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Wolfgang Hohenforst-Schmidt,1,9 Bernd Linsmeier,2 Paul Zarogoulidis,3 Lutz Freitag,4 Kaid Darwiche,4 Robert Browning,5 J Francis Turner,6 Haidong Huang,7 Qiang Li,7 Thomas Vogl,8 Konstantinos Zarogoulidis,3 Johannes Brachmann,9 Harald Rittger1 1Medical Clinic I, “Fuerth” Hospital, University of Erlangen, Fuerth, Germany; 2Department of Thoracic Surgery, Medinos Clinic Sonneberg, Sonnerberg, Germany; 3Pulmonary Department-Oncology Unit, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 4Department of Interventional Pneumology, Ruhrlandklinik, University Hospital Essen, University of Essen-Duisburg, Tueschener Weg, Essen, Germany; 5Pulmonary and Critical Care Medicine, Interventional Pulmonology, National Naval Medical Center, Walter Reed Army Medical Center, Bethesda, MD, USA; 6Division of Interventional Pulmonology and Medical Oncology, Cancer Treatment Centers of America, Western Regional Medical Center, Goodyear, AZ, USA; 7Department of Respiratory Diseases Shanghai Hospital, II Military University Hospital, Shanghai, People’s Republic of China; 8Department of Diagnostic and Interventional Radiology, Goethe University of Frankfurt, Frankfurt, Germany; 9II Medical Clinic, “Coburg” Hospital, University of Wuerzburg, Coburg, GermanyAbstract: Tracheomalacia or tracheobronchomalacia (TM or TBM) is a common problem especially for elderly patients often unfit for surgical techniques. Several surgical or minimally invasive techniques have already been described. Stenting is one option but in general long-time stenting is accompanied by a high complication rate. Stent removal is more difficult in case of self-expandable nitinol stents or metallic stents in general in comparison to silicone stents. The main disadvantage of silicone stents in comparison to uncovered metallic stents is migration and plugging. We compared the operation time and in particular the duration of a sufficient Dumon stent fixation with different techniques in a patient with severe posttracheotomy TM and strongly reduced mobility of the vocal cords due to Parkinson’s disease. The combined approach with simultaneous Dumon stenting and endoluminal transtracheal externalized suture under cone-beam computer tomography guidance with the Berci needle was by far the fastest approach compared to a (not performed) surgical intervention, or even purely endoluminal suturing through the rigid bronchoscope. The duration of the endoluminal transtracheal externalized suture was between 5 minutes and 9 minutes with the Berci needle; the pure endoluminal approach needed 51 minutes. The alternative of tracheobronchoplasty was refused by the patient. In general, 180 minutes for this surgical approach is calculated. The costs of the different approaches are supposed to vary widely due to the fact that in Germany 1 minute in an operation room costs on average approximately 50–60€ inclusive of taxes. In our own hospital (tertiary level), it is nearly 30€ per minute in an operation room for a surgical approach. Calculating an additional 15 minutes for patient preparation and transfer to wake-up room, therefore a total duration inside the investigation room of 30 minutes, the cost per flexible bronchoscopy is per minute on average less than 6€. Although the Dumon stenting requires a set-up with more expensive anesthesiology accompaniment, which takes longer than a flexible investigation estimated at 1 hour in an operation room, still without calculation of the costs of the materials and specialized staff that the surgical approach would consume at least 3,000€ more than a minimally invasive approach performed with the Berci needle. This difference is due to the longer time of the surgical intervention which is calculated at approximately 180 minutes in comparison to the achieved non-surgical approach of 60 minutes in the operation suite.Keywords: stent, airway, cone-beam computer tomography, Berci needle, Dumon stents, tracheobronchomalacia

Wolfgang Hohenforst-Schmidt,1 Paul Zarogoulidis,2 Filiz Oezkan,3 Christian Mahnkopf,4 Gerhard Grabenbauer,5 Alfons Kreczy,6 Rolf Bartunek,7 Kaid Darwiche,3 Lutz Freitag,3 Qiang Li,8 Haidong Huang,8 Thomas Vogl,9 Patrick LePilvert,10 Theodora Tsiouda,11 Kosmas Tsakiridis,12 Konstantinos Zarogoulidis,2 Johannes Brachmann11II Medical Clinic, Coburg Clinic, University of Würzburg, Coburg, Germany; 2Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University of Duisburg-Essen, Essen, Germany; 4II Medizinische Klinik, Klinik für Kardiologie, Angiologie, Pneumologie, Klinikum Coburg, 5Department of Radiotherapy, 6Department of Pathology, Cytology and Molecular Diagnostics, 7Institute of Diagnostic and Interventional Radiology, Coburg Clinic, University of Wüerzburg, Coburg, Germany; 8Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People’s Republic of China; 9Department of Diagnostic and Interventional Radiology, Goethe University of Frankfurt, Frankfurt, Germany; 10Interventional Drug Delivery Systems and Strategies (ID2S2), Medical Cryogenics, Lakeland Court Jupiter, FL, USA; 11Internal Medicine Unit, Theagenio Cancer Hospital, Thessaloniki, 12Cardiothoracic Surgery Department, Saint Luke Private Hospital, Thessaloniki, GreeceAbstract: Vasointestinal peptide metabolism plays a key physiological role in multimodular levels of vasodilatory, smooth muscle cell proliferative, parenchymal, and inflammatory lung reactions. In animal studies, vasointestinal peptide relaxes isolated pulmonary arterial segments from several mammalian species in vitro and neutralizes the pulmonary vasoconstrictor effect of endothelin. In some animal models, it reduces pulmonary vascular resistance in vivo and in monocrotaline-induced pulmonary hypertension. A 58-year-old woman presented with dyspnea and mild edema of the lower extremities. A bronchoscopy was performed without any suspicious findings suggesting a central tumor or other infiltrative disease. Endobronchial ultrasound revealed enlarged pulmonary arteries containing thrombi, a few enlarged lymph nodes, and enlarged mediastinal tissue anatomy with suspicion for mediastinal infiltration of a malignant process. We estimated that less than 10% of the peripheral vascular bed of the lung was involved in direct consolidated fibrosis as demonstrated in the left upper lobe apex. Further, direct involvement of fibrosis around the main stems of the pulmonary arteries was assumed to be low from positron emission tomography and magnetic resonance imaging scans. Assuming a positive influence of low-dose radiation, it was not expected that this could have reduced pulmonary vascular resistance by over two thirds of the initial result. However; it was noted that this patient had idiopathic pulmonary arterial hypertension mixed with “acute” (mediastinal) fibrosis which could have contributed to the unexpected success of reduction of pulmonary vascular resistance. To the best of our knowledge, this is the first report of successful treatment of idiopathic pulmonary arterial hypertension, probably as a result of low-dose radiation to the pulmonary arterial main stems. The patient continues to have no specific complaints concerning her idiopathic pulmonary arterial hypertension.Keywords: radiation, pulmonary hypertension, denervatio

Wolfgang Hohenforst-Schmidt,1 Paul Zarogoulidis,2,3 Kaid Darwiche,3 Thomas Vogl,4 Eugene P Goldberg,5 Haidong Huang,6 Michael Simoff,7 Qiang Li,6 Robert Browning,8 J Francis Turner,9 Patrick Le Pivert,10 Dionysios Spyratos,2 Konstantinos Zarogoulidis,2 Seyhan I Celikoglu,11 Firuz Celikoglu,11 Johannes Brachmann11II Medical Clinic, Coburg Hospital, University of Wuerzburg, Coburg, Germany; 2Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany; 4Department of Diagnostic and Interventional Radiology, Goethe University of Frankfurt, Frankfurt, Germany; 5Biomaterials Science and Engineering, Department of Materials Science and Engineering, University of Florida, FL, USA; 6Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People's Republic of China; 7Bronchoscopy and Interventional Pulmonology, Pulmonary and Critical Care Medicine, Henry Ford Hospital, Wayne State University, School of Medicine, MI, USA; 8Pulmonary and Critical Care Medicine, Interventional Pulmonology, National Naval Medical Center, Walter Reed Army Medical Center, Bethesda, USA; 9Pulmonary Medicine, University of Nevada School of Medicine, National Supercomputing Center for Energy and the Environment University of Nevada, Las Vegas, USA; 10Interventional Drug Delivery Systems and Strategies (ID2S2), Medical Cryogenics, Jupiter, FL, USA; 11Pulmonary Department, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, TurkeyAbstract: Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR) negative stage IIIa–IV International Union Against Cancer 7 (UICC-7), and with Eastern Cooperative Oncology Group (ECOG) 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%–1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin–based systemic chemotherapy in (higher) standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of life than a non-small cell lung cancer in ECOG 0 of the same tumor node metastasis [TNM]-stage without central obstruction) for a chemotherapy-only protocol that differs from conventional cisplatin-based doublet chemotherapy by the route, target site, and dose paves the way for broader applications of this technique. Finally, future perspectives of this treatment and pharmaceutical design for intratumoral administration are presented.Keywords: cisplatin, lymph nodes, chemotherapy, intratumoral, lung cancer