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Kazuya Kondo



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    P1.05 - Interventional Diagnostics/Pulmonology (Not CME Accredited Session) (ID 937)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 3
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.05-04 - Cone-Beam CT Confirms the Status of Transbronchial Biopsy Under Virtual Bronchoscopic Navigation for Peripheral Lung Lesions (ID 13788)

      16:45 - 18:00  |  Author(s): Kazuya Kondo

      • Abstract
      • Slides

      Background

      CT guided transbronchial biopsy has been reported to have a high accuracy for the diagnosis of peripheral lung lesion. Recently, C-arm cone-beam CT (CBCT) with a flatpanel detector system has been developed and offers greater flexibility in orientating the detector around the patient than closed CT gantry systems. We have introduced CBCT to the transbronchial lung biopsy and report the usefulness of the method.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with undiagnosed peripheral lung lesions 3 cm or less in size between June 2016 and August 2017 were enrolled.An ultrathin bronchoscope was inserted as far as possible to the target bronchus by comparing the direct vision and virtual bronchoscopic navigation images displayed simultaneously at same monitor. After reaching the target bronchus, the biopsy forceps was introduced to the target bronchus under conventional fluoroscopy. After the biopsy forceps reach the target bronchus, a CBCT scan data was taken. We categorized the CBCT findings into three types according to positions of the target lesion and the forceps as follows: (Type A: The forceps clearly reached within the lesion. Type B: It could not be categorized into neither type A nor C. Type C: The forceps could not reach the lesion.). The diagnosis yields of biopsy or cytology results was examined.

      4c3880bb027f159e801041b1021e88e8 Result

      Twenty-two patients (12 males and 10 females) were included in the study and age ranged from 50 to 87 with average age of 72.8 years. Thirteen lesions were located at the upper lobe, seven lesions at lower lobe and one lesion at middle lobe. Size of the lesions ranged from 9 to 29 mm with average of 20 mm. They included 13 solid lesions and 8 mixed GGO lesions. Regarding CBCT type, A was 16 cases, B was 4 cases, and C was 1 case. Bronchoscopic diagnosis was malignant in 11 cases, benign in 10 cases (4 mycobacterium infections and 6 non-specific inflammations) and undiagnostic in 1 case. There was one false negative case whose bronchoscopic diagnosis as non-specific inflammation was finally proved as adenocarcinoma. Overall the diagnostic accuracy was 91%(20/22). Based on the CBCT category, the accuracy was 100% (17/17), 75% (3/4), 0% (0/1) in Type A, B and C respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      CBCT guided bronchoscopy is valuable in the diagnosis of peripheral lung lesions and useful for confirming the position of the forceps.

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      P1.05-14 - Autofluorescence Mode of Thoracoscope Improves Visceral Pleural Invasion Diagnosis in Non-Small Cell Lung Cancer (ID 14368)

      16:45 - 18:00  |  Author(s): Kazuya Kondo

      • Abstract
      • Slides

      Background

      Visceral pleural invasion of non-small cell lung cancer is an important prognostic factor, and tumors with visceral pleural invasion are classified as T2a, even if they are 3 cm or less. However, visceral pleural invasion is usually diagnosed by postoperative pathologic examination and it is difficult to diagnose it by preoperative imaging or intraoperative macroscopic findings. This study was conducted to evaluate the accuracy of autofluorescence mode diagnosis for visceral pleural invasion of non-small cell lung cancer compared with white light mode diagnosis.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Two thoracic surgeons blind to pathological diagnosis reviewed operation videos of 56 cases and evaluated visceral pleural invasion under white light mode and autofluorescence mode. These cases were selected according to the following criteria. 1) Primary non-small cell lung cancer patients who underwent video-assisted thoracic surgery from October 2011 to March 2018. 2) Tumor attached to visceral pleura on the lung window of CT images. 3) Thoracic cavity was explored using both white light and autofluorescence modes using a D-Light AutoFluorescence system (Karl Storz, Tuttlingen, Germany). 4) Lung tumors were resected and evaluated histopathologically using elastic stains. The mean age was 67 years and 31 patients (55%) were male. They included 43 adenocarcinomas, 11 squamous cell carcinoma and 2 others. The mean tumor size was 22 mm (7–30 mm). There were 9 pathological visceral pleural invasion positive cases. For white light mode, if either one of the following pleural change; 1) whitish, 2) granular, 3) hypervascular was observed at the tumor site, the tumor was diagnosed as visceral pleural invasion positive. For autofluorescence mode, we defined attenuation or a defect in autofluorescence of the pleura at the tumor site as a positive finding of visceral pleural invasion.

      4c3880bb027f159e801041b1021e88e8 Result

      The sensitivity, specificity, and accuracy of visceral pleural invasion diagnosis by white light vs autofluorescence mode were 77.8% vs 77.8%, 66.0%% vs 83.0%, and 67.9% vs 82.1%, respectively.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The specificity, and accuracy of visceral pleural invasion diagnosis was improved through the additional use of autofluorescence mode compared with white light mode alone.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.05-19 - CT and PET/CT Parameters of Lepidic Predominant Pattern Lung Adenocarcinoma and Invasiveness on Pathology (ID 14440)

      16:45 - 18:00  |  Author(s): Kazuya Kondo

      • Abstract
      • Slides

      Background

      The 8th edition of TNM classification of lung cancer introduced new categories of Tis and T1mi for adenocarcinoma. Patients classified into these categories are estimated to present 100% or near-100% disease-free survival after complete resection. It is expected we are able to identify them on preoperative imaging because they might fit for limited resection. A retrospective study was conducted evaluating preoperative radiologic parameters of lepidic predominant pattern lung adenocarcinoma to predict invasiveness on pathology.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Pathologically classified 20 adenocarcinoma in situ (AIS), 27 minimally invasive adenocarcinoma (MIA) and 8 lepidic predominant invasive adenocarcinoma (LPA) from 50 patients operated from January 2017 to March 2018 were evaluated. Preoperative CT parameters including maximum diameter, maximum area and mean CT value of the both whole lesions and solid components were evaluated. SUVmax of the lesions were measured at FDG-PET/CT images. Three experienced pathologist determined invasive size based on hematoxylin-eosin and Elastica van Gieson staining slides. Radiologic - pathologic associations were examined using Kruskal-Wallis test and the Spearman correlation coefficient.

      4c3880bb027f159e801041b1021e88e8 Result

      Increasing maximum diameter, maximum area and mean CT value of the whole lesions on CT were significantly associated with invasiveness (p=0.04, p=0.03 and p=0.002, respectively). Increasing maximum diameter and maximum area of the solid components were also significantly associated with invasiveness (p<0.001 and p<0.001, respectively). Higher SUVmax value of the lesions was significantly associated with invasiveness (p<0.015). However, we were not able to find any correlation between the radiologic parameters including maximum diameter of solid components and pathologic invasive size when we analyzed MIA and LPA cases. And, when we evaluated clinical T according to the 8th edition of TNM classification, the sensitivity to diagnose AIS, MIA and IPA were 57.1%, 14.8% and 87.5%, respectively, and the specificity to diagnose AIS, MIA and IPA were 97.5%, 82.1% and 48.9%, respectively,

      8eea62084ca7e541d918e823422bd82e Conclusion

      Both whole tumor size and solid component size increase in association with tumor invasiveness. And SUVmax value also increases with tumor invasion. However, it is difficult to predict pathologic invasive size based on radiologic parameters. It is expected that novel preoperative or intraoperative diagnostic tools for tumor invasiveness of lepidic predominant pattern lung adenocarcinoma will be developed.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.14 - Thymoma/Other Thoracic Malignancies (Not CME Accredited Session) (ID 946)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.14-16 - DNA Methylation of GNG4、GHSR、HOXD9 and SALL3 Genes Predict Malignant Behavior of Thymic Epithelial Tumors (ID 13558)

      16:45 - 18:00  |  Author(s): Kazuya Kondo

      • Abstract
      • Slides

      Background

      Our previous studies showed that DNA methylation of cancer-related genes-DAP-K, p-16, MGMT, HPP1 genes in thymic carcinoma (TC) was higher than that in thymoma (Lung Cancer 64:155-, 2009, 83:279-, 2013). Genome-wide screening for aberrantly methylated CpG islands was performed in 7 TC samples and 8 type-B3 thymoma samples using HumanMethylation 450 K BeadChip (Illumina, Santa Clara, CA, USA) analysis. We identified 22 genes as commonly hypermethylated in TC comparing with B3 thymoma. We picked up 4 cancer-related genes; GNG4, GHSR, HOXD9 and SALL3 from those genes as the most significant hypermethylated gene.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In total, 47 thymic tumour samples (thymoma; 31, carcinoma; 16) and 18 paired normal tissues were obtained from patients with histologically proven thymic epithelial tumor (TET), who underwent surgery at the Tokushima University Hospital (Tokushima, Japan) between 1990 and 2016. The methylation status of TET samples was validated by pyrosequencing.

      4c3880bb027f159e801041b1021e88e8 Result

      DNA methylation of GNG4 gene in TC was significantly higher than that in thymoma (34.6% versus 8.9%). In other 4 genes, DNA methylation in TC was significantly higher than that in thymoma (GHSR; 59.3% vs 34.2%, HOXD9; 37.3% vs 12.3%, SALL3; 33.5% vs 7.2%). In GHSR and HOXD9 genes, DNA methylation in thymoma was significantly higher than that in normal thymus. And in GNG4 and SALL3, DNA methylation in thymoma was similar to that in normal thymus.

      8eea62084ca7e541d918e823422bd82e Conclusion

      DNA methylation of several cancer-related genes in TC was significantly higher than that in thymoma or normal thymus. Epigenetic alteration may be related to progression or malignancy in TET.

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      P1.14-20 - The Expression of DNA Methylation of GAD1 Gene is an Indicator of Malignant Behavior in Thymic Epithelial Tumor. (ID 13354)

      16:45 - 18:00  |  Presenting Author(s): Kazuya Kondo

      • Abstract
      • Slides

      Background

      Genome-wide screening for aberrantly methylated CpG islands was performed in 7 thymic carcinoma (TC) samples and 8 type-B3 thymoma samples using HumanMethylation450 K BeadChip (Illumina, Santa Clara, CA, USA) analysis. We identified 22 genes as commonly hypermethylated in TC comparing with B3 thymoma. GAD1(glutamic acid decarboxylase 1)was one of the most significant hypermethylated genes in TC. GAD1 is the enzyme that synthesizes GABA. Recent some reports showed that it is significantly increased in neoplastic tissues. However, the mechanism underlying this increase remains elusive. In this study, we examine mRNA and protein expressions and DNA methylation of GAD1 in thymic epithelial tumors (TETs).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In total, 49 thymic tumour samples (A; 5, AB; 2, B1; 4, B2; 11, B3; 9, carcinoma; 18) and 20 paired normal tissues were obtained from patients with histologically proven TET, who underwent surgery at the Tokushima University Hospital (Tokushima, Japan) between 1990 and 2016. The methylation status of thymic epithelial tumor samples was validated by pyrosequencing in a larger cohort. The expression status was analysed by quantitative polymerase chain reaction (PCR) and immunohistochemistry (IHC).

      4c3880bb027f159e801041b1021e88e8 Result

      The previous study (Oncogene 2015, 1–14) showed that the key locus responsible for GAD1 reactivation was mapped to a DNA methylation-sensitive CTCF-binding site (CTCF-BS3) within the third intron of GAD1. We targeted this region for pyrosequencing. Pyrosequencing confirmed that DNA methylation of GAD1 gene of TC was significantly higher than that of thymoma (36.5% versus 7.3%, p<0.001), and that DNA methylation of GAD1 gene of thymoma was similar to that of normal thymus (7.3% vs 8.6%). Quantitative PCR and IHC staining revealed that GAD1 mRNA and protein expression levels of TC were higher than those of thymoma (RT-PCR; 8.84 vs 0.72). There were not differences of DNA methylation and expression of GAD1 among subtype of thymoma according to WHO histologic classification. There was a tendency of hypermethylated GAD1 gene in Stage IV comparing with other Stage (Masaoka’s clinical staging).

      8eea62084ca7e541d918e823422bd82e Conclusion

      TC frequently had DNA methylation of CTCF-binding site 3 in GAD1 gene, and high levels of mRNA and protein of GAD1. GAD1 may represent an epigenetic therapeutic target in TC.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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