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N. Ikeda

Moderator of

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    O28 - Endoscopy (ID 124)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 8
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      O28.01 - EBUS-centered vs. EUS-Centered Mediastinal Staging in Lung Cancer:<br /> a randomized controlled trial. (ID 1037)

      10:30 - 12:00  |  Author(s): H.J. Kang, G.K. Lee, B. Nam, M.S. Kim, J.M. Lee, H.S. Lee, J. Han, B. Hwangbo

      • Abstract
      • Presentation
      • Slides

      Background
      The impact of primary procedure and procedure sequence has not been studied in combined application of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in lung cancer staging.

      Methods
      In a randomized controlled trial, 160 patients with histologically confirmed or strongly suspected potentially operable non-small cell lung cancer were enrolled (Group A, n=80, EBUS-centered; Group B, n=80, EUS-centered). In Groups A and B, EBUS-TBNA and EUS-FNA with ultrasound bronchoscope were used as the first procedure, respectively, and secondary procedures were added.

      Results
      Diagnostic values were evaluated in 148 patients (74 in each group). In Groups A and B, the diagnostic accuracy (93.2% vs. 97.3%, respectively, p=0.2454) and sensitivity (85.3% vs.92.0%, respectively, p=0.4312) in detecting mediastinal metastasis were not statistically different. In Group A, adding EUS-FNA to EBUS-TBNA did not significantly increase the accuracy (91.9% to 93.2%; p=0.7540) and sensitivity (82.4% to 85.3%; p=0.7419). In group B, adding EBUS-TBNA to EUS-FNA increased the accuracy (86.5% to 97.3%; p=0.0160) and sensitivity (60.0% to 92.0%; p=0.0081). There were no inter-group differences in procedure time, cardio-respiratory parameters during procedures, complications, or patient satisfaction.

      Conclusion
      In combination of EBUS-TBNA and EUS-FNA in mediastinal staging, diagnostic values and patient satisfaction were not different between EBUS-centered and EUS-centered group. However, the necessity of EBUS-TBNA following EUS suggests EBUS-TBNA is a better primary procedure in endoscopic mediastinal staging.

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      O28.02 - Grey Scale Texture Analysis of Endobronchial Ultrasound Mini Probe Guide Sheath Images for Prediction of Benign or Malignant Aetiology. (ID 1059)

      10:30 - 12:00  |  Author(s): P. Nguyen, F. Bashirzadeh, J. Hundloe, O. Salvado, N. Dowson, R. Ware, I.B. Masters, D. Fielding

      • Abstract
      • Presentation
      • Slides

      Background
      Expert analysis of endobronchial ultrasound (EBUS) images obtained with the mini probe (MP) has established certain subjective criteria for predicting benign or malignant disease. Minimal data is available for objective analysis of these images. The aim of this study was to determine if greyscale texture analysis of EBUS-MP images could differentiate between benign and malignant peripheral lung lesions.

      Methods
      Digital EBUS-MP images with contrast set at 4 and gain set at 10 were included in this study. A region of interest (ROI) was mapped for each image and analysed in a prediction set. The ROIs were analysed for the following greyscale texture features in MATLAB (v7.8.0.347 (R2009a)); mean pixel value, difference between maximum and minimum pixel value, standard deviation of the mean pixel value, entropy, correlation, energy and homogeneity. Significant greyscale texture features were used to assess a validation set. Figure 1

      Results
      Eighty-five peripheral lung lesions were in the prediction set (47 malignant and 38 benign). Benign lesions had larger differences between maximum and minimum pixel values, larger standard deviations of the mean pixel values and a higher entropy than malignant lesions (p<0.0001 for all values). Eighty two peripheral lesions were in the validation set; 63/82 (76.8%) were correctly classified. Of these 45/49(91.8%) malignant lesions and 18/33 (54.5%) benign lesions were correctly classified. The negative predictive value for malignancy was 82% and the positive predictive value was 75%. Figure 1

      Conclusion
      Greyscale texture analysis of EBUS-MP images could assist in differentiating between benign and malignant peripheral lung lesions but tissue diagnosis is still important.

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      O28.03 - Clinical implication of ex vivo Raman Spectroscopy and in vivo NIR spectroscopy for diagnosis of peripheral lung cancer. (ID 3075)

      10:30 - 12:00  |  Author(s): J. Votruba, T. Bruha

      • Abstract
      • Presentation
      • Slides

      Background
      Due to a widespread use of a CT there is recently increased incidence of smaller peripheral lung lesions. Because of an obvious need for a morphological verification new bronchoscopy methods for biopsy of such small peripheral lesions are needed. We have utilized two methods of spectroscopic detection in peripheral lung cancer. In vivo method- NIR spectroscopy of penetrating light and ex vivo method-Raman spectroscopy of biopsy specimens. Correlation of these two methods gives us the insight into molecular biology of in vivo spectroscopic measurement. In vivo NIR spectroscopy together with transbronchial biopsy under fluoroscopic guidance appears to be useful and reliable method for peripheral lung cancer diagnosis.

      Methods
      We have designed a simple instrument for measurement of a penetrated NIR light through the lung tissue. It consists of two fibres of 1 mm in diameter contained in one bundle covered with insulation sleeving. One of the fibres is a detector; the other is a source fibre. The indicator fibre is 1,5 cm longer than the source fibre and it is separately covered with insulation till its ending. The ending is cut in the angle of 60 degrees and titan coated in order to facilitate NIR light transmission toward detector fibre. The detector fibre is connected to NIR spectroscope and the source fibre to NIR source. The instrument for ex vivo Raman spectroscopy measurement has been derived from above described system. The endings of fibres have been grinded down perpendicularly in order to allow systematic Raman measurement.

      Results
      In vivo measurement: Measurements of a normal lung tissue at various areas of a lung tissue show characteristic peak at 735 nm which is not present during cancer tissue spectroscopy. In cancer tissue in addition all detected spectra have got fixed ratio (with minimal dispersion) of two standardized transmittance values at two chosen wavelengths (773 and 823 nm)- mirroring the source values with its mild modification by tissue auto fluorescence. By help of those findings we utilized endobronchial measurement of NIR transmittance spectra in attempt to improve sensitivity of trans bronchial biopsy under fluoroscopic guidance. Ex vivo measurement: Biopsy specimens has been immediately transferred to Raman spectroscope laboratory (within 10 minutes) on temperature 8-10°C. For tissue Raman studies we used excitation at 785 nm. Raman spectra in the 700-1,800 cm(-1) range from lung tissue biopsies were obtained within 10 sec. Raman Spectroscopy results from biopsy specimens taken from the in vivo spectroscopy pathological areas showed higher signals for nucleic acid, tryptophan and lower signals for phospholipids and proline, compared to normal tissue.

      Conclusion
      In vivo NIR spectroscopy together with transbronchial biopsy under fluoroscopic guidance appears to be useful and reliable method for peripheral lung cancer diagnosis. Ex vivo Raman spectroscopy confirmed diagnostics value of in vivo measurements. Such device or its modifications could be easily included for example into the examination by electromagnetic navigation.

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      O28.04 - DISCUSSANT (ID 3978)

      10:30 - 12:00  |  Author(s): L. Thiberville

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      O28.05 - An analysis of a prospective study from the European Lung Cancer Working Party (ELCWP) looking at predictive factors for response to chemotherapy (CT): limitations in translational cooperative research. (ID 1941)

      10:30 - 12:00  |  Author(s): I. Cstoth, T. Berghmans, J. Lafitte, A. Meert, M. Paesmans, A. Scherpereel, N. Leclercq, J. Sculier

      • Abstract
      • Presentation
      • Slides

      Background
      Adequate tumour samplings for biological analyses are currently of major importance in treating oncological patients. Obtaining histological samplings from the primary lung cancer can be a challenge due to tumour accessibility, small biopsies or tolerance to bronchoscopy such as bleeding or dyspnoea in case of limited airflow capacity. The ELCWP developed a multicentre prospective study searching for predictive factors for response to chemotherapy based on genomic analyses. We aim to analyse the capability in obtaining adequate tumour samplings from the primary non small cell lung cancer (NSCLC) for studying the transcriptome (miRNA and mRNAs) with high throughput techniques.

      Methods
      All patients presenting with a suspected lung cancer were proposed participating to the study. To be evaluable for the primary endpoint of the study, patients needed to have a confirmed diagnosis of NSCLC treated with chemotherapy and assessable for response. During the diagnostic bronchoscopy, 3 biopsies were collected from the primary tumour, with a control sample from normally appearing bronchial mucosa. One was formalin fixed and paraffin embedded for pathological diagnosis. A second was used for transcriptome analysis and the third one was frozen and stored in a tissue bank. We are presenting the flow chart of the patients screened for entry in the ELCWP study and the limitations for obtaining tumour samplings in assessable patients.

      Results
      From 1/04/2009 to 12/06/2013, 307 patients suspected to have NSCLC were prospectively registered. Eleven are under evaluation for pending histological confirmation leaving 296 patients evaluable for the present analysis. In 25 cases, no lung cancer confirmation was obtained (other tumour n = 12, no pathological confirmation at all n = 6, benign lesion n = 6, other reason n = 1) and 6 further patients withdrew their initial consent. Among 265 pathologically confirmed lung cancer (samples obtained during bronchoscopy or by another technique), 38 small cell lung cancers (SCLC) and 227 NSCLC were diagnosed. In addition to the diagnostic biopsy, further samplings for genomic analyses could be obtained during the same bronchoscopy in 30/38 SCLC (79%) and 116/227 NSCLC (51%). Among 227 NSCLC, 107 were presenting with an advanced disease treated with a cisplatin-based chemotherapy and were assessable for response to chemotherapy (primary study endpoint). Among these 107 patients, 59 adequate tumour samplings could be obtained for transcriptome analysis (20% from the initial cohort and 55% among assessable patients).

      Conclusion
      This analysis of a prospective multicentre study is showing the difficulties and limitations in obtaining adequate tumour samplings for biological analyses when conducting translational cooperative research in non-small cell lung cancer.

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      O28.06 - Comprehensive management of central type early lung cancer (ID 1558)

      10:30 - 12:00  |  Author(s): N. Ikeda, N. Kajiwara, T. Ohira, M. Kakihana, J. Usuda, H. Honda, S. Maehara, Y. Shimada

      • Abstract
      • Presentation
      • Slides

      Background
      Tumor localization and the precise evaluation of tumor invasion are most important for the management of central type early stage lung cancer (CELC) and Photodynamic therapy (PDT) has come to be considered as the first choice of treatment for CELC. The present guidelines of PDT for CELC were established based mainly on the data obtained from studies since 1980’s. CELCs less than 1 cm in diameter showed a favorable cure rate by PDT, thus this was a good standard to decide the indications of PDT. To obtain complete response (CR) by PDT, evaluation of each lesion is extremely important, including the extent of the tumor on the bronchial surface and the depth of invasion in the bronchial wall. We postulate that the combination of comprehensive diagnosis and the new generation of photosensitizers may increase the CR rate and expand the indications of PDT for larger tumors.

      Methods
      Autofluorescence bronchoscopy (AFB) has been used in the objective evaluation of the margin of the tumor before endoscopic treatment and Endobronchial ultrasonography (EBUS) has been employed to determine the depth of tumor invasion. Ooptical coherence tomography (OCT) has been investigated for clinical use as well. Also, the relatively newer photosensitizer NPe6, which has a stronger antitumor effect than Photofrin has been extensively used for PDT. We routinely used these diagnostic methodologies and NPe6 since 2004.

      Results
      A total of 122 consecutive CELCs were treated by PDT using NPe6 in Tokyo Medical University and CR was obtained in 115 lesions (CR rate 94.3%). Of the 122 lesions examined in this study, 78 had a diameter of ≦1.0 cm and the rest of the 44 cancer lesions were >1.0 cm in size. The CR rate of CELC ≦1.0 cm in diameter was 93.6% (73/78) and for those >1.0 cm in diameter, 95.5% (42/44), respectively. There was no significant difference between tumor size and clinical response. The CR rate to NPe6-PDT is higher than that of Photofrin-PDT in our previous studies. This early result suggests that PDT with NPe6 has a stronger antitumor effect than Photofrin therefore similar treatment outcome even for larger tumors >1.0 cm in diameter should be possible.

      Conclusion
      Objective evaluation by a comprehensive approach using AFB and EBUS enables to select the optimal therapeutic strategy for CELC. These results suggest that PDT with NPe6 may have a similar treatment outcome regardless of tumor size, as long sufficient laser illumination of the entire tumor is possible.

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      O28.07 - Intra-operative scanning confocal endomicroscopy of pleural disease: in vivo diagnosis of malignancy (ID 2977)

      10:30 - 12:00  |  Author(s): P.L. Mitchell, S. Knight, P. Crowley, F. Putt, J. Gooi, S. Seevanayagam, S. Barnett, C. McDonald, P. Delaney

      • Abstract
      • Presentation
      • Slides

      Background
      The intra-operative diagnosis of pleural malignancy may facilitate surgical decision-making including the need for pleurodesis. A scanning laser confocal endomicroscopy device has been developed which allows histological-detail optical imaging of subsurface tissues in vivo. Confocal laser microscopy illuminates and detects light from a fixed point of a specimen which is scanned across a tissue plane and adjustable depths, providing a 3D structural view in a living body. Applied to screening of mucosal lesions in patients undergoing GI endoscopy, endomicroscopy obviates the need for many tissue biopsies and operators can rapidly learn to identify malignant tissues.

      Methods
      We performed the first intra-operative examination of pleural tissues using this equipment which is a thoracoscope-mounted endomicroscope device in patients administered iv fluorescein prior to imaging. Intra-operative endomicroscopic images were correlated with biopsies of pleural tissues.

      Results
      Sixteen patients were imaged: including mesothelioma 5 (2 biphasic) and pleural metastases from malignancies of lung 2, ovary 2 and one case each of breast, adenoidcystic (see figure), thyroid, colorectal, carcinoid and non-Hodgkin’s lymphoma, and also one benign case. We were able to image and identify normal mesothelium, sub-mesothelium, connective tissues and blood vessels (including RBC). Malignant cells and clusters of cells had a characteristic appearance including poor uptake of fluorescein and cellular pleomorphism. Appearances of mesothelioma correlated closely with histology. Glandular and papillary structures were identified in metastatic pleural tumour. In ovarian cancer calcification was readily identified as were psammoma bodies, while the typical cystic spaces surrounded by small dark cells mirrored closely the histological appearances of adenoidcystic carcinoma.

      Conclusion
      Images obtained on scanning confocal endomicroscopy of pleural malignancy generally correlated well with the histological appearance on biopsies. We plan now to extend our experience of malignancy and also the ability to discriminate between benign disease and malignancy of the pleura. Supported by a Tumour Stream Grant from the Victorian Cancer Agency. Figure: Endomicroscopy image of pleural metastases from adenoidcystic carcinoma of the parotid. Figure 1

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      O28.08 - DISCUSSANT (ID 3979)

      10:30 - 12:00  |  Author(s): T. Sutedja

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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Author of

  • +

    O28 - Endoscopy (ID 124)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 1
    • +

      O28.06 - Comprehensive management of central type early lung cancer (ID 1558)

      10:30 - 12:00  |  Author(s): N. Ikeda

      • Abstract
      • Presentation
      • Slides

      Background
      Tumor localization and the precise evaluation of tumor invasion are most important for the management of central type early stage lung cancer (CELC) and Photodynamic therapy (PDT) has come to be considered as the first choice of treatment for CELC. The present guidelines of PDT for CELC were established based mainly on the data obtained from studies since 1980’s. CELCs less than 1 cm in diameter showed a favorable cure rate by PDT, thus this was a good standard to decide the indications of PDT. To obtain complete response (CR) by PDT, evaluation of each lesion is extremely important, including the extent of the tumor on the bronchial surface and the depth of invasion in the bronchial wall. We postulate that the combination of comprehensive diagnosis and the new generation of photosensitizers may increase the CR rate and expand the indications of PDT for larger tumors.

      Methods
      Autofluorescence bronchoscopy (AFB) has been used in the objective evaluation of the margin of the tumor before endoscopic treatment and Endobronchial ultrasonography (EBUS) has been employed to determine the depth of tumor invasion. Ooptical coherence tomography (OCT) has been investigated for clinical use as well. Also, the relatively newer photosensitizer NPe6, which has a stronger antitumor effect than Photofrin has been extensively used for PDT. We routinely used these diagnostic methodologies and NPe6 since 2004.

      Results
      A total of 122 consecutive CELCs were treated by PDT using NPe6 in Tokyo Medical University and CR was obtained in 115 lesions (CR rate 94.3%). Of the 122 lesions examined in this study, 78 had a diameter of ≦1.0 cm and the rest of the 44 cancer lesions were >1.0 cm in size. The CR rate of CELC ≦1.0 cm in diameter was 93.6% (73/78) and for those >1.0 cm in diameter, 95.5% (42/44), respectively. There was no significant difference between tumor size and clinical response. The CR rate to NPe6-PDT is higher than that of Photofrin-PDT in our previous studies. This early result suggests that PDT with NPe6 has a stronger antitumor effect than Photofrin therefore similar treatment outcome even for larger tumors >1.0 cm in diameter should be possible.

      Conclusion
      Objective evaluation by a comprehensive approach using AFB and EBUS enables to select the optimal therapeutic strategy for CELC. These results suggest that PDT with NPe6 may have a similar treatment outcome regardless of tumor size, as long sufficient laser illumination of the entire tumor is possible.

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