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R. Miyazaki



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    MINI 19 - Surgical Topics in Localized NSCLC (ID 138)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      MINI19.07 - ICG Fluorescence Localization of Small Sized Pulmonary Nodules for VATS (ID 70)

      16:45 - 18:15  |  Author(s): R. Miyazaki

      • Abstract
      • Presentation
      • Slides

      Background:
      Video-assisted thoracoscopic wedge resection of multiple small, non-visible, and nonpalpable pulmonary nodules is a clinical challenge. We propose an indocyanine green (ICG) injection and intraoperative fluorescence detection with a near-infrared (NIR) fluorescence for localization of small sized pulmonary nodules.

      Methods:
      Fluorescence properties of ICG topically injected into the lung parenchyma were determined using a resected porcine lung and previously reported by the authors. In clinical study, 15 cases of VATS pulmonary resection for small sized pulmonary nodules were enrolled in the study. The ICG mixed with iopamidol was injected into the pulmonary nodules by CT-guided percutaneous injection. ICG fluorescence was visualized by a near-infrared (NIR) thoracoscope, then the target nodule was excised by VATS procedure.

      Results:
      Topically injected ICG / iopamidol mixture spot remained at the injected point of the lung parenchyma for more than 6 hours in each case, and each ICG fluorescence was identified at the pulmonary nodule with the NIR thoracoscope. Each target nodule was successfully removed with negative surgical margin.

      Conclusion:
      CT guided ICG injection and intraoperative NIR thoracoscopic detection is a feasible method to localize small sized pulmonary nodules.

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    P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P1.04-107 - Prediction of Molecular Tageting Drugs' Sensitivity Enabled by In-Vitro Drug Sensitivity Tests for Surgically Resected Lung Cancer (ID 1364)

      09:30 - 17:00  |  Author(s): R. Miyazaki

      • Abstract
      • Slides

      Background:
      The molecular target anticancer drugs such as EGFR-TKI and ALK inhibitor have dramatically changed the strategy of medical treatment for lung cancer. The investigation of each driver mutation is recommended to pick up the responder to the corresponding molecular targeting drugs. In-vitro anticancer drug sensitivity tests such as succinate dehydrogenase inhibition test (SDI) and the collagen gel-droplet embedded culture drug sensitivity test (CD-DST) are able to examine the sensitivities of the surgically resected fresh cancer tissue to multiple cytotoxic chemotherapeutic drugs at one time. We develop the method to predict the effect for multiple molecular targeting drugs for individual lung cancer patient by applying CD-DST or SDI.

      Methods:
      Firstly, we titrated the growth inhibitory effect of the molecular targeting drugs on cultured lung cancer cell lines (H460, A549, HCC827, H1975, H3122) using SDI and CD-DST. Secondly, we evaluated sensitivity of surgically resected cancer tissues obtained from 33 lung cancer patients to Erlotinib by using SDI or CD-DST. Finally, we compared the drug sensitivity and EGFR mutation profile.

      Results:
      Both Erlotinib and Crizotinib exhibited significantly stronger growth inhibitory effects on lung cancer cell lines with target gene alterations than the others without driver mutation or with T790M-mediated resistance to EGFR-TKI. In clinical study using SDI (n=21), 20μM of Erlotinib inhibited cell growth more in EGFR mutant cases (60.0 ± 9.8(%)), than in wild type EGFR cases (86.8 ± 13.9 (%)) (p = 0.0004). The area under the curve (AUC) of receiver operating characteristic (ROC) curve was 0.958 for cell viability. The ratio showed best combination of sensitivity and specificity for prediction of drug sensitivity at values >72.7 (93.3% sensitivity and 100% specificity). By using CD-DST method (n=12), the cell viabilities were 33.5 ± 21.2(%) in EGFR mutants, and 79.0 ± 18.6(%) in wild type EGFR cases (p = 0.026). The AUC of ROC was 0.963 for cell viability. The ratio showed best combination of sensitivity and specificity for prediction of drug sensitivity at values >55.9 (88.9% sensitivity and 100% specificity)

      Conclusion:
      The growth inhibitory effects of Erlotinib evaluated by both SDI and CD-DST were correlated with EGFR mutation profile. In-vitro drug sentivity tests may be able to predict the clinical effect of molecular targeted drugs.

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