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Jarrod D. Predina, MD, MTR, Andrew D

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1 A Clinical Trial of TumorGlow to Identify Residual Disease During Pleurectomy and Decortication 
Jarrod D. Predina, MD, MTR, Andrew D. Newton, MD, Christopher Corbett, BA, Leilei Xia, MBBS, Michael Shin, BA, Lydia Frenzel Sulfyok, BA, Olugbenga T. Okusanya, MD, Keith A. Cengel, MD, PhD, Andrew Haas, MD, Leslie Litzky, MD, John C. Kucharczuk, MD, Sunil Singhal, MD  The Annals of Thoracic Surgery  Volume 107, Issue 1, Pages (January 2019) DOI: /j.athoracsur Copyright © 2019 The Society of Thoracic Surgeons Terms and Conditions

2 Fig 1 Fluorescence-guided surgery with indocyanine green–identified malignant pleural mesothelioma (MPM) during pleural biopsy: Subject 1: Representative example of subject in which high levels of fluorescence were observed during pleural biopsy. Subject 1, sample images of a cluster of 1-mm MPM lesions (yellow gate) are displayed in (A) a traditional white-light view, (B) a monochromatic near-infrared (NIR) view, and (C) a merged NIR view. In subject 5, there were no lesions identified during (D) white light thoracoscopy or during (E) NIR monochromatic and (F) merged NIR evaluation. (G) For each subject, the signal-to-background fluorescence ratio (SBR) of biopsied lesions was recorded and categorized on the basis of the final pathologic diagnosis. (H) The SBR of biopsy-proven MPM was significantly higher than that of benign lesions (p < ). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2019 The Society of Thoracic Surgeons Terms and Conditions

3 Fig 2 Indocyanine green accumulates in resected malignant pleural mesothelioma (MPM) and displays fluorescence during cytoreductive surgery. Subject 12 is a representative example of postresection macroscopic and microscopic semiquantitative fluorescence evaluation. Resected specimens were evaluated ex vivo using a combination of (A) white-light views and (B, C) near-infrared (NIR) views. By using NIR fluorescence patterns, fluorescent samples (yellow gate) and nonfluorescent samples (blue gate) were isolated and submitted individually by a pathologist. As can be seen, (D–F) fluorescent lesions were cleanly dissected from surrounding tissue, whereas (G–I) nonfluorescent areas were also obtained. (J) After obtaining a pathologic diagnosis for each submitted specimen (n = 107), we plotted the signal-to-background fluorescence ratio (SBR) for true positives, false positives, true negatives, and false negatives. We found that the SBR of fluorescent MPM lesions (true positives) was higher than in benign lesions that displayed fluorescence (false positives) (p = 0.03). Both true positives and false positives displayed significantly higher fluorescence patterns than nonfluorescent benign tissues (true negatives) (p < 0.001). Single asterisk = p < 0.05; triple asterisk = p < The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2019 The Society of Thoracic Surgeons Terms and Conditions

4 Fig 3 Near-infrared (NIR) imaging with indocyanine green accumulates preferentially in malignant pleural mesothelioma (MPM). Specimens resected by standard-of-care approaches underwent macroscopic fluorescent profiling using a combination of (A) standard white-light views, NIR views, and (B) NIR merged views. All resected specimens then underwent a series of (C) histopathologic and (D) microscopic fluorescent analyses to determine accuracy and patterns of dye accumulation. Yellow gate indicates tumor by histopathologic review; blue gate indicates benign tissue by histopathologic analysis. (AU = arbitrary units; H&E = hematoxylin and eosin.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2019 The Society of Thoracic Surgeons Terms and Conditions

5 Fig 4 Fluorescence-guided surgery with indocyanine green identifies occult macroscopic residual disease after complete resection. After macroscopic resection using white light only, the ipsilateral hemithorax was then evaluated in near-infrared (NIR) imaging to determine whether residual disease was present. Data from subject 10 are used to illustrate the workflow. (A) The surgeon first completed pleurectomy and decortication. (B) All resected specimens underwent ex vivo macroscopic fluorescence evaluation. Next, the chest was reevaluated with NIR imaging to assess for residual disease. Examples of (C) a diaphragmatic implant and (D) an intercostal lesion are provided. Both lesions were malignant pleural mesothelioma by histopathologic review. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2019 The Society of Thoracic Surgeons Terms and Conditions


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