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T. Nagayasu



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    P3.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 211)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 2
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      P3.02-016 - How to Manage for Unexpected Bleeding During Thoracoscopic Anatomical Pulmonary Resection (ID 418)

      09:30 - 09:30  |  Author(s): T. Nagayasu

      • Abstract
      • Slides

      Background:
      The number of thoracoscopic pulmonary resection has been increasing due to the less invasiveness and development of endoscopic instruments and perioperative management of the patients. However, the intraoperative unexpected bleeding cases which required emergent conversion to thoracotomy were gradually reported. The aim of this retrospective study was to review our experience, management, and the outcome of unexpected bleeding during thoracoscopic surgery.

      Methods:
      All patients who underwent thoracoscopic anatomical pulmonary resection for primary lung cancer were analysed. Hemostatic procedures with angiorrhaphy and/or using the sealant were defined as intraoperative unexpected bleeding in this study. The location, cause, management of injured vessels, and perioperative outcome, including blood loss, hospital stay, the rate of morbidity and mortality were investigated to compare those without vessel injured.

      Results:
      From 2007 to 2014, a total of 241 thoracoscopic anatomical pulmonary resection was performed. 20 (8.3%) cases were required hemostatic procedures with angiorrhaphy and/or using the sealant. 15 (75%) cases of 20 were converted to thoracotomy. Injured vessels were pulmonary artery (n=13), vein (n=3), azygous vein (n=3), and superior vena cava (n=1), respectively. In pulmonary artery, the injury was seen in first branch (n=5) and small branches to right upper lobe (n=5). The main causes of injured vessels were related to the technical problems of energy devices and staplers. 16 (80%) cases were direct suture, ligation or division of injured vessels, and 3 cases were successfully controlled by TachoSil without converted to thoracotomy. Blood loss of 20 cases ranged from 150-2160 (median, 500) ml. 6 (30%) were administered with blood transfusion. Perioperative 5 comorbidities were identified in 4 patients, consisted of prolonged air leak in 2 patients and atrial fibrillation, transient recurrent laryngeal nerve palsy, and chylothorax in each patient. No mortality was identified in this study. The difference between vessel injured and non-injured patients in operation time (285 vs 235 minutes, average, p=0.003) and blood loss (804 vs 121 ml, average, p<0.001) were significant, but perioperative comorbidities including respiratory and cardiovascular complications and the duration of chest tube insertion (4.5 vs 3.5 days, average, p=0.20) and postoperative hospital stay (12.7 days vs 11.0 days, average, p=0.08) were not significant.

      Conclusion:
      The frequency of unexpected bleeding in this study was relatively high, but the management and the outcome of patients in this study were feasible in terms of safety. TachoSil is a useful sealant to be used next step for bleeding. For surgeons, it should be establish algorithms for this catastrophic intraoperative complication during thoracoscopic pulmonary resection.

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      P3.02-023 - Surgical Outcomes of Lung Cancer Combined With Interstitial Pneumonia. - Single Institutional Report - (ID 1102)

      09:30 - 09:30  |  Author(s): T. Nagayasu

      • Abstract
      • Slides

      Background:
      Several studies have reported that acute exacervation (AE) of idiopathic interstitial pneumonia (IIP) can occur after lung resection for patients with non-small cell lung cancer (NSCLC), though the strategy of the perioperative management is controversial.

      Methods:
      We examined our institutional data about the lung cancer patients from June 1994 through October 2013 at Nagasaki University Hospital in a retrospective manner.

      Results:
      A total of patients who underwent lung resection for NSCLC(1701 cases) was investigated, 58 had IIP, for an incidence rate of 3.8%. The majority of patients were men (52 cases, 89.6%) and ex- or current smokers (53 cases, 91.3%), and the average of Packs per year was 54.1 (range 30-150). Squamous cell carcinoma was the most common type of lung cancer (23 cases, 39.6%), and the second common type was adenocarcinoma (22 cases, 37.9%). Surgical procedure was wedge resection in 12 cases, segmentectomy in 6 cases, lobectomy in 39 cases, pneumonectomy in 1 case, respectively. 6 cases(10.3%) had AE of IIP following lung resection, 3 cases(50%) of those patient died in the hospital. The univariate analysis and multivariate analysis were carried out to identify possible risk factors for AE. The univariate analysis identified LDH and bleeding amount. Multivariate analysis further identified only LDH. As a treatment for AE, we performed steroid pulse therapy and administration of Neutrophil elastase inhibitor. In some cases that no effect was given by such treatments, we performed direct hemoperfusion with a polymyxin B immobilized fiber column and administered immunosuppressant.

      Conclusion:
      Patients with lung cancer combined with IIP increases the risk of chest surgery, and the prognosis of them is poor. Because the prediction of AE is often difficult, surgery and perioperative management should be done very carefully.

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    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P3.04-124 - High Expression of Trimethylated Histone H3 at Lysine 27 Predicts Better Prognosis in Non-Small Cell Lung Cancer (ID 486)

      09:30 - 09:30  |  Author(s): T. Nagayasu

      • Abstract
      • Slides

      Background:
      Lung cancer is still the leading cause of cancer death in both sexes throughout the world. The alterations in epigenomes such as DNA methylation and histone modifications play pivotal roles in carcinogenesis. It has been reported that DNA methylation level and global histone modification patterns may be possible predictors of cancer recurrence and prognosis in a large variety of cancer entities. One such repressive modification, the trimethylation of lysine 27 on histone H3 (H3K27me3), seemed to be an epigenetic label mediating gene silencing; and a mark for de novo DNA methylation in cancer cells by recruitment of DNA methyltransferase (DNMTs) , contributing to tumor progression through suppression of a certain gene expression. In fact, many recent studies have revealed that H3K27me3 may be involved in the characterization of various types of human cancers, excluding NSCLC. Interestingly, reports of H3K27me3 levels in different cancer samples are somewhat contradictory. It’s demonstrated that low H3K27me3 levels predicted poor outcome in breast, ovarian and pancreatic cancers while high levels predicted poor outcome in hepatocellular carcinoma and esophageal squamous cell carcinoma. Moreover, H3K27 methylation is catalyzed by its specific methyltransferase, EZH2. Overexpression of EZH2 was also found in a variety of cancers, resulting in worse clinical outcome. Although many reports on the role of H3K27me3 in carcinogenesis were available, its carcinogenic role in NSCLC and how it interacts with EZH2 and DNA methylation remain unclear.

      Methods:
      Expressions of H3K27me3 and its methyltransferase, enhancer of zeste homolog 2 (EZH2) together with proliferating cell nuclear antigen (PCNA) were evaluated by immunohistochemistry in normal lung tissue (n=5) and resected NSCLC patients (n=42). In addition, the specificity of antibody for H3K27me3 were testified by western blotting. The optimal cut-point of H3K27me3 expression for prognosis was determined by the X-tile program. The prognostic significance was determined by means of Kaplan-Meier survival estimates and log-rank tests.

      Results:
      Figure 1 Enhanced trimethylation of H3K27me3 was correlated with longer OS and better prognosis (P<0.05). Both univariate and multivariate analyses indicated that H3K27me3 level was a significant and independent predictor of better survival (hazard ratio, 0.187; 95% confidence interval, 0.066-0.531, P=0.002). Furthermore, H3K27me3 expression was positively correlated with DNA methylation level at CCGG sites while reversely related to EZH2 expression (P<0.05)



      Conclusion:
      H3K27me3 level defines unrecognized subgroups of NSCLC patients with distinct epigenetic phenotype and clinical outcome, and can probably be used as a novel predictor for better prognosis in NSCLC patients.

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