Tracheal Homograft Research Articles

Engineering tissues for children: building grafts that grow

In The Lancet, Martin Elliott and colleagues1 report the successful surgical management of an aortotracheal fistula in a 10-year-old boy with congenital tracheal stenosis. The child had undergone patch tracheoplasty and bare metal stent placement 6 days after birth, emergency repair of an aortotracheal fistula and tracheal homograft at age 3 years, subsequent replacement of the homograft for mediastinitis, and multiple interventions and stent placements up until the age of 10 years, when a tracheal stent eroded into the thoracic aorta.

Pediatric Tracheal Reconstruction Using Cadaveric Homograft

To examine the indications, risks, and surgical outcomes after tracheal reconstruction using cadaveric homograft in children. Retrospective medical record review. Tertiary referral center. Ten children (4 boys and 6 girls). Tracheal reconstruction using cadaveric homograft. Cause of stenosis, number and type of procedures before homograft reconstruction, severity of preoperative stenosis, surgical approach, homograft length, duration of stenting, number and type of procedures after reconstruction, and rates of decannulation and survival. Ten children (mean [SD] age, 8.4 [5.5] years) underwent 14 tracheal reconstructions using cadaveric homograft. Patients had an average of 7.0 (range, 1-16) procedures before homograft reconstruction, including an average of 2.8 (range, 0-6) major open airway reconstructions. Mean (SD) pretracheoplasty Myer-Cotton grade of stenosis was 3.80 (0.42) (range, 3-4), and all patients were tracheotomy dependent. A cervical approach was used in 12 reconstructions (86%), and 2 (14%) required median sternotomy. Mean (SD) homograft length was 3.9 (1.7) cm (range, 2-8 cm), which was approximately 0.60 times the length of the total recipient trachea. Mean (SD) duration of stenting for all homografts was 0.67 (0.46) years (range, 0.24-1.98 years). The survival rate was 90% after a mean follow-up of 5.47 (1.52) years (range, 3.32-7.55 years). Surviving patients required an average of 7.38 (5.52) procedures (range, 1-19) after homograft transplant, including an average of 1 major open airway reconstruction (range, 0-4). The mean (SD) grade of stenosis after the final homograft placement was 1.89 (1.27) (range, 1-4). Although the operation-specific decannulation rate was only 7% (1 of 14), the overall decannulation rate eventually reached 60%. Statistical bootstrapping methods and a multivariate regression model determined that increasing patient age (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), increasing number of prior procedures (1.26; 1.02-1.57), and increasing homograft length (2.42; 1.60-3.40 [P < .001]) were associated with an increased risk of no decannulation after tracheal homograft reconstruction. Tracheal reconstruction using cadaveric homograft is an option in children who have undergone multiple airway surgical procedures and present with long-segment stenoses that cannot be bridged using conventional methods. These patients must receive close postoperative follow-up. Subsequent procedures are almost always required before decannulation, and eventual decannulation rates are only 60%. Decannulation rates are lower in older patients who have previously undergone many procedures and require a long tracheal homograft.

Effects of Clarithromycin and Dexamethasone on Mucus Production in Isografted Rat Trachea

Objectives: The purpose of this study was to develop an animal model for the study of mucus overproduction and to assess the effect of a 14-membered macrolide antibiotic and a glucocorticoid on lipopolysaccharide (LPS)-induced mucus production. Methods: Tracheas from donor rats were homografted to recipient rats for 4 weeks, and the usefulness of this tracheal homograft model in the study of mucus production was examined. Results: Oral administration of clarithromycin (CAM) to recipient rats for 4 weeks significantly reduced LPS-induced mucus production in the homografted trachea. Dexamethasone administered for 4 weeks also significantly reduced the mucus volume in LPS-treated homografted trachea compared with that in the control rats. The implanted trachea containing control medium was not histologically different from normal trachea. When the medium instilled into the implanted trachea contained 1 µg/ml LPS, the volume and spinability of mucus produced in the tracheal lumen were significantly increased compared to those in the trachea instilled with control medium. Goblet cell metaplasia was also observed in the implanted trachea containing LPS. Conclusions: The present study shows that LPS-administered homografted trachea is a good animal model of chronic hypersecretory diseases of the upper and lower airways. CAM and dexamethasone could be treatment choices in such hypersecretory diseases.

The Fate of Homograft Tracheal Transplants in Sheep

An established method of tracheal substitution is not yet available, but homograft tracheal transplantation might provide a realistic tracheal replacement. With the objective of sequentially examining the healing of tracheal homografts, we have established a suitable large-animal model. Five sheep received orthotopic tracheal transplantation of a 4-cm cervical tracheal homograft. The trachea was supported for 6 weeks with a self-expanding polyester stent. The plan was to euthanize the animals after 2, 4, 8, 12 and 16 weeks, or whenever complications occurred. The implantation itself was performed without complications. After 2 weeks the homograft was firmly encapsulated by connective tissue, without signs of necrosis or abscess. The original mucous membrane no longer existed; the cartilage rings were exposed. In all animals that were euthanized at the later dates, the homografts were completely absorbed and replaced by inflammatory scar tissue. This, in turn, was covered with a shiny cellular surface layer. The results from this animal experiment reveal-contrary to data published to date-that tracheal homografts are not incorporated but absorbed. They are replaced by scar/granulation tissue that cannot secure the stability of the trachea. Therefore, further experiments with respect to the biocompatability of homografts appear to be necessary.

Fate of mucosal healing in transplanted deep frozen irradiated tracheal homograft

Deep-frozen irradiated tracheal homograft has been successfully employed for subglottic-tracheal reconstruction, as in our previous report. Morphologically, though the transplanted site appeared to have good mucosal healing, the fate of the donor mucosa is not known. The objective of this study was to determine the survival of the mucosa of donor trachea. University hospital-based, prospective study. Thirty samples from six sets of specimens, each set consisting of five samples of the tracheal mucosa, were studied. Of five samples in each set, 2 were taken from donors, one from a recipient, and another two from the transplanted sites, eight months postoperatively. The samples in each set of specimens were genetically matched by the process of DNA fingerprinting. Histological studies were done on the mucosa of donor and transplanted sites. The study demonstrated incompatibility between samples from recipient and transplanted site, and incompatibility between preoperative donor and recipient samples in all sets of specimens. The mucosa of donor trachea did not survive at the transplanted site. The apparently normal postoperative mucosal lining actually represents migration of the recipient mucosa. The fate of transplanted donor tracheal mucosa is elucidated, and may substantially explain the mechanism of rejection resistance.

Tracheal matrices, obtained by a detergent-enzymatic method, support in vitro the adhesion of chondrocytes and tracheal epithelial cells

Several attempts have been performed to achieve a suitable tracheal replacement for the treatment of different conditions characterized by a lack of sufficient tissue for surgical reconstruction. Actually, tracheal homografts can induce long-term stenosis and their growth potential is not known. Thus, in this work porcine tracheal matrices have been obtained by a detergent-enzymatic method. The treatment decreased the antigenicity of matrices which were able to support the in vitro adhesion of both chondrocytes and tracheal epithelial cells. On the contrary, only few cells were observed in tracheal matrices prepared with formalin, Thimerosal, and acetone, suggesting that the long-term stenosis occurring in vivo is probably because of an insufficient cell ingrowth. In summary, our results indicate that the detergent-enzymatic method allows us to obtain tracheal matrices which can function as a promising support to achieve an in vitro tissue-engineered cell-matrix construct.

The management of congenital tracheal stenosis

This paper reviews current concepts and results in the management of congenital tracheal stenosis (CTS). Diagnostic options are considered and the requirements for successful management defined. Chief amongst these is a multi-disciplinary approach with individualised patient management. Severe long-segment CTS represents the biggest challenge to clinicians and the worst problems for affected families. Near-death episodes are frequent in affected infants and some cannot be ventilated and require ECMO. Associated cardiovascular anomalies are frequent. Patients require immediate resuscitation and transfer to a specialist unit. After careful assessment, accurate diagnosis and discussion, primary resection and end-to-end repair with a slide technique should always be the first option, with concomitant repair of associated cardiac anomalies. If this is impossible because of the severity of the lesion, some form of patch tracheoplasty will be indicated. Cardiopulmonary bypass is often required. Patches include pericardium, autograft trachea, carotid artery, cartilage, and allograft trachea. Mortality ranges from 0 to 30% in the literature, which largely comprises single-centre long-term experience. Recurrence is common and can be managed by stenting and tracheal homograft implantation. Long-term quality of life of survivors is little reported but seems good. Physiological data are lacking. To improve results, we suggest a treatment algorithm to rationalise care.

The management of congenital tracheal stenosis

This paper reviews current concepts and results in the management of congenital tracheal stenosis (CTS). Diagnostic options are considered and the requirements for successful management defined. Chief amongst these is a multidisciplinary approach with individualised patient management.Severe long-segment CTS represents the biggest challenge to clinicians and the worst problems for affected families. Near-death episodes are frequent in affected infants and some cannot be ventilated and require Extra-Corporeal Membrane Oxygenation (ECMO). Associated cardiovascular anomalies are frequent. Patients require immediate resuscitation and transfer to a specialist unit.After careful assessment, accurate diagnosis, and discussion, primary resection and end-to-end repair with a slide technique should always be the first option, with concomitant repair of associated cardiac anomalies. If this is impossible because of the severity of the lesion, some form of patch tracheoplasty will be indicated. Cardiopulmonary bypass is often required. Patches include pericardium, autograft trachea, carotid artery, cartilage, and allograft trachea.Mortality ranges from 0% to 30% in the literature, which largely comprises single-centre long-term experience. Recurrence is common and can be managed by stenting and tracheal homograft implantation. Long-term quality of life of survivors is little reported but seems good. Physiological data are lacking.To improve results, we suggest a treatment algorithm to rationalise care.

Alterações epiteliais e cartilaginosas em cirurgia traqueal: estudo experimental em cobaias

FORMA DE ESTUDO: Experimental. MATERIAL E MÉTODO: Transplante homógeno de traquéia foi realizado em 51 cobaias (Cavia Porcellus). RESULTADO: Observamos reepitelização do enxerto a partir da traquéia receptora da cobaia, evoluindo de epitélio escamoso de 1 a 3 células nos animais com 3, 7 e 14 dias de observação para epitélio ciliado após 60 a 120 dias do transplante. A viabilidade do enxerto traqueal era boa, com reabsorção parcial da cartilagem e formação de estenose traqueal parcial, mas sem sinais clínicos evidentes de obstrução respiratória durante o tempo de observação dos animais.

Cryopreserved, irradiated tracheal homograft transplantation for laryngotracheal reconstruction in human beings

Subglottic tracheal stenosis is a common clinical entity. Management in severe cases is often problematic. Various techniques for tracheal replacement have been used with varying degrees of success. In this study we used cryopreserved, irradiated tracheal homografts, the use of which in human beings has not been reported previously. In a sterile setup, the tracheas were harvested from donor cadavers within 24 hours of death. The grafts were initially kept at 57°C for 20 minutes; they were then placed in a –70°C chamber for another 2 to 3 days or more and were irradiated to 25 kGy (2.5 million rad). Finally, the grafts were stored at –70°C until usage. Seven patients underwent the surgery, but only 4 are presented here. In the remaining 3 patients, the follow-up time was too short to be evaluated. Four patients, 2 male and 2 female (aged 2-40 years, mean 16 years), with severe subglottic tracheal stenosis underwent segmental tracheal graft reconstruction. Immunosuppressant medications were not given to any patient. Follow-up ranged from 18 to 20 months. Three patients successfully underwent decannulation, and 1 patient had local infection and dislodgment of the intraluminal stent with subsequent restenosis. The postoperative tracheal lumen appeared to be near normal, with histologic evidence of normal respiratory epithelium at the grafted site. In conclusion, cryopreserved, irradiated tracheal homograft transplantation is a valuable alternative for subglottic tracheal reconstruction. (Otolaryngol Head Neck Surg 2000;122:911-6.)

Cryopreserved, Irradiated Tracheal Homograft Transplantation for Laryngotracheal Reconstruction in Human Beings

Subglottic tracheal stenosis is a common clinical entity. Management in severe cases is often problematic. Various techniques for tracheal replacement have been used with varying degrees of success. In this study we used cryopreserved, irradiated tracheal homografts, the use of which in human beings has not been reported previously. In a sterile setup, the tracheas were harvested from donor cadavers within 24 hours of death. The grafts were initially kept at 57 degrees C for 20 minutes; they were then placed in a -70 degrees C chamber for another 2 to 3 days or more and were irradiated to 25 kGy (2.5 million rad). Finally, the grafts were stored at -70 degrees C until usage. Seven patients underwent the surgery, but only 4 are presented here. In the remaining 3 patients, the follow-up time was too short to be evaluated. Four patients, 2 male and 2 female (aged 2-40 years, mean 16 years), with severe subglottic tracheal stenosis underwent segmental tracheal graft reconstruction. Immunosuppressant medications were not given to any patient. Follow-up ranged from 18 to 20 months. Three patients successfully underwent decannulation, and 1 patient had local infection and dislodgment of the intraluminal stent with subsequent restenosis. The postoperative tracheal lumen appeared to be near normal, with histologic evidence of normal respiratory epithelium at the grafted site. In conclusion, cryopreserved, irradiated tracheal homograft transplantation is a valuable alternative for subglottic tracheal reconstruction.

Pediatric tracheal homograft reconstruction: A novel approach to complex tracheal stenoses in children

Purpose: Tracheal stenosis can be a life-threatening problem in children. Long-segment tracheal stenosis and recurrent tracheal stenosis are especially problematic. Tracheal homograft reconstruction represents a novel therapeutic modality for these patients. Methods: Cadaveric trachea is harvested, fixed in formalin, washed in thimerosal (Methiolate), and stored in acetone. The stenosed tracheal segment is opened to widely patent segments proximally and distally. The anterior cartilage is excised and the posterior trachealis muscle or tracheal wall remains. A temporary silicone rubber intraluminal stent is placed and absorbable sutures secure the homograft. Regular postoperative bronchoscopic treatment clears granulation tissue. The stent is removed endoscopically after epithelialization over the homograft. Twenty-four children with severe tracheal stenosis (age 5 months to 18 years, mean ± standard error of the mean = 8.18 ± 1.21 years) underwent tracheal homograft reconstruction. All but one had had previous unsuccessful reconstructive attempts. Ten lesions were congenital, nine were posttraumatic, and five were due to prolonged intubation. Results: Follow-up ranged from 5 months to 10 years (3.79 ± 0.70 years). Twenty patients survive (20/24 = 83%), 16 without any airway problems. Four patients are still undergoing treatment. One patient requiring emergency extracorporeal membrane oxygenator support before the operation died 10 days after tracheal homograft reconstruction. Another patient with severe preoperative mediastinal sepsis died 3.5 months after tracheal homograft reconstruction. Two patients with functional airways died late of unrelated problems. Conclusions: Tracheal homograft reconstruction demonstrates encouraging short-term to medium-term results for children with severe recurrent tracheal stenosis. Postoperative bronchoscopic and histologic studies provide evidence of epithelialization and support the expectation of good long-term results. (J T horac C ardiovasc S urg 1996;112:1549-60)

Successful complete tracheal resection in a three-month-old infant

We report an infant with severe long-segment tracheal stenosis in whom the posterior trachea was formed by complete cartilage rings and the anterior trachea was almost totally formed by a solid cartilage plate. The child was successfully treated initially by complete resection of the trachea and primary end-to-end repair and subsequently with tracheal homograft transplantation for secondary stenosis.

Extracorporeal membrane oxygenation as a bridge to definitive tracheal surgery in children

Extracorporeal membrane oxygenation was used as a bridge for three infants with complicated long segment congenital tracheal stenosis to tracheal homograft transplantation with cadaveric tracheal homograft and for one child, with an extensive traumatic tracheal laceration caused by aspiration of a sharp foreign body, to definitive tracheal repair. In all four cases mechanical ventilation was impossible and death almost certain without extracorporeal membrane oxygenation. (J P EDIATR 1996;128:386-8)

Tracheal reconstruction in children using cadaveric homograft trachea.

We report the use of cadaveric human tracheal homograft in the treatment of severe long segment congenital tracheal stenosis in children. Five children (aged 5 months-8 years) with severe life-threatening airway obstruction due to long segment congenital tracheal stenosis had failed conventional management. All were ventilator dependent or rapidly deteriorating at the time of surgery, two were on extracorporeal membrane oxygenation, and no alternative therapy was available. The stenosed trachea was removed and the posterior trachealis muscle left in situ when possible. Surgical technique involved the use of cardiopulmonary bypass in four of five cases. Stored cadaveric tracheal homograft tissue was shaped and inserted over a silastic intra-luminal stent which was kept in place for up to 3 months. Regular bronchoscopy was necessary postoperatively to clear granulation tissue, which resolved on removal of the stent. Four patients are all now without stents, intubation or tracheostomy. Three are without airway problems 16, 14, and 9 months after surgery and one attends for occasional dilatation of a distal tracheal stenosis, but is now at home despite other severe multiple congenital problems. One patient presented with complete disruption of the trachea and mediastinal sepsis and was supported on extracorporeal membrane oxygenation prior to surgery; this patient eventually died of airway failure and sepsis. The application of cadaveric human tracheal homograft to congenital tracheal stenosis is novel. Its use in five children who would otherwise have died has provided an extra therapy in an extremely difficult group of patients.

Cryopreserved Trachea—A New Arterial Conduit: Early Hemodynamic and Radiographic Performance

Synthetic arterial conduits perform well in a vast range of applications; however, there are certain situations where these grafts are not ideal. In an ef fort to find a superior graft, the authors evaluated the use of rat tracheas as cryopreserved homograft arterial conduits. Twenty-four retired breeder Wistar rats received cryopreserved homograft tracheas as arterial grafts in the infrarenal abdominal aorta. After graft implan tation, the animals were allowed to recover and assigned to groups of 4 animals to be sacrificed at the end of one, two, three, six, twelve and twenty-four weeks. The animals were followed up clinically and then the grafts were evaluated hemodynamically, angiographically, and by gross histolog. Four animals (17%) died owing to ruptured aneurysmal grafts—1 in the two-week group, 1 in the six-week group, and 2 in the twelve-week group. One animal in the six week group had a patent but aneurysmal graft at the time of sacrifice. There were no pressure gradients, graft stenoses, or anastomotic strictures in any of the surviving animals. The authors conclude that the use of cryopreserved tracheal homograft as an interposition graft, while feasible, is associated with an unac ceptably high incidence of aneurysm formation.

Tracheal Homograft as Aortic Conduit: Early Phase Results

The aim of this study was to evaluate the performance of tracheal homografts as aortic conduits. Fourteen tracheal grafts freshly procured from rats were preserved by the following two methods: cryopreservation (n = 6) and treatment with glutaraldehyde 0.2 % (n = 8). The explanted tracheae were stored for ten to twenty days prior to implantation. They were subsequently implanted into the infrarenal aorta of the recipient rats. The average length replaced was 1 to 1.5 cm. The grafts were then evaluated after a period of one (n = 6, 2 cryopreserved, 4 gluteraldehyde), two (n = 4, 2 cryopreserved, 2 glutaraldehyde), and three (n = 4, 2 cryopreserved, 2 gluteraldehyde) weeks for their performance, morphol ogy, and histopathology. The rats did well postoperatively with adequate distal perfusion. Two of the 6 rats with cryopreserved grafts had reduced flow as evidenced by lack of pulsation in the aorta distal to the graft, and histologic examination revealed incompletely occluding thrombus adherent to the luminal surface. The remaining cyropreserved and glutaraldehyde-fixed grafts had good flow and did not show any radiologic evidence of narrowing at the site of anastomosis or in the region of the graft. Histopathologic examination showed that the glutaraldehyde-treated homografts had better morphology, intact carti lage, and no or mild inflammatory response. The cryopreserved tracheal homo grafts showed degenerative changes in the cartilage. The inflammatory response was moderate, and the mucosa was either ruptured or absent. In the 2 that had reduced flow, there was marked cartilage necrosis and inflammatory response with thrombus formation in the lumen. This early phase study shows that tracheal homografts functioned well as conduits in the aortic position and gluaraldehyde treated homografts have better morphology than cryopreserved homografts.

Tracheal autograft revascularization

A series of experiments were conducted to assess the possibility of revascularizing tracheal homografts with an omental pedicle flap. Three different experiments were performed. In Group I (N = 4) a ten-ring tracheal allograft was embedded into the greater omentum of a recipient animal for 30 days. At reexploration these four allografts were found to have been transformed into a tube consisting mainly of connective tissue. To provide more collateral circulation, we immediately reanastomosed an eight-ring tracheal autograft in Group II animals (N = 7). Collateral blood supply was possibly available from the surrounding mediastinal tissues, the recipient trachea, and the transposed omental graft. Tracheal malacia and loss of rings 4,5, and 6 was a consistent finding and cause of death. A third group of animals (Group III) underwent a similar operation with the addition of free bone grafts being applied to the external surface of the autograft to impede significant tracheal stenosis. The long-term results and the findings when the animals were put to death were the same as in Group II. We conclude that the omental pedicle graft cannot sustain chondrocyte viability. Thus a reliable method for revascularization of a tracheal transplant remains to be found.

Cialitkonservierte Trachealtransplantate ? eine M�glichkeit bei Trachealstenosen?

A successful transplantation of cialit-conserved tracheal homografts depends on revitalisation and persistent shape. Histological controls after 11 months show a far extending transformation in vital tissue and maintained structure, but the tissue is still not sufficient for a lasting replacemant of a tracheal segment.

Tracheal homograft in dogs

If the heart and kidney can be transplanted easily we thought it feasible to transplant the trachea, from one member of the animal species to another of the same species, under the umbrella of immuno-suppression.