Takeshi Nagayasu

Nagasaki University, Nagasaki, Nagasaki, Japan

Are you Takeshi Nagayasu?

Claim your profile

Publications (404)649 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Genetic factors are important in lung cancer, but as most lung cancers are sporadic, little is known about inherited genetic factors. We identified a three-generation family with suspected autosomal dominant inherited lung cancer susceptibility. Sixteen individuals in the family had lung cancer. To identify the gene(s) that cause lung cancer in this pedigree, we extracted DNA from the peripheral blood of three individuals and from the blood of one cancer-free control family member and performed whole-exome sequencing. We identified 41 alterations in 40 genes in all affected family members but not in the unaffected member. These were considered candidate mutations for familial lung cancer. Next, to identify somatic mutations and/or inherited alterations in these 40 genes among sporadic lung cancers, we performed exon target enrichment sequencing using 192 samples from sporadic lung cancer patients. We detected somatic 'candidate' mutations in multiple sporadic lung cancer samples; MAST1, CENPE, CACNB2 and LCT were the most promising candidate genes. In addition, the MAST1 gene was located in a putative cancer-linked locus in the pedigree. Our data suggest that several genes act as oncogenic drivers in this family, and that MAST1 is most likely to cause lung cancer.Journal of Human Genetics advance online publication, 16 July 2015; doi:10.1038/jhg.2015.75.
    Journal of Human Genetics 07/2015; DOI:10.1038/jhg.2015.75 · 2.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the clinical characteristics and therapeutic outcomes of patients who underwent surgery for stage III thymoma in Japan. Using the Japanese nationwide database, which contains the records of 2,835 patients with thymic epithelial tumors who underwent treatment between 1991 and 2010, we extracted and analyzed the records of those who underwent surgery for stage III thymoma. A total of 310 patients (170 males, 140 females; median age, 58 years) were analyzed. Involved sites were the lung in 194 (62.6%), the pericardium in 151 (48.7%), the great vessels in 126 (40.6%), the phrenic nerve in 84 (27.1%), and the chest wall in 7 (2.3%). Complete resection (R0) was achieved in 247 (79.7%) cases. Induction therapies were administered to 42 (13.5%) patients, and postoperative therapies were administered to 147 (47.4%). In R0 cases, 68 (27.5%) experienced recurrence. The pleural space was the most frequent site of recurrence (46; 18.6%). The 10-year overall and disease-free (in R0) survival rates were 80.2% and 51.6%, respectively. Multivariate analyses revealed that age (p = 0.002), male sex (p = 0.017), induction therapy (p < 0.001), and type B histology (p = 0.037) were independent adverse predictors for overall survival. Chest wall invasion was the only independent adverse predictor for disease-free survival, although the factor analysis was marginal for overall survival. The outcomes of surgery for patients with stage III thymoma were favorable unless chest wall invasion was present; however, the role of complete resection and appropriate multimodal treatment plan require further investigation. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    The Annals of thoracic surgery 07/2015; DOI:10.1016/j.athoracsur.2015.04.059 · 3.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies have shown that cancer cells surviving in a microenvironment characterized by hypoxia, low pH, and low glucose level have an ability to adapt to the adverse conditions. We measured the pH in the central tumor area of primary lung cancer, and evaluated its association with clinicopathological factors. There was a negative correlation between the tumor size and pH;with an increase in the tumor size, the pH decreased. Cancer cells grow at a markedly low pH compared with the physiological environment. There is a possibility that this low pH is a microenvironment that is appropriate rather than adverse for the growth and development of cancer cells.
    Kyobu geka. The Japanese journal of thoracic surgery 07/2015; 68(7):491-494.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pulmonary emphysema is a progressive disease with airspace destruction and an effective therapy is needed. Keratinocyte growth factor (KGF) promotes pulmonary epithelial proliferation and has the potential to induce lung regeneration. The aim of this study was to determine the possibility of using KGF gene therapy for treatment of a mouse emphysema model induced by porcine pancreatic elastase (PPE). Eight-week-old BALB/c male mice treated with intra-tracheal PPE administration were transfected with 80 μg of a recombinant human KGF (rhKGF)-expressing FLAG-CMV14 plasmid (pKGF-FLAG gene), or with the pFLAG gene expressing plasmid as a control, into the quadriceps muscle by electroporation. In the lung, the expression of proliferating cell nuclear antigen (PCNA) was augmented, and surfactant protein A (SP-A) and KGF receptor (KGFR) were co-expressed in PCNA-positive cells. Moreover, endogenous KGF and KGFR gene expression increased significantly by pKGF-FLAG gene transfection. Arterial blood gas analysis revealed that the PaO2 level was not significantly reduced on day 14 after PPE instillation with pKGF-FLAG gene transfection compared to that of normal mice. These results indicated that KGF gene therapy with electroporation stimulated lung epithelial proliferation and protected depression of pulmonary function in a mouse emphysema model, suggesting a possible method of treating pulmonary emphysema.
    Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry 06/2015; 48(3):83-94. DOI:10.1267/ahc.15004 · 1.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A rare case of an intrahepatic multicystic tumor is described. A 26-year-old man visited our hospital because of abdominal discomfort. Contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography revealed a 10 × 7 cm multicystic tumor of the bile duct in the right side of the liver. The gross appearance of the tumor resembled an intraductal papillary neoplasm of the bile duct, and right hepatectomy with regional lymphadenectomy was performed. Histologically, these cystic lesions were composed of variably and irregularly dilated duct structures lined by columnar epithelium resembling bile duct lining. There were no atypical cells and no papillary growth of the epithelial cells. Interestingly, the dilated ducts contained inspissated bile, and the inter-cystic parenchyma contained variable but irregularly distributed and hamartomatous hepatic parenchyma with an abnormal lobular pattern. Though it had atypical features of a hamartoma in some aspects (age, smooth muscle), this case could finally be regarded as a variant of multicystic biliary hamartoma.
    Clinical Journal of Gastroenterology 05/2015; 8(3). DOI:10.1007/s12328-015-0574-y
  • [Show abstract] [Hide abstract]
    ABSTRACT: To retrospectively review the clinical, radiological and pathological data in patients who underwent surgical resection for pulmonary pleomorphic carcinoma (PC), and to analyse the prognostic predictors of survival. The data were retrospectively examined for 33 consecutive patients (28 males and five females) who had undergone surgical resection for pulmonary PC. Cox's proportional-hazards model was used to analyse the prognostic predictors of survival. The size of the tumours ranged from 1.1 to 12.0 cm (mean 5.4 cm). The majority (26) of the tumours were located at the lung periphery, five tumours had cavitation, two had calcification and 14 had peritumoral ground-glass opacity. Most of the tumours showed heterogeneous enhancement and contained a low-density area (LDA) within the tumour. The 5-year overall survival of surgically resected PC was 36 % (standard error = 0.093). A multivariate analysis revealed the LDA grade [hazard ratio (HR), 2.019], pathological stage (HR, 7.552) and pathological N factor (HR, 0.370) to be significant predictors of a poorer prognosis. A greater component of LDA within the tumour on contrast-enhanced CT is associated with a poorer prognosis in patients with PC. • PC has a poorer prognosis than other conventional NSCLC. • The five-year OS of surgically resected PC was 36 %. • A greater component of LDA on contrast-enhanced CT suggests a poorer prognosis.
    European Radiology 05/2015; DOI:10.1007/s00330-015-3811-3 · 4.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lung herniation is rare. We describe two cases; one cured by surgery, and the other observed without surgery. A 61-year-old man underwent minimally invasive cardiac surgery for mitral valve plasty. Four weeks postoperatively, chest computed tomography (CT) revealed exacerbating lung herniation and emergency surgery was performed. A 75-year-old man with metastatic tumor underwent partial resection of the left lower lobe through a 10-cm access window. Three months postoperatively, follow-up chest CT revealed prolapse of a small part of the upper lobe at the site of incision. However, he remained asymptomatic and was observed on an outpatient basis.
    General Thoracic and Cardiovascular Surgery 05/2015; DOI:10.1007/s11748-015-0556-5
  • Cancer Research 05/2015; 75(9 Supplement):P2-01-23-P2-01-23. DOI:10.1158/1538-7445.SABCS14-P2-01-23 · 9.28 Impact Factor
  • Gastrointestinal Endoscopy 05/2015; 81(5):AB390. DOI:10.1016/j.gie.2015.03.1568 · 4.90 Impact Factor
  • Atsushi Nanashima, Takeshi Nagayasu
    [Show abstract] [Hide abstract]
    ABSTRACT: To assess the clinical application and usefulness of the liver hanging maneuver (LHM), proposed by Belghiti, for major hepatectomy, including its (1) historical development, (2) usefulness and application and (3) advantages and disadvantages, by reviewing the English literature published during the period 2001-2014. In major hepatic transection via the anterior approach, the deep area of transection around the vena cava is critical with regard to bleeding during right hemi-hepatectomy. Belghiti and other investigators identified avascular spaces that are devoid of short hepatic veins at the front of the vena cava and behind the liver. Forceps can be inserted into this space easily and then maneuvered to lift the liver using hanging tape. This procedure, termed LHM significantly reduces intraoperative blood loss and the transection time during right hemi-hepatectomy. LHM has been used in various anatomical hepatectomy procedures worldwide, including laparoscopic hepatectomy. The use of LHM markedly improves the amount of intraoperative blood loss, operative time and postoperative outcome. We conclude that the application of LHM is an important development in the field of liver surgery, although a further evaluation of its true impact on clinical outcomes is necessary.
    Surgery Today 04/2015; DOI:10.1007/s00595-015-1166-7 · 1.21 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sublobar resection procedures, such as segmentectomy and wedge resection, can be used for resectable lung cancer when the cancer is small or the condition of the patient is poor. In such cases, intraoperative lymph node (LN) exploration is necessary to avoid incomplete resection of potential N1 or N2 disease. The semi-dry dot-blotting (SDB) method was developed to detect intraoperative LN metastasis as a quick, cost-effective procedure that does not require special technical expertise. This study examined whether SDB can sufficiently identify LN metastasis in lung cancer patients. This study prospectively examined 147 LNs from 50 lung cancer patients who underwent surgery at Nagasaki University Hospital between April 2011 and June 2013. The SDB method uses antigen-antibody reactions with anti-pancytokeratin as the primary antibody and detects cancer cells using chromogen. To identify LN metastases, each LN was examined by the SDB method during surgery along with intraoperative pathological diagnosis (ope-Dx) and permanent pathological diagnosis (permanent-Dx). Compared with permanent-Dx, SDB offered 94.7% sensitivity, 97.7% specificity and 97.2% accuracy, while ope-Dx exhibited 84.2% sensitivity, 100% specificity and 98.0% accuracy. For 3 cases, micrometastases were detected by the SDB method but not by ope-Dx. Three LNs from lobar stations showed pseudo-positive results by the SDB method because of the presence of alveolar epithelium. The SDB method offers acceptably high accuracy in detecting LN metastasis, especially for mediastinal LNs, and represents a potential alternative for the intraoperative diagnosis of LN metastasis, even in the absence of a pathologist. © 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 04/2015; DOI:10.1093/ejcts/ezv118 · 2.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The number of patients with cardiovascular comorbidities is increasing due to aged society. We evaluated perioperative management of primary lung cancer patients with cardiovascular comorbidities. Between 2010 and 2013, 458 patients underwent lung cancer surgery at out hospital. 60(13%)patients had cardiovascular comorbidities (excluding hypertension and arrhythmia). Forty three(72%) patients were angina pectoris and myocardial infarction, and 7 (12%)were valve disease. In patients with cardiovascular comorbidities, high age, renal dysfunction, low % diffusing capacity for carbon monoxide and limited lymph node dissection were significantly seen. There was one patient with no symptoms of angina with the calcification of coronary artery detected by chest computed tomography(CT)before surgery. Percutaneous coronary artery intervention followed elective lung surgery was successfully performed. Short-term surgical results of patients with cardiovascular comorbidities were acceptable compared to those without.
    Kyobu geka. The Japanese journal of thoracic surgery 04/2015; 68(4):249-254.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Photodynamic diagnosis (PDD) is an imaging technology that is based on the fundamental biological features of cancer cells. Five-aminolevulinic acid (ALA), a precursor of photosensitizing protoporphyrin IX (PpIX) has been applied. In fact, ALA-mediated PDD provides good visualization for certain tumors. However, there have been few studies on clinical application of PDD for gastrointestinal (GI) cancers. This study was aimed to investigate the feasibility of ALA-mediated PDD for navigation of upper GI tumors. Using a newly developed endoscope equipped with a blue laser light excitation, ALA-mediated PDD was conducted in 27 lesions from 23 patients with upper GI tumors including 2 Barrett's intramucosal cancers. ALA solution was given orally 3hours before PDD. All the adenocarcinomas came under clinical stage I, and the tumors were resected endoscopic submucosal dissection and/or laparoscopic surgery. Red fluorescence signal and intensity was assessed as for clinicopathological features of the cases. The laser-based endoscopy could detect upper GI tumors as red fluorescent navigation (PDD-positive) in 23 of the 27 lesions. All but one intestinal typed tumors in histopathology were significantly PDD-positive, whereas each signet ring cell carcinoma was PDD-negative. There was a significant difference in tumor size between the PDD-positive and -negative tumors. The elevated lesions emitted significantly more intense fluorescence. Fluorescence navigation by ALA-mediated PDD provided sufficient detection of upper GI tumors in particular for the intestinal typed tumors. Thus, ALA-PDD using the blue laser-equipped endoscope offers a promising diagnostic tool, in particular their specific screening. Copyright © 2015. Published by Elsevier B.V.
    Photodiagnosis and photodynamic therapy 03/2015; 12(2). DOI:10.1016/j.pdpdt.2015.03.006 · 2.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to evaluate the factors contributing to the outcomes of bronchoplasty for lung cancer by analysing a single institution's data for a 30-year period. A retrospective review of 213 patients who underwent bronchoplasty for lung cancer between 1980 and 2010 was undertaken. The patients were divided into two groups by the date of surgery: the first period was 1980-95, and the second period was 1996-2010. Bronchoplasty and broncho-angioplasty were performed in 100 (75.8%) and 32 (24.2%) patients, respectively, in the first period and 61 (75.3%) and 20 (24.7%) patients, respectively, in the second period. Overall 90-day operative morbidity and mortality rates were 25.8 and 9.8%, respectively, in the first period and 45.7 and 2.5%, respectively, in the second period. Thirty-day mortality rates were 6.8% in the first period and 0% in the second period. Five-year survival was 41.1% (n = 132) in the first period and 61.5% (n = 81) in the second period (P = 0.0003). Comparing bronchoplasty and broncho-angioplasty, the 5-year survival was 45.6 and 26.5%, respectively, in the first period (P = 0.0048) and 60.9 and 62.1%, respectively, in the second period (P = 0. 8131). Using multivariate analysis to identify potential prognostic factors, the type of operation (broncho-angioplasty), postoperative complications and histology (non-squamous cell carcinoma) were significant factors affecting survival in the first period, but none of the factors significantly affected survival in the second period. When the rates of pN2 or N3 histological type disease were compared in each period, the rate of pN2 or N3 disease in non-squamous cell carcinoma was 51.4% in the first period and 45.5% in the second period; both were significantly higher than in squamous cell carcinoma (31.6 and 16.9%, respectively; P = 0. 0365 and 0.0073). The present study suggests that progress in the preoperative staging system and perioperative medical management, as well as surgery, has contributed to current improvements in patients undergoing bronchoplasty and broncho-angioplasty. However, since nodal status in non-squamous cell carcinoma is not precisely evaluated before the operation, the indication for bronchoplasty should be considered carefully. © 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 02/2015; DOI:10.1093/ejcts/ezv065 · 2.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adiponectin (Adipoq), a peptide hormone secreted from the white adipose tissue, may play a role in the anti-aging and/or anti-tumor effects of calorie restriction (CR). We analyzed metabolic traits in Adipoq gene-overexpressing mice fed ad libitum with a regular diet (RD) or a high-fat diet (HFD), or fed 30% CR of RD initiated at 12weeks of age. Adipoq-RD and -HFD mice at 6months of age showed reduced blood glucose and insulin concentrations, and thus increased insulin sensitivity, compared with WT mice fed a RD or a HFD. In the epididymal white adipose tissue in Adipoq mice, senescence-like changes such as upregulation of p53 protein and of biomarkers of inflammation, Cd68 and Ccl2 mRNA, were ameliorated compared with WT-RD and WT-HFD mouse tissues. Resistance to stress induced by lipopolysaccharide was also strengthened in Adipoq mice compared with WT mice. These metabolic changes and stress resistance were also noted in the WT-CR mice, suggesting that Adipoq plays a part in the effect of CR. In contrast, in an allograft tumor growth model, tumor growth was not inhibited in Adipoq mice. The present findings suggest that Adipoq plays a part in the anti-aging, but not in the anti-tumor, effects of CR. Copyright © 2015. Published by Elsevier Inc.
    Experimental Gerontology 02/2015; 64. DOI:10.1016/j.exger.2015.02.011 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The present study was designed to define the clinicopathological characteristics of multiple cancers (MC) in 597 patients with hepatobiliary and pancreas (HBP) malignancies who underwent curative resection, in order to clarify risk factors and prognostic significance. Patients' demographics, clinicopathological parameters and survival rates were compared between solitary (SC) and MC HBP malignancies for 267 patients with hepatocellular carcinoma (HCC), 77 with intrahepatic cholangiocarcinoma (ICC), 84 with extrahepatic bile duct carcinoma (BDC), 72 with gallbladder carcinoma (GBC) and 97 with pancreatic cancer (PC). MC was observed in 66 patients (11%) and more than three cancers were observed in 13 (2.2%). The mean age of patients of the MC group was significantly higher than that of the SC group. The proportion of Nagasaki atomic bomb survivors among the MC group was significantly higher than among the SC group. These findings were significant in HCC and ICC. The histopathological aggressiveness of malignancies was lower with HCC, BDC and PC. In HCC, the disease-free survival of MC patients with more than three tumors was significantly lower than those with SC and double cancers. In GBC, the overall survival of the MC group was significantly better than the SC group. In PC, the disease-free and overall survival were significantly better in MC than SC. Careful follow-up for second or third occurrence of primary malignancies after primary curative treatment for HBP malignancy is necessary. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 02/2015; 35(2):1073-83. · 1.87 Impact Factor
  • Source
    Atsushi Nanashima, Takeshi Nagayasu
    [Show abstract] [Hide abstract]
    ABSTRACT: Photodynamic therapy (PDT) is an effective local treatment modality as a cancer-specific laser ablation in malignancy of some organs including digestive tracts or bile duct. In Japan, PDT has been applied at the early period after the first clinical induction in 1980's. Although the useful efficacy was clarified, PDT has not been fully applied because of the phototoxicity of the porfimer sodium. The next generated talaporfin-sodium was used for PDT, in which phototoxicity was reduced and, however, the clinical efficacy for digestive tract malignancy has not yet been clarified. By proceeding the experimental and clinical trials, it is necessary to clarify the evidence of efficacy as a local powerful treatment with the conventional surgery, brachiotherapy and chemotherapy in the future step.
    International Journal of Molecular Sciences 02/2015; 16(2):3434-40. DOI:10.3390/ijms16023434 · 2.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The patient was a 57-year-old female who felt muscle weakness and visited a physician. Hypokalemia was pointed out, and she was referred to our hospital for detailed examination and treatment. Hormone-related tests and imaging were performed, and the patient was diagnosed as Cushing syndrome. Moreover, an ectopic adrenocorticotropic hormone (ACTH)-producing tumor was suspected. The whole body was examined to find a tumor, but no apparent lesion was found, except for a small nodule of 5-mm in size was present in the right middle pulmonary lobe on chest computed tomography (CT). It was decided to perform surgical resection for both diagnosis and treatment. Pathological diagnosis was a typical carcinoid. On immunostaining, ACTH-positive cells were detected, and the lesion was definitely diagnosed as an ectopic ACTH-producing tumor. Since the ACTH level after surgery returned to normal, the lesion was concluded to be completely excised.
    Kyobu geka. The Japanese journal of thoracic surgery 02/2015; 68(2):83-7.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thymectomy is regarded as a useful therapeutic option for myasthenia gravis (MG), though perioperative management in MG patients is largely empirical. While evidence-based medicine is limited in the perioperative management of MG patients, treatment guidelines are required as a benchmark. We selected issues faced by physicians in clinical practice in the perioperative management of extended thymectomy for MG, and examined them with a review of the literature. The present guidelines have reached the stage of consensus within the Japanese Association for Chest Surgery.
    General Thoracic and Cardiovascular Surgery 01/2015; 63(4). DOI:10.1007/s11748-015-0518-y
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Reactive oxygen species function as key metabolites that can impair biological processes. In lung transplantation, severe oxidative stress is expected when ischemia/reperfusion injury, acute allograft rejection, and various infections occur. Case Report Two clinical cases in which serial measurements of the oxidative stress response (levels of diacron-reactive oxygen metabolites) were taken during hospitalization using a Free Radical Elective Evaluator are reported. In the first case, a 30-year-old man underwent right single lung transplantation for juvenile pulmonary emphysema. Immunosuppression was maintained using tacrolimus, mycophenolate mofetil, and steroid. The oxidative stress response fluctuated significantly (p<0.01) during the infections caused by bronchial stenosis compared to the stable condition. No acute rejection was seen during hospitalization. In the second case, a 44-year-old woman underwent right single lung transplantation for lymphangioleiomyomatosis. Immunosuppression was maintained by the same regimen as in case 1. The patient's postoperative course was uneventful, and there was no allograft rejection or infection. The oxidative stress response remained at the non-stress level. Conclusions The oxidative stress response was measured by the levels of diacron-reactive oxygen metabolites in lung transplantation. High oxidative stress responses were seen during exposure to infections. This might become a non-invasive marker of complications after transplantation.
    01/2015; 16:255-8. DOI:10.12659/AJCR.893026

Publication Stats

2k Citations
649.00 Total Impact Points


  • 1999–2015
    • Nagasaki University
      • • Department of Surgery
      • • Department of Surgical Oncology
      • • Department of Translational Medical Sciences
      Nagasaki, Nagasaki, Japan
  • 1996–2015
    • Nagasaki University Hospital
      Nagasaki, Nagasaki, Japan
  • 2011–2012
    • Ehime Prefectural Central Hospital
      Matuyama, Ehime, Japan