 |
|
The Natural History of Congenital Cholesteatoma
Peter J. Koltai, MD;
Marc Nelson, MD;
Roberto J. Castellon, MD;
Erea-Noel Garabedian, MD;
Jean-Michel Triglia, MD;
Stephane Roman, MD;
Gilles Roger, MD
Arch Otolaryngol Head Neck Surg. 2002;128:804-809.
ABSTRACT
| |
Objectives To describe the natural history of congenital cholesteatoma (CC) and
to determine whether such a description provides clues about the origins and
end points of these lesions.
Design A retrospective qualitative analysis of intraoperative illustrations
of 34 consecutive patients with 35 CCs (1 bilateral).
Setting Two tertiary care children's hospitals.
Patients Thirty-four children with CC, mean age, 5.6 years (range, 2-13 years).
Results Congenital cholesteatoma originates generally, but not universally,
in the anterior superior quadrant. The progression of growth is toward the
posterior superior quadrant and attic and then into the mastoid. Contact with
the ossicular chain generally results in loss of ossicular continuity and
in conductive hearing loss.
Conclusions Congenital cholesteatoma appears to have a predictable trajectory of
growth, starting as a small pearl in the middle ear, eventually growing to
involve the ossicles and mastoid, and causing varying degrees of destruction
and functional impairment. The clinical picture of a young child with otorrhea,
conductive hearing loss, tympanic membrane perforation in a nontraditional
location, and a mastoid filled with cholesteatoma may represent the end point
in the natural history of CC, despite the fact that this type of lesion is
outside the accepted definition of CC.
INTRODUCTION
CONGENITAL cholesteatoma (CC) presents early in life as a white pearly
mass behind an intact tympanic membrane, usually in the anterior superior
quadrant of the middle ear. As it grows, it typically expands into other areas
in a predictable sequence. A classification system for this lesion based on
this sequence of growth has been proposed.1
In this article, we present a series of intraoperative illustrations
from 35 consecutive CCs to show the sequence of growth. We also describe 2
children with atypical cases of CC suggesting that mastoid invasion and tympanic
membrane perforation may be part of the natural history of CC. The clinical
course of a third patient is described and used to illustrate a theory of
CC origin.
PATIENTS AND METHODS
Between July 1, 1989, and June 30, 2000, 34 children were treated for
CC at the children's hospitals of The Cleveland Clinic and Albany Medical
Center. The mean ± SD age was 5.6 ± 2.8 years (range, 2-13 years).
One of the children had bilateral CCs, resulting in 35 CCs in this series.
The medical records from these children were added to a database for a quantitative
analysis of outcomes and classifications of CC. In addition, we prepared templates
from intraoperative illustrations of the 35 CCs maintained by one of us (P.J.K.).
Each drawing was oriented to a right ear template. These were arranged in
order of increasing size to simulate the presumed natural growth pattern of
CC (Figure 1).
|
|
|
|
Figure 1. Intraoperative illustrations,
each oriented to a right ear template, arranged in order of increasing size
to simulate the presumed natural growth pattern of congenital cholesteatoma.
|
|
|
RESULTS
The intraoperative drawings arranged by size and spread of the cholesteatomas
provide a visual representation of much of the natural history of CC. Most
lesions start out as a matrix-enclosed spherical keratin pearl in the anterior
superior quadrant. The pearl grows like a round balloon inflating. Anterior
growth is toward the eustachian tube, and an early sign of a growing CC can
be otitis media with effusion secondary to obstruction of the eustachian tube
by the lesion. Later, negative pressure causes the drum to retract, which
puts the CC into relief, making it more discernible on otoscopy.
Inferior growth, resulting in extension of the CC toward the hypotympanum,
is seen with continued spherical enlargement. The matrix rind remains smooth,
without fully assuming the irregular topography of the hypotympanic cavity.
Posterior growth is toward the handle of the malleus, and, generally,
as it proceeds, the CC follows the contour of the underside of the drum, developing
an indentation under the handle of the malleus. Beyond the handle of the malleus,
the expansion is toward the incudostapedial joint and the stapes superstructure,
as well as up toward the incudomalleolar joint, around the incus, and into
the attic. Once the CC reaches the incudostapedial joint, there appears to
be progressive ossicular destruction, starting with osteolysis of the long
process of incus and the capitulum of the stapes. Eventually, variable amounts
of the long process of incus are lost, as are the crura of the stapes, although
we have seen complete envelopment of the ossicles without any erosion. The
footplate remains uninvolved. Further posterior extension fills the facial
recess and sinus tympani, with the CC following and adhering to the complex
topography of this area of the middle ear.
Superior growth, which seems to be concurrent with posterior growth,
is upward into the anterior epitympanum, in front of the head of the malleus.
Here, the amount of room for expansion is limited, and the lesion stops growing
like a sphere and adapts to the contour of the space.
The progressive growth of the CC from the attic into the antrum and
then into the mastoid follows the overall pattern of the enlargement of other
categories of middle ear cholesteatomas. Unlike the middle ear phase of CC
growth, with its distinct development and spread, the mastoid phase is generic.
However, there is one significant difference: the mastoid of very young children
(ages 3-6 years) with CC tends to be well pneumatized with few, but large,
air cells. It is structurally different from the fully developed normal mastoid
of the older child and the sclerotic, poorly pneumatized mastoids of children
with chronic otitis media. The smaller, more open architecture of the developing
mastoid is more accommodating of rapid spread of the CC into its structure.
Although the air cell septa may be vulnerable to osteolysis, the otic capsule
appears to be spared by the CC, although extension around the labyrinth into
the petrous apex cells occurs.
The medial and lateral growth of CC is bounded by the promontory and
tympanic membranes, respectively. We have not seen evidence of medial bone
erosion or any extension of the CC into the otic capsule in the middle ear.
Lateral growth is seen initially as a pearly bulge of the tympanic membrane,
which, unlike the ossicles, seems compliant and resistant to the growth of
the lesion.
COMMENT
The question of whether CC can cause rupture of the tympanic membrane
is an interesting one, because the presence of a perforation places the lesion
outside the accepted definition of CC. Nevertheless, it is reasonable to suppose
that, with sufficient growth of the CC, tympanic membrane perforation is a
possibility, and this supposition is also supported by clinical evidence.
We have seen several cases (not included in this analysis because of the aforementioned
problems with definition) of young children (ages 3-6 years) presenting with
sudden unrelenting otorrhea, with little or no history of otitis media. The
culture from the drainage usually grows Pseudomonas aeruginosa,
Staphylococcus aureus, or both. The computed tomographic (CT) scan
generally shows complete occupation of the mastoid by soft tissue that is
causing osteolysis of the mastoid septa. On exploration, tympanic membrane
rupture has been observed at various points on the drum other than the pars
flaccida or the posterior quadrant. At mastoidectomy, the entire mastoid,
from antrum to tip, is host to the cholesteatoma.
The clinical picture of a very young child with otorrhea of several
months' duration, maximum conductive hearing loss, tympanic membrane perforation
in a nontraditional location, and a mastoid full of cholesteatoma probably
represents the end point in the natural history of CC. In these young children,
tympanic membrane perforation and otorrhea always seem to be coincidental
with complete occupation of the mastoid with cholesteatoma. This suggests
2 possible, perhaps related, mechanisms of CC growth in the late stages. One
is that the volume of cholesteatoma exceeds the capacity of the middle ear
and mastoid, resulting in tympanic membrane perforation. The other is that
tympanic membrane perforation and subsequent infection accelerate the growth
of the CC, resulting in complete filling of the middle ear and mastoid. Acquired
cholesteatoma can also present with otorrhea and complete cholesteatoma invasion
of the middle ear and mastoid, but tympanic perforation and otorrhea typically
occur well before the entire mastoid is involved.
Two cases of unusual presentation and circumstance shed some additional
light on the end point of the natural history of CC and provide further evidence
that mastoid invasion and tympanic membrane perforation are part of that history.
A third case illustrates a theory of origin of CC.
CASE 1
This case occurred in a 4-year-old boy with a well documented history
of bilateral recurrent acute otitis media treated with antibiotics, but with
no history of tube insertion or previous otorrhea associated with episodes
of acute otitis media. He presented initially with a history of left-sided
otorrhea, which on culture grew P aeruginosa. This
was treated with systemic antibiotics and antibiotic ear drops. Despite this
therapy, the drainage continued and he eventually was referred to us with
left-sided mastoiditis. An audiogram showed a 50-dB conductive hearing loss
on the left and a 30-dB conductive hearing loss on the right. A tympanogram
could not be obtained on the left, and the right side showed a flat type B.
A CT scan showed soft tissue opacification of the left middle ear and mastoid,
with thinning and destruction of the mastoid septa and cortex (Figure 2). The CT scan also demonstrated similar opacification of
the right middle ear and mastoid (Figure 3).
|
|
|
|
Figure 2. Axial computed tomographic scan
of the left temporal bone of a 4-year-old boy with destructive cholesteatoma
involving the middle ear and mastoid. The tympanic membrane on the left was
not intact (case 1). This ear was not included in the composite Figure 1 because
the lesion fell outside the definition of congenital cholesteatoma.
|
|
|
|
|
|
|
Figure 3. Axial computed tomographic scan
of the right (R) temporal bone of the same child as in Figure 2, demonstrating
a right-sided destructive cholesteatoma occupying the entire right mastoid.
This ear corresponds to number 29 on the composite Figure 1. P indicates posterior.
Scales are in centimeters.
|
|
|
At exploration of the left ear, a large cholesteatoma occupying the
middle ear and mastoid was found. There was erosion of the posterior canal
wall, with keratin abutting the posterior canal wall skin. There was loss
of the stapes superstructure and long process of incus, as well as complete
encirclement of the malleus and incus heads. A canal wall down tympanomastoidectomy
with a wide meatoplasty was performed.
At the same operation, the right ear was examined with a microscope.
A CC occupying the anterior and posterior quadrants of the middle ear was
seen through an intact tympanic membrane. A subsequent exploratory tympanotomy
and mastoidectomy of the right ear revealed a CC extending from the eustachian
tube back underneath the malleus, up into the anterior attic around the heads
of the incus and malleus, and into the mastoid. A canal wall up tympanomastoidectomy
with incus interposition was performed.
CASE 2
This cholesteatoma was in a 3-year-old boy with no history of otitis
media. It had been discovered 4 months previously during surgery for an aural
polyp that appeared to originate on the left posterior canal wall. His tympanic
membrane was intact, and a myringotomy and tube placement were performed.
During the procedure, keratin in the middle ear was biopsied and found to
contain cholesteatoma. At referral, he had an indwelling pneumatic equalization
tube and what appeared to be a white mass occupying the middle ear behind
the tympanic membrane. An audiogram showed a 40-dB conductive hearing loss
in the left ear and normal hearing in the right ear. A CT scan showed soft
tissue opacification of the left middle ear and mastoid, with thinning and
destruction of the mastoid septa and cortex (Figure 4). The CT scan of the right temporal bone showed no abnormalities.
|
|
|
|
Figure 4. Axial computed tomographic scan
of the left (L) temporal bone of a 3-year-old boy with destructive cholesteatoma
involving the middle ear and mastoid (case 2). This ear corresponds to number
31 on the composite Figure 1. R indicates right. Scales are in centimeters.
|
|
|
At exploration of the left ear, the tympanic membrane was intact, with
an indwelling ventilation tube and a CC behind it. There was a fistula between
the skin of the posterior canal and the mastoid through a defect in the posterior
canal wall. The mastoid was completely occupied by cholesteatoma. In the middle
ear there was loss of the stapes superstructure and long process of incus,
as well as complete encirclement of the malleus and incus heads. A canal wall
down tympanomastoidectomy with a wide meatoplasty was performed.
CASE DISCUSSION
In the first patient, the location in the left ear rendered the lesion
outside the accepted definition of CC. Nevertheless, with the contralateral
right ear having a moderate-sized CC that fell well within the definition,
it seemed reasonable to conclude that the left-sided lesion, like the right-sided
one, originated as a CC. It is not unusual for children to have bilateral
CC,2-5
but this case was unusual in demonstrating the continuity of a bilateral late-stage
CC in which the tympanic membrane was perforated on one side but not on the
other.
In the second patient, the location in the left ear was initially thought
to put the lesion outside the accepted definition of CC. However, because
the otorrhea was originating from a defect in the posterior canal wall and
the tympanic membrane was intact, this lesion was classified as a CC. Similar
observations of posterior canal wall destruction have been reported.6-7 Except for the loss of tympanic membrane
integrity, the trajectory of destructiveness of the left ears in the first
and second patients was similar clinically and on CT imaging. Both demonstrate
end-stage lesions of CC, with the second case being slightly less advanced
than the first, and both highlight the problems of defining the origin of
a cholesteatoma that has spread far enough to destroy the function of the
ear. Our intent, with this analysis of late disease, is not to change the
definition of CC but to deepen our understanding of the end stages of this
disease.
FOUR THEORIES OF CC ORIGIN
Like the end stages of CC, its origin continues to be a source of controversy
and debate. The competing theories of the pathogenesis of CC fall into 4 broad
categories: implantation, invagination, metaplasia, and epidermoid formation.
Implantation
Friedberg,8 House and Sheehy,9 and Herdman and Wright10
suggested that a possible rare cause of CC is implantation of squamous epithelium
in the middle ear during ventilation tube insertion. Northrop et al11 observed viable squamous epithelial cells in the
amniotic fluid present in the middle ears of neonates and hypothesized that
this was a possible source of CC. However, these authors presented no evidence
that these cells could implant to form a CC.
Invagination
Several variations of the invagination theory have been proposed,12-13 most based on Ruedi's14
suggestion that otitis media causes an inflammatory injury of the tympanic
membrane that invaginates into the middle ear to form a CC. A review of the
literature fails to reveal any buttressing histologic or clinical evidence
for this postulate. Moreover, Karmody et al15
suggest that for plausibility the invagination theory demands in utero inflammation
of the tympanic membrane.
The epithelial migration theory is an alternative version of the invagination
theory, independent of otitis media, which was proposed by Aimi.16
This theory suggests that ectoderm from the embryonic external auditory canal
overcomes a hypothetical restrictive mechanism of the tympanic ring and migrates
into the middle ear. Although this theory also lacks definitive clinical documentation
and requires several hypothetical hurdles for serious consideration, it presents
an attractive possible explanation for the 4 cases in Figure 2 (images 32-35) in which CC occurred in the posterior and
inferior parts of the middle ear, in proximity to the site of the embryonic
tympanic ring. The clinical course of the patient described in Case 3 would
appear to support the epithelial migration theory.
CASE 3
A 3-year-old girl with no history of otitis media was referred after
her pediatrician noted a white pearly mass behind her right tympanic membrane
in the posterior inferior quadrant adjacent to the tympanic ring. An audiogram
showed no hearing abnormalities. A CT scan showed dense soft tissue adjacent
to the tympanic membrane and posterior tympanic ring, extending some distance
into the hypotympanum (Figure 5).
At exploratory tympanotomy, a CC was found to adhere to the underside of the
drum and the posterior inferior annulus. It dissected free as a single pearl
from the tympanic membrane, the annulus, and the hypotympanum. The child healed
without incident and has had no recurrence of her lesion. This case illustrates
1 of 4 theories of CC origin discussed herein.
|
|
|
|
Figure 5. Coronal computed tomographic scan
of the right (R) temporal bone of a 3-year-old girl with a hypotympanum congenital
cholesteatoma (case 3). This ear corresponds to number 34 on the composite
Figure 1. L indicates left.
|
|
|
Metaplasia
The metaplasia theory was proposed by Sade et al17
and is based on their observation that squamous metaplasia, some with keratinization,
can occur in the middle ear in response to otitis media. They postulated that
such keratinizing metaplastic change of the mucosa can possibly result in
CC. However, Friedberg8 has pointed out the
discrepancy between the consistent location of CC (in the anterior superior
quadrant) and the inconsistent location of middle ear metaplasia. Like the
invagination theory, the metaplasia theory appears to require in utero inflammation
of the tympanic membrane to be plausible.15
Epidermoid Formation
The epidermoid formation theory of CC is based on Michaels'18 observation of a rest of squamous epithelial cells,
which occasionally keratinize, in the lateral wall of the embryonic tympanic
cavity below the level of the pars flaccida. The rest of the cells, which
he termed an epidermoid formation, was noted in more
than half of the specimens examined. It was observed as early as the tenth
week of gestation and consistently disappeared by 33 weeks of gestation. This
observation had also been made by Teed19 50
years earlier and was verified by Wang20 and
McGill21 and their colleagues. McGill et al
pointed out in 1991 that confirmation of the epidermoid formation theory would
require finding intermediate forms of anterior superior quadrant epithelial
cell rests between 33 weeks of gestation, when epidermoid formations involute,
and early childhood, when CC typically presents. Seven years later, Karmody
et al15 described finding such evidence in
2 postmortem investigations: a keratinizing epidermoid formation in the temporal
bone of a 3 -month-old boy and a nonkeratinizing epidermoid formation
in the temporal bone of a 7-month-old boy. In addition, Potsic et
al22 described a 4-month-old girl with bilateral
CC confirmed at exploratory tympanotomy.
Although we have no cases that contribute new evidence to support any
one theory about the pathogenesis of CC, one observation that must be accounted
for by any plausible explanation of the origin of CC is the very young age
of the children in whom it was found (mean age, 5.6 years; range, 2-13 years).
This is consistent with findings from other large series.6, 21-24
In contrast, the mean ± SD age of 991 children with acquired
cholesteatoma from 4 institutions was 9.7 ± 3.3 years,1
significantly older than the children with CC in this series (P<.001). These are separate populations with different diseases,
which suggests a relationship between early age and the pathogenesis of CC.
Age-related pathogenesis could support either an embryonic origin (the migration
and epidermoid formation theories) or an origin related to otitis media during
infancy (the invagination and metaplasia theories). However, the observation
that only 48.7% among the series1 of 991 children
with acquired cholesteatoma had a history of otitis media (acute otitis media
or otitis media with effusion) weakens the argument for a causative role of
otitis media. One would have to invoke a hypothetical history of "silent otitis
media" in a large number of children to salvage this line of reasoning, which
seems inelegant and unnecessarily complicated.
CONCLUSIONS
- The origin of CC remains uncertain, but a substantial
body of evidence suggests that most CC begins as an embryonic epidermoid formation
in the anterior mesotympanum that fails to involute.
- The mass is usually in the anterior superior quadrant,
but does not consistently remain there and may variably occupy the middle
ear and mastoid and result in ossicular destruction and conductive hearing
loss.
- The progression of growth is from the middle ear,
initially into the posterior superior quadrant and attic, and finally into
the mastoid.
- The clinical picture of a young child with otorrhea,
conductive hearing loss, tympanic membrane perforation in a nontraditional
location, and a mastoid filled with cholesteatoma may represent the end point
in the natural history of CC, despite the fact that this type of lesion is
outside the accepted definition of CC.
AUTHOR INFORMATION
Accepted for publication January 9, 2002.
We greatly appreciate the efforts of Scott J. Beam in the preparation
of the manuscript.
Corresponding author: Peter J. Koltai, MD, Section of Pediatric Otolaryngology,
The Cleveland Clinic Foundation, 9500 Euclid Ave, Desk A71, Cleveland, OH
44195 (e-mail: koltaip{at}ccf.org).
From the Section of Pediatric Otolaryngology, The Cleveland Clinic
Foundation, Cleveland, Ohio (Drs Koltai and Nelson); Division of Otolaryngology,
Albany Medical College, Albany, NY (Dr Castellon); and Children's Hospital
Armand Trousseau, Paris (Drs Garabedian and Roger), and La Timone Children's
Hospital, Marseille (Drs Triglia and Roman), France.
REFERENCES
| |
1. Nelson M, Roger G, Koltai PJ, et al. Congenital cholesteatoma: classification, management, and outcome. Arch Otolaryngol Head Neck Surg. 2002;128:810-814.
FREE FULL TEXT
2. Nishizaki K, Yamamoto S, Fukazawa M, Yuen K, Ohmichi T, Masuda Y. Bilateral congenital cholesteatoma. Int J Pediatr Otorhinolaryngol. 1996;34:259-264.
PUBMED
3. Fedok FG, Bellissimo JB, Wiegand DA. Bilateral congenital aural cholesteatoma. Otolaryngol Head Neck Surg. 1990;103:1028-1030.
PUBMED
4. Suetake M, Kobayashi T, Takasaka T. Bilateral congenital cholesteatomas associated with ossicular anomalies:
a case report. Am J Otol. 1991;12:132-134.
PUBMED
5. Braganza RA, Kearns D. Bilateral congenital cholesteatomas. Am J Otolaryngol. 1993;14:191-193.
PUBMED
6. Rizer FM, Luxford WM. The management of congenital cholesteatoma: surgical results of 42
cases. Laryngoscope. 1988;98:254-256.
PUBMED
7. Huang TS, Lee FP. Congenital cholesteatoma: a review of twelve cases. Am J Otol. 1994;15:276-281.
PUBMED
8. Friedberg J. Congenital cholesteatoma. Laryngoscope. 1994;104(pt 2):1-24.
9. House JW, Sheehy JL. Cholesteatoma with intact tympanic membrane: a report of 41 cases. Laryngoscope. 1980;90:70-76.
ISI
| PUBMED
10. Herdman R, Wright JLW. Grommets and cholesteatoma in children. J Laryngol Otol. 1988;102:1000-1002.
ISI
| PUBMED
11. Northrop C, Piza J, Eavey RD. Histological observations of amniotic fluid cellular content in the
ear of neonates and infants. Int J Pediatr Otorhinolaryngol. 1986;11:113-127.
FULL TEXT
|
ISI
| PUBMED
12. Sobol SM, Reichert TJ, Faw KD. Intramembranous and mesotympanic cholesteatomas associated with an
intact tympanic membrane. Ann Otol Rhinol Laryngol. 1980;89:312-317.
PUBMED
13. Tos M. A new pathogenesis of mesotympanic (congenital) cholesteatoma. Laryngoscope. 2000;110:1890-1897.
FULL TEXT
|
ISI
| PUBMED
14. Ruedi L. Cholesteatoma formation in the middle ear in animal experiments. Acta Otolaryngol. 1959;50:233-242.
PUBMED
15. Karmody CS, Byahatti SV, Blevins N, Valtonen H, Northrop C. The origin of congenital cholesteatoma. Am J Otol. 1998;19:292-297.
PUBMED
16. Aimi K. Role of the tympanic ring in the pathogenesis of congenital cholesteatoma. Laryngoscope. 1983;93:1140-1146.
PUBMED
17. Sade J, Babiacki A, Pincus G. The metaplastic and congenital origin of cholesteatoma. Acta Otolaryngol. 1983;96:119-129.
PUBMED
18. Michaels L. An epidermoid formation in the developing middle ear: possible source
of cholesteatoma. J Otolaryngol. 1986;15:169-174.
ISI
| PUBMED
19. Teed RW. Cholesteatoma verum tympani: its relationship to the first epibranchial
placode. Arch Otolaryngol. 1936;24:455-474.
20. Wang RG, Hawke M, Kwok R. The epidermoid formation (Michaels' structure) in the developing middle
ear. J Otolaryngol. 1987;16:327-330.
PUBMED
21. McGill TJ, Merchant S, Healy GB, Friedman EM. Congenital cholesteatoma of the middle ear in children: a clinical
and histopathological report. Laryngoscope. 1991;101:606-613.
PUBMED
22. Potsic WP, Wetmore RF, Marsh RR. Congenital cholesteatoma of the middle ear: fifteen years' experience
at the Children's Hospital of Philadelphia. In: Sanna M, ed. Cholesteatoma and Mastoid Surgery. Rome, Italy: CIC Edizioni Internazionali; 1997:422-431.
23. Grundfest KM, Ahuja GS, Parisier SC, Culver SM. Delayed diagnosis and fate of congenital cholesteatoma (keratoma). Arch Otolaryngol Head Neck Surg. 1995;121:903-907.
ABSTRACT
24. Levenson MJ, Michaels L, Parisier SC, Juarbe C. Congenital cholesteatomas in children: an embryologic correlation. Laryngoscope. 1988;98:949-955.
PUBMED
RELATED ARTICLE
Congenital Cholesteatoma: Classification, Management, and Outcome
Marc Nelson, Gilles Roger, Peter J. Koltai, Erea-Noel Garabedian, Jean-Michel Triglia, Stephane Roman, Roberto J. Castellon, and Jeffrey P. Hammel
Arch Otolaryngol Head Neck Surg. 2002;128(7):810-814.
ABSTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Diagnosis of Pediatric Cholesteatoma
Isaacson
Pediatrics 2007;120:603-608.
ABSTRACT
| FULL TEXT
Congenital Cholesteatoma: Classification, Management, and Outcome
Nelson et al.
Arch Otolaryngol Head Neck Surg 2002;128:810-814.
ABSTRACT
| FULL TEXT
|
