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Dynamic Tissue Expansion of the Larynx in a Canine Model
Ron Eliashar, MD;
Isaac Eliachar, MD;
Terry Gramlich, MD;
William Davros, PhD;
Kaven Moffett;
Marshall Strome, MD
Arch Otolaryngol Head Neck Surg. 2001;127:309-315.
ABSTRACT
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Objectives To test whether staged, progressive, monitored, dynamic tissue expansion
is possible in the larynx and to evaluate its effectiveness in dilating and
augmenting constricting cicatricial lesions.
Design Animal study.
Setting Research facility, tertiary care medical center.
Subjects Thirteen dogs, 3 with laryngotracheal stenosis.
Interventions Dogs underwent laryngeal splits, tracheostomy, and insertion of inflatable
stents. In 7 normal dogs, stents were progressively inflated by air in predetermined
increments during 11 days. In 3 normal dogs and 3 with laryngotracheal stenosis,
stents were gradually expanded by water. Stents were kept in place for 21
days. After removal, dogs were observed for 25 days. Five died of complications
of tracheostomy.
Main Outcome Measures Airway diameter measured by endoscopy before the induction of stenosis,
before the laryngeal splitting procedure, after stent removal, and before
euthanasia.
Results The lumen increased, then shrank somewhat after stent removal. In 2
surviving dogs with laryngotracheal stenosis and water-expanded stents, the
lumen was 82.5% larger than baseline at stent removal and 71.0% larger at
euthanasia. In 2 surviving normal dogs with water-expanded stents, lumen size
increased by 50.0% at stent removal, and in 1 dog surviving to day 46, it
was 17.0% larger. In 5 surviving dogs with air-inflated stents, lumen size
was 39.0% larger at stent removal and 8.0% larger at day 46. Histologically,
fibrous tissue developed in the gaps between the splayed margins of the laryngeal
cartilages.
Conclusions The larynx may be dynamically expanded. Although the maximal diameter
is not maintained, final cross-sectional areas are larger.
INTRODUCTION
LARYNGOTRACHEAL stenosis (LTS) may be congenital or acquired. The incidence
of LTS has increased over the years because of improved health care of premature
intubated infants, patients receiving prolonged assisted ventilation, and
patients with trauma, chronic illness, and/or cancer.1
Stenoses of more than 70% of the lumen diameter at any level of the airway
are usually clinically restrictive and often must be surgically treated.2 Managing such stenoses is quite complicated. An adequate
stable airway must be established without jeopardizing other laryngeal functions,
such as airway protection, speech, and coughing. Despite the availability
of various surgical treatment options for LTS, none produces completely satisfactory
results.
Tracheotomy bypasses the stenotic area. It may be complicated, however,
by plugging, decannulation, infection, and even death. It may also further
damage the already impaired airway and compromise quality of life. Decannulation
and closure are therefore important goals in the treatment of LTS.3
Endoscopic techniques for treating LTS include dilatation with bougies
or with rigid bronchoscopes combined with instrumental removal of scar tissue
or laser ablation. After surgery, stenosis tends to recur and often worsens.
Many patients require numerous procedures before the stenosis can be resolved.2, 4, 5, 6
Open surgical laryngotracheal reconstruction is often more effective
than endoscopic dilatation and is indicated whenever the laryngeal skeleton
is involved in the stenosing process, or when there is weakening (malacia)
and collapse of the skeletal framework. Postoperative intraluminal stenting
may be used to support the airway from within, bolster grafts and flaps, and
maintain the lumen during healing.3, 4
Prolonged stenting may be complicated by inflammation, bacterial contamination,
infection, granulation tissue formation, scarring, and restenosis. Recently,
miniplates have been used to provide a rigid external framework support for
laryngotracheal reconstruction, thus avoiding prolonged stenting. However,
the incidence of complications such as infection, dislodgment, and intrusion
or extrusion of grafts is still high.5
Long-term indwelling expandable stents have been used in structures
such as arteries, the urethra, the biliary tree, the venous system, and the
esophagus. These long-term stents have also been used successfully in selected
cases of tracheobronchial stenosis or malacia and were recently tested in
the upper airway, with promising results.3, 7, 8, 9
They acutely expand the lumen to its desired diameter and stent it during
a prolonged period to maintain the desired dimensions. Unfortunately, many
of these stents may become embedded in the surrounding tissue. Some may cause
damage and most are irreversibly implanted.7
Chronic tissue expansion usually involves the use of an implant to gradually
increase the amount and dimensions of tissue available in a given area. Such
procedures can be used to expand skin, blood vessels, and nerves to be used
in grafting procedures.10 Our search of the
literature to date has not disclosed any application of scheduled progressive
incremental tissue expansion methods to treat LTS. Dynamic expansion of the
laryngotracheal complex may be an optional treatment in either a primary or
a secondary role when used with other reconstructive procedures.
A new inflatable, low-pressure, high-volume laryngeal stent was recently
developed by one of us (I.E.). When tested in canines, it was safe and biocompatible,
with minimal reversible local tissue reaction.11
Because of its monitored dynamic inflatable and expandable properties, this
stent is suitable as a designated intralaryngeal tissue expander to treat
stenosing lesions in the larynx. The goal of this study was to test whether
the new concept of staged, progressive, monitored, dynamic tissue expansion
is possible in the larynx and to evaluate its effectiveness in dilating and
augmenting constricting cicatricial lesions.
MATERIALS AND METHODS
The study was approved by the Animal Research Committee of The Cleveland
Clinic Foundation, Cleveland, Ohio, and the animals received humane care in
compliance with the Principles of Laboratory Animal Care formulated by the
National Society for Medical Research and the Guide for the Care and Use of
Laboratory Animals prepared by the National Academy of Sciences.
Thirteen mongrels (Canis familiaris), each
weighing between 10 and 12 kg, were divided into 3 study groups (Table 1). The study protocol is shown in Table 2.
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Table 1. Experimental Groups
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Table 2. Experimental Protocol*
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The stent was designed by one of us (I.E.) and produced and developed
at Hood Laboratories Inc (Pembroke, Mass). It is made of biocompatible medical-grade
silicon, is easily inserted, and, when in place, is retained in position by
conforming with the intralaryngeal configuration. Once inflated it is secured
and stabilized in its position. Air pressures within the stent can be carefully
monitored and adjusted with a digital pressure-volume gauge attached to a
1-way valved Luer connector. A thin flexible tube extends from the Luer connector
into the lower pole of the stent. However, silicon may leak air, so the stent
may also be expanded with water. When water is used, the stent is inflated
to the same volume as when air is used.
INDUCTION OF LTS
Laryngotracheal stenosis was induced in 3 dogs by a previously proved
technique.12 Each dog was anesthetized with
intramuscular ketamine hydrochloride (20 mg/kg) and intramuscular xylazine
hydrochloride (1.5 mg/kg) and placed in the supine position with its mouth
kept open with a bite blocker. The tongue was extended and the exposed larynx
sprayed with topical anesthetic spray (Cetacaine; Cetylite Industries Inc,
Pennsauken, NJ). The epiglottis was lifted with the tip of a 3.5-mm 30°
telescope (Hopkins; Karl Storz Endoscopy, Culver City, Calif), connected through
a video camera to a monitor. The junction between the lower part of the cricoid
cartilage and the upper part of the first tracheal ring was traumatized by
electrocautery with a curved insulated suction-cautery tip connected to a
standard Bovie electrosurgical cautery system and operated at 40 power units.
The mucosa and underlying cartilage were injured at 4 equally spaced points,
with the use of 2- to 3-second exposures. The dogs were then observed for
14 to 16 days, during which all 3 developed LTS restricting the airway by
more than 70%.
LARYNGEAL SPLIT, LONG-TERM TRACHEOSTOMY, AND INSERTION OF STENT
Each dog was anesthetized with intravenous pentobarbital sodium (25-30
mg/kg). A No. 6 tube was introduced through the mouth and advanced under endoscopic
guidance into the trachea. The anterior part of the neck was then shaved,
a circular area of skin overlying tracheal rings 5 to 10 and measuring 5 cm
in diameter was excised, and the margins were vastly undermined. The strap
muscles were separated and sutured sideways. The anterior cartilaginous skeleton
of the laryngotracheal complex was split in the midline from below the vocal
cords to the second tracheal ring. Care was taken to preserve the mucosa.
In animals with previously established stenosis, scar tissue was split as
well down to the mucosa, which was left intact.
By means of a previously described technique,13
a permanent tube-free, self-sustaining tracheostomy was then performed. Before
the upper skin flap of the tracheostomy was sutured, the inflatable stent
was inserted through the stoma (Figure 1) under endoscopic guidance. It was secured in its position by means of a suture
passed through the petiole of the epiglottis, and by passing the flexible
inflating tube through the anterior tracheal wall and the skin. The upper
skin flap was then sutured to the trachea and a temporary tracheotomy tube
was placed to ventilate the animal until it fully recovered from the general
anesthetic. The tube was removed when spontaneous ventilation was reestablished,
and the dogs remained tube free throughout the study period.
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Figure 1. The inflatable stent is introduced
through the tracheostoma. The level of the cricoid cartilage is marked on
the right. The flexible tube used for inflation extends from the lower pole
of the stent on the left.
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DYNAMIC EXPANSION
Postoperatively, study subjects received acetaminophen, 10 mg/kg, when
required to control pain. Daily suctioning and routine local care of the wound
were provided for the tracheostomy site. Two methods were used to dynamically
expand the laryngeal lumen.
1. In groups 1 and 2, the stent was initially filled with 6 mL of water.
Then, 0.2 mL was added every other day until the stent was filled with a total
of 7 mL of water. This volume was previously found to be equal to the volume
of the maximally air-inflated stent.
2. In group 3, the stent was gradually inflated with air during a period
of 11 days. Starting at a pressure of 30 mm Hg, the pressure of the stent
(and thus its volume) was adjusted gradually every 2 days until a pressure
of 40 mm Hg was achieved (intraluminal stent pressure should not exceed the
physiologic arteriolar blood pressure of approximately 40 mm Hg14).
The air pressure within the balloon was monitored manometrically twice daily.
The stent was left in its place in its maximally expanded or inflated
state for 10 more days, to promote healing of the larynx in the desired dimension.
During the whole period, the dogs received adequate oral nutrition and local
tracheostomy care. Twenty-one days postoperatively, the stent was removed
with the animal under general anesthesia, and the expanded laryngeal airway
diameter was measured and documented.
ENDOSCOPIC EXAMINATION AND VIDEO DOCUMENTATION
Endoscopic examinations with video documentation were performed before
the induction of stenosis, before the laryngeal splitting procedure, after
stent removal, and before the animals were euthanatized. To ensure consistency
in measurements, the tip of the telescope was always positioned at the plane
of the free edges of the true vocal cords. The videotaped examination was
reviewed in a computerized laboratory by means of Adobe Photoshop 4.0 and
Illustrator 6.0 software (Adobe Systems Inc, San Jose, Calif). The luminal
area at the junction of the cricoid cartilage and the first tracheal ring
was measured in dogs with normal larynges. The narrowest area of the remaining
subglottic lumen was measured in dogs with LTS. The area of the lumen was
calculated by the following formula:

THREE-DIMENSIONAL COMPUTED TOMOGRAPHY AND VIRTUAL BRONCHOSCOPY
Virtual bronchoscopy, a new noninvasive technique for performing a simulated
endoscopy, produces images of endoluminal structures similar to the images
seen in actual endoscopic examinations. Thin-section computed tomographic
helical data are reformulated to present a realistic surface rendering of
the inner walls of the airway or of other hollow structures.15, 16, 17, 18
Three-dimensional computed tomography and virtual bronchoscopy were performed
during the stenting period and after stent removal.
OBSERVATION AND EUTHANASIA
After stent removal, the animals were observed for an additional 25
days. During that period, the dogs had no indwelling stents or obturators
within their larynges.
At the end of the observation period, the animals were euthanatized
with an overdose of intravenous pentobarbital sodium (75 mg/kg). Before laryngectomy,
the airway diameter was again measured and documented. The larynges were then
excised and sent for macroscopic and histopathologic examinations. They were
sectioned longitudinally through the posterior midline aspect. Sections through
the sites of the anterior laryngeal split were obtained and stained with hematoxylin-eosin.
The expansile tissue response achieved by the dynamic inflatable stent
was assessed by comparing the baseline diameter of the airway with the diameters
measured during the different stages of the study. Each dog served as its
own control.
RESULTS
Five dogs died at some point during the study of complications of the
tracheostomy. Unfortunately, dogs do not tolerate the establishment of a tracheotomy
(because the cannula induces substantial secretions and can become occluded
or dislodged) or of a tracheostomy (because the surrounding skin and fur may
collapse and occlude the stoma, or the stoma may gradually constrict). Too
many dogs are therefore lost.19 However, the
canine model was chosen in the current study because the canine's laryngotracheal
complex is similar to the human region in anatomy, vascularity, innervation,
and physiologic features. It is therefore the most widely used and comparable
model.
The mean percentage change from the initial cross-sectional area in
the surviving dogs is shown in Table 3.
An example of consecutive endoscopic examinations of 1 dog is shown in Figure 2.
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Table 3. Luminal Size Increases After Dynamic Tissue Expansion*
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Figure 2. Consecutive endoscopic examinations
of a dog with induced laryngotracheal stenosis and a stent expanded with water.
A, Subglottic region before induction of stenosis. B, Laryngotracheal stenosis
before balloon dilatation and laryngeal split (day 14). C, After stent removal
(day 21). D, At day 46.
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On 3-dimensional computed tomography performed during the stenting period
(Figure 3) and on pathological examination
performed at the completion of the study (Figure 4), a wide gap between the free margins of the expanded cricoid
and thyroid cartilages was found. Fibrous tissue bridged this expanded wide
gap (Figure 5). Only a small amount
of granulation tissue, predominantly caused locally by the retaining suture,
was found at stent removal, and in all cases it was spontaneously resolved
by the time of death (Figure 2).
There were no signs of perichondritis or of cartilage necrosis.
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Figure 3. Three-dimensional computed tomography
of a larynx containing an inflated stent. A gap of 9.76 mm between the free
margins of the expanded cricoid cartilage is seen.
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Figure 4. Macroscopic appearance of an expanded
larynx after 46 days. A wide gap between the free margins of the expanded
cricoid and thyroid cartilages is seen.
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Figure 5. Histologic section through area
of laryngeal split at day 46. Cartilage (left) is adjacent to dense fibrous
tissue that bridged the expanded wide gap. There are no signs of perichondritis
or of cartilage necrosis (hematoxylin-eosin, original magnification x25).
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COMMENT
The larynx is a hollow tube made of a cartilaginous skeleton. The lumen
cannot be expanded beyond the natural diameter without splitting the cartilaginous
skeleton. In laryngotracheal reconstruction procedures, the stenotic laryngeal
segment may be split anteriorly, posteriorly, laterally, or in combinations
of the above. Widening and stability of the lumen are maintained by interpositioned
grafts, by a stent, or by both.6 Most reconstructive
techniques rely on autologous rib or nasal septal cartilages for expansion.
Harvesting these cartilages, however, requires additional surgical procedures
that must be performed on a separate location away from the laryngotracheal
surgical field. These cartilages may also be displaced, rejected, or infected.
Extended or prolonged periods of postoperative stenting with the tracheotomy
tube in place are usually required, which increases the risks of complications
or failures.20, 21
For chronic gradual tissue expansion, a distensible implant is used
to encourage growth of additional tissue. Skin has been the primary target
of long-term tissue expansion because it expands in response to tension, and
because it readily synthesizes new connective tissue. However, tissue expanders
have also been used with success in animal models to lengthen peripheral nerves,
ureters, and small bowel.10, 22, 23
We therefore presumed that a staged, progressive, incremental dynamic tissue
expansion, combined with splitting of the laryngeal skeleton and preservation
of intact internal mucoperichondrium, would allow gradual expansion of the
skeleton and the mucosa without pressure-induced tissue necrosis. Eventually
this might lead to permanent stable enlargement of the lumen, which may enable
closure of a preexisting tracheotomy.
We believe that the ideal laryngeal expanding stent should replicate
the characteristics of the stent described in 1990 by Eliachar and Nguyen.1 It should be available in different sizes and shapes;
it should be safe with no risk of airway obstruction; and it should not cause
marked foreign-body reaction. It should be soft and smooth to avoid mucosal
abrasion and pressure necrosis. Ease and safety of insertion and removal are
mandatory. Stabilization and safe maintenance in position should be achieved
by atraumatic means. A dynamic versatile stent with progressive expansile
features should also be readily distensible at monitored rates.
The Eliachar laryngotracheal stent (Hood Laboratories Inc) provides
internal laryngeal support and controls aspiration.1
Recently, a new inflatable, low-pressure, high-volume balloonlike stent was
designed (Hood Laboratories Inc). It is flexible, thin-walled, and preformed
to fit the inner contours of the larynx. In a canine model, it was safe and
biocompatable, causing only minimal, reversible local tissue reaction.11 The air pressure inside the stent can be manometrically
monitored to the finest degree and may be periodically adjusted by a readily
available digital pressure-volume gauge. In its clinical human application,
the stent is readily introduced, safely maintained in position without retaining
sutures, easily monitored, and easily removed.
We therefore assumed that this stent could serve as a laryngeal tissue
expander after an anterior laryngeal splitting procedure. The suggested tissue
expansion process is as follows: (1) distention of the intact mucoperichondrium,
(2) separation and spreading of the split cartilage skeletal segments, (3)
ingrowth of fibrous tissue into the expanded gaps between the skeletal segments,
and (4) overall stable and sustained expansion of the laryngeal skeleton and
of its lumen. The staged, gradual, slow inflation of the stent is intended
to avoid trauma caused by rapid expansion, which may result in pressure sores,
inflammation, and scarring, with potential necrosis and eventual restenosis.
We propose the term safe splitting to describe
longitudinal sterile section of the thyroid and cricoid cartilages down to
but not through the intraluminal mucoperichondrium or the stenotic scar tissue.
Safe splitting allows gradual stretching of the intact mucosa and internal
perichondrium. Maintaining an intact membrane inside the larynx prevents pressure
ischemic damage to the mucosa and reduces contamination and infection of the
cartilage and surrounding soft tissue. In this preliminary study, we performed
only anterior splits to maintain the integrity of the mucoperichondrium, which
we had hoped would prevent complicating factors such as infection. Future
studies might also incorporate lateral or posterior cricoid splits.
Air is the preferred medium for stent inflation and tissue expansion.
It is less traumatic than water, being more flexible and shock absorbing.
The stent used in this study is produced of silicon, which is known to leak
air, albeit slowly. Therefore, the use of air for expansion was difficult,
requiring frequent monitoring and reinflation. While possible in humans, it
is a laborious task in the animal laboratory setting. Water is well retained
by the new stent and is more consistent and reliable in achieving predictable
expansion, but is potentially more traumatic to the surrounding tissue, being
less flexible.
The results of our preliminary study clearly show that dynamic expansion
is a viable option as a new treatment for LTS. Although the larynx does not
maintain the maximal postexpansion diameter, the final cross-sectional area
is larger than the initial pretreatment area. Our results suggest that stenotic
larynges are particularly amenable to dynamic expansion. Water-filled stents
seem to be more effective than air-filled stents but may be more traumatic.
These factors should be carefully considered in future clinical applications.
When expansion by water is attempted, the volume and pressure increments should
be small and closely monitored. The proposed tissue expansion procedure may
be used primarily or secondarily in conjunction with other reconstructive
treatments. It does not require the use of grafts, and the stenting period
may be completed within 21 days.
CONCLUSIONS
This novel animal study suggests that the stenotic laryngotracheal complex
may be dynamically expanded by specially designed stents. This opens up new
opportunities in managing laryngotracheal stenosis. Further animal and human
studies with longer observation periods and larger numbers are warranted.
AUTHOR INFORMATION
Accepted for publication July 13, 2000.
This study was funded by The Cleveland Clinic Foundation. Hood Laboratories
Inc supported the study by supplying the stents free.
Presented in part at the 14th Annual Meeting of the American Society
of Pediatric Otolaryngology, Palm Desert, Calif, April 29, 1999.
From the Department of Otolaryngology/Head & Neck Surgery, Hadassah
University Hospital, Jerusalem, Israel (Dr Eliashar); and Departments of Otolaryngology
and Communicative Disorders (Drs Eliachar and Strome), Anatomic Pathology
(Dr Gramlich), and Radiology (Dr Davros and Ms Moffett), The Cleveland Clinic
Foundation, Cleveland, Ohio. From 1997 to 1998 Dr Eliashar was a research
fellow in The Cleveland Clinic Foundation. Dr Eliachar receives royalties
from Hood Laboratories Inc Pembroke, Mass.
Corresponding author: Isaac Eliachar, MD, Department of Otolaryngology
and Communicative Disorders (A71), The Cleveland Clinic Foundation, 9500 Euclid
Ave, Cleveland, OH 44195 (e-mail: eliachi{at}ccf.org).
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