Tracheal prosthesis: An experimental study with Marlex

EXPERIMENTAL

AND

Tracheal

MOLECULAR

Prosthesis:

PATHOLOGY

141-150 (1962)

1,

An

Experimental

S.DONALDGREENBERG,ARTHURC. Department

JR.,AND

BEALL,

of Pathology and the Cora Baylor University College Received

Study

with

STUART A. WALLACE

and Webb Mading Department of Medicine, Houston, Texas

December

Marlex’

of Surgery,

23, 1961

INTRODUCTION A completely satisfactory method for reconstruction of circumferential tracheal defects is not available. Tracheal grafts of skin, cartilage, bone, fascia, aorta, trachea, and mucosa of the urinary bladder have been tried without success (Greenberg, 1958). Tracheal prosthesesof polyethylene, glass, vitalium and stainless steel tubes, tantalum and stainlesssteel mesh, stainless steel coiled spring, Ivalon sponge, nylon cloth, and other polyvinal plastics also have met with failure (Greenberg, 1960). Studies from this laboratory demonstrated that tubes of Marlex mesh will function in most cases as an acceptable prosthesis for circumferential lengths of cervical trachea and are reported in detail elsewhere (Beall, et al., 1960, 1962; Greenberg, 1960; Greenberg and Willms, 1962a). This report is concerned primarily with the morphologic features of these prostheses. METHOD Twenty-one mongrel dogs weighing 8 kg or more were used. Under intravenous pentobarbital sodium anesthesia(30 mg per kilogram body weight) a midline cervical incision was made. The strap muscleswere retracted laterally, exposing the trachea. Seven ring lengths of cervical trachea were resected and replaced with tubes of heavy Marlex meshsutured inside the severed tracheal ends (Figs. la, 1b) . The strap muscleswere allowed to fall against the mesh, and the wounds were closed without drainage. Penicillin and streptomycin were given daily for 3 to 5 days. Bronchoscopic examinations were performed at three-month intervals and, if epithelization appeared complete, biopsieswere taken. At the time of death or sacrifice the specimenswere examined grossly and microscopically. Microscopic preparations were processedby both paraffin and celloidin techniques, and the tissueswere stained with hematoxylin and eosin. RESULTS Of the twenty-one dogs, there was one operative death, and one animal died from anesthesiaprior to bronchoscopy. Four died between 4 and 5 months following operation of asphyxia from stenosisof the prosthesis, and two animals died early in the study from anastomotic dehiscence.Six dogs were sacrificed at intervals from 1 to 1.5 months postoperatively, and seven dogs are living from 11 to 16 months after 1 Supported in part American Cancer Society

by the Louisa

Willig

and the U. S. Public

Memorial Grant for Cancer Health Service (HTS-5387). 141

Research

from

The

142

S. D. GREENBERG,

A. C. BEALL,

JR.,

AND

S. A. WALLACE

operation. Two of these latter seven animals demonstrate some stricture formation within the prosthesis at bronchoscopy, but only one has clinical stridor. These seven dogs are still being followed and will be sacrificed at yearly intervals to determine if further epithelization occurs with the passage of time. In any event, these prostheses appear to be functioning satisfactorily for periods up to 18 months. As such a prosthesis has been successfully used once clinically (Ellis and Harrington, 1962) and further clinical usage is imminent, it is felt that this progress report is indicated.

FIG.

la.

Marlex

prosthesis

in

situ

in

cervical

trachea.

Neither wound infection nor pneumonia was noted. Tissue for microscopic examination was available for study in fifteen of the twenty-one animals. Gross examination of the lumina revealed in most a relatively smooth graywhite surface (Figs. 2a, 2b). There was no suppuration, and in several prostheses it was believed initially that epithelial regeneration was complete. In an occasional prosthesis the Marlex was not incorporated within the host’s tissue and lay bare in the lumen except for attachment at the suture line. Microscopically, regeneration of respiratory epithelium was quite variable and was usually most marked adjacent to the anastomotic sites (Table I). Many areas

MARLEX

TRACHEAL

143

PROSTHESIS

of the prostheses were lined by granulation tissue (Fig. 3). In some specimens there were foci of stratified squamous epithelium, dysplastic respiratory epithelium, and ciliated respiratory epithelium within the same areas (Figs. 4a, 4b, 4~). As shown by repeated biopsies, a striking finding was the variation in type of epithelium covering the prostheses, not only from area to area, but also in the same area from time to time. Chronic inflammatory reaction within the walls of the prostheses was a constant finding, varying only in degree. In general, the prostheses of less than six months duration had the more acute inflammatory reaction; however, in a few of

FIG. lb. Specimen lage ring of the host

one month trachea.

postoperatively.

The

Marlex

tube

lies within

the adjacent

carti-

the prostheses of longer duration there was acute as well as chronic inflammation. In one specimen the lymphoid infiltrate progressed to formation of lymphoid follicles with active germinal centers. In six of the prostheses the inflammatory reaction extended within the Marlex mesh. In two specimens the surface of the Marlex prosthesis was in line with that of the host trachea, and regenerating epithelium encircled the Marlex fibers (Figs. 5a, 5b, SC). In the majority of prostheses, regenerated ciliated respiratory epithelium was found only in islands. Throughout, there appeared to be a direct relationship between subsidence of the acute inflammatory reaction and regeneration of respiratory epithelium.

144

FIG.

central

FIG.

zation;

S. D. GREENBERG,

2a. Specimen portion there

A. C. BEALL,

6 months postoperatively. The is mild overgrowth of connective

Zb. Specimen 15 months postoperatively however, microscopic study revealed

JR.,

AND

Marlex tissue.

S. A. WALLACE

mesh

is seen at either

end.

In

the

(Dog 14, No. P-79). There appears to be epithelialmost complete absence of epithelium.

Dog

16

during

1.5” (N-14)

a Biopsies

obtained

15

endoscopy

biopsy

killed

biopsy

15

(P-79)

11” 12”

14

(T-23)

10”

killed

13’” (P-23)

(P-59)

9

killed

killed

biopsy

(P-58)

8

; dogs still

living.

due to stenosis

14

(Q-7) (P-28)

6 7

due to stenosis

death,

death

obtained

death,

biopsy

(P-21)

5

killed

(S-45) (Q-29)

(N-71)

4

anesthetic

killed

biopsy

(P-77)

3

1

killed

Specimen

12

(P-47)

2

1

Duration (months)

11

(P-42)

1

number

TABLE

I

Mucosa

FINDINGS

ulcerated

autolysis

ulcerated;

Respiratory

and squamous

epithelium

with

epithelium

; no epithelium

; no epithelium

and squamous

ulcerated

ulcerated

epithelium

focus

of

at

ad-

ad-

ad-

minute

(2 cm)

with

; no epithelium epithelium, epithelium

Almost complete ulceration squamous epithelium

Ulceration

Respiratory

Completely

Completely

Areas of respiratory anastomosis

epithelium

epithelium

epithelium

no epithelium

ulcerated ; squamous to the anastomoses

ulcerated ; squamous to anastomoses

ulcerated ; squamous to anastomoses

Areas of squamous area of respiratory

Completely

Extreme

Completely

Largely jacent

Largely jacent

Largely jacent

Largely ulcerated ; squamous and ciliated respiratory epithelium adjacent to anastomoses

MICROSCOPIC

inflammation lumen

inflammation;

autolysis

Granulation licles

Granulation

tissue,

tissue,

tissue

tissue Granulation

tissue Granulation

tissue

Marlex

with

involving

the

Marlex

focal

in-

in

fol-

not involved involved

fithe not involved

about

within

sloughed

about

lymphoid

with

Marlex

Marlex

; Marlex

extending

Marlex tissue

:

extending

Wall

variable of Marlex Granulation

Granulation

Inflammation volvement

Acute inflammation; areas

Mild

Extreme

Acute inflammation Marlex Acute inflammation

Mild inflammation: brous connective

Acute into

Acute inflammation, Marlex

146

mucosal

FIG.

stroma.

S. D. GREENBERG,

surface

is formed

4a. Stratified X 448.

A. C. BEALL,

by granulation

squamous-like

tissue.

epithelium.

JR.,

AND

S. A. WALLACE

x 6.

Note

the inflammatory

reaction

in the underlying

MARLEX

FIG.

crowding,

4b.

Regenerating and variation

FIG.

4c.

TRACHEAL

respiratory epithelium in size of the nuclei.

Regenerated

respiratory

PROSTHESIS

with dysplastic X 448.

epithelium.

147

change.

Note

Note

the cilia.

the hyperchromatism,

X 448.

FIG. Sa. Specimen 7 months postoperatively epithelium adjacent to the anastomosis regenerated portion is lined by granulation tissue. X 3.

(Dog 9, No. P-59). There is no stenosis. The around and about the Marlex mesh. The major

FIG. Sb. Anastomosis site. A cartilage ring of the host trachea spaces were occupied by the Marlex mesh. X 13.

is seen below.

The

large

rounded

MARLEX

FIG.

stroma.

SC. Stratified squamous-like Elsewhere there was a short

TRACHEAL

epithelium. Note strip of respiratory

PROSTHESIS

the acute inflammatory epithelium. x 160.

reaction

in

the

DISCUSSION Tracheal reconstruction presents several problems. The trachea functions not only to convey air, but also to move the mucous blanket by action of the ciliated epithelium (Hilding, 1961). In this study the Marlex prostheses provided a patent airway in the majority of animals, but no prosthesis had complete regeneration of ciliated respiratory epithelium. However, no difficulty with retained secretions was encountered. This may be, in part, explained by the horizontal posture of the dog in contrast to the upright posture of man. Following insertion of the Marlex tube, fibrous connective tissue proliferated and infiltrated the mesh to a variable extent. In one dog, one month postoperatively, the Marlex was enveloped completely. In four of the animals the newly formed connective tissue in the mid-portion of the prostheses almost occluded the lumina between 4 and 5 months after operation. It appeared that the maximum ingrowth of connective tissue occurs prior to 6 months following operation, and usually no significant stenosis develops following this period. Within the lumen an inflammatory reaction with formation of granulation tissue was noted 1 month after operation. In large areas the inflammatory reaction, both acute and chronic, persisted until 16 months (Table I). With time there was generally a transition from an acute to a chronic inflammatory reaction, but with little tendency toward regression. The Marlex itself does not stimulate a significant inflammatory response (Usher and Wallace, 1958). However, because of its proximity

150

S. D. GREENBERG,

A. C. BEALL,

JR.,

AND

S. A. WALLACE

to the lumen, the mesh is frequently involved in the infiltration of lymphocytes, plasma cells, and neutrophilic granulocytes. In occasional prostheses the inflammatory reaction was less severe with only scattered lymphocytes and plasma cells within compact, partially hyalinized, connective tissue stroma. Regeneration of epithelium originates from the host epithelium at either end of the prosthesis (Greenberg and Willms, 1962b). Initially, the reserve (basal) cells proliferate to form a single cell lining. These cells, in turn, form squamous, columnar, and columnar ciliated epithelium. The epithelium dips in and around the Marlex and ends abruptly with granulation tissue. Epithelial regeneration is dependent upon the underlying stroma, and regeneration will not take place as long as an acute inflammatory reaction remains. With chronic inflammation the epithelium assumes a squamous pattern. From this point on, epithelization is characterized by marked variation from area to area and from time to time. SUMMARY In most cases heavy Marlex mesh will serve replacement of a seven-ring circumferential portion Respiratory epithelium does not regenerate to consists of granulation tissue and varying degrees With time, there is no resolution of the chronic becomes more severe.

as a satisfactory air-way following one-stage of cervical trachea in the dog. completely line the prostheses. The mucosa of epithelial regeneration. inflammatory reaction; rather, occasionally it

REFERENCES A. C., JR., HARRINGTON, 0. B., USHER, F. C., and MORRIS, G. C., JR. (1960). Circumferential replacement of the trachea with Marlex mesh: Preliminary report. Surg. Forunz 11, 40-41. BEALL, A. C., JR., HARRINGTON, 0. B., GREENBERG, S. D., MORRIS, G. C., JR., and USHER, F. C. (1962). Circumferential replacement of the cervical trachea with heavy Marlex mesh. Arch. Surg. In press. ELLIS, P. R., JR., and HARRINGTON, 0. B. (1962). The use of heavy Marlex mesh for tracheal reconstruction following resection for malignancy. J. Thoracic Cardiovascular Surg. In press. GREENBERG, S. D. (1958). Tracheal homografts in dogs. Arch. Otokwyngol. 67, W-586. GREENBERG, S. D. (1960). Tracheal reconstruction: an experimental study. Arch. Otolaryngol 72, 565-574. GREENBERG, S. D., and WILLMS, R. K. (1962a). Tracheal prostheses: an experimental study in dogs. Arch. Otoluvyngol. In press. GREENBERG, S. D., and WILLMS, R. K. (1962b). Regeneration of respiratory epithelium. Arch. Pathol. 73, 53-58. HILDING, A. C. (1961). Cigarette smoke and the physiologic drainage of the bronchial tree. Diseases of Chest 39, 357-362. USHER, F. C., and WALLACE, S. A. (1958). Tissue reaction to plastics. A comparison of nylon, orlon, dacrcn, teflon and Marlex. Arch. Surg. 76, 997-999. BEALL,