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Takashi Kanou
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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): Takashi Kanou
- Abstract
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): Takashi Kanou
- Abstract
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.
