensating for cellular loss caused by AID cytotoxicity. AID expression in such regenerating tissue should predispose cells to malignant transformation via its mutagenic activity.
    PLoS ONE 02/2015; 10(2):e0117986. DOI:10.1371/journal.pone.0117986 · 3.53 Impact Factor
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    ABSTRACT: Previous comparative reports of stereotactic body radiotherapy (SBRT) and surgery for non-small cell lung cancer (NSCLC) suffered from short follow-up, mixed extents of resection and inclusion of benign lesion. We aimed to make comparisons of long-term outcomes between a pure series of video-assisted thoracoscopic surgery (VATS) lobectomy and SBRT for biopsy-proven clinical stage I NSCLC. We retrospectively compared overall survival (OS), cause-specific survival (CSS), recurrence-free survival (RFS), local control, regional lymph node (LN) control, and distant control between VATS lobectomy (n = 413) and SBRT (n = 104) for biopsy-proven clinical stage I NSCLC at our institution between 2003 and 2009. Propensity score matching was used to adjust the confounding effects in estimating treatment hazard ratios. Forty-one VATS lobectomy patients and 41 SBRT patients were matched blinded to outcome (1:1 ratio, caliper distance; 0.5). After propensity score matching, the follow-up period of the whole cohort ranged from 5 to 120 months with a median of 48. After propensity score matching there were significant differences in OS (p = 0.0016), CSS (p = 0.0015), RFS (p < 0.0001), local control (p = 0.0019), and distant control (p < 0.0001) and no significant difference in regional LN control (p = 0.11). The VATS lobectomy patients and SBRT patients had 68.5% and 37.3% of 5-year OS, 83.5% and 56.7% of 5-year CSS, and 60.4% and 19.5% of 5-year RFS, respectively. Our results suggest VATS lobectomy may offer significantly more favorable long-term outcomes than SBRT in potentially operable patients with biopsy-proven clinical stage I NSCLC. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    The Annals of Thoracic Surgery 02/2015; DOI:10.1016/j.athoracsur.2014.11.009 · 3.63 Impact Factor
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    ABSTRACT: Cancer-associated fibroblasts (CAFs) communicate with cancer cells and play important roles in cancer invasion. We previously reported that local invasion of cancer cells was frequently observed in lung adenocarcinoma patients with podoplanin(PDPN)-expressing CAFs. However, the underlying mechanisms of this phenomenon have remained unclear. In this study, we established a novel collagen invasion assay model in which cancer cells and CAFs were co-cultured; we analyzed the mechanisms governing how cancer cell invasion was promoted by PDPN(+)CAFs. By observing the dynamic movement of both CAFs and cancer cells in the collagen matrix, we found that PDPN(+)CAFs invaded the matrix to a greater extent, with more cancer cells invading within the “tracks” created by the CAFs, compared with control CAFs. The knockdown of PDPN in CAFs decreased the invasion of both the CAFs and the cancer cells. PDPN(+)CAFs displayed a higher RhoA activity, and treatment with a ROCK inhibitor cancelled the increased invasion ability of PDPN(+)CAFs and subsequently decreased the number of invaded cancer cells. After intravenous injection in the mouse tail vein, PDPN(+)CAFs invaded and promoted cancer cell invasion into the lung parenchyma, compared with control CAFs. Among the patients with lung adenocarcinoma, we observed some cases with PDPN(+)CAFs at the invasive front of the tumor. These cases predominantly exhibited pleural invasion of cancer cells, known as pathological invasiveness. Our results indicated that PDPN(+)CAFs were tumor-promoting CAFs that lead and enhance the local invasion of cancer cells, suggesting that the invasion activity of CAFs themselves could be rate-determining for cancer cell invasion. This article is protected by copyright. All rights reserved.
    International Journal of Cancer 02/2015; DOI:10.1002/ijc.29464 · 6.20 Impact Factor
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    ABSTRACT: Postoperative myasthenic crisis (POMC) is one of the serious complications after extended thymectomy for patients with myasthenia gravis (MG). This study aims to clarify the risk factors of POMC occurrence. The clinical data of 55 MG patients (25 male, 30 female; median age, 51 years) who underwent extended thymectomy at Kyoto University from 2000 to 2013 were retrospectively reviewed. Surgical outcomes and pre- and perioperative predictive factors of POMC were analysed. The preoperative Myasthenia Gravis Foundation of America stage was I, II, III and IV in 24, 22, 8 and 1 patients, respectively. Ten patients (18.2%) developed POMC; 6 required prolonged intubation over 24 h and 4 required reventilatory support. All patients were weaned after 5.6 (2-26) days of ventilator support, and were discharged. Univariate analysis revealed a correlation with a high preoperative anti-acetylcholine receptor antibody titre (P = 0.009), history of myasthenic crisis (MC) (P = 0.0004) and unstable MG after preoperative medical therapy (P = 0.003). Multivariate logistic regression analysis showed history of MC (odds ratio, 11.84; 95% confidential interval, 1.05-372; P = 0.045) and unstable MG (odds ratio, 29.45; 95% confidential interval, 2.00-1063; P = 0.013) independently predicted POMC. The surgical response rate was not significantly different between the two groups (66.7% with POMC, 85.4% without POMC; P = 0.334). POMC occurred more frequently in unstable MG before surgery or in patients with a history of MC. Adequate preoperative medical therapy and perioperative care should be provided to these patients. © 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 01/2015; DOI:10.1093/ejcts/ezu530 · 2.40 Impact Factor
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    ABSTRACT: Hypoxia-inducible factor 1 (HIF-1) plays a role in tumour metastases; however, the genes that activate HIF-1 and subsequently promote metastases have yet to be identified. Here we show that Ubiquitin C-terminal hydrolase-L1 (UCHL1) abrogates the von Hippel-Lindau-mediated ubiquitination of HIF-1α, the regulatory subunit of HIF-1, and consequently promotes metastasis. The aberrant overexpression of UCHL1 facilitates distant tumour metastases in a HIF-1-dependent manner in murine models of pulmonary metastasis. Meanwhile, blockade of the UCHL1-HIF-1 axis suppresses the formation of metastatic tumours. The expression levels of UCHL1 correlate with those of HIF-1α and are strongly associated with the poor prognosis of breast and lung cancer patients. These results indicate that UCHL1 promotes metastases as a deubiquitinating enzyme for HIF-1α, which justifies exploiting it as a prognostic marker and therapeutic target of cancers.
    Nature Communications 01/2015; 6:6153. DOI:10.1038/ncomms7153 · 10.74 Impact Factor
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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; DOI:10.1002/cncr.29166 · 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; DOI:10.1093/ejcts/ezu490 · 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; DOI:10.1007/s11748-014-0510-y
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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; DOI:10.1093/icvts/ivu416 · 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. DOI:10.1186/1471-2164-15-1079 · 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; DOI:10.1093/ejcts/ezu463 · 2.40 Impact Factor
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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.
    12/2014; 2(12). DOI:10.14814/phy2.12244

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5k Citations
1,446.79 Total Impact Points


  • 2008–2015
    • Kyoto University
      • Department of Thoracic Surgery
      Kioto, Kyōto, Japan
  • 2013
    • Kobe City Medical Center General Hospital
      Kōbe, Hyōgo, Japan
  • 1988–2012
    • Okayama University
      • • Department of Cancer and Thoracic Surgery
      • • Department of Hematology, Oncology and Respiratory Medicine
      Okayama, Okayama, Japan
  • 1998–2008
    • Minami Okayama Medical Center
      Okayama, Okayama, Japan
  • 2007
    • Kagawa Prefectural Central Hospital
      Takamatu, Kagawa, Japan
  • 2006–2007
    • Osaka City University
      • Graduate School of Medicine
      Ōsaka, Ōsaka, Japan
  • 2003
    • St. Vincent's Hospital Sydney
      Sydney, New South Wales, Australia
  • 2002
    • Keio University
      Edo, Tōkyō, Japan
  • 1993–1998
    • Barnes Jewish Hospital
      San Luis, Missouri, United States