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Naoko Ose



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    EP1.17 - Treatment of Early Stage/Localized Disease (ID 207)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.17-32 - Long-Term Outcomes of Pulmonary Resection for Lung Cancer Patients with Chronic Kidney Disease (Now Available) (ID 434)

      08:00 - 18:00  |  Author(s): Naoko Ose

      • Abstract
      • Slides

      Background

      The increasing prevalence of chronic kidney disease (CKD) may hinder the perioperative management and postoperative follow-up of lung cancer. To our knowledge, this study is the first to evaluate the surgical outcomes of surgery for non-small cell lung cancer (NSCLC) in patients with CKD as a preoperative comorbidity.

      Method

      Among 671 patients who underwent surgery for NSCLC between 2007 and 2014 at our hospital, 55 (8%) had CKD and we retrospectively analyzed the surgical outcomes of these patients.

      Result

      Most patients with CKD were elderly and male. Patients with CKD had a higher frequency of smoking habit, cardiovascular disease, and pulmonary diseases, and a notably lower pulmonary function, resulting in receiving limited pulmonary resection. There were no marked differences in the frequency of surgical complications between patients with and without CKD (p = 0.16). Squamous cell carcinoma was more frequently diagnosed in patients with CKD than in those without it. The 5-year disease-free survival rates in patients with and without CKD were 60.0% and 69.7% (p = 0.06), respectively, and the 5-year overall survival rates were 68.9% and 80.0%, respectively, showing significant differences (p = 0.01). The rate of receiving supportive care was higher in patients with CKD when recurrence observed.

      Conclusion

      CKD is associated with a poorer overall survival in patients who undergo lung cancer resection for recurrent disease. As patients with CKD tend to have a poor respiratory function, thoracic surgeons should carefully select the resection type to balance the therapeutic benefit and invasiveness.

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    P1.15 - Thymoma/Other Thoracic Malignancies (ID 184)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.15-07 - Combined Aortic Arch Resection for Thymic Cancer Using Total Rerouting of Supra-Arch Vessels (ID 3014)

      09:45 - 18:00  |  Author(s): Naoko Ose

      • Abstract
      • Slides

      Background

      Surgery for aortic arch involvement in thymic cancer cases is challenging, and generally requires provision of extracorporeal circulation with circulatory arrest or use of a cerebral protection technique. With the aim to reduce morbidity, we developed a novel surgical technique that includes total rerouting of supra-arch vessels under a beating heart condition.

      Method

      With our technique, the tumor and aortic arch are accessed through a median sternotomy and lateral thoracotomy. The proximal portion of a trifurcation graft is anastomosed to the ascending aorta with a side-clamping technique under a cardiopulmonary bypass, then the 3 distal branches of the graft are sequentially anastomosed to supra-aortic vessels. Next, the ascending aorta distal to the anastomosis of the trifurcated graft and descending aorta are clamped, with perfusion of the heart performed via the femoral and right axillary arteries. Finally, the tumor is resected along with the aortic arch and involved organs, followed by reconstruction of the arch with a tube graft.

      Result

      Case 1: A 61-year-old male, diagnosed with cStage III (cT4N0M0) thymic cancer with invasion to the aortic arch, underwent concurrent chemoradiotherapy with carboplatin and paclitaxel, after which complete resection of thymic cancer was performed with total aortic arch replacement and a left lobectomy using our new technique. Operative and CPB times were 738 and 130 minutes, respectively, and blood loss was 4210 ml. The patient was extubated on postoperative day (POD) 1. After an uneventful postoperative course, he was discharged on POD 45 and free of recurrence 8 months later.

      Case 2: A 45-year-old male diagnosed with cStage IVa (cT4N0M1a) thymic cancer with malignant pericardial effusion underwent chemotherapy with carboplatin and paclitaxel, followed by S-1 administration. Liver dysfunction developed due to chemotherapy and surgery was considered. Thoracoscopic findings ruled out pericardial dissemination, thus complete resection of thymic cancer combined with total aortic arch replacement, a left pneumonectomy, and right pulmonary reconstruction were performed. Operative and CPB times were 958 and 254 minutes, respectively, and blood loss was 7980 ml. Extubation was done on POD 2. After an uneventful postoperative course, the patient was discharged on POD 45 and free of recurrence 2 years later.

      Conclusion

      Total arch replacement with total rerouting of the supra-arch vessels under a beating heart condition is effective for thymic cancer patients with aortic involvement. Our novel method has potential to avoid side-effects associated with deep hypothermic circulatory arrest and ischemia-reperfusion injury.

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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-57 - The Role of Arl4c in the Carcinogenesis Process of Lung Adenocarcinoma (Now Available) (ID 2884)

      10:15 - 18:15  |  Author(s): Naoko Ose

      • Abstract
      • Slides

      Background

      The aberrant activations of EGF / Ras and Wnt / β-catenin signaling are known to be closely involved in carcinogenesis and malignant transformation of various cancers, but the mechanism in carcinogenesis is unknown in detail. The expression of ADP-ribosylation factor (ARF) -like 4c (Arl4c) is induced by the EGF / Ras and the Wnt / β-catenin signalling, and immunohistochemical analyses of tissue specimens obtained from lung adenocarcinoma patients revealed that Arl4c was not observed in non-tumor regions but was strongly expressed at high frequencies in tumor lesions. In addition, the positivity of Arl4c expression was not correlated with the tumor’s T grade or N grade. These findings suggest that this protein may be involved in the process of carcinogenesis of lung adenocarcinoma. In this study, we analyzed the role of Arl4c in the carcinogenesis process of lung adenocarcinoma, using immunohistochemical analyses of tissue specimens, and normal human small airway epithelial cell (SAEC) cancer model in vitro.

      Method

      Using the specimens resected from patients who performed lung resection, Arl4c expression was immunohistochemically examined in Atypical Adenomatous Hyperplasia (AAH), which is a pre-cancerous stage, and relationships between Arl4c expression and clinicopathological characteristics were analyzed. In vitro, to establish an immortalized SAEC, we introduced hTERT, CDK4 and DN-p53 to SAEC (SAEC-Triple) with retroviral vector plasmids. Then, we established cell lines stably expressing Arl4c. Using these cells, we assessed the proliferative capacity in a two-dimensional (2D) plastic dish culture and 3D Matrigel culture. In addition, to assess the cell tumorigenic ability , we performed the 2D clonogenic colony formation assay.

      Result

      The expression of Arl4c was observed in 22 of 27 patients (81%) with AAH, while Arl4c-positive cells were never observed in the alveolar epithelium of non-AAH region. No significant difference in clinicopathologic characteristics between Arl4c positive and Arl4c negative groups. In vitro, Alr4c were transfected into SAEC-Triple and confirmed the expression of these proteins by the western blotting. In 2D culture, there was no significant difference between the cell proliferation capacity of SAEC-Triple with Arl4c and that of SAEC-Triple with control vector. In contrast, when SAEC-Triple were grown in 3D Matrigel, stable expression of Arl4c was remarkably increased sphere areas. In a 2D clonogenic colony formation assay, the number of colonies was much higher in SAEC-Triple with Arl4c compared to SAEC-Triple with control vector (P < 0.05). Consistent with these findings, Phosphorylation of Erk1/2 was significantly increased in SAEC-Triple with Arl4c compared with cells expressing control.

      Conclusion

      Arl4c expression in AAH lesion indicated that Arl4c involved in the processes of lung carcinogenesis. Arl4c promotes proliferative capacity by activating Phosphorylation of Erk1/2.

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    P2.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 187)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.16-16 - Calf Circumference Is Associated with Postoperative Outcomes in Lung Cancer Patients Who Underwent Surgery (Now Available) (ID 1764)

      10:15 - 18:15  |  Author(s): Naoko Ose

      • Abstract
      • Slides

      Background

      Sarcopenia has gained considerable attention as a poor prognostic factor in lung cancer after surgical resection. Calf circumference (CC) is an easy-to-measure, non-invasive clinical indicator that reflects body muscle mass as well as subcutaneous fat. For this property, many studies have reported that CC is capable of screening sarcopenia, aside from the assessment of nutritional status. In this study, we investigated the association between CC and postoperative outcomes in lung cancer patients.

      Method

      Between 2007 and 2016, 873 lung cancer patients underwent surgery in our institution. Patients who received induction therapy (n=33), with a prior history of the disease that could affect the diameter of lower limb (n=5), and with missing data (n=17) were excluded in advance, leaving 818 patients for this retrospective analysis. CC was measured prior to surgery in the occasion of hospital admission. We chose 34 cm for men and 33 cm for women as the CC cutoff value for predicting low muscle mass, following the previous report in Japan (Kawakami R et al. Geriatr Gerontol Int.). The patient characteristics, operative factors, and surgical outcomes were examined to compare the groups. The Kaplan-Meier method was used to estimate long-term survival.

      Result

      The mean age of all patients was 67.9 years. There were 473 men and 345 women, and each of their average CC was 34.4 cm and 32.0 cm. In the smaller CC (s-CC) group (n=427), the average age and the female proportion were significantly higher, whereas BMI, %VC, %FEV1 and %DLco, in addition to the proportion of the other cancer history were significantly lower (P<0.01 each) compared with the other group (n=391). As for operative factors, there were no significant differences in surgical approach, type of resection, operation time and intraoperative bleeding, except that the ratio of systematic hilar and mediastinal lymph node dissection was lower (P<0.01) in the s-CC group. Though overall postoperative complications were equivalent (27.2% vs. 23.0%), complications grade 3 or higher were more frequent in the s-CC group (10.5% vs. 5.9%, P=0.02). The 5-year DFS (65.1% vs. 77.9%, P=0.01) and OS (77.9% vs. 81.7%, P=0.03) were significantly poorer in the s-CC group.

      Conclusion

      The smaller CC was associated with severe postoperative complications and poor DFS and OS in patients with resected lung cancer. CC was useful for assessing sarcopenia and therefore predicting postoperative outcomes.

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