Catheter Injectable Hydrogel-Based Scaffolds for Tissue Engineering Applications in lung disease.

BACKGROUND: Chronic lung diseases, especially emphysema and pulmonary fibrosis, are the third leading cause of mortality worldwide. Their treatment includes symptom alleviation, slowing of the disease progression, and ultimately organ transplant. Regenerative medicine represents an attractive alternative. OBJECTIVES: To develop a dual approach to lung therapy by engineering a platform dedicated to both remodeling pulmonary architecture (bronchoscopic lung volume reduction) and regeneration of lost respiratory tissue (scaffold). METHODS: The authors developed a hydrogel scaffold based on the natural polymers gelatin and alginate. The unique physical properties allow its injection through long catheters that pass through the working channel of a bronchoscope. The scaffold might reach the diseased area; thus, serving a dual purpose: remodeling the lung architecture as a lung volume reduction material and developing a platform for tissue regeneration to allow for cell or organoid implant. RESULTS: The authors' novel hydrogel scaffold can be injected through long catheters, exhibiting the physical and mechanical properties necessary for the dual treatment objectives. Its biocompatibility was analyzed on human fibroblasts and mouse mesenchymal cells. Cells injected with the scaffold through long narrow catheters exhibited at least 70% viability up to 7 days. CONCLUSIONS: The catheter-injectable gelatin-alginate hydrogel represents a new concept, which combines tissue engineering with minimal invasive procedure. It is an inexpensive and convenient to use alternative to other types of suggested scaffolds for lung tissue engineering. This novel concept may be used for additional clinical applications in regenerative medicine.

Neo-adjuvant Chemo-Radiation to 60 Gray Followed by Surgery for Locally Advanced Non-Small Cell Lung Cancer Patients: Evaluation of Trimodality Strategy.

BACKGROUND: Neoadjuvant chemo-radiation therapy (CRT) dosages in locally advanced non-small cell lung cancer (NSCLC) were traditionally limited to 45 Gray (Gy). OBJECTIVES: To retrospectively analyze outcomes of patients treated with 60 Gy CRT followed by surgery. METHODS: A retrospective chart review identified patients selected for CRT to 60 Gy followed by surgery between August 2012 and April 2016. Selection for surgery was based on the extent of disease, cardiopulmonary function, and response to treatment. Pathological response after neoadjuvant CRT was scored using the modified tumor regression grading. Local control (LC), disease free survival (DFS), and overall survival (OS) were estimated by the Kaplan-Meier method. RESULTS: Our cohort included 52 patients: 75% (39/52) were stage IIIA. A radiation dose of 60 Gy (range 50-62Gy) was delivered in 82.7%. Surgeries performed included: lobectomy, chest-wall resection, and pneumonectomy in 67.3%, 13.4%, and 19.2%, respectively. At median follow-up of 22.4 months, the 3 year OS was 74% (95% confidence interval [CI] 52-87%), LC was 84% (95%CI 65-93), and DFS 35% (95%CI 14-59). Grade 4-5 postoperative complications were observed in 17.3% of cases and included chest wall necrosis (5.7%), bronco-pleural fistula (7.7%), and death (3.8%). A major pathologic regression with < 10% residual tumor occurred in 68.7% of patients (36/52) and showed a trend to improved OS (P = 0.1). Pneumonectomy cases had statistically worse OS (P = 0.01). CONCLUSIONS: Major pathologic regression was observed 68.7% with 60 Gy neoadjuvant CRT with a trend to improved survival. Pneumonectomy correlated with worse survival.

Long-term Imaging of the Lungs After Sealant Bronchoscopic Lung Volume Reduction.

PURPOSE: The aim of the study was to assess the pulmonary temporal changes after bronchoscopic lung volume reduction (BLVR) using sealants for treatment of emphysema. MATERIALS AND METHODS: We retrospectively assessed all chest computerized tomography (CT) and F-18 fluorodeoxyglucose (FDG) positron emission tomography CT scans of patients treated at our institution with BLVR. RESULTS: Eleven patients were treated with sealants: 4 with biological sealants and 7 with synthetic sealants. The first CT scan after biological sealant treatment showed no abnormalities in 8 lobes and 5 nodules, and 3 consolidations in 7 lobes. All findings resolved within 3 months, except for a nodule that decreased after 2 months and remained stable for 9 years. The first CT scan after utilizing the synthetic sealant showed abnormalities in each treated lobe: 19 nodules/masses (16 cavitary, 3 solid) and 3 consolidations. Follow-up CT scans were available for 16 nodules/masses: 1 resolved, 12 slowly decreased in size, 1 remained unchanged, and 2 grew. Of 3 consolidations 1 resolved and 2 decreased in size. FDG positron emission tomography CT scans performed in 2 patients showed FDG uptake higher than mediastinal background activity in 2 nodules in the same patient. CONCLUSIONS: Pulmonary changes after BLVR are variable. After treatment with biological sealants, most findings resolve within 3 months. In contrast, after synthetic sealants, although the majority regress over time, some show waxing and waning in growth that can mimic malignancy. FDG uptake in some of these lesions is suggestive of chronic inflammation. Radiologists should be aware of the spectrum of these pulmonary changes to avoid misdiagnosis of lung cancer.

Feasibility of Confocal Laser Microscopy in CT-Guided Needle Biopsy of Pulmonary and Mediastinal Tumors: A Proof-of-Concept Pilot Study.

This report describes the use of confocal laser microscopy (CLM) with CT-guided transthoracic needle biopsy (TTNB) for the diagnosis of heterogeneous large mediastinal and lung tumors. The procedure was performed in five patients diagnosed with a mediastinal mass and five patients diagnosed with a lung mass. CLM was used before CT-guided TTNB. Fluorescein administration allowed for the identification of blood vessels in both locations. Malignant cells were identified in mediastinal masses. Complications included one case of pneumothorax. In large tumors, CLM allows vascularized tissue to be differentiated from necrotic and fibrotic areas before biopsy.

Interventional pulmonology: a new medical specialty.

Interventional pulmonology (IP) is the newest chapter in respiratory medicine. IP includes both diagnostic and therapeutic methods. Nanotechnology, in both instrumental engineering and optical imaging, will further advance this competitive discipline towards cell diagnosis and therapy as part of the future's personalized medicine.