Thomas Fux1, Cecilia Österholm2, Raquel Themudo3, Oscar Simonson4, Karl-Henrik Grinnemo5, Matthias Corbascio6. 1. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Section Cardiothoracic Surgery and Anesthesiology, Division of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden. Electronic address: thomas.fux@sll.se. 2. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. 3. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Division of Radiology, Karolinska University Hospital, Stockholm, Sweden. 4. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Cardiothoracic Surgery and Anesthesiology, Uppsala University Hospital, Uppsala, Sweden. 5. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Cardiothoracic Surgery and Anesthesiology, Uppsala University Hospital, Uppsala, Sweden. 6. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Heart and Vascular Division, Karolinska University Hospital, Stockholm, Sweden.
Abstract
OBJECTIVE: Synthetic tracheal grafts seeded with autologous bone marrow-mononuclear cells (BM-MNCs) have been described as becoming living and functional grafts representing a promising option for tracheal replacement for pathologies unamenable by segmental resection or autologous repair. This study aimed to present the first long-term follow-up of these procedures in humans. METHODS: We retrospectively analyzed 3 patients who received synthetic tracheal grafts seeded with BM-MNCs implanted. RESULTS: Patient 1 was a 37-year-old man with mucoepidermoid carcinoma, the first-ever human to receive a synthetic tracheal graft seeded with BM-MNCs. Patient 2 was a 30-year-old man with adenoid cystic carcinoma, and patient 3 was a 22-year-old woman with an iatrogenic tracheal injury. All patients developed graft-related complications necessitating multiple surgical reinterventions. Patient 1 was hospitalized for 8 months before dying from respiratory failure secondary to graft dehiscence 32 months after implantation. Patient 2 died 3.5 months after implantation from undisclosed causes. Patient 3 received a second synthetic tracheal graft after 11 months and an allogeneic trachea and lung transplantation 45 months after the primary implantation. Patient 3 underwent 191 surgical interventions after the primary implantation and spent 55 months in the intensive care unit before dying from airway bleeding. All patients' bronchoscopic, histologic, and radiologic investigations demonstrated graft-associated complications, including anastomotic fistulae and obstructive granulation tissue, without graft vascularization, mucosal lining, or integration into adjacent tissues. CONCLUSIONS: Synthetic tracheal grafts seeded with BM-MNCs do not become living functional tracheal grafts and lead to debilitating complications and death.
OBJECTIVE: Synthetic tracheal grafts seeded with autologous bone marrow-mononuclear cells (BM-MNCs) have been described as becoming living and functional grafts representing a promising option for tracheal replacement for pathologies unamenable by segmental resection or autologous repair. This study aimed to present the first long-term follow-up of these procedures in humans. METHODS: We retrospectively analyzed 3 patients who received synthetic tracheal grafts seeded with BM-MNCs implanted. RESULTS:Patient 1 was a 37-year-old man with mucoepidermoid carcinoma, the first-ever human to receive a synthetic tracheal graft seeded with BM-MNCs. Patient 2 was a 30-year-old man with adenoid cystic carcinoma, and patient 3 was a 22-year-old woman with an iatrogenic tracheal injury. All patients developed graft-related complications necessitating multiple surgical reinterventions. Patient 1 was hospitalized for 8 months before dying from respiratory failure secondary to graft dehiscence 32 months after implantation. Patient 2 died 3.5 months after implantation from undisclosed causes. Patient 3 received a second synthetic tracheal graft after 11 months and an allogeneic trachea and lung transplantation 45 months after the primary implantation. Patient 3 underwent 191 surgical interventions after the primary implantation and spent 55 months in the intensive care unit before dying from airway bleeding. All patients' bronchoscopic, histologic, and radiologic investigations demonstrated graft-associated complications, including anastomotic fistulae and obstructive granulation tissue, without graft vascularization, mucosal lining, or integration into adjacent tissues. CONCLUSIONS: Synthetic tracheal grafts seeded with BM-MNCs do not become living functional tracheal grafts and lead to debilitating complications and death.