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Takahiro Nakajima



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    MTE 08 - Technical Details of EBUS and EUS (Sign Up Required) (ID 557)

    • Event: WCLC 2017
    • Type: Meet the Expert
    • Track: Pulmonology/Endoscopy
    • Presentations: 1
    • Moderators:
    • Coordinates: 10/16/2017, 07:00 - 08:00, Room 502
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      MTE 08.01 - Technical Aspects of EBUS-TBNA for Clinicians (ID 7785)

      07:00 - 08:00  |  Presenting Author(s): Takahiro Nakajima

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Since the clinical introduction of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in 2004, EBUS-TBNA has become accepted worldwide due to its minimal invasiveness but high diagnostic ability. EBUS-TBNA is an image-guided procedure, and the instruments and devices used for endobronchial ultrasonography as well as transbronchial needle aspiration have continuously evolved. Furthermore, such device improvements have been accompanied by improvements in the techniques of ultrasound visualization, sampling with a dedicated needle, and specimen handling. Initially, the only indication of EBUS-TBNA was nodal staging of lung cancer; however, now its indications have expanded to not only malignant diseases but also benign diseases, such as sarcoidosis or tuberculosis. EBUS-TBNA has also recently been used for the important tasks of “core sampling” and “rebiopsy”. The advent of immune checkpoint inhibitors and novel tyrosine kinase inhibitors has resulted in additional applications of EBUS-TBNA in the era of precision medicine. In 2016, the American College of Chest Physicians published a guideline focusing on the technical aspects of EBUS-TBNA. This guideline described several techniques of EBUS-TBNA for which the evidence level had been thought too difficult to grade. The ungraded consensus-based statement managed this limitation well and thus became a useful technical guide for clinicians. The guideline also described sedation to be used when performing EBUS-TBNA. Since many patients who underwent EBUS-TBNA suffered from severe coughing during the procedure, the guideline recommended performing moderate or deep sedation in the first paragraph. In addition, performing the procedure in a more comfortable condition for clinicians was required, which would help them perform the procedure repeatedly following the necessary treatment course as mentioned above. The first report of an EBUS image analysis was the classification of B-mode features of benign and malignant lymph nodes by the first generation EBUS ultrasound processor with 7.5MHz radiofrequency. Owing to improvements in ultrasound processors and increased radiofrequency to 10MHz, EBUS image analyses are now being increasingly performed, including the use of various new Doppler features and image analysis technologies, such as gray scale texture analyses and fractal dimension analyses. The latest ultrasound processor equipped with elastography is capable of depicting the relative stiffness of the targeted tissue within the region of interest. However, whether or not a spectrum analysis of EBUS radiofrequency can provide precise information of the target histology is still being investigated. After all, EBUS-TBNA is a sampling modality, so “tissue is the issue” remains the point of focus. However, we often encounter cases with multiple nodes within the same nodal station. In addition, some metastatic lymph nodes are unable to be diagnosed due to the limited metastatic area within the lymph node (micrometastasis). Advances in EBUS image analyses may help reduce examination time and medical resource usage as well as allow for more precise TBNA needle control. The dedicated TBNA needle was originally developed from the needle used for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The handle of the needle was designed to be manipulated by the operator alone. The initial size of the needle was 21 and 22 gauge. Now, however, several types of dedicated needles are commercially available from different manufacturers; currently available needle sizes are 19, 21, 22, and 25 gauge, and each tip is designed for a specific purpose. The size (amount) of the biopsied material, the degree of blood contamination, and the quality of the histological structure (degree of tissue crushing) can all be affected by needle selection. Although the optimum needle type is still unclear, clinicians may need to select a needle depending on the character of the targeted lesion and the purpose of the biopsy. Specimen handling is another important issue. EBUS-TBNA is basically a needle biopsy procedure; therefore, the obtainable material is fundamentally cytological material. We can often obtain “core” specimens, even when using TBNA which is a cytological sampling procedure. We first introduced the “tissue coagulation clot” method for the EBUS-TBNA “core” specimen. The “core” usually consists of tumor tissue fragments floating in coagulation tissue. By modifying the specimen-processing protocol, a good quality cell block can be made and used for pathological evaluations, including immunohistochemistry and ancillary testing, such as fluorescence in situ hybridization. We now need to determine any genetic alterations in lung cancer prior to starting treatment. The rapid on-site evaluation of the obtained material during the procedure may play a crucial role in sample processing, despite the lack of any clear evidence that this improves the diagnosis rate so far. We still need to develop the optimum specimen handling protocol in order to maximize the utility of microsamples obtained by EBUS-TBNA. Finally, training for EBUS-TBNA is still important for both mentors and mentees. We recently described the utility of a biosimulator for advanced EBUS-TBNA training to encourage efficient sampling. Many training models, including low- and high-fidelity models, and courses were developed, and the trainees were evaluated by dedicated evaluators. Performing high-quality training is crucial to ensuring a safe procedure as well as a high diagnostic yield. EBUS-TBNA is a still-evolving technology, and we clinicians need to continue brushing up our skills and seeking better ways to examine and treat patients. More clinical studies are needed to address the issues still unresolved by the current technical guideline.

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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-034 - Non-Invasive Qualitative Diagnosis of Lung Cancer Enabled by Spectrum Analysis of Ultrasound (ID 9376)

      09:30 - 16:00  |  Author(s): Takahiro Nakajima

      • Abstract

      Background:
      Ultrasound has been widely utilized in clinical to visualize the internal structure of the objective non-invasively. However ultrasound image can’t distinguish malignant lesion from the normal tissue. Spectrum analysis of ultrasound is a newly developed technology which may reflect on the histological feature. We examine if the spectrum analysis is able to distinguish malignant tissue from normal tissue.

      Method:
      Spectrum was measured using a prototype ultrasound processor EUME5 given by Olympus Japan. three parameters of spectrum such as Midband-fit(M), Intercept(I), and Slope(S) were measured for the objective tissue. In animal study, human lung cancer Xenograft were created in nude mice for each lung cancer cell line (A549, H460, HCC827, and H3122). In clinical setting, surgically excised lungs including lung cancers were examined spectrum analysis for both lung cancers (n=19, 106 slices) and normal lungs (n=17, 65 slices).

      Result:
      Four different Xenografts exhibited significant differences of spectrum data. In the clinical study, the mean value of M, I and S of both lung cancers and normal lungs were M: -43.22 ±4.09 vs -39.31±3.87(p<0.01,) I: -55.28±3.19 vs -54.13±2.4 (N.S), S: -1.43±0.35 vs -1.73±0.30 (p<0.01)

      Conclusion:
      Each lung cancer Xenograft of different histology showed different spectrum value. Spectrum analysis is likely to reflect the histological feature. In clinical, M and S showed statistically different values between lung cancer and normal lung. Based on spectrum value, a malignant tumor can be distinguished from the normal lung in the ultrasound image.

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    P1.16 - Surgery (ID 702)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Surgery
    • Presentations: 1
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      P1.16-008 - Near-Infrared Fluorescence-Guided Pulmonary Segmentectomy Following Endobronchial Indocyanine Green Injection (ID 8561)

      09:30 - 16:00  |  Author(s): Takahiro Nakajima

      • Abstract

      Background:
      Near infrared (NIR) fluorescence-guided pulmonary segmentectomy following endobronchial or intravenous indocyanine green (ICG) administration has been developed and reported. The aim of this study is to prospectively validate the feasibility and safety of NIR fluorescence-guided pulmonary segmentectomy following endobrochial ICG injection using navigational bronchoscopy.

      Method:
      Patients who underwent pulmonary segmentectomy were prospectively enrolled in this study. Using preoperative CT datasets a 3D image of target segments was reconstructed for lung volumetry and a bronchial road map was created to determine the bronchus for ICG injection. The ICG concentration was 0.125 mg/mL. Immediately after intubation the ICG was injected into the target bronchi using an ultrathin bronchoscope followed by air flushing to expedite ICG dispersion to the periphery. A NIR thoracoscope (PINPOINT, Novadaq) was used to detect ICG fluorescence and determine intersegmental plane for pulmonary segmentectomy. Usefulness and safety of this technique were evaluated by 1) whether ICG demarcation lines correspond to intersegmental lines expected from pulmonary veins, 2) whether large bronchi and vessels in adjacent segments emerge when dividing intersegmental planes using electrical cautery. The patients were followed up to 1 month after surgery to see if any complication existed.

      Result:
      Eight male and 7 female patients with a mean age of 66.5 ± 9.6 years were enrolled. Segmentectomy regions included right S1, S2, S6, S8 and S10 segments, and left S1+2+3, lingular, S6, S8, S9+10, and basilar segments. The average bronchoscopic procedure time was 14.3 ± 8.0 minutes. Vital signs were kept stable before and after the bronchoscopic procedure. The mean injected volume of ICG solution was 21.2 ± 8.8 mL as per a case. In 13 out of 15 cases (86.7%), NIR fluorescence guidance was recognized as effective for pulmonary segmentectomy. Intersegmental plane could not be determined in 2 cases likely due to insufficient air flushing, leading to the failure of ICG dispersion to the periphery. There was no complications developed intraoperatively. The average operation time was 193 ± 41 minutes, with a mean bleeding of 110 ± 101 mL. The average duration of drainage was 3.1 ± 1.0 days. Recurrent air leakage happened on postoperative day 6 in 1 case. Otherwise, no procedure related adverse event was noted.

      Conclusion:
      NIR fluorescence-guided pulmonary segmentectomy following endobrochial ICG injection using navigational bronchoscopy appeared to be safe and feasible. Sufficient air flushing may be the key for clear ICG demarcation of referred segments.

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    P2.07 - Immunology and Immunotherapy (ID 708)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P2.07-008 - Does PD-L1 Expression of the Archive Surgical Specimen of Primary Tumor Predict the Sensitivity of Recurrence to Nivolumab in Patients with NSCLC? (ID 8041)

      09:30 - 16:00  |  Author(s): Takahiro Nakajima

      • Abstract
      • Slides

      Background:
      Nivolumab is an immune checkpoint inhibitor targeting human IgG4 programmed death 1 for advanced or recurrent non-small lung cancer (NSCLC), and programmed death ligand 1 (PD-L1) expression of tumor tissue is expected to be a biomarker of the sensitivity to Nivolumab. More recent biopsy is likely to be more suitable since PD-L1 expression of tumor cells is influenced by time or by anti-tumor therapies such as chemotherapy or radiotherapy, and most clinical studies have referred to the PD-L1 expression using the latest biopsy samples before administration of Nivolumab. Therefore, it remains controversial whether PD-L1 expression of the archive specimen obtained at the time of initial surgery for primary disease is correlated with the sensitivity of recurrent diseases to Nivolumab.

      Method:
      We retrospectively reviewed 10 NSCLC patients who had undergone radical surgery for primary tumor and received Nivolumab for their recurrent diseases. The median interval between the initial surgery and Nivolumab administration was 28.1 months (2-75), and median number of anti-tumor regimens prior to Nivolumab was 2.2 (1-5). Archive specimens of primary tumors and second biopsy samples of recurrent diseases from the 10 patients were stained to measure PD-L1 expression both with the PD-L1 IHC 28-8 pharmDx Daco (assay 28-8), and with the PD-L1 IHC 22C3 pharmDx Daco (assay 22C3).

      Result:
      Among the 10 patients, complete response (CR)/partial response (PR)/ stable disease (SD)/progressive disease (PD) for Nivolumab were 1/2/3/4 patients, respectively. All patients had PD-L1 expressions as tumor proportion score (TPS)≧1%, of which 7 showed TPS≧10% in the assay 28-8. All 3 patients (30%) with CR/PR showed TPS≧10%. The TPS obtained by assays 28-8 and 22C3 were similar in 9 of 10 patients. Two patients underwent biopsies for their recurrent sites, which showed decreased PD-L1 expression compared with primary tumor, resulted in PD for Nivolumab.

      Conclusion:
      The PD-L1 expressions of surgical archive specimen might be almost associated with the sensitivity to Nivolumab, however, time and antitumor therapies may modulate the PD-L1 expressions and might be able to affect the sensitivity to Nivolumab. Further pre-clinical and clinical studies are warranted to evaluate the availability of surgical archive specimen in the treatment of postoperative recurrence by the immunocheckpoint inhibition.

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    P2.12 - Pulmonology/Endoscopy (ID 713)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Pulmonology/Endoscopy
    • Presentations: 1
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      P2.12-006 - Evaluation of New 25G Needle in EBUS-TBNA Comparing Conventional 22G Needle in Diagnosis for Nodal Metastasis of Lung Cancer (ID 10271)

      09:30 - 16:00  |  Author(s): Takahiro Nakajima

      • Abstract

      Background:
      Dedicated 22G needle is usually used for EBUS-TBNA, which is a main diagnostic tool for nodal staging in lung cancer. Recently new 25G needle is developed and expected less invasive nodal biopsy. Although, diagnostic yield and complication of the EBUS-TBNA using 25G needle are still unclear.

      Method:
      From September 2016 to May 2017, 39 hilar or mediastinal lymph nodes in 25 patients were consecutively biopsied using both 22G (Olympus, Tokyo, Japan) and 25G (Boston Scientific, MA) needles for diagnosis or staging of lung cancer. Concordance rates of rapid on-site cytologic evaluation and cytological and pathological diagnosis between the EBUS-TBNAs using the two types of needles were evaluated. And also, bleeding score of cytological specimen (0-3: higher is more contaminated) and calculated area of histological core (the number of high-power field microscopically in paraffin-embedded slides) were compared for evaluating sample qualities. The results obtained from EBUS-TBNA using 22G needle were regarded as control to evaluate the diagnostic ability of that using 25G needle in this analysis.

      Result:
      No complication was recorded during the study period. Thirty three Mediastinal nodes (#2(n=2), #3(n=1), #4R(n=16), #4L(n=2), #7(n=12)) and 6 hilar nodes (#10(n=1), #11(n=3), #12(n=2)) were biopsied and concordance rate between 22G and 25G was 87% (34/39) in the rapid on-site cytologic evaluation, 95% (37/39) in the cytological diagnosis and 85% (35/39) in the histological diagnosis. Final decision whether metastatic or not according to the combined cytologic and histologic diagnosis in the EBUS-TBNA using 22G needle was 19 metastases and 20 benign nodes, and the concordance rate with the two types of needles was 92% (36/39). In the 3 nodes with discrepancy, 2 nodes were diagnosed as lung cancer metastasis by the 25G needle sampling. Both bleeding score and calculated area of histological core showed no significant difference (p=0.3 and 0.7) between 22G and 25G, with respective values of 1.8±0.9 vs. 2.0 ±0.7, and 20±2.2 vs. 21±2.2.

      Conclusion:
      EBUS-TBNA using 25G needle is feasible and as useful as that using conventional 22G.

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    WS 04 - Minimally Invasive Diagnosis and Staging of Lung Cancer – Interventional Pulmonology Hands-On Workshop (Ticketed Session) (ID 766)

    • Event: WCLC 2017
    • Type: Workshop
    • Track: Pulmonology/Endoscopy
    • Presentations: 1
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      WS 04.03 - Specimen Acquisition and Processing (ID 11038)

      13:00 - 17:00  |  Presenting Author(s): Takahiro Nakajima

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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