Israel Medical Association Journal

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.

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.

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.