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F.J. Herth

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    MS22 - The Mediastinum 2013 (ID 39)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 4
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      MS22.1 - The Anatomy of the Mediastinum / CT Imaging (ID 562)

      14:00 - 15:30  |  Author(s): N. Kurimoto

      • Abstract
      • Presentation
      • Slides

      Abstract
      Overview of ultrasound imaging of the right and left bronchi using the radial probe The positional relationship between the peribronchial organs in EBUS images taken from the trachea corresponds to those in a reversed CT image (CT scans are cross-sectional images looking from the caudal direction). EBUS images taken distal to the bifurcation of the left and right main bronchi, however, are cross-sectional images of planes perpendicular to the long axis of the bronchus, and therefore have different positional relationship between the peribronchial organs to the CT images. To fully understand EBUS, it is essential to understand the positional relationship between the peribronchial organs during visualisation while the probe is being pulled out. 1. Right bronchi 1) Right lower lobe bronchi When the balloon is inflated in the right basal bronchus, the inferior pulmonary vein (V6) passes on the dorsal side of the bronchus, whereas anterior to the bronchus the pulmonary artery divides into A8, A9 and A10 positioned between 9 o’clock and 2 o’clock. As the probe is pulled back, A8, A9 and A10 meet at the 12 o’clock direction and the direction of the pulmonary artery changes gradually to the 3 o’clock direction. When the probe is pulled further back, it approaches the bifurcation of B6. Pulling the probe back further, the opening of the middle lobe bronchus, indicated by reflection of the ultrasound pulse, appears at 12 o’clock. The pulmonary artery has gradually moved round to the 2 o’clock position. 2) From the right intermediate bronchus to the right main bronchus As the probe is pulled from the distal intermediate bronchus to a point immediately below the origin of the upper lobe bronchus, the pulmonary artery crosses the bronchus from the right to the left. In the central section of the intermediate bronchus, the superior pulmonary vein can sometimes be seen anterior to the pulmonary artery. When the probe is pulled further back, the origin of the upper lobe bronchus is indicated by reflection of the ultrasound pulse at 3 o’clock. Pulling the probe back further, A1+3, originating from the pulmonary trunk, can be seen crossing horizontally anterior to the right main bronchus. Retracting the probe further, the origin of the left main bronchus at the carina is indicated by reflection of the ultrasound pulse at 9 o’clock. 2. Left bronchi 1) Left lower lobe bronchi When the balloon is inflated in the left basal bronchus, the inferior pulmonary vein (V6) passes on the dorsal side of the bronchus, whereas the A8, A9 and A10 branches of the pulmonary artery meet at 9 o’clock. As the probe is pulled back, it approaches the bifurcation of B6. Pulling the probe back further, the opening of the upper lobe bronchus, indicated by reflection of the ultrasound pulse, appears at 11 o’clock. The pulmonary artery is located below the origin of the upper lobe bronchus. 2) Left main bronchus The distal section of the left main bronchus is characterised by the left pulmonary artery at 10 o’clock, the descending aorta at 7 o’clock, and the left atrium from 1 o’clock to 3 o’clock. As we enter the central section of the left main bronchus, the left atrium disappears, and the oesophagus appears at 6 o’clock. The subcarinal (#7) lymph node is often visible medial to the oesophagus. Ultrasound imaging of mediastinal and hilar lymph nodes for EBUS-TBNA by the Convex Bronchoscope #7 LN: Subcarinal lymph node For approaching #7 LN, the convex bronchoscope is inserted into right main bronchus. While scanning at 9 o’clock direction, we can confirm the largest area of the #7 LN. While rotating right handed and scanning at 11 o’clock direction, we can watch the right main pulmonary artery. 11R LN: right intralobar lymph node (between right lower lobe bronchus and right middle lobe bronchus) For approaching #11R LN, the convex bronchoscope is inserted into right basal bronchus. While scanning at 12 o’clock direction, we can confirm the largest area of the #11R LN. While rotating right handed and scanning at 3 o’clock direction, we can watch the right pulmonary artery. 11R LN: right intralobar lymph node (between right intermediate trunk and right upper lobe bronchus) For approaching #11R LN, the convex bronchoscope is inserted into right intermediate trunk. On the bronchoscopic findings, right upper bronchus is locates at 12 o’clock direction from the intermediate trunk. While scanning at 12 o’clock direction, we can confirm the largest area of the #11R LN. While rotating left handed and scanning at 9 o’clock direction, we can watch the right main pulmonary artery. 11L LN: left intralobar lymph node For approaching #11R LN, the convex bronchoscope is inserted into left basal bronchus. On the bronchoscopic findings, left upper lobe bronchus is locates at 12 o’clock direction from left lower lobe bronchus. While scanning at 12 o’clock direction, we can confirm the largest area of the #11L LN. While rotating left handed and scanning at 10 o’clock direction, we can watch the right pulmonary artery. 4L LN For approaching #4L LN, the convex bronchoscope is inserted to the distal site of the trachea. On the bronchoscopic findings, the left side of the trachea is locates at 12 o’clock direction. While scanning at 12 o’clock direction, we can confirm the largest area of the #4L LN. While pushing the scope to distal site about 1-2cm, we can watch the left main pulmonary artery. While pushing the scope to proximal site about 1-2cm, we can watch aortic arch. 4R LN For approaching #4R LN, the convex bronchoscope is inserted to the distal site of the trachea. On the bronchoscopic findings, the membranous portion of the trachea is locates at 6 o’clock direction. While scanning at 2 o’clock direction, we can confirm the largest area of the #4R LN. While scanning 4R LN, we can watch superior vena cava (SVC) just below. While pushing the scope to proximal site about 1-2cm, we can watch aortic arch #4R LN.

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      MS22.2 - Further Staging Using Imaging - PET, MRI and PET/CT (ID 563)

      14:00 - 15:30  |  Author(s): E. Hsiao

      • Abstract
      • Presentation
      • Slides

      Abstract
      PET and PET/CT FDG PET scans have shown high sensitivity and specificity in detecting mediastinal nodal involvement. It works by detecting increased accumulation of F-18 fluorodeoxyglucose (FDG) in the neoplastic cells which have a deranged glucose metabolism. FDG undergoes similar uptake and metabolic pathway glucose molecules. The accumulation of positron emitting F-18 isotope can then be used to localise these hypermetabolic neoplastic tissue. Both 2003 and 2007 guidelines of the American College of Chest Physicians (ACCP) endorsed the use of PET imaging as a non-invasive staging tool for non-small cell lung cancer[1, 2]. FDG PET scan has become the standard of care in staging primary lung cancer. It is recognised as the most accurate non-invasive tool in the staging of lung cancer. It is also widely accepted that PET scanning improves detection of distant metastatic disease as well as unsuspected N2 or N3 disease particularly in the high-risk patients. Therefore, several series have shown that the use of PET imaging reduces unnecessary or futile surgical resection. Traditionally, a standard uptake value (SUVmax) of 2.5 or above is used as a threshold for malignancy, but this was initially based on the uptake of peripheral lung masses with diameter >2cm. Whether this can be applied to mediastinal nodes is questionable. The special resolution of a current generation PET scanner is approximately 7mm. Nonetheless, small or non-enlarged lymph nodes with highly aggressive tumour metastasis may be detected based on the higher intensity of uptake compared to the background. While FDG PET is clinically useful, it is an imperfect technique. The meta-analysis carried out by Silvestri et al [3]in the third edition of ACCP guideline demonstrated that the median sensitivity and specificity for detecting mediastinal metastases were 80% and 88% respectively. The findings demonstrate that PET is more accurate than CT scanning (median sensitivity 55% and median specificity 81%) [3]. However, it is important to know that neither technique is perfect. Interestingly, an increasing number of recent studies were performed using integrated PET/CT scanner. The meta-analysis by the ACCP showed a median sensitivity of 62% and median specificity of 90%[3]. The specificity is slightly higher although the sensitivity is lower. The reason for this observation remains unclear. Nonetheless, PET/CT hybrid cameras have superseded the role of stand alone PET scanners in nowadays. False negative results are more often seen with adenocarcinoma in situ, well-differentiated invasive adenocarcinoma, and typical carcinoid tumours. Small volume or micrometastasis can also be missed due to the finite spatial resolution of PET and perhaps by all imaging techniques. Studies have demonstrated that PET scanning is less sensitive for lymph nodes measuring <7-10mm diameter, and micrometastases have been detected in non enlarged lymph nodes without abnormal FDG uptake by invasive sampling[4]. Furthermore, in the presence of a central FDG avid lung cancer, N1 disease can be missed by FDG PET imaging in up to 25% of cases[5]. In the evolution of a peripheral T1A lesion particularly if the density of the nodule is ground glass or sub-solid. It is well known that these types of neoplasms have low incidence of mediastinal metastasis though the risk is not nil. It is important that the interpretation of a negative PET scan to be combined with clinical judgement as well as the pre-test likelihood of mediastinal metastasis. Furthermore the local availability and expertise in invasive biopsy procedures are also important factors. False positive findings are often due to infection or inflammation. Common causes include sarcoidosis, silicosis, reactive changes, fungal or mycobacterial infections. In summary, it is important to confirm N2 and N3 disease with tissue sampling to avoid delay or missing potentially curative surgery. In the presence of negative of PET and CT findings in the mediastinum, that the decision to operate or to have invasive tissue sampling requires careful consideration and clinical judgement. Combined with invasive mediastinal staging techniques Transbronchial biopsy has shown a median sensitivity of 78% and specificity of 100% in a systemic review. The sensitivity has been reported to be high in patients with positive CT or PET/CT findings. Occasional false positive results have been reported to be approximately 7%. The median negative predictive value in this systemic review is 77%. Endobronchial ultrasound with needle aspiration can achieve a median negative predicted value of 91%. This is further improved with combined EBUS and EUS which have a median negative predictive value is 96%[3]. For most patients undergoing PET/CT staging, the need of invasive mediastinal staging is not eliminated. It is important to confirm the presence of N2 or N3 disease in patients without evidence of metastatic disease to avoid withholding potentially curative surgery. FDG PET/CT can guide needle biopsy as to which nodal stations are considered high risk. Targeting lymph nodes with a higher pretest probability further decreases the inherent false negative rate of needle biopsy. The location of FDG avid nodal stations is important as to which technique will be most appropriate. For example, the identification of an FDG supraclavicular node (N3) can lead to ultrasound guided percutaneous biopsy. An FDG avid aortopulmonary lymph node may be sampled by using Chamberlain procedure, CT guided fine needle aspiration, or extended cervical mediastinoscopy. In cases with enlarged mediastinal lymph node with negative PET, confirmation by invasive techniques is also advised, as up to 21% of these can still have nodal involvement[4, 6]. There are two exceptions to the rule. First, it is known that in a patient with a peripheral T1 tumour (<3 cm), negative FDG uptake and no enlarged lymph node in the mediastinum carries a high negative predicted value with false negative rate being only 4%[3]. Therefore invasive staging is not recommended in these patients given the similar negative predicted value in a combined EBUS and EUS needle biopsy. Secondly, in lung cancer patients with infiltrative mediastinal mass on CT or PET/CT either from overt T4 disease or bulky nodal disease would not require invasive mediastinal staging. MRI and emerging Techniques MR imaging has mainly been used to evaluate non-small cell lung carcinoma when there is possible involvement of superior sulcus or brachial plexus. It is currently not a routine clinical tool in mediastinal nodal staging. New studies albeit with relatively smaller patient sample size have shown that MRI can detect nodal metastasis particularly using STIR and diffusion weighted imaging (DWI) [7, 8]. Several studies have shown comparable efficacy in relation to the PET/CT staging techniques[9]. Diffusion weighted imaging detect random thermal motion of water molecules, known as Brownian motion. Tissues with restricted diffusion will have a lower apparent diffusion coefficient (ADC) values. Hypercellular density, larger cellular nuclei and dense tumour cell membranes are known to cause restricted diffusion in malignant tissue. A study has confirmed the negative relationship between the SUV on FDG PET/CT scans and the lower ADC values on MRI[10]. Furthermore, MRI has the ability to differentiate tumour tissue from vasculature and mediastinal fat. It is therefore potentially useful to delineate direct tumour invasion of the mediastinum, chest wall, diaphragm or spinal column. More research is required in this field of MR mediastinal staging. The latest development in PET/MR imaging technique [11]using hybrid scanner will provide a fertile ground for future research in the use of non-invasive mediastinal staging. References 1. Silvestri, G.A., M.K. Gould, M.L. Margolis, et al., Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest, 2007. 132(3 Suppl): p. 178S-201S. 2. Physicians, A.C.o.C. and H.a.S.P. Committee, Diagnosis and management of lung cancer: ACCP evidence-based guidelines. American College of Chest Physicians. Chest, 2003. 123(1 Suppl): p. D-G, 1S-337S. 3. Silvestri, G.A., A.V. Gonzalez, M.A. Jantz, et al., Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 2013. 143(5 Suppl): p. e211S-250S. 4. de Langen, A.J., P. Raijmakers, I. Riphagen, et al., The size of mediastinal lymph nodes and its relation with metastatic involvement: a meta-analysis. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 2006. 29(1): p. 26-29. 5. Pozo-Rodríguez, F., J.L. Martín de Nicolás, M.A. Sánchez-Nistal, et al., Accuracy of helical computed tomography and [18F] fluorodeoxyglucose positron emission tomography for identifying lymph node mediastinal metastases in potentially resectable non-small-cell lung cancer. J Clin Oncol, 2005. 23(33): p. 8348-8356. 6. De Leyn, P., D. Lardinois, P.E. Van Schil, et al., ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 2007. 32(1): p. 1-8. 7. Usuda, K., X.-T. Zhao, M. Sagawa, et al., Diffusion-weighted imaging is superior to positron emission tomography in the detection and nodal assessment of lung cancers. Ann Thorac Surg, 2011. 91(6): p. 1689-1695. 8. Ohno, Y., H. Koyama, M. Nogami, et al., STIR turbo SE MR imaging vs. coregistered FDG-PET/CT: quantitative and qualitative assessment of N-stage in non-small-cell lung cancer patients. J Magn Reson Imaging, 2007. 26(4): p. 1071-1080. 9. Pauls, S., S.A. Schmidt, M.S. Juchems, et al., Diffusion-weighted MR imaging in comparison to integrated [¹⁸F]-FDG PET/CT for N-staging in patients with lung cancer. European Journal of Radiology, 2012. 81(1): p. 178-182. 10. Heusch, P., C. Buchbender, J. Köhler, et al., Correlation of the Apparent Diffusion Coefficient (ADC) with the Standardized Uptake Value (SUV) in Hybrid 18F-FDG PET/MRI in Non-Small Cell Lung Cancer (NSCLC) Lesions: Initial Results. Rofo, 2013. 11. Kohan, A.A., J.A. Kolthammer, J.L. Vercher-Conejero, et al., N staging of lung cancer patients with PET/MRI using a three-segment model attenuation correction algorithm: Initial experience. Eur Radiol, 2013.

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      MS22.3 - Minimally Invasive and Endoscopic Options (ID 564)

      14:00 - 15:30  |  Author(s): D. Gompelmann

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MS22.4 - Surgical Techniques for Definitive Staging (ID 565)

      14:00 - 15:30  |  Author(s): U. Pastorino

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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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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    E07 - Staging in the Molecular Era (ID 7)

    • Event: WCLC 2013
    • Type: Educational Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      E07.1 - TNM Classification with Image Guided Interventions Such as EBUS / EUS (ID 403)

      14:00 - 15:30  |  Author(s): F.J. Herth

      • Abstract
      • Slides

      Abstract
      ENDOBRONCHIAL ULTRASOUND The integration of ultrasound technology and flexible fiberbronchoscopy enables imaging of lymph nodes, lesions and vessels located beyond the tracheobronchial mucosa. Developed in 2002, the EBUS-bronchoscope looks similar to a normal bronchovideoscope, but is 6.9mm wide and has a 2mm instrument channel and a 30 degree side viewing optic. Furthermore, a curved linear array ultrasonic transducer sits on the distal end and can be used either with direct contact to the mucosal surface or via an inflatable balloon which can be attached at the tip. This allows a conventional endoscopic picture side-by-side with the ultrasonic view. US scanning is performed at a frequency of 7.5-12 MHz with tissue penetration of 20 – 50mm. An ultrasound processor processes the US image. Procedure: The actual TBNA is performed by direct transducer contact with the wall of the trachea or bronchus. When a lesion is outlined, a needle of 21 gauge (NA-201SX-4022; Olympus Corporation, Tokyo, Japan) can be advanced through the working channel and lymph nodes can be punctured under real-time ultrasound visualisation. At the same time colour Doppler can be used to identify surrounding vascular structures. Once the target lymph node or mass has been clearly identified with EBUS, the needle is inserted under real-time US guidance. Suction is applied with a syringe, and the needle is moved back and forth inside the lesion. Lymph node stations that can be reached via EBUS are the highest mediastinal (station 1), the upper paratracheal (2L and 2R), lower paratracheal (4R and 4L), the subcarinal (station 7), the hilar (station 10) as well as the interlobar (station 11) and the lobar nodes (station 12). The highest staging N should be biopsied first otherwise the needle needs to be changed each time. Results: In recently published meta-analysis EBUS-TBNA has been shown to have a high-pooled sensitivity of 93% and specificity of 100% . Multiple publications have shown that even in patients with lymph nodes under 1cm (which had been termed N0 by CT criteria), with the use of EBUS-TBNA a large percentage could still be shown to have N2/N3 disease (some despite also being negative on PET-CT). Complications such as bleeding or infection are very rare and have only been reported as case reports. Endoesophageal ultrasound Gastroenterologists have been using this technique for many years in the investigation of oesophageal and pancreatic malignancies. Mediastinal EUS-FNAs were first used in the early 1990s and have subsequently become a popular method to diagnose a variety of intra-abdominal and intrathoracic masses, including mediastinal lesion. Procedure The linear EUS-Scope (has the same basic architecture as the EBUS and uses a scanner of between 5 and 10 MHz. The penetrating ultrasound depth can be up to 8cm. Needles used for biopsy are 19 or 21gauge, again equipped with a stylet. The procedure is usually performed on an outpatient basis and takes approx 30min. However, EUS-FNA has limited access as only lymph node stations 2L, 4L, 7, 8 and 9 are accessible through a transesophageal approach. Lymph node station 5 is not routinely accessible via EUS, and may require transvascular FNA.. Results. EUS is especially useful in staging of the posterior mediastinum. Multiple publications and a meta-analysis on EUS-FNA have shown a high sensitivity and specificity. Even in patients without mediastinal lymph node enlargement on CT, EUS-FNA has been able to demonstrate metastases in 25% of lung cancer patients. Also, the left adrenal can be reached and identified in 97% of cases. It has a so-called ‘seagull’ shape on ultrasound and is particularly well visualised in cases of metastatic enlargement. Furthermore, the left lobe of liver can also be reached. The hilar and pre-carinal lymph nodes cannot be reached. EUS is also more accurate and has a higher predictive value than either PET scan or CT for posterior mediastinal lymph nodes. The procedure carries only a very small risk of mediastinitis or bleeding. . For both techniques it´s important to remember, however, that with EBUS and EUS the negative predictive value is limited and therefore samples which do not contain tumour cells require follow up with a more definitive procedure such as mediastinoscopy or VATS. Combining EBUS and EUS For tissue sampling of mediastinal lymph nodes after conventional TBNA, the present authors prefer minimally invasive methods such as EBUS-TBNA and EUS-FNA to more invasive procedures such as mediastinoscopy and VATS. EUS-FNA and EBUS-TBNA have been shown to prevent mediastinoscopies to a large extent. EBUS-TBNA and EUS-FNA have a complementary reach in analysing mediastinal nodes whereby EBUS has access to the paratracheal, subcarinal and hilar regions and EUS to the lower mediastinum and aortopulmonary window. As shown above, EUS and EBUS provide access to different areas of the mediastinum. In combining techniques, most lymph node stations as well as the left adrenal gland can be reached (apart from stations 5 and 6). In six recent series the accuracy of EUS-FNA and EBUS-TBNA used in combination for the diagnosis of mediastinal cancer was 95% . Using the EBUS-Scope for both endobronchial as well as endoesophagel sampling, the sensitivity for cancer detection could be shown to be as high as 96% (EUS 89%, EBUS 91%), specificity 100% and negative predictive value of 96% (EUS 82%, EBUS 92%). CONCLUSION Overall, EBUS and EUS are safe and effective techniques for the staging of the mediastinum. They are minimally invasive and reduce the number of invasive staging procedures. Currently, the main limitation for EBUS and EUS are that they are predominantly performed at centres of excellence and hence only on selected patients. Training of physicians and surgeons remains the issue and performance of an adequate amount of procedures per year is required in order to maintain competency. Reimbursement remains an issue in some countries as well as the actual implementation into cancer guidelines within the hospitals. Increasingly both techniques are being used in hospitals across the world improving the diagnostic yield. Combined EBUS and EUS ought to be regarded as the “first techniques into the mediastinum”, called “complete endo-echo staging”.

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