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Antoni Rosell



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    MA 20 - Recent Advances in Pulmonology/Endoscopy (ID 685)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Pulmonology/Endoscopy
    • Presentations: 2
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      MA 20.06 - Discerning Lung Cancer Cell Patterns with Confocal Endomicroscopy (ID 8640)

      15:05 - 15:10  |  Presenting Author(s): Antoni Rosell

      • Abstract
      • Presentation
      • Slides

      Background:
      Probe-based confocal endomicroscopy (pCLE) allows confocal microscopy of lung tissue in vivo but limited evidence is available. The objective was to discriminate pCLE patterns of lung cancer in vivo.

      Method:
      Fluorescence properties of methylene blue (MB) were examined ex vivo in confocal microscope. Next, 15 regions of the central airways were studied in vivo with pCLE and a representative image chosen for analysis with ImageJ software. Biopsy was performed for final diagnosis.

      Result:
      Ex vivo study showed no differences between 1% and 2% MB concentrations and rapid extinction of fluorescence after 10 minutes of MB application (figure). In vivo study included samples of bronchial mucosa (n = 6), inflammation (n = 3) and tumor (n = 6). pCLE image evaluation (table) showed inflammation and tumor nuclei were bigger (except SCLC) and occupied a greater area. Fluorescence of tumor nuclei was more intense. Non fluorescent area was inferior for both inflammation and tumor samples. Number of nuclei could not discriminate between normal and tumor.Figure 1 Table. Imaging features evaluated in pCLE frames

      Area occupied by nuclei (µm[2]) Intensity of nuclei (UA) Mean size of nuclei (µm[2]) Non-fluorescent area (µm[2]) Number of nuclei (µm[2])
      Bronchial epithelium (mean(SD)) 97,769(9,451) 126(9) 107(10) 67,100(12,567) 937(84)
      Inflammation (mean(SD)) 117,381(22,166) 122(27) 127(15) 35,124(32,630) 933(225)
      B cell lymphoma 138,354 145 185 49,269 746
      Adenocarcinoma 155,033 198 177 5,225 875
      Squamous cell carcinoma 102,805 145 155 54,301 663
      Small cell lung cancer 107,201 157 63 11,257 1,687
      Non-small cell lung cancer 113,173 187 122 32,359 926
      Hamartoma 120,188 145 114 25,438 1,058




      Conclusion:
      1. MB fluorescence is unaffected by stain concentration 2. There is exponential extinction of MB over time 3. Lung cancer cell pattern distinction in vivo is feasible Funded by Fundació MaratóTV3, SEPAR and FUCAP

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      MA 20.08 - Classification of Confocal Endomicroscopy Patterns for Diagnosis of Lung Cancer (ID 9874)

      15:15 - 15:20  |  Presenting Author(s): Antoni Rosell

      • Abstract
      • Presentation
      • Slides

      Background:
      Solitary pulmonary nodules diagnosis and management is so challenging that nNew endoscopic techniques are being introduced to reduce uncertainty in peripheral pulmonary lesions (PPL) diagnosis and management. increase its diagnostic yield. Probe-based confocal laser endomicroscopy (pCLE) is a technique that can microscopically image the lung tissue in vivo during flexible bronchoscopy, though it can be difficult for pulmonologists to distinguish cellular patterns in a monochrome vision under respiratory and cardiac movements. . The goal of this work is to explore explore if Computed-Aided Diagnoses (CAD) tools can obtain a reliable diagnoses with pCLE in lung cancer.

      Method:
      A pilot study using 2 different methods for pCLE pattern analysis was performed:, one based on visual analysis by 3 experts and the other one based on computeron computerized analysis of visual patterns called Graphcom. Twelve 12 pCLE videos ( obtainedobtained using mMethylene blue dye (1%) and Alveloflex-Cellvizio 660nm miniprobe) were selected from patients with endobronchial lesionsperipheral SPNs (6 with lung adenocarcinoma cancer and 6 with inflammatory disease) during rigid bronchoscopy under general anesthesia. Afterwards, Vvideo sequences from pCLE were visually explored by one of the authors to select between 10 and 15 framesimages that presented a clear cellular pattern, without artifacts. . These images were shown to 3 observers who were familiar with confocal images but ignored the final histopathological diagnosis for a blind visual labellinglabeling. Images were also computationally analyzed using methods from social networks community analysis in a graph representation of pCLE images based on visual features to potentially overlapping groups of images that share common visual properties.

      Result:
      Our preliminary results indicate that on average visual analysis with 3 independent experts can only achieve a 60.2% of accuracy and has large variability amongst observers, while the accuracy of the proposed unsupervised image pattern classification rai(GraphCom) sesrises to 83,4.4%.

      Conclusion:
      Visual inspection of CLE images from lung tissue fails to provide accurate diagnosis. CLE images contain enough visual information for in vivo detection of neoplastic cell patterns that could be discriminated using cComputation methods and graph structural analysis applied to deep-learning feature spaces can increase diagnostic accuracy of pCLE images against visual analysis (83.4% vs 60.2%). Future studies are needed to apply this method in a real time scenario during bronchoscopy for PPL diagnoses.

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    MTE 19 - Laser Therapy for Early Stage and Airway Obstruction (Sign Up Required) (ID 568)

    • Event: WCLC 2017
    • Type: Meet the Expert
    • Track: Pulmonology/Endoscopy
    • Presentations: 1
    • Moderators:
    • Coordinates: 10/17/2017, 07:00 - 08:00, Room 317
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      MTE 19.02 - Ablative Therapy for Early Stage Lung Cancer (ID 7802)

      07:30 - 08:00  |  Presenting Author(s): Antoni Rosell

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The fact that an early cancer is early in its nature implies that a curative therapy should be offered. However, radical treatments such as surgery and radiotherapy might not be the best options for various reasons. Firstly, the amount of normal tissue that has to be removed or denaturalized can contraindicate the treatment, secondly the unresectabilitiy for some central tumors, and finally the concern that metachronous lesions can occur and might need further intervention. Thus, the use of bronchoscopic therapies in the management of lung cancer limited to the airways has brought light to the management of early lung cancer. Several techniques are available to treat endoluminal superficial lesions, including laser, electrocautery, argon-plasma coagulation, photodynamic therapy, cryotherapy and brachytherapy. The curative potential of all these therapies has been demonstrated, as all of them are able to effectively destroy the depth of an early lung central cancer, which counts no more than 5 mm of malignant tissue. The definition of early lung cancer used in the studies of bronchoscopic therapies does not exactly correspond with the actual definitions of the TNM classification and differs among authors. Nagamoto et al. observed that squamous cell carcinoma (SCC) ≤ 3 mm thick and with longitudinal extension ˂ 20 mm was associated with no nodal involvement (1). Konaka et al. suggested that hypertrophic lesions of ˂ 1 cm are either carcinoma in-situ (CIS) or micro-invasive tumor within the muscle layer, while nodular and polypoid lesions ≥ 1 cm are more likely invasive beyond the cartilaginous layer (2). According to these, Mathur et al. defined early stage cancer as radiographically occult SCC that is endoscopically superficial, ˂ 2 cm in surface area with clearly visible margins and not invading beyond the bronchial cartilage (3). Later, the Japan Lung Cancer Society defined the bronchoscopic criteria of central type early stage lung cancer as that located subsegmental or more proximal, ˂ 2 cm with bronchoscopically recognizable margin and proven SCC (4). The new 8th edition of the TNM classification incorporates new definitions in the early stages including some special situations. Superficial spreading tumors in the central airways are those confined to the tracheal or bronchial wall regardless of size and location, and are labeled T1a ss. Carcinoma in situ (classified as Tis) now includes both squamous cell carcinoma in situ (SCIS, or squamous dysplasia) and adenocarcinoma in situ (AIS, which is localized, ≤ 3 cm and shows pure lepidic growth, lacking stromal, vascular, alveolar space or pleural invasion). Minimally invasive adenocarcinoma is classified as T1a(mi) and corresponds to solitary adenocarcinoma ≤ 3 cm with a predominantly lepidic pattern and ≤ 0.5 cm invasion. The invasive component is defined as histologic type other than lepidic or tumor cells infiltrating myofibroblastic stroma. In our setting, it is important to remark that examination of small biopsy specimens cannot exclude or quantify invasive components for AIS and T1a(mi) respectively. Although AIS can be highly suspected from biopsies with pure lepidic pattern together with a CT correlation of the ground glass component, AIS and T1a(mi) require examination of the entire resection specimen. The accuracy of the diagnostic techniques for early lung cancer represents the first step for defining the lesions suitable for endobronchial therapy. High definition bronchoscopy, autofluorescence bronchoscopy (AFB) and narrow band imaging (NBI) have been used for defining the margins of the lesion, the latter having a higher specificity. To evaluate the shallowness of the tumor, radial endobronchial ultrasound (rEBUS) and optical coherence tomography (OCT) have been used (6). Also, the combination of AFB and OCT have shown good results for both detection and characterization of premalignant lesions of the centrals airways (7). Thin-section CT (≤ 1 mm) and PET-CT might also be useful in the evaluation of premalignant lesions (8,9). Treatment success is directly dependent on lesion accessibility and the capability to correctly delineate the margins and shallowness of the lesions (10). Once the boundaries of the lesion are defined, choosing a technique over another depends mainly on the expertise of the bronchoscopist and availability of the therapy. Bibliography: 1. Nagamoto N, Saito Y, Ohta S, et al. Relationship of lymph node metastasis to primary tumor size and microscopic appearance of roentgenographically occult lung cancer. Am J Surg Pathol. 1989;13(12):1009-13. 2. Konaka C, Hirano T, Kato H, et al. Comparison of endoscopic features of early-stage squamous cell lung cancer and histological findings. Br J Cancer. 1999;80(9):1435-9. 3. Mathur PN, Edell E, Sutedja T, et al. Treatment of early stage non-small cell lung cancer. Chest. 2003;123(1 Suppl):176S-80S. 4. The Japan Lung Cancer Society Classification of Lung Cancer Kanehara. Tokyo. 2010. 5. Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization Classification of Lung Tumors. J Thorac Oncol. 2015;10:1243-60. 6. Kurimoto N, Murayama M, Yoshioka S, et al. Assessment of usefulness of endobronchial ultrasonography in determination of depth of tracheobronchial tumor invasion. Chest. 1999;115:1500-6. 7. Lam S, Standish B, Baldwin C, et al. In vivo optical coherence tomography imaging of preinvasive bronchial lesions. Clin Cancer Res. 2008;14:2006-11. 8. Sutedja TG, Codrington H, Risse EK, et al. Autofluorescence Bronchoscopy Improves Staging of Radiographically Occult Lung Cancer and Has an Impact on Therapeutic Strategy. Chest. 2001;120:1327-32. 9. Pasic A, Brokx HA, Comans EF, et al. Detection and staging of preinvasive lesions and occult lung cancer in the central airways with 18F-fluorodeoxyglucose positron emission tomography: a pilot study. Clin Cancer Res. 2005;11(17):6186-9. 10. Sutedja TG, van Boxem AJ, Postmus PE. The curative potential of intraluminal bronchoscopic treatment for early-stage non-small-cell lung cancer. Clin Lung Cancer. 2001;2:264-70; discussion 71-2 Figure 1 Figure 2 Endobronchial therapies for early lung cancer

      Therapy Principle Depth Main Risks Considerations
      LASER Thermal ablation with laser light +++ (but variable) Airway perforation, hemorrhage, airway fire, respiratory failure. Those of thermal therapies*
      Electrocautery Thermal ablation through electric flow current +++ (but variable) Airway perforation, hemorrhage, airway fire, respiratory failure. Those of thermal therapies*. Caution with pacemakers. Cheaper than laser.
      Argon Plasma Coagulation (APC) Thermal ablation with electric current through argon gas 2-3 mm Airway fire, respiratory failure. Those of thermal therapies*. Caution with pacemakers.
      PDT Non-thermal ablation with light in previously photosensitized tissues 3 mm Respiratory failure. Skin sun burn. Produces intense photosensitivity. Delayed results and need for repeat bronchoscopy.
      Cryotherapy Thermal cellular damage though freezing and tawing 3 mm Respiratory failure. Superficial bleeding Delayed results.
      Brachytherapy Radiation therapy applied directly to tumor through endobronchial catheter Variable Ulcera, fibrosis, stenosis, haemoptysis Accumulative radiation dose. High-complexity and need for multidisciplinary team.






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    P1.12 - Pulmonology/Endoscopy (ID 698)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Pulmonology/Endoscopy
    • Presentations: 1
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      P1.12-009 - Experience with Fully Covered Metallic Stents in Patients with Malignant Airway Obstruction (ID 10273)

      09:30 - 09:30  |  Presenting Author(s): Antoni Rosell

      • Abstract
      • Slides

      Background:
      Airway stenting provides a solution to restore patency of the airways in 
patients with malignant conditions that are 
unsuitable for surgical procedures. Their use has been associated with significant improvement in 
symptoms and quality of life. There is little experience with recent commercially available fully covered metallic stents.

      Method:
      All patients who underwent fully silicon covered nitinol mono-filament Aerstent® (Leufen, Bess, Germany) placement at the Hospital Universitari de Bellvitge from September 2013 and February 2017 were retrospectively reviewed for medical records, bronchoscopy and microbiological results, as well as stent related complications and patient survival.

      Result:
      66 stents were implanted in 54 patients during this 36 months period, with mean age of 59 years (43-81 years). The main indication of stent placement was lung cancer in 41 (76%) patients (22 squamous, 9 adenocarcinoma, 5 undetermined NSCLC, 4 small-cell lung cancer and 1 atypical carcinoid). Stents were deployed with rigid bronchoscopy under fluoroscopic control in main bronchus (n=42), trachea (n=7), and main carina (Y shape n=17). Photocoagulation with YAP laser and/or mechanical debulking was necessary in 44 (66.6%) procedures prior to stenting. Seven stents (10.6%) required repositioning after deployment using rigid grasping forceps. Major bleeding occurred in 12 procedures (18.1%) and was successfully managed with endoscopic methods. No immediate complications occurred after the procedures. In 52 cases (96.3%) immediate and significative clinical improvement in dyspnoea was registered. Median survival after first stent deployment was 144 days (6-484). 7 patients died within 30 days after the procedure. 50 patients (92%) had stent related complications during follow up (table 1).

      Table 1. Rate and time to complications
      Patients (n= 54) Time (mean) in days to detection
      Mucostasis 42 (77%) 28.2
      Colonization 22 (40.1%) 47.1
      Granulation tissue 20 (27%) 48.8
      Migration 7 (13%) 18.7
      Silicon detachment 12 (22.2%) 84.5


      Conclusion:
      In our case series, Aerstent (Leufen, Bess) has provided immediate dyspnoea relief in 96.3% of patients, without significative complications during deployment or within the first 24 hours. Mucostasis is the most common complication (77%) and is detected during the first month (mean 28.2 days).

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