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Ann Thorac Surg 2002;73:1995-2004
© 2002 The Society of Thoracic Surgeons

Review

Tracheal replacement: a critical review

Hermes C. Grillo, MD*a,b

a Division of General Thoracic Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
b Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA

* Address reprint requests to Dr Grillo, Massachusetts General Hospital, Blake 1570, 55 Fruit Street, Boston, MA 02114 USA
e-mail: pguerriero{at}partners.org


   Abstract
Top
 Abstract
Introduction
 Need for tracheal replacement
 Requirements for replacement
 Approaches to replacement
 Foreign materials
 Implantation of nonviable...
 Autogenous tissues
 Tissue engineering
 Tracheal transplantation
 Conclusions
 Selected references *
 Footnotes
 References
 
This review discusses the need for tracheal replacement, distinct from resection with primary anastomosis, the requirements for replacement, and the many efforts over the past century to accomplish this goal experimentally and clinically. Approaches have included use of foreign materials, nonviable tissue, autogenous tissue, tissue engineering, and transplantation. Biological problems in each category are noted.


   Introduction
Top
 Abstract
 Introduction
Need for tracheal replacement
 Requirements for replacement
 Approaches to replacement
 Foreign materials
 Implantation of nonviable...
 Autogenous tissues
 Tissue engineering
 Tracheal transplantation
 Conclusions
 Selected references *
 Footnotes
 References
 
Experimental and clinical tracheal and bronchial repair or anastomosis began fitfully in the late 19th century. A few examples of limited tracheal resection and primary anastomosis, almost wholly cervical, plus staged cervical repairs, were cited in the first half of the 20th century. At midcentury, Rob and Bateman [1], and Belsey [2] confirmed a generally held belief that tracheal resection and primary anastomosis could not be carried out if excision exceeded 2 cm. Surgeons therefore turned to a search for a prosthetic tracheal replacement.

In the 1950s and 1960s, experimental investigation of the potential extent of tracheal resection with primary anastomosis by anatomical mobilization and without prosthesis [3–7] greatly widened these possibilities. Approximately half of the adult trachea could be removed surgically and reanastomosis performed. Although a great expansion of tracheal surgical procedures followed application these principles, investigators continued to seek tracheal replacement for those relatively few lesions, chiefly neoplastic, that could not be managed by the techniques thus developed [8, 9].

The categories of tracheal replacements that were explored are reviewed here in some detail, although complete review is nearly impossible, so attracted have surgeons been by the illusory simplicity of developing a conduit to replace native trachea. No predictable and dependable replacement has yet been found. The intent of this review is not to discourage thoughtful exploration toward this goal, but to provide information that may forestall fruitless repetition of past failures. To this end, fundamental biological constraints have been emphasized. Considerable additional literature in German, French, and Japanese has been slighted, and apology is made for these oversights.


   Need for tracheal replacement
Top
 Abstract
 Introduction
 Need for tracheal replacement
Requirements for replacement
 Approaches to replacement
 Foreign materials
 Implantation of nonviable...
 Autogenous tissues
 Tissue engineering
 Tracheal transplantation
 Conclusions
 Selected references *
 Footnotes
 References
 
Most tracheal lesions can now be resected and primary reconstruction safely effected [8, 9]. The general limits of safe resection are about half of the tracheal length in adults and probably one third in small children. Limits vary widely depending on age, body build, local anatomy, pathology, and prior treatment. Lengthier, nonneoplastic lesions that cannot be removed safely followed by primary reconstruction, can usually be managed in the long term with T tubes or stents. The silicone airway so provided is at least as satisfactory as any prosthetic device yet fashioned for surgical tracheal replacement. Any tracheal replacement technique offered as an alternative must therefore be wholly dependable and provoke minimal complications or risk of fatality [10]. The special case and previously challenging problem of long segment congenital tracheal stenosis is now safely and effectively managed by slide tracheoplasty [11]. The remaining need for tracheal substitution is to permit extirpation of those few tumors of extended length, chiefly adenoid cystic carcinoma, in which invasion of larynx or mediastinum does not prohibit complete resection with reconstruction to the larynx. Few such patients are seen annually, even in clinics in which airway surgical procedures are performed frequently. Currently, these patients are managed palliatively with irradiation, stents, and T tubes. A safe and dependable method of tracheal replacement would indeed be useful and welcome for these few patients.


   Requirements for replacement
Top
 Abstract
 Introduction
 Need for tracheal replacement
 Requirements for replacement
Approaches to replacement
 Foreign materials
 Implantation of nonviable...
 Autogenous tissues
 Tissue engineering
 Tracheal transplantation
 Conclusions
 Selected references *
 Footnotes
 References
 
Belsey [2] iterated the requirements for tracheal replacement to be (1) a laterally rigid but longitudinally flexible tube, and (2) a surface of ciliated respiratory epithelium. The second criterion has proved to be desirable, but not essential [12, 13]. Patients can clear secretions by cough despite conduits lined with squamous metaplastic epithelium, skin, or foreign materials (silicone tubes, coated stents, metallic and other solid prostheses). Furthermore, the conduit must be initially airtight and become integrated into adjacent tissues, so that chronic inflammation, granulation tissue, infection, and erosion do not occur. Immunosuppressive therapy is undesirable for many reasons, especially because the principal need for tracheal replacement is extensive carcinoma (adenoid cystic and squamous cell). Finally, for a method to be practically considered, the technique of construction or insertion of the conduit must be surgically straightforward and the results predictably successful.

Other authors [14, 15] have added further that materials for tracheal replacement must be biocompatible, nontoxic, nonimmunogenic, and noncarcinogenic; must not dislocate or erode over time; ideally should provide or facilitate epithelial resurfacing; should avoid stenosis or late buckling; should resist bacterial colonization; should avoid accumulation of secretions; and must be permanent constructions.


   Approaches to replacement
Top
 Abstract
 Introduction
 Need for tracheal replacement
 Requirements for replacement
 Approaches to replacement
Foreign materials
 Implantation of nonviable...
 Autogenous tissues
 Tissue engineering
 Tracheal transplantation
 Conclusions
 Selected references *
 Footnotes
 References
 
The belief that persisted for many years that only a few centimeters of trachea could be resected circumferentially and the trachea safely anastomosed [1, 2], stimulated the early search for a tracheal prosthesis. Today, the need for replacement is recognized to be much more limited. The quest continues because of the more closely defined needs that have been presented. In general, lines of research have included (1) trials of a host of foreign materials with many technical modifications to avoid complications of implantation; (2) implantation of nonviable tissues, including fixed trachea; (3) adaptation and transfer of autogenous tissues with or without scaffolding of foreign materials as patches or tubes; (4) tissue engineering of needed components such as cartilage; and (5) transplantation of allografts with and without immunosuppressive therapy, preservation, and vascularization procedures. Success has been announced episodically over the decades in each of these categories, but thus far no one replacement method has held for the long term in any safe and practicable manner.

The technique of lateral tracheal excision, principally for tumors, was practiced for many years, because of fear of creating tracheal discontinuity, which, it was believed, could not be reapproximated. The defect in the trachea was patched with a variety of foreign material and tissues [8]. The technique has been abandoned largely because of the frequency of recurrence of tumor due to inadequate margins resulting from the compulsion to save sufficient tracheal wall for structural reason. Also, necrosis and leakage of devascularized patches was often fatal, if they occurred in the mediastinum. However, combinations of vascularized tissue flaps (such as pericardium) and supporting foreign materials (such as Marlex) did succeed in healing in some cases, even if they were rarely successful oncologically.


   Foreign materials
Top
 Abstract
 Introduction
 Need for tracheal replacement
 Requirements for replacement
 Approaches to replacement
 Foreign materials
Implantation of nonviable...
 Autogenous tissues
 Tissue engineering
 Tracheal transplantation
 Conclusions
 Selected references *
 Footnotes
 References
 
The apparent simplicity of tracheal replacement encouraged trials of tubular conduits, initially of solid material. Because these foreign materials could not become incorporated by local tissues, problems of migration, dislodgement, infection, and obstruction usually arose. Epithelization, of course, was impossible. Furthermore, solid tubes can never be removed, because the connective tissue tract formed around them proceeds to obstruct with new connective tissue formation and by contraction [16] in the absence of a stent. Attention then turned to porous materials—often meshes of various substances—which might encourage tissue ingrowth and possibly even epithelization in time.

Solid prostheses
Foreign materials were used early on to form tubular replacements for resected trachea. The trachea was replaced experimentally, most often in dogs, with tubes of stainless steel [17, 18]; tight coils of steel wire [19]; Vitallium [4, 17]; glass [17]; polyethylene [16, 20–24]; Lucite [4, 19]; silicone [25–28]; Teflon [18, 29, 30]; Ivalon [4, 31]; polyvinyl chloride [32]; polyethylene, polyurethane, silicone elastomer, and Teflon combinations [33]; rigid and flexible silicone elastomer with Dacron cover [34]; and tubes of Teflon, Ivalon, and silicone elastomer [35].

Solid prostheses were also tried clinically in occasional cases: stainless steel [36, 37], steel coil [19], silicone [38, 39], polythene (polyethylene) [40, 41], Teflon [42], polyethylene and Tantalum [33], and Lucite [20]. Anastomoses after short resections were also carried out over splinting polythene stents [43].

Borrie and colleagues [26, 27] added suturable subterminal fabric cuffs to a silicone prosthesis, which was intussuscepted into the tracheal ends (experimentally in sheep), to prevent granulation tissue from obstructing the lumen and to encourage fixation of the prosthesis. Neville and his colleagues [38] used a similarly cuffed silicone tube clinically. Toomes and coworkers [39] experienced obstructive granulation tissue, migration, and vascular erosion with the same prosthesis. I personally have seen patients in consultation who had severe, recurrent, and insoluble granulation tissue obstruction at either end of a Neville prosthesis. Long segments of normal trachea had been excised to remove shorter stenotic lesions to accommodate the nonadjustable prostheses. In a number of patients, the original lesion could have been easily managed with a short resection and end-to-end anastomosis. Later, the prosthesis was placed inside an unresected stenotic trachea, where a silicone stent or T tube might have served better.

Solid prostheses, despite some successes for varied lengths of time, eventually tended to migrate, become dislodged, obstruct with granulation tissue at either end with subsequent stenosis, and encourage infection at the interface between foreign material, tracheal epithelium, and the granulation tissue bed. Erosion of the brachiocephalic artery not infrequently followed with fatal result. Complete epithelization rarely occurred beneath the prosthesis. Despite all of these complications, a rigid prosthesis can maintain an open airway for some time, despite a lack of healing. Such a result, however is, episodic and unpredictable. Daniel [17] mistakenly believed that tracheal rings regenerated structurally over a solid tube and Longmire [20] appeared to accept this unlikely event.

To date, nearly all surgical prostheses that have been successful—vascular conduits, heart valves, orthopedic devices—have been sited in potentially sterile mesenchymal tissues. No example of comparable success can be cited in the respiratory, gastrointestinal, or genitourinary tract. Here an interface inevitably persists among foreign material, chronically repairing connective tissue, and epithelium, which is a source of bacterial contamination. Trials of one material after another cannot be expected to solve this basic biological incompatibility.

Porous prostheses
To counter the usual failure of impervious solid prostheses, meshes made from a wide selection of materials were used experimentally. The porous structure was calculated to permit ingrowth of host connective tissue, incorporating the prosthesis into the tracheal site. It was found that a minimal porosity of 40 to 60 µm is necessary for capillary ingrowth [15]. It was hoped that this bed of autogenous new connective tissue would serve as a base for migration of adjacent tracheal epithelium. Regeneration of epithelium was described, with evolution from squamous to cuboidal to pseudostratified to ciliated cells [44, 45]. Meshes were sometimes supported with wire, plastic rings, or coils and sealed with tissues (such as omentum, fascia, pericardium) or biopolymers (such as fibrin sponge or reconstituted collagen) to prevent early air leakage. Experimental meshes included steel wire [16, 19, 24, 30, 46–48] variously wrapped with tissue for air tightness; stainless steel wire lined with dermis or various synthetic materials [18]; Tantalum [1, 3, 19, 24, 30, 49–51] with or without pleura or fascia; coated titanium fiber metal [52]; Marlex [24, 47, 53, 54]; Marlex with collagen [55], or with collagen reinforced by a polypropylene spiral [56, 57]; polytetrafluoroethylene (PTFE) [30, 58–62]; polyurethane [63]; Ivalon and wire [4, 64, 65]; Dacron and polyurethane [66]; and Teflon [30, 41].

The list of combinations is almost endless. Dacron was used [67] in patches of low and high porosity, with sloughing of the low-porosity material and eventual incorporation and epithelization of small patches of high-porosity Dacron over a prolonged period [66]. Experimental Z-plasty allowed tracheal approximation by relaxation and the sites of Z-plasty were patched with Dacron [68]. McCaughan [69] noted that silicone elastomer-reinforced Dacron produced granulations and stenosis. Surprisingly, ready incorporation of connective tissue and epithelization (in 5 to 7 weeks) of a 5-cm Gore-Tex (W.L. Gore and Assoc, Flagstaff, AZ) tube with reinforcing rings was reported [70], but details of epithelization and long-term results were lacking. Ingrowth of connective tissue in Dacron prostheses led to narrowing and obstruction [71]. Wide mesh Teflon with polypropylene rings [41] with an inner liner of solid polypropylene tube was also attempted.

Meshes were also used clinically as patches [72] or circumferentially: steel wire [19, 46]; Tantalum covered with fascia lata [73]; or skin and Tantalum gauze [74]; heavy Marlex [54, 75–78] sometimes covered with pedicled pericardium; and Ivalon and wire [63]. Pagliero and Shepherd [79] managed late postoperative dehiscence of the trachea by operative insertion of a stainless steel wire coil to splint open a connecting conduit of partly epithelized scar tissue.

Connective tissue ingrowth served to fix and incorporate some porous prostheses as noted. However, the continued proliferation of scar tissue most often led to obstruction and stenosis. Frequently, large sections of mesh, especially in longer segment replacements, remained uncovered by connective tissue and bacterial colonization followed. Epithelium generally failed to migrate sufficiently to cover the entire neotracheal surface, allowing continued cicatrix formation, usually in the center of the replacement [8]. Although very short interpositions might achieve full epithelization, which seemed to prevent further cicatrization, the rate and completeness of epithelial migration was usually insufficient to prevent central granulations, cicatrization, and stenosis. Obviously, very short tracheal replacements offered no solutions to the problem addressed.

Pearson and colleagues [54] endeavored experimentally to provide a source of epithelization by advancing partially detached terminal rings of cartilage, with mucous membrane intact, obliquely over Marlex replacements. Stenotic obstruction and brachiocephalic artery erosion attended some Marlex tracheal replacements in humans [54, 78] and experimental animals. Death occurred similarly with steel mesh prosthesis [19]. Marlex mesh that fails to become fully covered harbors bacteria (notably Pseudomonas aeruginosa), which produce purulent sputum and foul odor. One patient, who over many years had lost his wife, his job, and his friends because of intolerable halitosis from a Marlex reconstruction of cervical trachea, was finally relieved by its excision and placement of a silicone T tube. Thus, the dual problem of infection or of granulation tissue and scar formation, sometimes in irregular patterns, tends to prevent even incorporation of porous prostheses [41]. An impervious inner liner prevents the overgrowth of obstructing granulation tissue, but full epithelization was not seen and such an internal liner can never be removed [41].


   Implantation of nonviable tissues
Top
 Abstract
 Introduction
 Need for tracheal replacement
 Requirements for replacement
 Approaches to replacement
 Foreign materials
 Implantation of nonviable...
Autogenous tissues
 Tissue engineering
 Tracheal transplantation
 Conclusions
 Selected references *
 Footnotes
 References
 
Cadaver trachea and other tissues, fixed chemically, frozen, or lyophilized, have been used both experimentally and clinically as tracheal replacements. Such implantation has mistakenly been called "transplantation" or described as a "tracheal allograft" despite its nonviable, denatured status. Bioprosthesis may be a better term, because a fixed tissue is more akin to tanned leather than it is to transplanted tissue in the usual sense. Preserved or lyophilized tissues are usually replaced in time by host scar tissue [80], the rate possibly dependent on the locus of implantation. Dead tissue cannot be expected to function as a template for regeneration of the complex structure of the trachea in accord with any basic biological processes yet identified.

Experimentally, Scherer and associates [15] processed rat, guinea pig, and pig tracheas chemically, including tanning with glutaraldehyde, and variously implanted tracheal segments and window patches as autografts, allografts, and xenografts. Rejection seemed to be avoided. Variable long-term morphologic survival of cartilage and epithelization occurred in rats, but not in pigs. Pressman and Simon [23] used sterilized and lyophilized aortic homografts over polyethylene tubes in dogs to exclude granulation tissue. Stenosis was prevented by the stent, but linear contraction stretched and deformed the proximal and distal ends of the trachea. The damaged rings calcified and tracheal epithelium surfaced the aortic graft. Marrangoni [81] in 1951 and Greenberg and Williams [82] in 1960 observed that lyophilized canine tracheal allografts lost their cartilage and were replaced by scar tissue. Björk and Rodriguez [31] implanted freeze-dried, formalin fixed. and 95% alcohol-treated allografts, with fatal stenosis or necrosis in all. Related laboratory experiences are described below in the section on Allografts: Preserved, Devascularized. These experiences are included in the Tracheal Transplantation section for completeness, because many investigators analyzed both fresh and preserved grafts in their experiments.

More recently, this avenue has been reexplored. Clinically, cadaver tracheal graft fixed in formalin and stored in merthiolate, implanted and observed more than 13 months, showed histologic disintegration and reduced allogenicity [83]. Jacobs and colleagues [84] further described "tracheal allograft reconstruction" in adults and children, using cadaver trachea treated with 4% formalin, followed by thimerosal, and stored in acetone. The cartilaginous portion of long stenoses of various etiologies (or the anterolateral portion in the case of congenital O-rings) were excised and replaced with the fixed tissue, supported by Dumon or Hood silicone intraluminal stents. Frequent bronchoscopy was necessary to remove exuberant granulation after stent removal, but complete epithelization was described after unspecified intervals, based on bronchoscopic visualization and histologic samples. Of 6 patients, 1 died of innominate artery fistula, 2 had tracheomalacia requiring stents, 1 with stent replacement subsequently removed "recently" needed frequent bronchoscopy for granulations, 1 underwent stenting with a tracheostomy tube, and 1 (operated on 6 months previously and who needed a tracheostomy tube) underwent decannulation for an unspecified time [84]. In summary, 1 patient in 6 was free of stents with an adequate airway over short term [84]. Somewhat better results were cited for 18 of 31 children (58%) so treated in Europe, but detailed follow-up data were not given to permit full appreciation of final their status [85].

If full epithelization does occur by migration of tracheal epithelium from the intact posterior wall strip, it must be over host granulation tissue that has replaced the cadaveric graft. This occurrence would explain the exuberant granulations described and also the development of serious malacia as the dead cartilage is resorbed and replaced by cicatrix. It is biologically inconceivable that wholly dead cartilage could become reconstituted as living cartilage. In effect, we appear to be dealing with an oversized patch tracheoplasty using fixed tissue rather than fresh autologous costal cartilage or pericardium. Indeed, in an earlier commentary, some authors [86] stated that the graft "becomes very fibrotic according to the samples of the few patients ... who have died ... There is no live cartilage in the donor trachea."


   Autogenous tissues
Top
 Abstract
 Introduction
 Need for tracheal replacement
 Requirements for replacement
 Approaches to replacement
 Foreign materials
 Implantation of nonviable...
 Autogenous tissues
Tissue engineering
 Tracheal transplantation
 Conclusions
 Selected references *
 Footnotes
 References
 
Free grafts with and without foreign material support
The use of autogenous tissue—such as omentum—to seal mesh prostheses was noted earlier. Foreign materials, however, have been used to support free grafts of autogenous tissues either as patches or in tubular form. Experimental patches or tubular constructions have used fascia [17, 50, 87, 88], tracheal wall [89] diced cartilage against wire mesh and glass cylinders [19], dermal grafts laced with wire [4], fascia with Tantalum wire support [1], pericardium [90], pericardium with Marlex, free periosteum with omental wrap [91, 92], bone strips and fibrocollagen [30], cartilage and perichondrial strips over silicone stents [93], costal cartilage, periosteum and rib over a polyethylene stent [94], periosteal patch applied to staggered intercartilaginous relaxing incisions [95] that was also applied clinically, composite patches of buccal mucosa and auricular cartilage [96], dura mater with wire [97], bladder mucosa with silicone elastomer or polyurethane stents [98, 99] with the epithelial face of the mucosa turned away from the lumen in order to form bone [74], and jejunal patches with microvascular reconstruction [100]. Tantalum-supported skin grafts [82], perichondrium from ear and rib, the latter on fascial flaps [101] that formed cartilage, became epithelized, but stenosed. Nasal cartilage with attached mucosa served as a patch [102] in dogs. The patch healed, but the cartilage was almost completely resorbed. The same occurred with tracheal wall [89]. Marshak and associates [103] later interposed cylinders of bladder mucosa surfaced over silicone elastomer tubes in dogs and achieved stable tubes lined with epithelium. However, edema followed removal of the stent and caused death by obstruction. A combination of scar tissue formation, contraction, and epithelization has been described in the healing of pericardial patches [104], sometimes misinterpreted as regeneration of cartilage from scar tissue [17, 28, 90].

Clinically, in 1943 and 1944, Belsey [2] performed two radical tracheal resections for "cylindroma," leaving a narrow strip of tracheal wall intact and reconstructing the defect with fascia lata supported by a coil of steel wire. Clagett and colleagues [40] also used this technique. A free bronchial patch [105] and free fascia lata [106] were also used in patients, the latter as early as 1912. The use of wire-supported dermal grafts to widen bronchi and trachea was extensively reported in the 1950s [107, 108]. Larger dermal grafts for tracheal repair were frequently unsuccessful [109, 110]. Dermal grafts wrapped around Tantalum tubes failed when used intrathoracically [12]. A patch of auricular cartilage was used to widen the lower trachea [111]. Free fascial grafts in small tracheal windows healed and epithelized [112]. Crafoord and Lindgren [113] used skin and cartilage to repair cervical trachea in 1945.

Costal cartilage [114] and, later, pericardium [115] were successfully used as patch grafts for treatment of long congenital stenosis, without specific revascularization. Only occasionally did necrosis occur [116]; re-epithelization was noted [104]. Pericardium was replaced with mature scar tissue [104]. Tracheal growth was also reduced [117]. Even with addition of an omental pedicled flap [118], a cartilage patch is in time resorbed.

Vascularized autogenous tissue flaps
Another route of reconstruction, either as a flap for tracheal repair after lateral or "window" resection or as a tube after circumferential resection, was to use the patient’s own tissues, preserving or reanastomosing the blood supply. Because relative rigidity is necessary, free grafts of cartilage, plastic rings, or meshes were added for support. Foreign material or cartilage autografts were implanted in mesenchymal tissue. In general, lateral resection of tumor is not favored because of the likelihood of inadequate resection, as well as problems in healing of free tracheal patches, especially when the patches are intrathoracic. A vascularized patch is less likely to necrose than a free patch. On rare occasions, this technique is still used when a long segment of lateral tracheal wall must be removed to obtain complete resection of an invasive secondary neoplasm. Where circumferential resection is not possible because of the length of neoplastic involvement, lateral excision of the wall and reconstruction with a pedicled pericardial flap supported by materials such as Marlex may be effective.

Experiments in vascularized flap repair of window defects have included pedicled intercostal muscle patch graft [119], pedicled periosteum [91], pedicled bronchus [120], and rib and pleural transfer with microvascular anastomosis for long anterior tracheal defects in dogs [121]. Half of these latter animals survived. Lofgren, Lindholm, and Jansson [122] performed in three stages a pedicled composite graft of buccal mucosa and Proplast (PTFE and pyrolytic graphite), with a connective tissue "external" layer, for repair of lateral tracheal defects in beagles.

Clinically, Nowakowski [123] used local skin flaps in 1909 to close cervical tracheal defects. Other flaps used have included pedicled intercostal muscle and pleura [124], without the wire supports for flaps that had been previously used in dogs; periosteum on a muscular pedicle for lateral repair [125]; rotated bronchus [126]; pedicled diaphragm to posterior tracheal wall [127]; and pedicled patch of pericardium supported by Marlex for repair of a long lateral defect (J.C. Wain, unpublished). A pedicled intercostal periosteal flap was used to repair tracheoesophageal fistula [128].

The use of cartilage grafts and hyoid bone transfers to enlarge the stenotic larynx either anteriorly or posteriorly is an extensive topic by itself [129] and will not be discussed here.

Autogenous tube construction
The cervical trachea has been reconstructed experimentally by formation of a cutaneous trough, supported by cartilage or plastic rings, with staged closure of the trough [12, 130, 131]. Edgerton and Zovickian [12] reviewed early attempts at creation of skin flaps, including tubed pedicles, supported with rib or costal cartilage and sometimes lined with split grafts. In 1964, Grillo and associates [6] designed a staged repair of the cervical trachea to replace a cervical tracheal segment devolved with its blood supply into the mediastinum for primary intrathoracic anastomosis. A cutaneous tube was formed in stages, supported by polypropylene rings inserted between dermis and the attached platysma [131]. In 1939 Serrano and colleagues [132] inserted a series of bilateral hemi-rings of cartilage carved from costal arch to provide support when a skin trough was finally closed anteriorly.

Doctors Joo Hyun Kim and H.C. Grillo (unpublished) constructed staged tracheal replacements in dogs by allowing the perichondrium of two costal cartilages to form a cartilaginous tube around a silicone mold in situ, later lining this tube with buccal mucosa, and, finally, transferring it to a thoracic site with blood supply from the still-attached but mobilized intercostal muscle pedicles. As might be expected in such a complex repair, only a percentage of preparations fully succeeded. The work was, therefore, not published.

Papp and colleagues [133] wrapped intercostal muscle, stiffened with cartilage and lined with skin around a stent, in dogs. The complexity of the procedure led to high mortality. Krespi and colleagues [134] wrapped a pleural periosteal flap around a silicone elastomer stent and after 6 weeks in a subcutaneous location, moved the tube to an orthotopic location, but with uncertain results. Botta and Meyer [135] used a rat model and prepared in multiple stages a connective tissue tube with allografts of tracheal cartilage, previously prepared to reduce antigenicity, around a silicone elastomer tube, later lined with buccal mucosa, with regional supply from implantation. Their tube was eventually anastomosed by microsurgical technique to cervical vessels. The complexity was clinically daunting. Kon and Van den Hooff [136] also produced cylinders of cartilage by wrapping rib perichondrium around a silicone rod implanted in tissue.

Another line of experimental reconstruction with host tissue has been the use of adjacent esophagus to replace a long segment of trachea. Mural splinting is required to maintain patency, although, amazingly enough, in some experiments the splinting seems to have been unneeded. In my laboratory, placement of a series of discontinuous polypropylene rings failed when the adjacent supported segments caused obstruction by sliding laterally. A suggestion that an esophageal segment be substituted for trachea just to provide a channel for a T tube [137] seems to overlook the magnitude of operation that is then needed for esophageal replacement. In an effort to avoid the necessity of a major operation for later esophageal replacement, revascularized segments of small intestine have also been used experimentally [138]. Given the collapsibility of small intestine, it is difficult to understand how respiration was possible, unless the interposed segment was very short.

Clinically, multistaged cutaneous tubes have been widely used for construction of cervical trachea. Multiple trough techniques have been devised and used [12, 139–149]. Edgerton and Zovickian [12] attained success in multistaged flap reconstruction of cervical trachea clinically. Grillo [13] described clinical application of his two-staged technique. Although successful in a few patients, the technique is not recommended because of an overall low success rate. It should be noted that staged repairs of the type listed have no application intrathoracically where an airtight airway must be attained immediately. Failure of healing, likely to occur in some cases after complex repairs, could cause fatal mediastinitis in the chest.

Esophagus in situ has also been used to patch the membranous tracheal wall and to serve as a long linear patch for congenital stenosis [150, 151]. Fonkalsrud and colleagues [152, 153] tried unsuccessfully to replace trachea with a segment of esophagus for agenesis and for stricture.


   Tissue engineering
Top
 Abstract
 Introduction
 Need for tracheal replacement
 Requirements for replacement
 Approaches to replacement
 Foreign materials
 Implantation of nonviable...
 Autogenous tissues
 Tissue engineering
Tracheal transplantation
 Conclusions
 Selected references *
 Footnotes
 References
 
As described in the prior section, inducing formation of a cartilaginous tube by wrapping perichondrium around an inert cylinder (providing a lining with buccal mucosa or skin graft) is, in a sense, tissue engineering. However, current use of the term implies formation of tissue by cultivated cells introduced into a framework of biodegradable synthetic polymer, which guides the shape and size of a macrostructure, such as a tube [154]. Thus, chondrocytes placed on a template of polyglycolic acid fibers after incubation and implantation produced cartilage of selected shape and size over 4 weeks [155]. Vascularized connective tissue surrounded the implants and lined the inner surface. The structure resisted collapse and was used to replace segments of trachea in rats. In further experiments, effort was made to seed the inner surface with tracheal epithelial cells [156]. Work in this area continues. A combination of these two technical concepts—the "growth" of a segment for tracheal replacement and its implantation where the vascularized tube may later be swung into place—may in time become a useful technique. In benign disease a T tube could provide an interim airway.


   Tracheal transplantation
Top
 Abstract
 Introduction
 Need for tracheal replacement
 Requirements for replacement
 Approaches to replacement
 Foreign materials
 Implantation of nonviable...
 Autogenous tissues
 Tissue engineering
 Tracheal transplantation
Conclusions
 Selected references *
 Footnotes
 References
 
Nonrevascularized grafts
Autografts: fresh, devascularized
In 1918, Burket [157] reported successful fresh autografts of three- to nine-ring segments in 4 of 8 dogs. The other animals, which also had two allografts, died with tracheal strictures. These animals died in 7 and 8 days in contrast with longer survival for autografts (except for one early "breakdown"). The author did not comment on this difference between autografts and allografts. Experiments since have shown that immediate orthotopic reimplantation of an animal’s own trachea after excision (a fresh autograft) was most often unsuccessful because regeneration of local blood supply is too slow to nourish the complex tissues of the trachea [3, 26, 31, 89, 158–160]. However, variable results have been reported experimentally with devascularized autografts of different lengths with survival of the graft likely with short segments [25, 159, 161], or with bronchial patches placed in the trachea [49, 161]. With very short segments replanted, animals survived but the cartilage was often resorbed and the segment converted to fibrous tissue [35]. With longer segments, dissolution, stenosis, and obstruction followed [159] due to loss of blood supply.

Mayer and coworkers [162] found that continuous local infusion of basic fibroblast growth factor appeared to enhance early revascularization and epithelial regeneration in tracheal isograft segments in rats when implanted in omentum. Olech and colleagues [163], in contrast, detected no beneficial effect of growth factor, but basic fibroblast growth factor was administered as a single local application in a carrier.

Allografts: fresh, devascularized
Fresh tracheal allografts without aid of immunosuppressive therapy initiate rejection [161, 164–166]. Uniform failure of fresh allografts of any length occurs [12, 25, 35, 89, 159], even with immune suppression (Imuran, Decadron) in the absence of revascularization. Neville and associates [159] identified the same processes as seen with autografts, with survival only in very short grafts in which the resulting fibrous tissue was too limited to obstruct the lumen. With longer allografts, all dogs died. Allografts of partial tracheal wall removal [167] prevented obstruction, but grafts were replaced by flaccid scar.

Fresh tracheal allografts were early demonstrated to necrose and liquefy [14], or, if short, to result in fibrous stenosis [3, 49, 161, 168, 169]. Beigel and coworkers [164] found from experimentation in inbred rats that tracheal transplants carry antigens and have an immunogenic action from the donor, and that mucosa is rejected and replaced by recipient’s cells. Hence, they concluded that tracheal transplants follow the same rules as other tissues in opposition to the earlier belief that the trachea had weak antigenicity [170]. Bujia and colleagues [165] also agreed that mucosa from human trachea was likely the major antigenic structure responsible for immunogenic action of tracheal allografts.

Allografts: preserved, devascularized
In 1950, Jackson and coworkers [14] found that partly de-epithelized, Merthiolate-treated, and cold-preserved canine allografts failed in repair of extensive defects. Cartilage resorption and scar replacement produced collapse and obstruction. In 1952, Davies and colleagues [171] found that fresh canine allografts preserved in Tyrode’s solution or 4% formaldehyde narrowed to complete obstruction in 1 to 3 weeks. Epithelium and cartilage disappeared and fibrosis occurred. Pacheco and colleagues [161] described destruction and fibrosis of fresh allografts (short enough so that autografts in concurrent experiments survived), and stenosis of allografts preserved in alcohol or saline or when lyophilized. Björk and Rodriguez [31] confirmed this finding in grafts preserved in Tyrode’s solution at -4°C, lyophilized grafts, and in grafts formalinized or preserved in alcohol. Keshishian and coworkers [19] observed liquefaction and necrosis of canine allografts preserved in Tyrode’s solution at -4°C. Cryopreserved cartilaginous allografts placed on tracheal window defects in piglets appeared to survive with some resorption and become epithelized [172].

Keshishian and colleagues [19] also transplanted six-ring allografts in dogs after about 2 weeks of preservation in Tyrode’s solution. All necrosed. Diced autogenous costal cartilage molded between glass and stainless steel mesh survived in rectus muscle, but not as a tracheal replacement. When half the cartilage was allograft, the implant failed in muscle, too. Lenot and associates [173] used a pig model and demonstrated necrosis of devascularized tracheal allografts pretreated with glutaraldehyde, glycerol, lyophilization, or cryopreservation. Immunosuppressive agents and steroids were not given. All died from resulting airway obstruction. Although response varied somewhat in accordance with methods of preservation, the results were uniformly disastrous—the result of ischemic necrosis of epithelium, submucosa, and cartilage [173].

This slow accumulation of evidence in both autografts and allografts treated in a variety of ways clarified that blood supply was critical if successful tracheal transplantation was ever to be possible. Macchiarini [174] summarized as follows: "(D)evascularized tracheal allografts necrose whatever the conservation procedure. Only a living substitute, therefore vascularized, can pretend to fulfill the anatomic mechanical and antiinfectious functions of the trachea."

Vascularized grafts
Revascularization of an orthotopic tracheal graft can be accomplished indirectly with pedicled omentum, intercostal muscle, musculofascial flap, or other pedicles, or directly by vascular anastomoses.

Autografts: fresh, indirectly vascularized
Several researchers [175–177] used omentopexy to revascularize free tracheal grafts in rats and in dogs with considerable success. Nakanishi and associates [160] demonstrated that omental wrapping allowed fresh tracheal autografts to recover from the early ischemic changes as new vessels connected to the graft. Morgan and colleagues [178] had earlier demonstrated the neovascularizing potential of omentum for bronchi. Fell and colleagues [179] found an intercostal pedicle flap to function similarly in bronchial autografts. Li and colleagues [180] noted better vascularization and survival of autografts initially reimplanted in the omentum abdominally and transferred 2 weeks later to a tracheal site on an omental pedicle.

However, even with omental revascularization, canine autografts longer than 4 cm (8 to 10 rings) frequently showed stenosis or dissolution in their central portions due to ischemia [181]. Introducing omentum into an autograft split at the midpoint did, however, provide vascularity sufficient to prevent central graft necrosis [182]. Balderman and Weinblatt [183] did not find that omental wrapping sustained chondrocyte viability in eight-ring tracheal autografts in dogs. Li and associates [180] improved epithelial and chondrocyte survival by preliminary implantation of autografts into omentum about 2 weeks before transfer to an orthotopic location. Others [184, 185] showed survival of omental-wrapped autografts with normal histologic structure. Murai and colleagues [186] removed cartilage rings from long autografts to improve omental contact and revascularization of epithelium.

Allografts: fresh or preserved and indirectly vascularized
Fresh allografts with omental revascularization have failed, most probably due to rejection [183–185, 187–189]. Recovery of epithelium from initial damage before establishment of vascular supply from omentum, which is seen in autografts, failed to occur in allografts [190]. Cryopreserved allografts with omental flap revascularization survived without immunosuppressive therapy [184, 185, 191]. Cryopreservation seems to inhibit allogenicity while structural integrity appears to be maintained. Mukaida and coworkers [192] observed gradual replacement of graft epithelium by recipient epithelial cells after 50 to 60 days. Deschamps and associates [193] noted some deterioration of cartilage in allografts implanted in abdominal muscle for vascularization, despite cryopreservation. Other tracheal elements seem to be unchanged. Moriyama and associates [194] found that cryopreservation of allografts reduced acute rejection and permitted early revascularization, but that chronic rejection then led to vascular occlusion and atrophy.

Tojo and coworkers [195] in orthotopic cryopreserved tracheal allografts in rats without immune suppression also identified the late (2 months) graft epithelium to be of recipient origin while the chondrocytes were of donor origin. They concluded that recipient origin of epithelium over the donor trachea accounted for the reduced antigenicity of the cryotransplanted trachea. Inutsuka and colleagues [196] noted the feasibility of cryopreservation of tracheocarinal allografts in dogs (for 3 weeks at -80°C) and subsequent viability in 75% without immunosuppressive therapy. The effectiveness of cryopreservation is unexplained.

Based on the likelihood that the mucosa and not the cartilage is the major antigenic structure of the trachea, Liu and coworkers [189] removed epithelium with a detergent. Omental revascularization was provided. Cartilage remained viable. Allografts (without immunosuppressive therapy) were incorporated without stenosis, compared with granulation tissue formation and stenosis in untreated controls. Yokomise and colleagues [187] reported long-term (longer than 1 year) survival of heavily irradiated five-ring allografts (100,000 cGy) with an omental pedicle for vascularization. No immunosuppressive therapy was given. This survival is likely the result of ablation of tracheal epithelium by irradiation, because the epithelium seems to have strong antigens [164], whereas cartilage does not [197].

Major histocompatibility complex antigens (MHC II, MHC I) are expressed in epithelium and mixed glands of the trachea and not in cartilage [165]. Moriyama and colleagues [188] found that immunosuppressive therapy was essential for tracheal graft survival along with omentopexy in dogs. Davreux [198] showed that tracheal allograft viability in rats, wrapped in omentum and heterotopically implanted, was improved with cyclosporin A. Central portions of longer grafts were less well-vascularized. Late endothelial repopulation by host cells was cited. The trachea survived where control skin grafts did not. Ueda and Shirakusa [199] experienced failure in four of six carinal allografts in dogs with omental wrapping and immunosuppressive therapy. Failure was attributed to failure of blood supply, even in short-segment grafts. Delaere and colleagues [200, 201] concluded that initial heterotopic tracheal transplantation (in rabbits), using a fascial vascular carrier flap with a 2-week delay to orthotopic placement with immunosuppressive therapy, improved success in allotransplantation.

Clinical tracheal allotransplantation has been tried in humans, with success reported in 1 patient after 9 weeks [170]. The donor trachea was first implanted heterotopically in the sternocleidomastoid muscle and pedicled orthotopically in 3 weeks. No immunosuppressive therapy was used. In another human long-segment allograft with omental revascularization and immunosuppressive therapy, necrosis and stenosis occurred, requiring a stent that could not be removed [202]. Its "success" must be questioned.

Direct revascularization
The arterial and venous supply of the trachea does not lend itself easily to direct revascularization. The vessels are of tiny diameter and segmental in distribution. Khalil-Marzouk [203] faced this problem by preparing a composite thyrotracheal graft, anastomosing the thyroid artery to the common carotid artery. Venous anastomosis was not done. In the absence of immunosuppressive therapy, cartilage was preserved but tracheal soft tissues necrosed. With cyclosporin and hydrocortisone, all tracheal tissues survived.

Macchiarini and colleagues [204], in a heterotopic pig model using cyclosporin, observed preservation of tracheal grafts, including epithelium, but only when both arterial and venous anastomosis was accomplished. Venous infarction occurred in the absence of venous anastomosis. Khalil-Marzouk’s observations are difficult to reconcile with this result. Grafts were 9 to 11 cm long. Isolated areas of submucosal necrosis, especially in membranous wall, repaired within a week [205]. These investigators also explored experimental thyrotracheoesophageal transplantation [206], adding perfusion of the arterial system of the graft with Euro-Collins solution.

In double-lung transplantation, direct bronchial artery revascularization has been done to prevent the still major threat of ischemia at the tracheal anastomosis. Couraud and colleagues [207] harvested an aortic patch at the origin of the right intercostobrachial artery connecting it to the recipient aorta with a saphenous vein graft. Daly and colleagues [208] anastomosed the largest bronchial artery in a patch of donor descending aorta to the left internal thoracic artery.

Strome and associates [209] described fresh laryngeal transplantation with complete HLA matching, which included a five-ring segment of trachea, thyroid, and parathyroids, and a portion of attached pharyngeal wall, plus both superior laryngeal nerves and right recurrent nerve, to replace a totally scarred larynx due to trauma years previously. Arterial, venous, and neural anastomoses were done, and perfusion was established early in the procedure. Over time, the patient regained vocal cord function and normal deglutition. Despite one episode of rejection, health and function were good at 40 months, with continued immunosuppressive therapy [209]. This success, if generally repeatable, would seem to encourage a similar trial for the trachea. However, the quality of life issues involved in providing a functional larynx and voice are not comparable with providing a conduit for the trachea. Because tracheal transplantation would presently be applicable only to benign disease, the efficiency and safety of a T tube currently in use must be compared with the hazard of operation and the chronic disease state of immunosuppressive therapy now necessary for any tracheal transplantation.


   Conclusions
Top
 Abstract
 Introduction
 Need for tracheal replacement
 Requirements for replacement
 Approaches to replacement
 Foreign materials
 Implantation of nonviable...
 Autogenous tissues
 Tissue engineering
 Tracheal transplantation
 Conclusions
Selected references *
 Footnotes
 References
 
The flood of tracheal transplantation experiments in recent years, as noted above, has clarified some issues. Free autografts—an experimental procedure by definition—can sometimes succeed if they are short and at least vascularized by omentum. Fresh allografts require immunosuppressive therapy to counteract rejection and will succeed only, and then somewhat unpredictably, with omental revascularization, if very short in length. Cryopreserved allografts may survive under the same conditions without immunosuppressive therapy, but for unknown duration. Optimal regimens for immunosuppressive therapy and preservation have not been established. Other techniques for reducing antigenicity have been tried in the laboratory. Long grafts show necrosis or proliferation of granulation tissue progressing to stenosis in their center. Epithelization fails to proceed centrally. Arterial revascularization, because of the multiplicity and small size of blood vessels supplying the trachea, thus far demands transplantation of adjacent organs that share blood supply with the trachea—the thyroid gland and at least part of the esophagus. With these present limitations, the prospects for justifiable tracheal transplantation as a solution for extended tracheal resection, which is most often needed for malignant disease, remains remote. Substituting "tracheal" for "hand" makes Lundborg’s [210] opinion applicable in the nonneoplastic situation: "Only if the rejection process can be managed and controlled in an acceptable way ... [can] the procedure ... be justified. ... A [tracheal] transplantation is not necessary for a patient’s survival—we are dealing with a potentially life-threatening surgical procedure to treat a nonlife-threatening condition. [Tracheal] transplantation is a life-supporting procedure aiming at increased life quality."


   Selected references *
Top
 Abstract
 Introduction
 Need for tracheal replacement
 Requirements for replacement
 Approaches to replacement
 Foreign materials
 Implantation of nonviable...
 Autogenous tissues
 Tissue engineering
 Tracheal transplantation
 Conclusions
 Selected references *
Footnotes
 References
 


   Footnotes
Top
 Abstract
 Introduction
 Need for tracheal replacement
 Requirements for replacement
 Approaches to replacement
 Foreign materials
 Implantation of nonviable...
 Autogenous tissues
 Tissue engineering
 Tracheal transplantation
 Conclusions
 Selected references *
 Footnotes
References
 
* The reference section of the print version of this article contains 81 selected references, the numbers of which correspond to their text citation numbers. The complete list of all 210 references is viewable at: http://ats.ctsnetjournals.org. Back


   References
Top
 Abstract
 Introduction
 Need for tracheal replacement
 Requirements for replacement
 Approaches to replacement
 Foreign materials
 Implantation of nonviable...
 Autogenous tissues
 Tissue engineering
 Tracheal transplantation
 Conclusions
 Selected references *
 Footnotes
 References
 

  1. Rob C.G., Bateman G.H. Reconstruction of the trachea and cervical oesophagus. Br J Surg 1949;37:202-205.
  2. Belsey R. Resection and reconstruction of the intrathoracic trachea. Br J Surg 1950;38:200-205.[Medline]
  3. Ferguson D.J., Wild J.J., Wangensteen O.H. Experimental resection of the trachea. Surgery 1950;28:597-619.
  4. Michelson E., Solomon R., Maun L., Ramirez J. Experiments in tracheal reconstruction. J Thorac Cardiovasc Surg 1961;41:748-759.
  5. Cantrell J.R., Folse J.R. The repair of circumferential defects of the trachea by direct anastomosis: experimental evaluation. J Thorac Cardiovasc Surg 1961;42:589-598.
  6. Grillo H.C., Dignan E.F., Miura T. Extensive resection and reconstruction of mediastinal trachea without prosthesis or graft: an anatomical study in man. J Thorac Cardiovasc Surg 1964;48:741-749.
  7. Mulliken J., Grillo H.C. The limits of tracheal resection with primary anastomosis. Further anatomical studies in man. J Thorac Cardiovasc Surg 1968;55:418-421.[Medline]
  8. Grillo H.C. Surgery of the trachea. Curr Probl Surg 1970;Jul:3-59.
  9. Grillo H.C. Notes on the windpipe. Ann Thorac Surg 1989;47:9-26.[Free Full Text]
  10. Grillo H.C. Tracheal replacement. Ann Thorac Surg 1990;49:864-865.[Free Full Text]
  11. Grillo H.C., Wright C.D., Vlahakes G.J., MacGillivray T.E. Management of congenital tracheal stenosis by means of slide tracheoplasty or resection and reconstruction, with long-term follow-up of growth after slide tracheoplasty. J Thorac Cardiovasc Surg 2002;123:145-152.[Abstract/Free Full Text]
  12. Edgerton M.T., Zovickian A. Reconstruction of the trachea and infraglottic larynx. Plast Reconstr Surg 1954;13:167-192.
  13. Grillo H.C. Circumferential resection and reconstruction of the mediastinal and cervical trachea. Ann Surg 1965;162:374-388.[Medline]
  14. Jackson T.L., O’Brien E.J., Tuttle W., Meyer J. The experimental use of homogenous tracheal transplants in the restoration of continuity of the tracheobronchial tree. J Thorac Surg 1950;20:598-612.
  15. Scherer M.A., Ascherl R., Geissdorfer K., et al. Experimental biosynthetic reconstruction of the trachea. Arch Otorhinolarynol 1986;243:215-223.
  16. Morfit H.M., Neerken A.J., Prevedel A., et al. Sleeve resection of the trachea. Experimental studies on regenerative capacity and principles of reconstruction and repair. Arch Surg 1955;70:654-661.
  17. Daniel R.A., Jr The regeneration of defects of the trachea and bronchi. An experimental study. J Thorac Surg 1948;17:335-349.[Medline]
  18. Wykoff T.W. A preliminary report on segmental tracheal prosthetic replacement in dogs. Laryngoscope 1973;83:1072-1077.[Medline]
  19. Keshishian J.M., Blades B., Beattie E.J. Tracheal reconstruction. J Thorac Surg 1956;32:707-727.
  20. Longmire W.P., Jr The repair of large defects of the trachea. Ann Otol Rhinol Laryng 1948;57:875-883.[Medline]
  21. Grindlay J.H., Clagett O.T., Moersch H.J. Resection and anastomosis of the trachea: an experimental study. Ann Otol Rhinol Laryngol 1949;58:1225-1229.
  22. Craig R.L., Holmes G.W., Shabart E.J. Tracheal resection and replacement with a prosthesis. J Thorac Surg 1953;25:384-396.
  23. Pressman J.J., Simon M.B. Tracheal stretching and metaplasia of the tracheal rings from cartilage to bone following the use of aortic homografts. Am Surg 1959;25:850-856.
  24. Shaw R.R., Aslami A., Webb W.R. Circumferential replacement of the trachea in experimental animals. Ann Thorac Surg 1968;5:30-35.[Free Full Text]
  25. Spinazzola A.J., Graziano J.L., Neville W.E. Experimental reconstruction of the tracheal carina. J Thorac Cardiovasc Surg 1969;58:1-13.[Medline]
  26. Borrie J., Redshaw N.R. Prosthetic tracheal replacement. J Thorac Cardiovasc Surg 1970;60:829-835.[Medline]
  27. Borrie J., Redshaw N.R., Dobbinson T.L. Silastic tracheal bifurcation prosthesis with subterminal Dacron suture cuffs. J Thorac Cardiovasc Surg 1973;65:956-962.[Medline]
  28. Demos N.J., Mitnick H., McCally D., et al. Tracheal regeneration in long-term survivors with silicone prosthesis. Ann Thorac Surg 1973;16:293-300.[Abstract/Free Full Text]
  29. Kramish D., Morfit H.M. The use of a Teflon prosthesis to bridge complete sleeve defects in the human trachea. Am J Surg 1963;106:704-708.
  30. Bailey B.J., Kosoy J. Observations in the development of tracheal prostheses and tracheal transplantation. Laryngoscope 1970;80:1553-1565.[Medline]
  31. Björk V.O., Rodriguez L.E. Reconstruction of the trachea and its bifurcation. An experimental study. J Thorac Surg 1958;35:596-603.
  32. Moncrief W.H., Jr, Salvatore J.E. An improved tracheal prosthesis. Surg Forum 1958;9:350-352.
  33. McCall J.W., Whitaker C.W. The use of prostheses in the larynx and trachea. Ann Otol Rhinol Laryngol 1962;71:397-403.
  34. Cheng W.F., Takagi H., Akutsu T. Prosthetic reconstruction of the trachea. Surgery 1969;65:462-469.[Medline]
  35. Aronstam E.V., Nims R.M., Winn D.F., Jr Studies in segmental replacement of the thoracic trachea. J Surg Res 1961;1:108-110.[Medline]
  36. Jarvis F.J. Discussion. J Thorac Surg 1950;20:649.
  37. Cotton B.H., Penido J.R.F. Resection of the trachea for carcinoma. J Thorac Surg 1952;24:231-245.
  38. Neville W.E., Bolanowski P.J.P., Kotia G.G. Clinical experience with the silicone tracheal prosthesis. J Thorac Cardiovasc Surg 1990;99:604-613.[Abstract]
  39. Toomes H., Mickisch G., Vogt-Moykopf I. Experiences with prosthetic reconstruction of the trachea and bifurcation. Thorax 1985;40:32-37.[Abstract/Free Full Text]
  40. Clagett O.T., Moersch H.J., Grindlay J.H. Intrathoracic tracheal tumors: development of surgical techniques for their removal. Ann Surg 1952;136:520-530.
  41. Atamanyuk M.Y., Melrose D.G. The treatment of circumferential defects of the trachea. Br J Surg 1965;52:59-65.
  42. Ekeström S., Carlens E. Teflon prosthesis in tracheal defects in man. Acta Chir Scand 1959;245(Suppl):71-75.
  43. Clagett O.T., Grindlay J.H., Moersch H.J. Resection of the trachea: an experimental study and a report of a case. Arch Surg 1948;57:253-266.[Abstract/Free Full Text]
  44. Condon W.B. Regeneration of tracheal and bronchial epithelium. J Thorac Surg 1941;11:333-346.
  45. Wilhelm D.L. Regeneration of tracheal epithelium. J Path Bact 1953;65:543-550.
  46. Bucher R.M., Burnett E., Rosemond G.P. Experimental reconstruction of tracheal and bronchial defects with stainless steel wire mesh. J Thorac Surg 1951;21:572-583.
  47. Greenberg S.D., Willms R.K. Tracheal prostheses. An experimental study in dogs. Arch Otolaryngol 1962;75:335-341.[Abstract/Free Full Text]
  48. Poticha S.M., Lewis F.J. Experimental replacement of the trachea. J Thorac Cardiovasc Surg 1966;52:61-67.[Medline]
  49. Carter M.G., Strieder J.W. Resection of the trachea and bronchi. An experimental study. J Thorac Surg 1950;20:613-627.
  50. Swift E.A., Grindlay J.H., Clagett O.T. The repair of tracheal defects with fascia and tantalum mesh. J Thorac Surg 1952;24:482-492.
  51. Kiriluk L.B., Merendino K.A. An experimental evaluation in the dog of bronchial transplantation, bronchial, tracheal and tracheobronchial resection with reconstruction. Ann Surg 1953;137:490-503.
  52. Mendak S.H., Jr, Jensik R.J., Haklin M.F., Roseman D.L. The evaluation of various bio-absorbable materials on the titanium fiber metal tracheal prosthesis. Ann Thorac Surg 1984;38:488-493.[Abstract/Free Full Text]
  53. Beall A.C., Jr, Harrington O.B., Greenberg S.D., Morris G.C., Jr Tracheal replacement with heavy Marlex mesh. Arch Surg 1962;84:390-396.
  54. Pearson F.G., Henderson R.O., Gross H.E., et al. The reconstruction of circumferential tracheal defects with a porous prosthesis. An experimental and clinical study using heavy Marlex mesh. J Thorac Cardiovasc Surg 1968;55:605-616.[Medline]
  55. Sekine T., Nakamura T., Matsumoto K., et al. Carinal reconstruction with a Y-shaped collagen-conjugated prosthesis. J Thorac Cardiovasc Surg 2000;119:1162-1168.[Abstract/Free Full Text]
  56. Okumura N., Nakamura T., Natsume T., et al. Experimental study on a new tracheal prosthesis made from collagen-conjugated mesh. J Thorac Cardiovasc Surg 1994;108:337-345.[Abstract/Free Full Text]
  57. Teramachi M., Okumura N., Nakamura T., et al. Intrathoracic tracheal reconstruction with a collagen-conjugated prosthesis: evaluation of the efficacy of omental wrapping. J Thorac Cardiovasc Surg 1997;113:701-711.[Abstract/Free Full Text]
  58. Bottema J.R., Wildevuur C.R.H. Incorporation of microporous Teflon tracheal prostheses in rabbits: evaluation of surgical aspects. J Surg Res 1986;41:16-23.[Medline]
  59. Shaha A., MiMaio T., Morrey S., et al. Prosthetic reconstruction of the trachea. Am J Surg 1988;156:306-309.[Medline]
  60. Cull D.L., Lally K.P., Mair E.A., et al. Tracheal reconstruction with polytetrafluoroethylene graft in dogs. Ann Thorac Surg 1990;50:899-901.[Abstract/Free Full Text]
  61. Guijarro Jorge R., Sanchez-Palencia Ramos A., Cueto Ladrón de Guevara A., et al. Experimental study of a new porous prosthesis. Ann Thorac Surg 1990;50:281-287.[Abstract/Free Full Text]
  62. Hasse J. Patch-closure of tracheal defects with pericardium/PTFE. A new technique in extended pneumonectomy with carinal resection. Eur J Cardiothorac Surg 1990;4:412-416.[Abstract/Free Full Text]
  63. Nelson R.J., Goldberg L., White R.A., et al. Neovascularity of a tracheal prosthesis/tissue complex. J Thorac Cardiovasc Surg 1983;86:800-808.[Abstract]
  64. Taber R.E., Tomatis L. Experimental and clinical utilization of a prosthesis for replacement of the trachea. Arch Surg 1958;77:576-583.
  65. Yasargil E.E., Hess R. Beitrag zur plastichen. Überbrückung der thoracalen Trachealdefekte. Thoraxchirurg 1958;5:470-484.
  66. Jacobs J. Investigations into tracheal prosthetic reconstruction. Laryngoscope 1988;98:1239-1245.[Medline]
  67. Kaiser D. Alloplastic replacement of canine trachea with Dacron. Thorac Cardiovasc Surg 1985;33:239-243.[Medline]
  68. Worman L.W., Starr C., Narodick B.G. Tracheoplasty techniques for reconstruction after extensive resection. Am J Surg 1966;111:819.[Medline]
  69. McCaughan J.S., Jr Tracheal reconstruction with silastic reinforced Dacron. Arch Otolaryngol 1968;87:150-151.[Abstract/Free Full Text]
  70. Troján I., Kecskés L., Vécsei B., et al. Tracheal substitution in dogs with reinforced Gore-Tex prosthesis. Thorac Cardiovasc Surg 1985;33:337-340.[Medline]
  71. Leake D., Habal M., Pizzoferrato A., Vespucci A. Prosthetic replacement of large defects of the cervical trachea in dogs. Biomaterials 1985;6:17-22.[Medline]
  72. Podoshin L., Fradis M. Reconstruction of the anterior wall of the cervical trachea using knitted Dacron. Ear Nose Throat J 1976;55:294-296.
  73. Cahan W.G. Carcinoma of intrathoracic trachea: excision and repair by tantalum gauze-fascia lata graft. J Thorac Surg 1952;23:513-527.
  74. Edgerton M. One stage reconstruction of the cervical esophagus or trachea. Surgery 1952;31:239-250.
  75. Ellis P.R., Jr, Harrington O.B., Beall A.C., Jr, DeBakey M.E. The use of heavy Marlex mesh for tracheal reconstruction following resection for malignancy. J Thorac Cardiovasc Surg 1962;44:520-527.
  76. Beall A.C., Jr, Harrington O.B., Greenberg S.D. Tracheal reconstruction with heavy Marlex mesh. Arch Surg 1963;86:970-978.[Abstract/Free Full Text]
  77. Yeh T.J., Batayias G., Peters H., Ellison R.G. Metastatic carcinoma to the trachea: report of a case of palliation by resection and Marlex graft. J Thorac Cardiovasc Surg 1965;49:886-892.
  78. Moghissi K. Tracheal reconstruction with prosthesis of Marlex mesh and pericardium. J Thorac Cardiovasc Surg 1973;69:499-506.[Abstract]
  79. Pagliero K.M., Shepherd M.P. Use of stainless steel wire coil prosthesis in treatment of anastomotic dehiscence after cervical tracheal resection. J Thorac Cardiovasc Surg 1974;67:932-935.[Medline]
  80. Grillo H.C., McKhann C.F. The acceptance and evolution of dermal homografts freed of viable cells. Transplantation 1964;2:48-59.
  81. Marrangoni A.G. Homotransplantation of tracheal segments preserved by lyophilization; an experimental study. J Thorac Surg 1951;21:398-401.
  82. Greenberg S.D., Williams R.K. Tracheal reconstruction: an experimental study. Arch Otolaryngol 1960;72:565-574.
  83. Bujia J., Pitzke P., Krombach F., et al. Immunological behavior of preserved human tracheal allografts: immunological monitoring of a human tracheal recipient. Clin Transplant 1991;5:376-380.
  84. Jacobs J.P., Elliott M.J., Haw M.P., Bailey C.M., Herberhold C. Pediatric tracheal homograft reconstruction: a novel approach to complex tracheal stenosis in children. J Thorac Cardiovasc Surg 1996;112:1549-1560.[Abstract/Free Full Text]
  85. Jacobs J.P., Quintessenza J.A., Andrews T., Burke R.P., et al. Tracheal allograft reconstruction: the total North American and worldwide pediatric experiences. Ann Thorac Surg 1999;68:1043-1052.[Abstract/Free Full Text]
  86. Elliott M.J., Haw M.P., Jacobs J.P., et al. Tracheal reconstruction in children using cadaveric homograft trachea. Eur J Cardiothorac Surg 1996;10:707-712.[Abstract/Free Full Text]
  87. Davis J.S. The transplantation of free flaps of fascia. An experimental study. Ann Surg 1911;54:734-748.[Medline]
  88. Taffel M. The repair of tracheal and bronchial defects with free fascia grafts. Surgery 1940;8:56-71.
  89. Daniel R.A., Jr, Taliaferro R.M., Schaffarzick W.R. Experimental studies on the repair of wounds and defects of the trachea and bronchi. Dis Chest 1950;17:426-441.
  90. Bryant L.R. Replacement of tracheobronchial defects with autogenous pericardium. J Thorac Cardiovasc Surg 1964;48:733-740.
  91. Fonkalsrud E.W., Plested W.G., Mulder D.G. Tracheobronchial reconstruction with autologous periosteum. J Thorac Cardiovasc Surg 1966;52:666-674.[Medline]
  92. Cohen R.C., Filler R.M., Konuma K., et al. A new model of tracheal stenosis and its repair with free periosteal grafts. J Thorac Cardiovasc Surg 1986;92:296-304.[Abstract]
  93. Eckersberger F., Moritz E., Wolner E. Circumferential tracheal replacement with costal cartilage. J Thorac Cardiovasc Surg 1987;94:175-180.[Abstract]
  94. Sato R., Hasegawa I., Nakagawa J. Experimental study of tracheal reconstruction. J Thorac Surg 1957;34:526-538.
  95. Narodick B.G., Worman L.W., Pemberton A.H. Relaxation technique for tracheal reconstruction. Ann Thorac Surg 1965;1:190-196.[Free Full Text]
  96. Farkas L.G., Farmer A.W., McCain W.G., Wilson W.D. Replacement of a tracheal defect in the dog by a preformed composite graft. Plast Reconstr Surg 1972;50:238-241.[Medline]
  97. Sabás A.A., Uez J.B., Rojas O., et al. Replacement of the trachea with dura meter. Experimental work. J Thorac Cardiovasc Surg 1977;74:761-765.[Abstract]
  98. Rush B.F., Clifton E.E. Experimental reconstruction of the trachea with bladder mucosa. Surgery 1956;40:1105-1110.
  99. Barker W., Litton W. Bladder osteogenesis aids tracheal reconstruction. Arch Otolaryngol 1973;98:422-425.[Abstract/Free Full Text]
  100. Jones R.E., Morgan R.F., Marcella K.L., et al. Tracheal reconstruction with autogenous jejunal microsurgical transfer. Ann Thorac Surg 1986;41:636-638.[Abstract/Free Full Text]
  101. Ohlsen L., Nordin U. Tracheal reconstruction with perichondrial grafts. An experimental study. Scand J Plast Reconstr Surg 1976;10:135-145.[Medline]
  102. Drettner B., Lindholm C.E. Experimental tracheal reconstruction with composite graft from nasal septum. Acta Otolaryngol Scand 1970;70:401-407.
  103. Marshak G., Porter J.H., McAdams A.J. Reconstruction of the canine trachea with urinary bladder wall. Laryngoscope 1973;83:1090-1095.[Medline]
  104. Cheng A.T.L., Backer C.L., Holinger L.D., et al. Histopathologic changes after pericardial patch tracheoplasty. Arch Otolaryngol Head Neck Surg 1997;123:1069-1072.
  105. MacHale S.J. A new technique for repairing the major air passages. J Thorac Cardiovasc Surg 1972;64:6-10.
  106. Levit H. Deckung von Trachealdefecten durch line freie Plastik aus der Fascia lata femoris. Arch Klin Chir 1912;97:686-699.
  107. Gebauer P.W. Further experiences with dermal grafts for healed tuberculous stenosis of the bronchi and trachea. J Thorac Surg 1950;20:628-651.
  108. Evans B.H. Myxochondroma of the trachea. A case report. J Thorac Surg 1951;22:585-591.
  109. Paulson D.L. Plastic reconstruction of the trachea and bronchi. Am Rev Tuberc 1951;64:477-488.
  110. Abbott O.A., Van Fleit W.E., Roberto A.E. Experiences with extending the indications for the use of tracheal and bronchial grafts. J Thorac Surg 1955;29:217-237.
  111. Caputo V., Consiglio V. The use of patient’s own auricular cartilage to repair deficiency of the tracheal wall. J Thorac Cardiovasc Surg 1961;41:594-596.
  112. Neuhof H. Fascia transplantation into visceral defects. An experimental and clinical study. Surg Gynecol Obstet 1917;24:383-427.
  113. Crafoord C., Lindgren A.G.H. Mucous and salivary gland tumours in the bronchi and trachea. Acta Chir Scand 1945;92:481-506.
  114. Kimura K., Mukohara N., Tsugawa C., et al. Tracheoplasty for congenital stenosis of the entire trachea. J Pediatr Surg 1982;17:869-871.[Medline]
  115. Idriss F.S., DeLeon S.Y., Ilbawi M.N., et al. Tracheoplasty with pericardial patch for extensive tracheal stenosis in infants and children. J Thorac Cardiovasc Surg 1984;88:527-536.[Abstract]
  116. Backer C.L., Mavroudis C., Dunham C.E., et al. Re-operation after pericardial patch tracheoplasty. J Pediatr Surg 1997;32:1108-1112.[Medline]
  117. Dykes E.H., Bahoric A., Smith C., et al. Reduced tracheal growth after reconstruction with pericardium. J Pediatr Surg 1990;25:25-29.[Medline]
  118. Isugawa C., Nishijima E., Muraji T., et al. The use of omental pedicle flap for tracheobronchial reconstruction in infants and children. J Pediatr Surg 1991;26:762-765.[Medline]
  119. Blair E. Study of the viable intercostal pedicle graft in tracheobronchial surgery. J Thorac Surg 1958;36:869-878.
  120. Akl B.F., Mittelman J., Smith D.E., Butler C. A new method of tracheal reconstruction. Ann Thorac Surg 1983;36:265-269.[Abstract/Free Full Text]
  121. Watson J., Donald P.J., Gourley I.M., et al. Composite vascularized free-rib and pleural transfer for laryngotracheal reconstruction. Otolaryngol Head Neck Surg 1983;91:384-395.[Medline]
  122. Lofgren L.A., Lindholm C.E., Jansson B. Reconstruction of the airway with a composite alloplastic and autogenous graft. Acta Otolaryngol 1985;100:140-150.[Medline]
  123. Nowakowski K. Beitrag zur Tracheoplastik. Arch klin Chir 1909;90:847-861.
  124. Penton R.S., Brantigan O.C. The use of a viable pedicle graft for repairing an extensive tracheobronchial defect. Ann Surg 1952;135:709-714.
  125. Narodick B.G., Pemberton A.H., Worman L.W. Tracheoplasty by means of a periosteal pedicle graft. J Thorac Cardiovasc Surg 1964;47:572-576.
  126. Kergin F.G. Carcinoma of the trachea. J Thorac Surg 1952;23:164-168.
  127. Westaby S., Shepard M.P., Nohl-Oser H.C. The use of diaphragmatic pedicle grafts for reconstructive procedures in the esophagus and tracheobronchial tree. Ann Thorac Surg 1982;33:486-490.[Abstract/Free Full Text]
  128. Ross R.R. Repair of tracheal and esophageal defect by use of a pedicle graft. Surgery 1956;39:654-662.
  129. Cotton R.T. The problem of pediatric laryngotracheal stenosis: a clinical and experimental study on the efficacy of autogenous cartilaginous grafts placed between the vertically divided halves of the posterior lamina of the cricoid cartilage. Laryngoscope 1991;101(Suppl):1-34.[Medline]
  130. Fairchild F.R. Reconstruction of the trachea. Surg Gynecol Obstet 1927;44:119-122.
  131. Grillo H.C., Dignan E.F., Miura T. Experimental reconstruction of cervical trachea after circumferential resection. Surg Gynecol Obstet 1966;122:733-738.[Medline]
  132. Serrano A., Ortiz-Monasterio F., Andrade-Pradillo J. Reconstruction of the cervical trachea: a technique to obtain a permanently patent airway. Plast Reconstr Surg 1959;24:333-340.
  133. Papp C., McCraw J.B., Arnold P.G. Experimental reconstruction of the trachea with autogenous materials. J Thorac Cardiovasc Surg 1985;90:13-20.[Abstract]
  134. Krespi Y.P., Siller H.F., Baek S.M. Tracheal reconstruction with a pleuroperiosteal flap. Otolaryngol Head Neck Surg 1983;91:610-614.[Medline]
  135. Botta Y., Meyer R. Reconstruction expérimentale de la trachée par microchirurgie. Praxis 1978;67:1588-1592.[Medline]
  136. Kon M., Van den Hooff A. Cartilage tube formation by perichondrium: a new concept for tracheal reconstruction. Plast Reconstr Surg 1983;72:791-797.[Medline]
  137. Kato R., Onuki A.S., Watanabe M., et al. Tracheal reconstruction by esophageal interposition: an experimental study. Ann Thorac Surg 1990;49:951-954.[Abstract/Free Full Text]
  138. Letang E., Sánchez-Lloret J., Gimferrer J.M., et al. Experimental reconstruction of the canine trachea with a free revascularized small bowel graft. Ann Thorac Surg 1990;49:955-958.[Abstract/Free Full Text]
  139. LeJeune F., Owens N. Chronic laryngeal stenosis. Ann Otol Rhinol Laryngol 1935;44:354-363.
  140. Conley J.J. Rehabilitation of the airway system by neck flaps. Ann Otol Rhinol Laryngol 1962;71:404-410.
  141. Bryce D., Lawson V. The "trough" method of laryngotracheal reconstruction. Ann Otol Rhinol Laryngol 1967;76:793-803.[Medline]
  142. Kapur T.R. Tracheal injury and reconstruction. Br J Surg 1967;54:689-694.[Medline]
  143. Keim W.F. Total reconstruction of the cervical trachea. Arch Otolaryngol 1970;91:501-504.[Abstract/Free Full Text]
  144. Williams G.T. New material for a prosthesis used in tracheal reconstruction. J Laryngol Otol 1974;88:1175-1184.[Medline]
  145. Friedman W.A., Biller H.F., Som M.L. Repair of extended laryngotracheal stenosis. Arch Otolaryngol 1975;101:152-156.[Abstract/Free Full Text]
  146. Montgomery W.W. Reconstruction of the cervical trachea. Ann Otol Rhinol Laryngol 1964;73:5-11.
  147. In: Meyer R., ed. Reconstructive surgery of the trachea. New York: Thieme, 1982.
  148. Biller H.F., Lawson W., Weisberg V. Staged repair of extensive tracheal and laryngotracheal stenosis. Ann Otol Rhinol Laryngol 1986;95:586-589.[Medline]
  149. Eliachar I., Goldsher M., Moscona A.R., Hurwitz D.J. Reconstruction of the larynx and cervical trachea with the pectoralis major myocutaneous island flap. Head Neck Surg 1984;6:880-883.[Medline]
  150. Ein S.H., Friedberg J., Williams W.G., et al. Tracheoplasty—a new operation for complete congenital tracheal stenosis. J Pediatr Surg 1982;17:872-878.[Medline]
  151. Sasaki S., Hara F., Oowa T., et al. Esophageal tracheoplasty for congenital tracheal stenosis. J Pediatr Surg 1992;27:645-649.[Medline]
  152. Fonkalsrud E.W., Martelle R.R., Maloney J.V., Jr Surgical treatment of tracheal agenesis. J Thorac Cardiovasc Surg 1963;45:520-525.
  153. Fonkalsrud E.W., Suinida S. Tracheal replacement with autologous esophagus for tracheal stricture. Arch Surg 1971;102:139-142.[Abstract/Free Full Text]
  154. Mooney D.J., Vacanti J.P. Tissue engineering using cells and synthetic polymers. Transplant Rev 1993;7:153-162.
  155. Vacanti C.A., Paige K.T., Kim W.S., Sakata J., Upton J., Vacanti J.P. Experimental tracheal replacement using tissue engineered cartilage. J Pediatr Surg 1994;29:201-205.[Medline]
  156. Sakata J., Vacanti C.A., Schloo G.C., et al. Tracheal composite tissue engineered from chondrocytes, tracheal epithelial cells and synthetic biodegradable scaffolding. Transplant Proc 1994;26:3309-3310.[Medline]
  157. Burket W.C. Transplantation of the trachea. Bull Johns Hopkins Hosp 1918;29:35-40.
  158. Strandness D.E., Jr, Gustafson I.J., Payne J.T. Surgical resection of the thoracic trachea: an experimental study in dogs. J Thorac Surg 1957;34:269-277.
  159. Neville W.E., Bolanowski P.J.P., Soltanzadeh H. Homograft replacement of the trachea using immunosuppression. J Thorac Cardiovasc Surg 1976;72:596-601.[Abstract]
  160. Nakanishi R., Shirakusa T., Takachi T. Omentopexy for tracheal autografts. Ann Thorac Surg 1994;57:841-845.[Abstract/Free Full Text]
  161. Pacheco C.R., Rivero O., Porter J.K. Experimental reconstructive surgery of the trachea. J Thorac Surg 1954;27:554-564.
  162. Mayer E., Cardoso P.F.G., Puskas J.D., et al. The effect of basic fibroblast growth factor and omentopexy on revascularization and epithelial regeneration of heterotopic rat tracheal isografts. J Thorac Cardiovasc Surg 1992;104:180-188.[Abstract]
  163. Olech V.M., Keshavjee S.H., Chamberlain D.W., et al. Role of basic fibroblast growth factors in revascularization of rabbit tracheal autografts. Ann Thorac Surg 1991;52:258-264.[Abstract/Free Full Text]
  164. Beigel A., Steffins-Knutzen R., Muller B., et al. Tracheal transplantation. III. Demonstration of transplantation antigens on the tracheal mucosa of inbred rat strains. Arch Otorhinolaryngol 1984;241:1-8.[Medline]
  165. Bujia J., Wilmas E., Hammer C., Kastenbauer E. Tracheal transplantation: demonstration of HLA class II subregion gene products on human trachea. Acta Otolaryngol 1990;110:149-154.[Medline]
  166. Kalb T.H., Chuang M.T., Marom Z., Mayer L. Evidence for accessory cell function by class II MHC antigen-expressing airway epithelial cells. Am J Respir Cell Mol Biol 1991;4:320-329.
  167. Alonso W.A., Bridger G.P., Bordley J.E. Tracheal transplantation in dogs. Laryngoscope 1972;82:204-209.[Medline]
  168. Greenberg S.D. Tracheal homografts in dogs. AMA Arch Otolaryngol 1958;67:577-586.
  169. Harrington W.T., Hung W.C., Binns P.M. Experimental tracheal homografting. J Laryngol Otol 1977;91:101-110.[Medline]
  170. Rose K.G., Sesterhenn K., Wustrow F. Tracheal allotransplantation in man. Lancet 1979;1:433.[Medline]
  171. Davies O.G., Edmiston J.M., McCorkle H.J. The repair of experimental tracheal defects with fresh and preserved homologous tracheal grafts. J Thorac Surg 1952;23:367-376.
  172. Messineo A., Filler R.M., Bahoric A., Smith C.R. Repair of long tracheal defects with cryopreserved cartilaginous allografts. J Pediatr Surg 1992;27:1131-1135.[Medline]
  173. Lenot B., Macchiarini P., Dulmet E., et al. Tracheal allograft replacement. Eur J Cardiothorac Surg 1993;7:648-652.[Abstract/Free Full Text]
  174. Macchiarini P. La transplantation de trachée et trachéo-oesophagienne. Berançon, France: Université Franche-Comte, 1997.
  175. Messineo A., Filler R.M., Bahoric B., et al. Successful tracheal autotransplantation with a vascularized omental flap. J Pediatr Surg 1991;26:1296-1300.[Medline]
  176. Hirata T., Yamazaki F., Fukuse T., et al. Omentopexy for revascularization of free tracheal grafts in rats. Thorac Cardiovasc Surg 1992;40:178-181.[Medline]
  177. Borro J.M. Successful revascularization of large isolated tracheal segments. Eur J Cardiothorac Surg 1992;6:621-623.[Abstract/Free Full Text]
  178. Morgan E., Lima O., Goldberg M., et al. Successful revascularization of totally ischemic bronchial autografts with omental pedicle flaps in dogs. J Thorac Cardiovasc Surg 1982;84:204-210.[Abstract]
  179. Fell S.C., Mollenkopf F.P., Montefusco C.M., et al. Revascularization of ischemic bronchial anastomosis by an intercostal pedicle flap. J Thorac Cardiovasc Surg 1985;90:172.[Abstract]
  180. Li J., Xu H., Chen H., et al. Improvement of tracheal autograft survival with transplantation into the greater omentum. Ann Thorac Surg 1995;60:1592-1596.[Abstract/Free Full Text]
  181. Nakanishi R., Shirakusa T., Mitsudomi T. Maximum length of tracheal autografts in dogs. J Thorac Cardiovasc Surg 1993;106:1081-1087.[Abstract]
  182. Yokomise H., Inui K., Wada H., et al. Split transplantation of the trachea: a new operative procedure for extended tracheal resection. J Thorac Cardiovasc Surg 1996;112:314-318.[Abstract/Free Full Text]
  183. Balderman S.C., Weinblatt G. Tracheal autograft revascularization. J Thorac Cardiovasc Surg 1987;94:434-441.[Abstract]
  184. Tojo T., Niwaya K., Sawabata N., et al. Tracheal replacement with cryopreserved tracheal allograft: experiments in dogs. Ann Thorac Surg 1998;66:209-213.[Abstract/Free Full Text]
  185. Mukaida T., Shimizu N., Aoe M., et al. Experimental study of tracheal allotransplantation with cryopreserved grafts. J Thorac and Cardiovasc Surg 1998;116:262-266.[Abstract/Free Full Text]
  186. Murai K., Oizumi H., Masaoka T., et al. Removal of cartilage rings of the graft and omentopexy for extended tracheal autotransplantation. Ann Thorac Surg 1999;67:776-780.[Abstract/Free Full Text]
  187. Yokomise H., Inui K., Wada H., et al. High dose irradiation prevents rejection of canine tracheal allografts. J Thorac Cardiovasc Surg 1994;107:1391-1397.[Abstract/Free Full Text]
  188. Moriyama S., Shimizu N., Teramoto S. Experimental tracheal allotransplantation using omentopexy. Transplant Proc 1986;21:296-600.
  189. Liu Y., Nakamura T., Yamamoto Y., et al. Immunosuppressant-free allotransplantation of the trachea. The antigenicity of tracheal grafts can be reduced by removing the epithelium and mixed glands from the graft by detergent treatment. J Thorac Cardiovasc Surg 2000;120:108-114.[Abstract/Free Full Text]
  190. Nakanishi R., Shirakusa T., Hanagiri T. Early histopathologic features of tracheal allotransplant rejection. A study in nonimmunosuppressed dogs. Transplant Proc 1994;26:3715-3718.[Medline]
  191. Yokomise H., Inui K., Wada H., et al. Long-term cryopreservation can prevent rejection of canine tracheal allografts with preservation of graft viability. J Thorac Cardiovasc Surg 1996;111:930-934.[Abstract/Free Full Text]
  192. Mukaida T., Shimizu N., Aoe M., et al. Origin of regenerated epithelium in cryopreserved tracheal allotransplantation. Ann Thorac Surg 1998;66:205-208.[Abstract/Free Full Text]
  193. Deschamps C., Trastek V.E., Ferguson J.L., et al. Cryopreservation of canine trachea: functional and histological changes. Ann Thorac Surg 1989;47:208-212.[Abstract/Free Full Text]
  194. Moriyama H., Sasajima T., Hirata S., et al. Revascularization of canine cryopreserved tracheal allografts. Ann Thorac Surg 2000;69:1701-1706.[Abstract/Free Full Text]
  195. Tojo T., Kitamura S., Gojo S., et al. Epithelial regeneration and preservation of tracheal cartilage after tracheal replacement with cryopreserved allograft in the rat. J Thorac Surg Cardiovasc Surg 1998;116:624-627.
  196. Inutsuka K., Kawahara K., Takachi T., et al. Reconstruction of trachea and carina with immediate or cryopreserved allografts in dogs. Ann Thorac Surg 1996;62:1480-1484.[Abstract/Free Full Text]
  197. Gibson T., Davis W.B., Curran R.C. The long-term survival of cartilage homografts in man. Br J Plast Surg 1959;131:177-187.
  198. Davreux C.J. Improved tracheal allograft viability in immunosuppressed rats. Ann Thorac Surg 1993;55:131-134.[Abstract/Free Full Text]
  199. Ueda H., Shirakusa T. Carinal transplantation. Thorax 1992;47:968-970.[Abstract/Free Full Text]
  200. Delaere P.R., Liu Z.Y., Hermans R., et al. Experimental tracheal allograft revascularization and transplantation. J Thorac Cardiovasc Surg 1995;110:728-737.[Abstract/Free Full Text]
  201. Delaere P.R., Liu Z., Sciot R., Welvaart W. The role of immunosuppression in the long term survival of tracheal allografts. Arch Otolaryngol Head Neck Surg 1996;122:1201-1208.
  202. Levashov Y.N., Yablonsky P.K., Cherny S.M., et al. One-staged allotransplantation of thoracic segment of the trachea in a patient with idiopathic fibrosing mediastinitis, and marked tracheal stenosis. Eur J Cardiothorac Surg 1993;7:383-386.[Abstract/Free Full Text]
  203. Khalil-Marzouk J.F. Allograft replacement of the trachea. Experimental synchronous revascularization of composite thyrotracheal transplant. J Thorac Cardiovasc Surg 1993;105:242-246.[Abstract]
  204. Macchiarini P., Lenot B., de Montpréville V., et al. Heterotopic pig model for direct revascularization and venous drainage of tracheal allografts. J Thorac Cardiovasc Surg 1994;108:1066-1075.[Abstract/Free Full Text]
  205. Macchiarini P., Mazmanian G.-M., de Montpréville V.T., et al. Maximal preservation time of tracheal allografts. Ann Thorac Surg 1995;60:1597-1604.[Abstract/Free Full Text]
  206. Macchiarini P., Mazmanian G.-M., de Montpréville V.T., et al. Experimental tracheal and tracheoesophageal allotransplantation. J Thorac Cardiovasc Surg 1995;110:1037-1046.[Abstract/Free Full Text]
  207. Couraud L., Baudet E., Martigne C., et al. Bronchial revascularization in double-lung transplantation: a series of eight patients. Ann Thorac Surg 1992;53:88-94.[Abstract/Free Full Text]
  208. Daly R.C., Tadjikarimi S., Khagani A., et al. Successful double-lung transplantation with direct bronchial artery revascularization. Ann Thorac Surg 1993;56:885-892.[Abstract/Free Full Text]
  209. Strome M., Stein J., Esclamado R., et al. Laryngeal transplantation and 40 month follow-up. N Engl J Med 2001;344:1676-1679.[Medline]
  210. Lundborg G. Hand transplantation. Scand J Plast Reconstr Surg Hand Surg 1999;33:369-371.[Medline]



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 Arch Otolaryngol Head Neck SurgHome page
L. M. Janssen, G. J. V. M. van Osch, J. P. Li, N. Kops, K. de Groot, J. W. Von den Hoff, L. Feenstra, and J. A. U. Hardillo
Tracheal Reconstruction: Mucosal Survival on Porous Titanium
Arch Otolaryngol Head Neck Surg, May 1, 2009; 135(5): 472 - 478.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
A. Seguin, D. Radu, M. Holder-Espinasse, P. Bruneval, A. Fialaire-Legendre, M. Duterque-Coquillaud, A. Carpentier, and E. Martinod
Tracheal Replacement With Cryopreserved, Decellularized, or Glutaraldehyde-Treated Aortic Allografts
Ann. Thorac. Surg., March 1, 2009; 87(3): 861 - 867.
[Abstract] [Full Text] [PDF]

Home page
 Interact CardioVasc Thorac SurgHome page
H. Tsukada, S. Matsuda, H. Inoue, Y. Ikada, and H. Osada
Comparison of bioabsorbable materials for use in artificial tracheal grafts
Interact CardioVasc Thorac Surg, February 1, 2009; 8(2): 225 - 229.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
T. W. Gilbert, S. Gilbert, M. Madden, S. D. Reynolds, and S. F. Badylak
Morphologic Assessment of Extracellular Matrix Scaffolds for Patch Tracheoplasty in a Canine Model
Ann. Thorac. Surg., September 1, 2008; 86(3): 967 - 974.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Cardiothorac SurgHome page
H.-B. Ris, T. Krueger, C. Cheng, P. Pasche, P. Monnier, and L. Magnusson
Tracheo-carinal reconstructions using extrathoracic muscle flaps
Eur J Cardiothorac Surg, February 1, 2008; 33(2): 276 - 283.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
A. Abbasidezfouli, M. B. Shadmehr, M. Arab, M. Javaherzadeh, S. Pejhan, A. Daneshvar, and R. Farzanegan
Postintubation Multisegmental Tracheal Stenosis: Treatment and Results
Ann. Thorac. Surg., July 1, 2007; 84(1): 211 - 214.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Cardiothorac SurgHome page
Q. Tan, R. Steiner, L. Yang, M. Welti, P. Neuenschwander, S. Hillinger, and W. Weder
Accelerated angiogenesis by continuous medium flow with vascular endothelial growth factor inside tissue-engineered trachea
Eur J Cardiothorac Surg, May 1, 2007; 31(5): 806 - 811.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
A. Ernst and S. Ashiku
Tracheal Transplantation: Are We Any Closer to the Holy Grail of Airway Management?
Chest, November 1, 2006; 130(5): 1299 - 1300.
[Full Text] [PDF]

Home page
 ChestHome page
S. Jaillard, M. Holder-Espinasse, T. Hubert, M.-C. Copin, M. Duterque-Coquillaud, A. Wurtz, and C.-H. Marquette
Tracheal Replacement by Allogenic Aorta in the Pig
Chest, November 1, 2006; 130(5): 1397 - 1404.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Cardiothorac SurgHome page
J. F. Azorin, F. Bertin, E. Martinod, and M. Laskar
Tracheal replacement with an aortic autograft
Eur J Cardiothorac Surg, February 1, 2006; 29(2): 261 - 263.
[Abstract] [Full Text] [PDF]

Home page
 J Ultrasound MedHome page
L. F. Tintinago, D. A. Herrera, E. Medina, J. H. Patino, F. Cano, and C. S. Restrepo
Ultrasonographic Evaluation of a Vascularized Tracheal Transplantation
J. Ultrasound Med., August 1, 2005; 24(8): 1145 - 1149.
[Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
E. Martinod, A. Seguin, M. Holder-Espinasse, M. Kambouchner, M. Duterque-Coquillaud, J. F. Azorin, and A. F. Carpentier
Tracheal Regeneration Following Tracheal Replacement With an Allogenic Aorta
Ann. Thorac. Surg., March 1, 2005; 79(3): 942 - 948.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
K. A. Carden, P. M. Boiselle, D. A. Waltz, and A. Ernst
Tracheomalacia and Tracheobronchomalacia in Children and Adults: An In-depth Review
Chest, March 1, 2005; 127(3): 984 - 1005.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
H. Shi, Z. Xu, X. Qin, X. Zhao, and D. Lu
Experimental Study of Replacing Circumferential Tracheal Defects With New Prosthesis
Ann. Thorac. Surg., February 1, 2005; 79(2): 672 - 676.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
T. Walles, B. Giere, M. Hofmann, J. Schanz, F. Hofmann, H. Mertsching, and P. Macchiarini
Experimental generation of a tissue-engineered functional and vascularized trachea
J. Thorac. Cardiovasc. Surg., December 1, 2004; 128(6): 900 - 906.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
P. Macchiarini, T. Walles, C. Biancosino, and H. Mertsching
First human transplantation of a bioengineered airway tissue
J. Thorac. Cardiovasc. Surg., October 1, 2004; 128(4): 638 - 641.
[Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
T. Walles, B. Giere, P. Macchiarini, and H. Mertsching
Expansion of chondrocytes in a three-dimensional matrix for tracheal tissue engineering
Ann. Thorac. Surg., August 1, 2004; 78(2): 444 - 448.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
P. Macchiarini
Trachea-guided generation: Deja vu all over again?
J. Thorac. Cardiovasc. Surg., July 1, 2004; 128(1): 14 - 16.
[Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
J. Odell
Invited commentary
Ann. Thorac. Surg., February 1, 2004; 77(2): 405 - 405.
[Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
B. R. Beldholm, M. K. Wilson, R. M. Gallagher, D. Caminer, M. J. King, and A. Glanville
Reconstruction of the trachea with a tubed radial forearm free flap
J. Thorac. Cardiovasc. Surg., August 1, 2003; 126(2): 545 - 550.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Cardiothorac SurgHome page
L. Yang, S. Korom, M. Welti, S. P. Hoerstrup, G. Zund, F. J. Jung, P. Neuenschwander, and W. Weder
Tissue engineered cartilage generated from human trachea using DegraPol(R) scaffold
Eur J Cardiothorac Surg, August 1, 2003; 24(2): 201 - 207.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
H. C. Grillo
Tracheal replacement
J. Thorac. Cardiovasc. Surg., April 1, 2003; 125(4): 975 - 975.
[Full Text] [PDF]

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