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      Bronchoscopically Delivered Thermal Vapor Ablation of Human Lung Lesions

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          Abstract

          Background:

          The discovery that early diagnosis can reduce the mortality of lung cancer provides firm evidence that early surgical intervention is effective. However, surgical resection is available only to those who are healthy enough to tolerate the procedure. Vapor ablation may provide an additional method of treating the lung cancer patient, and has been studied in humans for emphysema treatment. In swine, we previously demonstrated that bronchoscopically delivered thermal vapor ablation (BTVA) could be accurately applied, was uniform, anatomically confined, and was tolerated by the animal. To provide evidence that BTVA may be a feasible method of treatment in humans, and since human and swine lungs have differing airway and segmental anatomy, we extended our studies to deceased human lungs to determine if anatomically confined and uniform ablations could be obtained with levels of energy comparable with our swine and human emphysema studies.

          Methods:

          We obtained fresh, deceased human lungs and performed BTVA with increasing energy in subsegmental regions of lung containing tumors as well as non–tumor-containing areas in order to determine if uniform ablations with sharp boundaries could be obtained in human lung.

          Results:

          We found that all ablations were anatomically contained. The frequency of uniform ablation effect was dependent on the total energy delivered and was achieved at a greater frequency than those with sharp boundaries. If a lung tumor was contained within the anatomy of the subsegment, the ablation zone completely surrounded the tumor.

          Conclusion:

          We conclude that BTVA may have a future role in the treatment of lung cancer and should be investigated further in clinical trials.

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          Most cited references11

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          Anatomy and bronchoscopy of the porcine lung. A model for translational respiratory medicine.

          The porcine model has contributed significantly to biomedical research over many decades. The similar size and anatomy of pig and human organs make this model particularly beneficial for translational research in areas such as medical device development, therapeutics and xenotransplantation. In recent years, a major limitation with the porcine model was overcome with the successful generation of gene-targeted pigs and the publication of the pig genome. As a result, the role of this model is likely to become even more important. For the respiratory medicine field, the similarities between pig and human lungs give the porcine model particular potential for advancing translational medicine. An increasing number of lung conditions are being studied and modeled in the pig. Genetically modified porcine models of cystic fibrosis have been generated that, unlike mouse models, develop lung disease similar to human cystic fibrosis. However, the scientific literature relating specifically to porcine lung anatomy and airway histology is limited and is largely restricted to veterinary literature and textbooks. Furthermore, methods for in vivo lung procedures in the pig are rarely described. The aims of this review are to collate the disparate literature on porcine lung anatomy, histology, and microbiology; to provide a comparison with the human lung; and to describe appropriate bronchoscopy procedures for the pig lungs to aid clinical researchers working in the area of translational respiratory medicine using the porcine model.
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            Segmental volume reduction using thermal vapour ablation in patients with severe emphysema: 6-month results of the multicentre, parallel-group, open-label, randomised controlled STEP-UP trial.

            Lung volume reduction of emphysematous lobes results in clinical improvement for patients with severe emphysema. However, some segments within a lobe are often substantially more diseased than others, thereby warranting a more targeted approach of the emphysematous parts of a lobe. We therefore did a study to assess whether or not selective sequential treatment of the more diseased upper lobe segments with bronchoscopic vapour ablation led to clinical improvement.
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              Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance

              Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance.
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                Author and article information

                Journal
                J Bronchology Interv Pulmonol
                J Bronchology Interv Pulmonol
                LBR
                Journal of Bronchology & Interventional Pulmonology
                Wolters Kluwer Health/Lippincott Williams & Wilkins
                1944-6586
                1948-8270
                April 2019
                25 July 2018
                : 26
                : 2
                : 108-113
                Affiliations
                [* ]Department of Medicine, University of Wisconsin–Madison, Madison, WI
                []Uptake Medical Technology Inc., Seattle, WA
                Author notes
                Reprints: J. Scott Ferguson, MD, Department of Medicine, University of Wisconsin–Madison, 5233 UW Medical Foundation Building, 1685 Highland Avenue, Madison, WI 53705 (e-mail: jsferguson@ 123456medicine.wisc.edu ).
                Article
                00007
                10.1097/LBR.0000000000000535
                6467549
                30048418
                ffd1816e-9008-4483-9457-8cd4b05ccc1e
                Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/

                History
                : 8 March 2018
                : 20 June 2018
                Categories
                Original Investigations
                Custom metadata
                TRUE

                lung cancer,bronchoscopy,ablation
                lung cancer, bronchoscopy, ablation

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