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Tissue compatibility and biodegradation of new absorbable stents for tracheal stabilization: An experimental study
Tissue Compatibility and Biodegradation of New Absorbable Stents for Tracheal Stabilization: An Experimental Study By Harald
Lochbihler,
Jiirgen Miinchen,
l Newly designed absorbable stents for temporary tracheal stabilization were implanted into the trachea of 35 Wistar rats. The stents consisted of Vicryl filaments in a homogenous PDS melt. Compatibility and biodegradation were investigated over a study period of up to 24 weeks. After the animals were killed, the trachea was examined with an optic and scanning electron microscope. During the first 2 weeks erosive mucosal defects appeared in the trachea, as well as distinct polyps of granulation tissue, focal metaplasia of the epithelium, and inflammatory infiltrates of the lamina propria. During the period leading to the sixth week, the granulations flattened and mild fibrotic alterations evolved. After the eighth week no stent residues could be detected, whereas only slight signs of chronic fibrotic inflammation persisted. No evidence for aspirations of foreign bodies or progressive inflammatory changes of the mediastinum was found. Copyright o 1997 by W.B. Saunders Company
INDEX PDS.
WORDS:
Tracheal
stenting,
absorbable
stents,
Vicryl,
T
RACHEAL STENOSIS STILL remains an unsolved problem. Presently available treatments include various tracheoplastic procedures;1-4 the lack of a unique, widely used method reflects the need for a successful1 technique. Stenting the tracheal lumen in severe cases of obstruction has often been recommended with the employment of tubular silicone and metal wire stents. Stents provide a feasible approach for endoscopic implantation, but they are afflicted with several potential complications such as arrosion, breakage, dislocation, secretory obstruction, and lumen reduction. The formerly used stents found greater applicability for permanent or palliative tracheoplastic methods. In pediatric surgery, however, either a long-term supply, which takes tracheal growth into consideration, or a temporary, short-term fixation of tracheoplastic grafts is optimal. Successful reconstructions in an animal model included esophageal interposition and free revascularized small bowel grafts.5,6 Tracheal reconstructions also require temporary stenting. The goal of our study was to investigate absorption times and compatibility of new absorbable tracheal stent materials. MATERIALS
AND
METHODS
Absorbable, synthettc stents, manufactured out of unfustoned Vtcryl filaments m homogenous PDS-melt, have become recently available (Ethicon. HamburgNorderstedt). These tubes have lengths of 0.5 cm with outside diameters of 0.28 cm They show good suspensory properties because of their structure and relatively wide lumens (internal dimension 0.2 cm). The external dimension of the stents Journal
ofPed/atric
Surgery,
Vol32,
No 5 (May),
1997:
pp 717-720
Hoelzl, and Hans-Georg Germany
Dietz
corresponds to the internal tracheal diameter of a 6-week-old rat. The length of these tubes guarantee a good anchorage of the stents inside the trachea. Vicryl consists of diglycolyl-dilactyl-units, and PDS 1s an aliphatic polyester. Both compounds contain ester bonds and can therefore be hydrolyzed (Fig 1). The exposition of absorbable materials m an aqueous environment is critical for degradation, whereas enzymatic degradation is not important. For both previously mentioned materials, the mechanisms of btodegradation have been investigated in terms of the decrease of the tensile strength of wound sutures in animal experimentation. Thirty-five male Wistar rats, at a mean age of 6 weeks and with a mean body weight of 130 g, were randomly divided into seven groups of five rats each. In every animal the same operation was performed. The trachea was exposed by median collar approach through preparation of the thyroid gland and longitudinal division of the pretracheal muscles. After tracheal incision in the most inferior collum site the stent was inserted, pushed cranially, and placed just below the cricoid (Fig 2). According to the protocol, the rats (n = 35) were killed in groups at intervals of 1, 2, 4, 6, 8, 12, and 24 weeks after operation (group I through VII). Animals with severe respiratory obstruction were pretermly killed to prevent them from suffering. The clinical course was observed by a veterinarian and through daily visits of the investigator. After death the whole mediastinum of the rat was macroscopically examined and measured. The respiratory tract with the entire trachea and lungs was then fixed with formalin. Paraffin sections were made and studied with the optic microscope after hematoxylin-eosin staining. These examinations were carried out together with the pathologist, who made a report for every animal that described the extent of the stenosis in the stented area, the degree of inflammation, and the location of stent residues. In one additional animal, the stented trachea was analyzed 2 weeks after operation with a scanning electron microscope.
RESULTS
Clinical Course The clinical course was marked by a variable stridor. particularly during the first postoperative weeks. In this period, five animals had to be sacrificed because of inflammatory obstruction of the stented segment. The pathological results showed erosive and distinctly granulating tracheitis, which caused stenosis by polyps of granulation tissue.
From the Department of Pediatric Surgery, Dr v. Haunersches Kinderspital, LMU Miinchen and the Department of Pathology, LMU Mzinchen, Germany Address reprint requests to Hans-Georg Dietz, MD, Department oj Pediatric Surgery, Ltd OA der Klinik, University of Miinchen, Lindwunnstrasse 4, 80337, Mtinchen. Germany. Copynght o 1997 by WB. Saunders Company 0022-3468/97/3205-OOI4$03.00/0 717
LOCHBIHLER,
718
Fig 1. Photograph showing stent material of Vicryl filaments in a homogenous PDS-melt (The implanted stems had lengths of 0.5 cm with outside diameters of 0.28 cm and internal diameters of 0.2 cm). The stents were manufactured by Ethicon Hamburg/Norderstedt, Germany.
Macroscopic Examinations Macroscopic examinations did not show any impairment in the surrounding mediastinum, nor in the lungs themselves. Only a discreet increase of the consistency of the tracheal wall in the stented region was regularly noted. The external tracheal diameters at the time of death showed no clear thickening of the stented areas compared with the unstented tracheal segments. Histomorphology
1 and 2 WeeksAfter Operation
Histomorphologically, the stent materials did not change during the first 2 weeks. Foreign material could well be detected by the polarizing microscope. Next to the stent a small amount of mucus, histiocytes, and granulocytes was observed. Furthermore, the tracheal mucosa adjoin-
III-YIYYUI
Fig 3. Granulation ing microscope).
tissue
,,_.,.,,
HOELZL,
AND
DIET2
,,,, ,,, ,,,,, ,,,,,
and stent
material
after 2 weeks
(polariz-
ing to the stent material showed erosive or flat ulcerous defects and polyps of granulation tissue, which caused a moderate stenosis in one animal. The respiratory epitelium in the stented area was partly replaced by stratified nonkeratinizing epithelium. The lamina propria was infiltrated by granulocytes and few lymphocytes (Figs 3 and 4). 4 WeeksAfter Operation Four weeks after the operation stent material was still observed, but showed increasing fragmentation. In four animals the amount of foreign body material was distinctly reduced. Additionally, flattened polyps of granulation tissue were observed, indicating initial stages of fibrosis. The tracheal mucosa was infiltrated with few siderophages and a varying quantity of inflammatory cells. 6 WeeksAfter Operation Six weeks after the operation, only one animal showed focal fragmentated stent material, while in the other four
Fig 2. Implantation trachea below cricoid.
of the stent
by median
collar
approach
in the
Fig 4. Granulation tissue and stent material ning electron microscope, original magnification,
after 2 weeks x800).
(scan-
ABSORBABLE
STENTS
FOR TRACHEAL
STABILIZATION
719
animals no more stent material was observed. The cellular infiltrate in the discreet polypous eminent mucosa yielded to mild fibrosis with some siderophages in the lamina propria.
1. Degradation
Foreign body material could no longer be found 8, 12, or 24 weeks after operation. In all animals of these three groups except one, discreet signs of chronic fibrotic inflammation of the mucosa with little siderosis remained. Only one animal (group VII) showed signs of a lympho-plasmacellular laryngitis and tracheitis (Fig 5). Simple Biodegradability No evidence of pulmonary alterations was observed at any point (ie, after aspiration of foreign bodies). The trachea distal of the stent showed normal respiratory mucosa at all times. Scanning Electron Microscope Findings In addition, granulations were documented with a scanning electron microscope. However, in the first postoperative weeks, an intact tracheal epithelium could be demonstrated in large regions of the stented trachea (Table 1). DISCUSSION
In general, the expandable stent, woven of metallic wire, seems to fit best to clinical needs, because metallic materials, mostly titanium alloys, have a “shape memory effect” facilitating their insertion. The biomechanical properties of the stented trachea, as shown by strain measurements with the use of incremental forces, showed significant differences between stented and unstented segments.7 The architecture of these stents influences the degree of dilation and the depth of embedding in the tracheal wall. These wire stents could actually be advantageous to pediatric surgery. Although the easy stent
inflammation
and no more
of the Stent
in the Stented
Material,
Region,
Stent Material
1st week (group I) 2nd week
8, 12, or 24 WeeksAfter Operation
Fig 5. Discreet signs of chronic fibrotic foreign body material after 8 weeks.
Table
(group 4th week (group
Outcome
Stent stable
Drstrnct
granulation
Exitus of two animals
Stent stable
Distinct
granulation
Exitus
of three
anrmals Partial fragmentatron
Flat granulation
Variable
stridor
Ill)
Drstinct fragmentation
Fiat granulation
Variable
stridor
IV)
Stem
loss
Drscreet
fibrosis
Normal
condition
Stent
loss
Drscreet
fibrosrs
Normal
condition
Stent
loss
Discreet
fibrosis
Normal
condition*
with
lympho-plasmacellular
(group V) 12th week (group VI) 24th week (group VII) *One
of the Trachea
Trachea
II)
6th week (group 8th week
Condition
and Outcome
anrmal
tracheitrs.
removal is described in some cases, it has been documented that a tissue-covered, long-term inserted foreign body will not always perform in this fashion.* A further risk of the wire stent is fatigue breakage, which can be avoided by employing a silicone stent. For both stents, however, there are disadvantages, ranging from injury of healthy tissue to airway obstruction for as long as the stent is implanted. Also the bacterial overgrowth decreases not until stent removal.9 Biodegradability is the greatest advantage of absorbable stents, the simplicity of which could be proved in our study. This stent showed good stability for 2 weeks, after which increasing fragmentation appeared. However, the absorption time of the stent could be altered by the composition of its materials. There were neither signs of progressing inflammation or tissue incompatibility in the implantation site, nor indications for aspiration of stent fragments. However, there were complications, also observed in former stent experiments. Granulation tissue existed for the most part at both ends of the implanted stents. and was probably caused by mechanic irritation. These marked granulations could have been bronchoscopically ablated, but this was not necessary in our animal model. This accounts for the high rate of severe dyspnea and the high postoperative mortality rate (14%). However, in the clinical application, this complication could be well managed by bronchoscopic revisions. Lympho-plasmacellular laryngitis and tracheitis, displayed by one animal 24 weeks after operation was probably caused by infection. Open procedure for insertion of our new stent is advantageous for the anchorage in the trachea. However, this stent could be well pushed forward from a collar approach. Bronchoscopical insertion through the glottis, however, would also be possible. The experimental application showed sufficient suspensory properties of absorbable stents. In a larger animal model a larger stent
720
LOCHBIHLER,
could cause less relative loss of lumen size. However, an additional biomechanical test should be performed with regard to anatomic proportions. A larger animal model would naturally be closer to the human experience. This
HOELZL,
AND
DIETZ
was a first trial with new absorbable stents. These could be potentially applied for support of reconstructive interventions in future experimental models, like stabilizing transplanted bowel segments.
REFERENCES 1. Hoffer ME. Tom LW. Wetmore RF. et al: Congenital tracheal stenosis. The otolaryngologist’s perspective. Arch Otolaryngol Head Neck Surg 120~449-453.1994 2. Jaquiss RD, Lusk RP. Spray TL, et al: Repar of long-segment tracheal stenosis in infancy. J Thorac Cardlovasc Surg 110:1504-1512, 1995 3. Johnson DG: Tracheal reconstruction. Sem Pediatr Surg 3:244252,1994 4. Messineo A, Filler RM, Joseph T, et al: Tracheoplasty without stent. using preshaped cryopreservedcartilage allografts m neonatal pigs. .I Pediatr Surg 29:697-700, 1994 5. Kato R, On&i AS, Watanabe M. et al: Tracheal reconstruction by esophageal Interposition: An experimental study. Ann Thorac Sug 49:951-954, 1990
6. Letang E, Sanchez-Lloret J. Gimferrer JM. et al. Experimental reconstruction of the canme trachea with a free revascularized small bowel graft. Ann Thorac Surg 49:955-958, 1990 7. Vinograd I, Klin B, Brosh T, et al: A new intratracheal from nitinol. an alloy with “shape memory effect.” .I Thorac Surg 107:1255-1261, 1994 8. Filler RM, Forte V, Fraga JC, Matute metallic airway stenes for tl-acheobronchial Pechatr Surg 30: 1050-1055, 1995 9. Matt BH, Myer CM 3d, Harrison tissue. A study of bacteriology. Arch 117:538-541.1991
stent made Carchovasc
J: The use of expandable obstruction in children. J
CJ. et al: Tracheal Otolaryngol Head
granulation Neck Surg
Lochbihler,
Jiirgen Miinchen,
l Newly designed absorbable stents for temporary tracheal stabilization were implanted into the trachea of 35 Wistar rats. The stents consisted of Vicryl filaments in a homogenous PDS melt. Compatibility and biodegradation were investigated over a study period of up to 24 weeks. After the animals were killed, the trachea was examined with an optic and scanning electron microscope. During the first 2 weeks erosive mucosal defects appeared in the trachea, as well as distinct polyps of granulation tissue, focal metaplasia of the epithelium, and inflammatory infiltrates of the lamina propria. During the period leading to the sixth week, the granulations flattened and mild fibrotic alterations evolved. After the eighth week no stent residues could be detected, whereas only slight signs of chronic fibrotic inflammation persisted. No evidence for aspirations of foreign bodies or progressive inflammatory changes of the mediastinum was found. Copyright o 1997 by W.B. Saunders Company
INDEX PDS.
WORDS:
Tracheal
stenting,
absorbable
stents,
Vicryl,
T
RACHEAL STENOSIS STILL remains an unsolved problem. Presently available treatments include various tracheoplastic procedures;1-4 the lack of a unique, widely used method reflects the need for a successful1 technique. Stenting the tracheal lumen in severe cases of obstruction has often been recommended with the employment of tubular silicone and metal wire stents. Stents provide a feasible approach for endoscopic implantation, but they are afflicted with several potential complications such as arrosion, breakage, dislocation, secretory obstruction, and lumen reduction. The formerly used stents found greater applicability for permanent or palliative tracheoplastic methods. In pediatric surgery, however, either a long-term supply, which takes tracheal growth into consideration, or a temporary, short-term fixation of tracheoplastic grafts is optimal. Successful reconstructions in an animal model included esophageal interposition and free revascularized small bowel grafts.5,6 Tracheal reconstructions also require temporary stenting. The goal of our study was to investigate absorption times and compatibility of new absorbable tracheal stent materials. MATERIALS
AND
METHODS
Absorbable, synthettc stents, manufactured out of unfustoned Vtcryl filaments m homogenous PDS-melt, have become recently available (Ethicon. HamburgNorderstedt). These tubes have lengths of 0.5 cm with outside diameters of 0.28 cm They show good suspensory properties because of their structure and relatively wide lumens (internal dimension 0.2 cm). The external dimension of the stents Journal
ofPed/atric
Surgery,
Vol32,
No 5 (May),
1997:
pp 717-720
Hoelzl, and Hans-Georg Germany
Dietz
corresponds to the internal tracheal diameter of a 6-week-old rat. The length of these tubes guarantee a good anchorage of the stents inside the trachea. Vicryl consists of diglycolyl-dilactyl-units, and PDS 1s an aliphatic polyester. Both compounds contain ester bonds and can therefore be hydrolyzed (Fig 1). The exposition of absorbable materials m an aqueous environment is critical for degradation, whereas enzymatic degradation is not important. For both previously mentioned materials, the mechanisms of btodegradation have been investigated in terms of the decrease of the tensile strength of wound sutures in animal experimentation. Thirty-five male Wistar rats, at a mean age of 6 weeks and with a mean body weight of 130 g, were randomly divided into seven groups of five rats each. In every animal the same operation was performed. The trachea was exposed by median collar approach through preparation of the thyroid gland and longitudinal division of the pretracheal muscles. After tracheal incision in the most inferior collum site the stent was inserted, pushed cranially, and placed just below the cricoid (Fig 2). According to the protocol, the rats (n = 35) were killed in groups at intervals of 1, 2, 4, 6, 8, 12, and 24 weeks after operation (group I through VII). Animals with severe respiratory obstruction were pretermly killed to prevent them from suffering. The clinical course was observed by a veterinarian and through daily visits of the investigator. After death the whole mediastinum of the rat was macroscopically examined and measured. The respiratory tract with the entire trachea and lungs was then fixed with formalin. Paraffin sections were made and studied with the optic microscope after hematoxylin-eosin staining. These examinations were carried out together with the pathologist, who made a report for every animal that described the extent of the stenosis in the stented area, the degree of inflammation, and the location of stent residues. In one additional animal, the stented trachea was analyzed 2 weeks after operation with a scanning electron microscope.
RESULTS
Clinical Course The clinical course was marked by a variable stridor. particularly during the first postoperative weeks. In this period, five animals had to be sacrificed because of inflammatory obstruction of the stented segment. The pathological results showed erosive and distinctly granulating tracheitis, which caused stenosis by polyps of granulation tissue.
From the Department of Pediatric Surgery, Dr v. Haunersches Kinderspital, LMU Miinchen and the Department of Pathology, LMU Mzinchen, Germany Address reprint requests to Hans-Georg Dietz, MD, Department oj Pediatric Surgery, Ltd OA der Klinik, University of Miinchen, Lindwunnstrasse 4, 80337, Mtinchen. Germany. Copynght o 1997 by WB. Saunders Company 0022-3468/97/3205-OOI4$03.00/0 717
LOCHBIHLER,
718
Fig 1. Photograph showing stent material of Vicryl filaments in a homogenous PDS-melt (The implanted stems had lengths of 0.5 cm with outside diameters of 0.28 cm and internal diameters of 0.2 cm). The stents were manufactured by Ethicon Hamburg/Norderstedt, Germany.
Macroscopic Examinations Macroscopic examinations did not show any impairment in the surrounding mediastinum, nor in the lungs themselves. Only a discreet increase of the consistency of the tracheal wall in the stented region was regularly noted. The external tracheal diameters at the time of death showed no clear thickening of the stented areas compared with the unstented tracheal segments. Histomorphology
1 and 2 WeeksAfter Operation
Histomorphologically, the stent materials did not change during the first 2 weeks. Foreign material could well be detected by the polarizing microscope. Next to the stent a small amount of mucus, histiocytes, and granulocytes was observed. Furthermore, the tracheal mucosa adjoin-
III-YIYYUI
Fig 3. Granulation ing microscope).
tissue
,,_.,.,,
HOELZL,
AND
DIET2
,,,, ,,, ,,,,, ,,,,,
and stent
material
after 2 weeks
(polariz-
ing to the stent material showed erosive or flat ulcerous defects and polyps of granulation tissue, which caused a moderate stenosis in one animal. The respiratory epitelium in the stented area was partly replaced by stratified nonkeratinizing epithelium. The lamina propria was infiltrated by granulocytes and few lymphocytes (Figs 3 and 4). 4 WeeksAfter Operation Four weeks after the operation stent material was still observed, but showed increasing fragmentation. In four animals the amount of foreign body material was distinctly reduced. Additionally, flattened polyps of granulation tissue were observed, indicating initial stages of fibrosis. The tracheal mucosa was infiltrated with few siderophages and a varying quantity of inflammatory cells. 6 WeeksAfter Operation Six weeks after the operation, only one animal showed focal fragmentated stent material, while in the other four
Fig 2. Implantation trachea below cricoid.
of the stent
by median
collar
approach
in the
Fig 4. Granulation tissue and stent material ning electron microscope, original magnification,
after 2 weeks x800).
(scan-
ABSORBABLE
STENTS
FOR TRACHEAL
STABILIZATION
719
animals no more stent material was observed. The cellular infiltrate in the discreet polypous eminent mucosa yielded to mild fibrosis with some siderophages in the lamina propria.
1. Degradation
Foreign body material could no longer be found 8, 12, or 24 weeks after operation. In all animals of these three groups except one, discreet signs of chronic fibrotic inflammation of the mucosa with little siderosis remained. Only one animal (group VII) showed signs of a lympho-plasmacellular laryngitis and tracheitis (Fig 5). Simple Biodegradability No evidence of pulmonary alterations was observed at any point (ie, after aspiration of foreign bodies). The trachea distal of the stent showed normal respiratory mucosa at all times. Scanning Electron Microscope Findings In addition, granulations were documented with a scanning electron microscope. However, in the first postoperative weeks, an intact tracheal epithelium could be demonstrated in large regions of the stented trachea (Table 1). DISCUSSION
In general, the expandable stent, woven of metallic wire, seems to fit best to clinical needs, because metallic materials, mostly titanium alloys, have a “shape memory effect” facilitating their insertion. The biomechanical properties of the stented trachea, as shown by strain measurements with the use of incremental forces, showed significant differences between stented and unstented segments.7 The architecture of these stents influences the degree of dilation and the depth of embedding in the tracheal wall. These wire stents could actually be advantageous to pediatric surgery. Although the easy stent
inflammation
and no more
of the Stent
in the Stented
Material,
Region,
Stent Material
1st week (group I) 2nd week
8, 12, or 24 WeeksAfter Operation
Fig 5. Discreet signs of chronic fibrotic foreign body material after 8 weeks.
Table
(group 4th week (group
Outcome
Stent stable
Drstrnct
granulation
Exitus of two animals
Stent stable
Distinct
granulation
Exitus
of three
anrmals Partial fragmentatron
Flat granulation
Variable
stridor
Ill)
Drstinct fragmentation
Fiat granulation
Variable
stridor
IV)
Stem
loss
Drscreet
fibrosis
Normal
condition
Stent
loss
Drscreet
fibrosrs
Normal
condition
Stent
loss
Discreet
fibrosis
Normal
condition*
with
lympho-plasmacellular
(group V) 12th week (group VI) 24th week (group VII) *One
of the Trachea
Trachea
II)
6th week (group 8th week
Condition
and Outcome
anrmal
tracheitrs.
removal is described in some cases, it has been documented that a tissue-covered, long-term inserted foreign body will not always perform in this fashion.* A further risk of the wire stent is fatigue breakage, which can be avoided by employing a silicone stent. For both stents, however, there are disadvantages, ranging from injury of healthy tissue to airway obstruction for as long as the stent is implanted. Also the bacterial overgrowth decreases not until stent removal.9 Biodegradability is the greatest advantage of absorbable stents, the simplicity of which could be proved in our study. This stent showed good stability for 2 weeks, after which increasing fragmentation appeared. However, the absorption time of the stent could be altered by the composition of its materials. There were neither signs of progressing inflammation or tissue incompatibility in the implantation site, nor indications for aspiration of stent fragments. However, there were complications, also observed in former stent experiments. Granulation tissue existed for the most part at both ends of the implanted stents. and was probably caused by mechanic irritation. These marked granulations could have been bronchoscopically ablated, but this was not necessary in our animal model. This accounts for the high rate of severe dyspnea and the high postoperative mortality rate (14%). However, in the clinical application, this complication could be well managed by bronchoscopic revisions. Lympho-plasmacellular laryngitis and tracheitis, displayed by one animal 24 weeks after operation was probably caused by infection. Open procedure for insertion of our new stent is advantageous for the anchorage in the trachea. However, this stent could be well pushed forward from a collar approach. Bronchoscopical insertion through the glottis, however, would also be possible. The experimental application showed sufficient suspensory properties of absorbable stents. In a larger animal model a larger stent
720
LOCHBIHLER,
could cause less relative loss of lumen size. However, an additional biomechanical test should be performed with regard to anatomic proportions. A larger animal model would naturally be closer to the human experience. This
HOELZL,
AND
DIETZ
was a first trial with new absorbable stents. These could be potentially applied for support of reconstructive interventions in future experimental models, like stabilizing transplanted bowel segments.
REFERENCES 1. Hoffer ME. Tom LW. Wetmore RF. et al: Congenital tracheal stenosis. The otolaryngologist’s perspective. Arch Otolaryngol Head Neck Surg 120~449-453.1994 2. Jaquiss RD, Lusk RP. Spray TL, et al: Repar of long-segment tracheal stenosis in infancy. J Thorac Cardlovasc Surg 110:1504-1512, 1995 3. Johnson DG: Tracheal reconstruction. Sem Pediatr Surg 3:244252,1994 4. Messineo A, Filler RM, Joseph T, et al: Tracheoplasty without stent. using preshaped cryopreservedcartilage allografts m neonatal pigs. .I Pediatr Surg 29:697-700, 1994 5. Kato R, On&i AS, Watanabe M. et al: Tracheal reconstruction by esophageal Interposition: An experimental study. Ann Thorac Sug 49:951-954, 1990
6. Letang E, Sanchez-Lloret J. Gimferrer JM. et al. Experimental reconstruction of the canme trachea with a free revascularized small bowel graft. Ann Thorac Surg 49:955-958, 1990 7. Vinograd I, Klin B, Brosh T, et al: A new intratracheal from nitinol. an alloy with “shape memory effect.” .I Thorac Surg 107:1255-1261, 1994 8. Filler RM, Forte V, Fraga JC, Matute metallic airway stenes for tl-acheobronchial Pechatr Surg 30: 1050-1055, 1995 9. Matt BH, Myer CM 3d, Harrison tissue. A study of bacteriology. Arch 117:538-541.1991
stent made Carchovasc
J: The use of expandable obstruction in children. J
CJ. et al: Tracheal Otolaryngol Head
granulation Neck Surg