Human Tracheal Transplantation.

Long-segment tracheal airway defects may be congenital or result from burns, trauma, iatrogenic intubation damage, or tumor invasion. Although airway defects <6 cm in length may be reconstructed using existing end-to-end reconstructive techniques, defects >6 cm continue to challenge surgeons worldwide. The reconstruction of long-segment tracheal defects has long been a reconstructive dilemma, and these defects are associated with significant morbidity and mortality. Many of these defects are not compatible with life or require a permanent extended-length tracheostomy that is fraught with complications including mucus plugging and tracheoesophageal fistula. Extensive circumferential tracheal defects require a reconstructive technique that provides a rigid structure able to withstand the inspiratory pressures, a structure that will biologically integrate, and contain functional ciliated epithelium to allow for normal mucociliary clearance. Tracheal transplantation has been considered the reconstructive "Holy Grail;" however, there has been a long-held scientific dogma that revascularization of the trachea was not possible. This dogma stifled research to achieve single-staged vascularized tracheal transplantation and prompted the introduction of many creative and inventive alternatives. Throughout history, alloplastic material, nonvascularized allografts, and homografts have been used to address this dilemma. However, these techniques have largely been unsuccessful. The recent introduction of a technique for single-staged vascularized tracheal transplantation may offer a solution to this dilemma and potentially a solution to management of the fatal tracheoesophageal fistula.

Common pathogenesis for sirenomelia, OEIS complex, limb-body wall defect, and other malformations of caudal structures.

Decades of clinical, pathological, and epidemiological study and the recent application of advanced microarray and gene sequencing technologies have led to an understanding of the causes and pathogenesis of most recognized patterns of malformation. Still, there remain a number of patterns of malformation whose pathogenesis has not been established. Six such patterns of malformation are sirenomelia, VACTERL association, OEIS complex, limb-body wall defect (LBWD), urorectal septum malformation (URSM) sequence, and MURCS association, all of which predominantly affect caudal structures. On the basis of the overlap of the component malformations, the co-occurrence in individual fetuses, and the findings on fetal examination, a common pathogenesis is proposed for these patterns of malformation. The presence of a single artery in the umbilical cord provides a visible clue to the pathogenesis of all cases of sirenomelia and 30%-50% of cases of VACTERL association, OEIS complex, URSM sequence, and LBWD. The single artery is formed by a coalescence of arteries that supply the yolk sac, arises from the descending aorta high in the abdominal cavity, and redirects blood flow from the developing caudal structures of the embryo to the placenta. This phenomenon during embryogenesis is termed vitelline vascular steal.

Pediatric Tracheal Lobular Capillary Hemangioma: A Case Report and Review of the Literature.

Chronic cough is a common complaint in the pediatric population and can have many different etiologies. We present a rare case of a tracheal lobular capillary hemangioma (LCH), also known as pyogenic granuloma, causing chronic cough in a child. In this case, the tracheal LCH was managed successfully with laser ablation. A review of the literature reveals only 2 other reported pediatric cases of tracheal LCH. Laryngoscope, 131:1729-1731, 2021.

Three-dimensional printing for surgical planning of a double aortic arch case.

BACKGROUND AND AIM: Over the past years, three-dimensional (3D) models of patient-specific anatomical conditions are being used to improve the comprehension and surgical management of a variety of diseases. It is an additional diagnostic tool that aids clinical decision-making. Furthermore, this technology is still not routinely used in the medical field since its availability is limited by cost and complex process. METHODS AND RESULTS: We describe a patient with a balanced-type double aortic arch encircling trachea and esophagus. Considering the clinical symptoms, surgical decompression of these structures and defined aortic arch reconstruction was indicated. The 3D printed model revealed narrowing of the left aortic arch at the junction of the descending thoracic aorta that did not clearly appear on the conventional images reconstruction. The left aortic arch was divided and the symptoms completely disappeared. No immediate or late complications occurred. CONCLUSION: 3D printed models can be helpful in surgical planning of congenital heart malformations. It should be strongly considered as an additional tool in complex cases.

Real-time confirmation of tracheal decompression.

AIMS: The primary objective was to highlight the role of intraoperative bronchoscopic guidance during the management of central airway obstruction. MATERIALS & METHODS: A 6-month-old child presented with recurrent chest infections due to innominate artery compression of distal trachea. Aortopexy was performed under real-time bronchoscopic guidance. RESULTS: Intraoperative bronchoscopic guidance helped in confirm a successful release of the central airway obstruction. DISCUSSION: When operations similar to aortopexy are performed for release of airway obstructions, intraoperative bronchoscopic guidance is a valuable tool for confirming a successful outcome. CONCLUSION: The successful surgical management of central airway obstruction due to an innominate artery compression of the distal trachea under real-time bronchoscopic guidance in a 6-month-old child is described.

In vivo clearance of nanoparticles by transcytosis across alveolar epithelial cells.

Nanoparticles in polluted air or aerosolized drug nanoparticles predominantly settle in the alveolar lung. Here, we describe a novel, highly effective pathway for the particles to cross the alveolar epithelium and reach the lymph and bloodstream. Amorphous silica nanoparticles, suspended in perfluorocarbon, were instilled into the lungs of mice for intravital microscopy. Particles formed agglomerates that settled on the alveolar wall, half of which were removed from the lung within 30 minutes. TEM histology showed agglomerates in stages of crossing the alveolar epithelium, in large compartments inside the epithelial cells and crossing the basal membrane into the interstitium. This pathway is consistent with published kinetic studies in rats and mice, using a host of (negatively) charged and polar nanoparticles.

Indocyanine Green Fluorescence Imaging of the Tracheal Blood Flow During Esophagectomy.

BACKGROUND: Tracheobronchial ischemia and necrosis are uncommon causes of pulmonary complications that can be lethal on development. Surgical manipulation considering tracheal blood flow is important in radical esophagectomy with extensive lymph node dissection. This study introduces a novel method for assessing tracheal blood perfusion using indocyanine green (ICG) fluorescence imaging. MATERIALS AND METHODS: Twenty patients who underwent esophagectomy with lymph node dissection for esophageal cancer were prospectively enrolled in this study. Tracheal blood flow after esophagectomy was quantitatively assessed using ICG fluorescence imaging. Region-of-interest software was used, and a time-intensity curve was created for the quantitative assessment of tracheal blood flow. RESULTS: We assessed ICG fluorescence imaging of the trachea during esophagectomy for esophageal cancer in all 20 cases. In the quantitative assessment of this pilot study, postoperative tracheal ischemic change and sputum discharge disorder tended to be associated with decreased tracheal blood flow (P = 0.084, P = 0.044). Resection of the right bronchial artery (BA) tended to be associated with decreased tracheal blood flow (P = 0.109), but the preoperative treatment, including chemotherapy and chemoradiotherapy, did not influence tracheal blood flow (P = 0.861, P = 0.435). The subgroup analysis of the preoperative chemoradiation group showed that the tracheal blood flow was significantly reduced with right BA resection compared with right BA preservation (P = 0.049). CONCLUSIONS: We assessed ICG fluorescence imaging of the trachea during esophagectomy for esophageal cancer. Further studies are needed to explore the significance of the assessment of tracheal blood flow during esophagectomy using ICG fluorescence imaging.

Preservation of Microvascular Integrity in Murine Orthotopic Tracheal Allografts by Clopidogrel.

BACKGROUND: Survival after lung transplantation is mainly limited by the development of chronic lung allograft dysfunction (CLAD). The aim of this study was to investigate if platelet inhibition by clopidogrel has a functionally relevant influence on the microvascular integrity of orthotopic tracheal allografts as an anatomic basis for the development of CLAD. METHODS: We orthotopically transplanted C57Bl/6 (H-2) tracheas into CBA.J (H-2) recipients who afterwards received clopidogrel (1 mg/kg). Morphometric analysis was performed by measuring epithelial height in proportion to thickness of the lamina propria (epithelium-lamina propria ratio). Tissue oxygenation was determined using a fluorescence quenching technique, and graft perfusion monitoring was performed by laser Doppler flowmetry and lectin-binding assay. Immunohistochemistry was used for detection of CD31 and inducible nitric oxide synthase while iron deposition was shown with Prussian blue reaction. Quantitative reverse transcription polymerase chain reaction analysis was used for gene expression analysis. RESULTS: Isografts maintained good oxygenation and perfusion throughout the experiment, while both were drastically reduced in allografts. Treatment with clopidogrel attenuated graft hypoxia and reduced loss of perfusion. Additionally, clopidogrel led to increased epithelium-lamina propria ratio while iron deposition was impaired. Gene expression analysis revealed elevated levels of angiogenic vascular endothelial growth factor in the clopidogrel group. Improved endothelial function was shown by immunohistochemistry (CD31, inducible nitric oxide synthase). CONCLUSIONS: Continuous administration of clopidogrel significantly improved tissue oxygenation, limited microvascular leakiness, and prevented airway ischemia. These data demonstrate that clopidogrel ameliorates microvascular injury during acute airway rejection, which is a known predisposing factor for the development of CLAD.

Endothelial Hypoxia-Inducible Factor-2α Is Required for the Maintenance of Airway Microvasculature.

BACKGROUND: Hypoxia-inducible factors (HIFs), especially HIF-1α and HIF-2α, are key mediators of the adaptive response to hypoxic stress and play essential roles in maintaining lung homeostasis. Human and animal genetics studies confirm that abnormal HIF correlates with pulmonary vascular pathology and chronic lung diseases, but it remains unclear whether endothelial cell HIF production is essential for microvascular health. The large airway has an ideal circulatory bed for evaluating histological changes and physiology in genetically modified rodents. METHODS: The tracheal microvasculature of mice, with conditionally deleted or overexpressed HIF-1α or HIF-2α, was evaluated for anatomy, perfusion, and permeability. Angiogenic signaling studies assessed vascular changes attributable to dysregulated HIF expression. An orthotopic tracheal transplantation model further evaluated the contribution of individual HIF isoforms in airway endothelial cells. RESULTS: The genetic deletion of Hif-2α but not Hif-1α caused tracheal endothelial cell apoptosis, diminished pericyte coverage, reduced vascular perfusion, defective barrier function, overlying epithelial abnormalities, and subepithelial fibrotic remodeling. HIF-2α promoted microvascular integrity in airways through endothelial angiopoietin-1/TIE2 signaling and Notch activity. In functional tracheal transplants, HIF-2α deficiency in airway donors accelerated graft microvascular loss, whereas HIF-2α or angiopoietin-1 overexpression prolonged transplant microvascular perfusion. Augmented endothelial HIF-2α in transplant donors promoted airway microvascular integrity and diminished alloimmune inflammation. CONCLUSIONS: Our findings reveal that the constitutive expression of endothelial HIF-2α is required for airway microvascular health.

Tracheal replacement revisited: Use of a vascularized tracheal transplant in a porcine model.

OBJECTIVES/HYPOTHESIS: To determine if a long segment of trachea can be transplanted as a vascularized organ and to determine if a tracheal transplant is a potential surgical option for a long-segment circumferential tracheal defect. STUDY DESIGN: Animal model. METHODS: Four (two donors and two recipients) adult domestic Yorkshire swine were used. Two sets of transplants were performed from a donor to recipient pig. The transplant was placed heterotopically (not in continuity with the airway), and the recipient animals were monitored for 14 days to ensure the transplants were well vascularized. Immunosuppressive therapies included methylprednisolone, cyclosporine, and azathioprine. Gross as well as histological examination of multiple tissues types including mucosa, cartilage, muscle, and blood vessels were performed postsacrifice on day 14. RESULTS: Recipient animal weights ranged from 40 to 42 kilograms. Both recipient pigs survived the full 14 days of study and exhibited normal activity and appetite. Ischemia time of transplanted grafts ranged from 63 to 72 minutes. Transplanted tracheas included a minimum of 15 cartilaginous rings and measured greater than 10 cm in length. Both grafts maintained a robust blood supply throughout the duration of study. CONCLUSIONS: The entire visceral compartment can be reliably transplanted, either as a single component (trachea) or as a chimeric flap with multiple components (trachea, esophagus, larynx, and pharynx). Further studies in the swine model should be considered to study the effects of transplanting the trachea orthotopically into the native airway. Further studies are needed into the reliability of this technique of transplantation in humans. LEVEL OF EVIDENCE: NA Laryngoscope, 128:S1-S9, 2018.

[Long-term oucomes of tracheal transplantation: success and unsolved problems]. / Otdalennyi rezul'tat transplantatsii trakhei: uspekh i nereshennye problemy.

AIM: To analyze long-term outcomes of tracheal transplantation. MATERIAL AND METHODS: There were 1128 patients with cicatricial tracheal stenosis who have been operated at the Petrovsky Russian Research Center for Surgery and the Sechenov First Moscow State Medical University for the period 1963-2015. RESULTS: Operations have become safer. Postoperative morbidity and mortality reduced from 41.4% (1963-1980) to 5.6% (2001-2015) and from 21.9% (1963-1980) to 0.5% (2001-2015), respectively. Tracheal transplantation was performed in 2 cases and fundamentally different tracheal structures were applied. Donor thyreotracheal complex with restored blood supply through thyroid vessels was used in the first case (2006). Perennial experimental trials preceded clinical application of this technique. In the second case (2010) we applied scientific results of foreign colleagues (cellular technologies and methods of regenerative medicine to create artificial trachea). Patients are still alive after 12 and 8 years, respectively. Restoration of blood supply of donor trachea is possible through thyroid collaterals. This technique is successful in long-term period. Tissue-engineered trachea cannot be considered true trachea due to no all tracheal components. However, such trachea provides air-conducting, evacuation and protective functions. Tracheomalacia requires further researches as one of the main problems of tracheal transplantation.

Prevalence of major vessels anterior to the trachea at sites of potential front-of-neck emergency airway access in adults.

BACKGROUND: Several case reports have described anatomical variations that can cause difficulty with front-of-neck airway access, such as major vessels anterior to the trachea. The prevalence of these anomalies is unknown. METHODS: We screened 500 consecutive thoracic computed tomography (CT) scans in adult patients performed independently in any public hospital in Western Australia. The prevalence of major vessels anterior to the trachea in the anterior triangle of the neck was determined. RESULTS: In the suprasternal notch, 264 CT scans (53%) demonstrated part of a major vessel anterior to the trachea, most commonly the brachiocephalic artery. At 10, 20, and 30 mm above the suprasternal notch, respectively, 126 (25%), 48 (9%), and 5 (1%) CT scans showed a major vessel anterior to the trachea. None showed a major vessel anterior to the cricothyroid membrane. In the suprasternal notch, a major vessel was anterior to the trachea in 10 of 120 CT scans (8%) that had a manubrio-cricoid distance <25 mm, and 108 of 116 CT scans (93%) that had a manubrio-cricoid distance >50 mm. In a logistic-regression model, increased length of trachea above the manubrium was a strong predictor of major vessels anterior to the trachea in the suprasternal notch, whilst sex, age, thoracic kyphosis, tracheal diameter, and the origin of the brachiocephalic artery were not strong predictors. CONCLUSIONS: It is common for patients to have some portion of a major vessel anterior to the trachea at sites where an emergency tracheostomy might be performed.

Development of a functional airway-on-a-chip by 3D cell printing.

We used 3D cell printing to emulate an airway coupled with a naturally-derived blood vessel network in vitro. Decellularized extracellular matrix bioink derived from porcine tracheal mucosa (tmdECM) was used to encapsulate and print endothelial cells and fibroblasts within a designated polycarprolactone (PCL) frame. Providing a niche that emulates conditions in vivo, tmdECM gradually drives endothelial re-orientation, which leads to the formation of a lumen and blood vessel network. A fully-differentiated in vitro airway model was assembled with the printed vascular platform, and collectively reproduced a functional interface between the airway epithelium and the vascular network. The model presented respiratory symptoms including asthmatic airway inflammation and allergen-induced asthma exacerbation in physiological context. Because of the adaptable and automated nature of direct 3D cell printing, we expect that this will have relevance in vivo and high reproducibility for production of high-content platforms for preclinical trials in biomedical research.

Tracheal Transplantation: State of the Art and Key Role of Blood Supply in Its Success.

The trachea is one of the most difficult organs to transplant because its segmental blood supply involves blood vessels that are too small to allow for microvascular anastomosis. Through an ingenious sequence of revascularization and wound-healing mechanisms under temporary immunosuppression, the authors have developed a tracheal allotransplantation technique that allows the creation of a true chimeric trachea. The donor component of this chimeric trachea is tolerated permanently based on immune ignorance. This technique holds great promise for the development of a standardized approach for the repair of large tracheal defects.

Recognition and Management of Life-Threatening Tracheovascular Fistulae and How to Prevent Them.

Formation of a fistula between trachea and a major artery or vein in the root of the neck threatens life quickly from combination of major external bleeding and hemorrhagic shock, and asphyxiation from flooding of the proximal airways with blood. This complication can occur after cervical tracheostomy open or percutaneous, tracheal resection, cervical exentration and anterior mediastinal tracheostomy, and laryngectomy. The recognition of its occurrence is clinical based on a high index of clinical suspicion. The life-saving operation for this complication carries potential risk for ischemic stroke. Impairment of arterial perfusion to the right arm and ischemia is another potential complication.

Blunt Tracheobronchial Trauma.

This article provides an overview of current literature on blunt tracheobronchial injury, and discusses the presentation of tracheobronchial injuries in clinical and radiographic forms. A review of the current data on repair is provided with an outline of surgical management.

Factors Favoring and Impairing Healing of Tracheal Anastomosis.

The factors governing successful healing of and impairing of tracheal and bronchial anastomosis are best understood by reviewing the normal histologic changes accompanying healing, governing factors, and biochemical advances made in the last 5 decades. Normal wound healing factors, also relevant to tracheal and bronchial reconstruction, rely on precise handling of tissues without interfering with tissue perfusion, careful selection and placement of sutures, and steps to minimize tension. Impairments of satisfactory healing are well recognized in gastrointestinal surgery and apply to tracheal and carinal resection, and sleeve bronchial resection.

Intraoperative Endotracheal Cuff Pressure Study: How Education and Availability of Manometers Help Guide Safer Pressures.

INTRODUCTION: Endotracheal intubation is a medical procedure that is often indicated in both the perioperative and critical care environments. Cuffed endotracheal tubes (ETT) allow for safer and more efficient delivery of positive pressure ventilation, as well as create a barrier to reduce the risk of micro-aspiration and anesthetic pollution in the operating room environment. Over-inflation of the endotracheal cuff can lead to serious and harmful sequelae. This study aimed to assess if departmental education paired with ready access to a manometer to assess cuff pressure would result in an improvement in the proportion of ETT cuff pressures in the goal range. MATERIALS AND METHODS: A quality improvement study was conducted at the San Antonio Military Medical Center (SAMMC; Department of Defense hospital in San Antonio, TX). The initiative was divided into three key periods: pre-implementation, implementation, and post-implementation. During the pre-implementation period, ETT cuff pressures were obtained to assess the baseline state of ETT cuff pressures for patients in the operating room; the proportion of in-range (20-30 cmH2O) pressures was calculated. During the implementation phase, operating rooms were equipped with manometers and anesthesia departmental education was performed regarding the use of the manometers. Three months later, post-implementation cuff pressures were measured in the OR, and the proportion of in-range pressures was again calculated. RESULTS: The pre-implementation data showed an average cuff pressure of 48.92 cmH2O and a median of 38.5 cmH2O. Of the 100 pre-implementation pressures, 20 were in the goal range. Post-implementation data had an average cuff pressure of 41.96 cmH2O and a median of 30 cmH2O. A chi-squared test of pressures in the safe range from the pre-implementation versus post-implementation values yielded a highly significant p-value of 0.0003. CONCLUSION: The data from this study clearly demonstrated a statistically significant improvement in the proportion of in-range cuff pressures following the quality improvement initiative. This study supports the use of department-wide education and the availability of manometers in each OR to yield safer cuff pressures for intubated patients. This study did not aim to determine an optimal ETT cuff pressure, but utilized data already available to determine a safe cuff pressure. Further research needs to be performed to assess whether routine monitoring of cuff pressure results in improved patient outcomes.