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T. Kishimoto



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    ORAL 14 - Biology 2 (ID 112)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      ORAL14.02 - Clinical Significance of Soluble CD26 in Malignant Pleural Mesothelioma (ID 354)

      16:45 - 18:15  |  Author(s): T. Kishimoto

      • Abstract
      • Presentation
      • Slides

      Background:
      There is no established diagnostic marker for malignant pleural mesothelioma (MPM). CD26 is a 110 kDa, multifunctional, membrane-bound glycoprotein on the surface of many cell types that has dipeptidyl peptidase IV (DPPIV) enzyme activity. The aim of this study was to evaluate the clinical significance of soluble CD26 in patients with MPM.

      Methods:
      The study included 80 MPM patients, 79 subjects with past asbestos exposure (SPE), and 134 patients with other benign pleural diseases (OPD) that were included as a control group. Soluble CD26 levels and DPPIV activity in serum and/or pleural fluid were determined using an ELISA kit. To make a comparative review of the usefulness of sCD26, we determined serum and pleural fluid soluble mesothelin-related peptides (SMRP). SMRP was measured by the chemiluminescent enzyme immunoassay (CLEIA) based on 2-step sandwich method.

      Results:
      Serum sCD26 levels and DPPIV enzyme activity in patients with MPM were significantly decreased compared with those in the SPE group (P=0.000). The level of serum sCD26 was significantly decreased in patients with advanced stages of MPM compared with those with earlier stages (P=0.047). The median OS of patients with MPM who had higher DPPIV enzyme activity was significantly longer than that of those with lower DPPIV enzyme activity (P=0.032). The sCD26 levels in the pleural fluid of MPM patients with an epithelioid subtype were significantly increased compared with the OPD cohort (P=0.012). Moreover, DPPIV enzyme activity in the pleural fluid of patients with MPM with an epithelioid subtype were significantly increased compared with those in the OPD cohort (P=0.009). Patients with MPM who had lower specific DPPIV activity, determined as DPPIV/sCD26, showed significantly prolonged survival compared with those with higher specific DPPIV activity (P=0.028). Median values of serum and pleural fluid SMRP in MPM patients were 0.43 and 15.37 mmol/l, respectively. Median value of pleural fluid SMRP in epithelioid MPM was 17.28 mmol/l. Median values of serum SMRP in SPE and pleural fluid SMRP in OPD were 0.90 and 0.43 mmol/l, respectively. Pleural fluid SMRP in MPM was significantly higher than in OPD (P=0.000) and serum SMRP in MPM was significantly higher than in SPE (P=0.000).

      Conclusion:
      Serum sCD26 and DPPIV enzyme activity appear to be useful biomarkers for differentiating patients with MPM from SPE. The sCD26 levels or DPPIV enzyme activity in pleural fluid appear to be biomarkers in patients with an epithelioid subtype of MPM. DPPIV activity in serum or pleural fluid appears to be predictive for the prognosis of patients with MPM.

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    P2.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 225)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      P2.08-024 - CT Findings of Early Pleural Mesothelioma and Benign Asbestos Pleural Effusion (ID 272)

      09:30 - 17:00  |  Author(s): T. Kishimoto

      • Abstract
      • Slides

      Background:
      • Malignant pleural mesothelioma is known as disease of the poor prognoses. • Our purpose is to find useful CT findings for correct differentiation between Malignant Pleural Mesothelioma in the early stage (e-MPM) and Benign Asbestos Pleural Effusion (BAPE) to improve prognosis of MPM.

      Methods:
      • The BAPE group consisted of 36 patients diagnosed at Okayama Rosai Hospital since Jan 2000. In all BAPE patients thoracoscopic biopsies were conducted to exclude malignant diseases including MPM. • In e-MPM group, 66 patients who were diagnosed mesotheliomas with T1 or T2 (IMIG system) by the CT evaluation were studied. The e-MPM patients were selected from 2,742 mesothelioma death cases of Japanese vital statistics of 2003-05. • We evaluated CT scans taken at the time of diagnosis for each group. The evaluating items were presence of asbestosis, pleural plaque (PQ), rounded atelectasis (RA) and diffuse pleural thickening (DPT), as well as the grade and localization of pleural irregularities.

      Results:
      • In BAPE group (36 cases), the occurrence rate of asbestos-related lesions was significantly higher than in e-MPM group (66 cases) as follows; prevalence of asbestosis 17%/2% (*), PQ 92%/35% (**), RA 44%/0% (**) and DPT 25%/2% (**). (*P=0.0038 **P<0.001) • As for grade of pleural irregularity, no irregularity was found in 22%/9%, low-level irregularity in 72%/54%, high-level irregularity in 5%/23% and mass formation in 0%/14% of BAPE and e-MPM group patients, respectively. • As for localization (including overlap) of pleural irregularity, irregularity in mediastinal pleura was observed in 30%/74%, basal pleura in 91%/77% and interlobar pleura in 0%/55% of BAPE and e-MPM group patients, respectively. The mediastinal pleural thickening was minimal in BAPE group and found regressed in the follow-up CT scans.

      Conclusion:
      • In BAPE group the occurrence rate of asbestos-related lesions was higher than in e-MPM group. • Because the 5% of BAPE cases presented irregular pleural thickening, the differentiation with MPM was difficult in such case. • The mediastinal pleural thickening, which is considered to be a characteristic of MPM, was also observed in 30% of BAPE cases. However, the finding disappeared during observation. And no BAPE case with interlobar pleural irregularity was found. These findings can be useful for differentiation BAPE and e-MPM cases.

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    P3.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 226)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 2
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      P3.08-004 - The Evaluation of Radiological Features for Pleural Mesothelioma (ID 23)

      09:30 - 17:00  |  Author(s): T. Kishimoto

      • Abstract
      • Slides

      Background:
      The differences of radiological features for pleural mesothelioma from other diseases such as lung cancer and sarcomas or pleuritis et al. is not evaluated and the also the difference of features among the histological manufestation is also not clear.

      Methods:
      Four hundred and twenty four cases of pleural mesothelioma who were clinically diagnosed, were evaluated. The chest CT which patients first visited to hospital were classified into 7 category such as 1)uni-mass formation, 2)pleural rind, 3)slight thickening of pleura, 4)thickening of mediastinal pleura, 5)pleural effusion without pleural changes, 6)multi-mass formation and 7)specific type. Furthermore, evidence of pleural effusion and the radiological patterns of the histological differences were evaluated.

      Results:
      The number of mesothelioma who were definitely diagnosed was 383 cases and 51 cases were not diagnosed mesothelioma but lung cancer, sarcoma or pleuritis or benign asbestos pleurisy et al. were diagnosed histologically. For mesothelioma cases, 230(60.1%) cases showed epithelioid histology, 62 cases(16.2%) biohasic type and 86 cases(22.5%) were sarcomatoid type and 5 cases(1.3%) were specific type and 89.6% showed pleural effusion. For the radiological patterns for 383 cases, pleural rind pattern occupied 42.2% and multi-mass formation 14.1%, pleural effusion without pleural changes 12.9% and uni-mass formation occupied 8.6%. As for the histological features, biphasic type showed only 2 cases(2.9%) uni-mass formation and 13.2% showed thickening of mediastinal pleura and sarcomatoid type only 4.4% showed pleural effusion without pleural changes. Other 51 cases who were not diagnosed mesothelioma such as lung cancer et al. showed 30.9% of uni-mass formation, pleural rind 21.8% and pleural effusion without pleural changes 18.2%. And 80.4% of them showed pleural effusion.

      Conclusion:
      Pleural mesothelioma shows various types of radiological manifestation and also other diseases such as lung cancer or sarcomas or benign pleuritis show similar patterns. Therefore, we try to make differential diagnosis when we suspect pleural mesothelioma by chest CT.

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      P3.08-005 - Mesothelioma Diagnostic Panel Using Remote Digital Diagnostic System in Japan (ID 480)

      09:30 - 17:00  |  Author(s): T. Kishimoto

      • Abstract
      • Slides

      Background:
      The pathological diagnosis as mesothelioma is difficult even if experienced pathologists do. Also the diagnosis of imaging including CT has no conclusive evidences as mesothelioma. Accordingly comprehensive diagnosis based on discussion by several pathologists and/or radiologists is necessary. However most of diagnostic specialists are too busy to have a meeting at designated date and venue. New remote diaignostic system will solve those problems and the accurate diagnosis as mesothelioma can be made.

      Methods:
      The remote pathological diagnosis consists of scanning of tissue slide by scanning equipment (NanoZoomer®), transmission of the digital data to cloud system (Google) by Internet. We have developed a new system named “LOOKREC” including pathological data and imaging data (chest X-P,CT and so on). The pathologists and radiologists as a member of special diagnostic group obtain a special account and access to the data on cloud by Internet. The diagnotic opinions made by individuals are entered into the discussion sheet and the organizer will decide a final diagnosis including whether mesothelioma or not, which type of mesothelioma, based on individual diagnostic opinions.

      Results:
      In Japan, the annual number of occurrence of mesothelioma is over 1200. The compensation or relief system for mesothelioma patients has been established ten years ago, and the accurate diagnosis is always required for adequate management of those systems. The number of mesothelioma showing diagnostic problems is about 10% of all mesothelioma cases. The cases with some difficulties of differentiation between early epithelioid mesothelioma vs reactive mesothelial hyperplasia, pleuritis, localized methelioma vs lung cancer will be presented and the points of differential diagnosis will be discussed.

      Conclusion:
      The new remote diagnostic system using Internet has been developed. It is expected that diagnostic accuracy will be improved when the observation of pathological findings as well as imaging and effective disccussion on the web will be done by pathologists and radiologists.

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