Total colonic aganglionosis: diagnosis and treatment
Total colonic aganglionosis: diagnosis and treatment
Anupama Basnet and Shan Zheng
Shanghai, China
Background: Total colonic aganglionosis (TCA) is a
rare form of Hirschsprung's Disease (HD). The aim of this
review is to describe the diagnostic and therapeutic aspects
of TCA, and to discuss some surgical procedures, associated
complications, and long-term outcome.
Data resources: Surgical literatures in PUBMED,
MEDLINE of the last 10 years were reviewed. The data
on diagnosis, management and long-term follow-up of
children with total colonic aganglionosis were extracted
and analyzed.
Results: The diagnosis and treatment of TCA are
difficult, but histological evaluation has been confirmed in
the establishment of the diagnosis in recent years. Several
surgical techniques have been utilized for the treatment
of TCA. Nevertheless, little information is available for
optimal management of recurrent complications caused
by failed procedures.
Conclusions: Although TCA is a rare form of HD, its
diagnosis and management have improved in recent years
with a significant increase in survival rate and prognosis.
World J Pediatr 2006;2:97-101
Key words: total colonic aganglionosis;
nitric oxide;
acetylcholinesterase;
NAPDH-diaphorase;
treatment
Introduction
T
otal colonic aganglionosis (TCA) with or
without involvement of the small intestine is a
rare form of Hirschsprung's disease (HD) and
accounts for approximately 3% to 12% of all infants
with HD.[1,2] The prevalence in boys and girls is nearly
Author Affiliations: Department of Pediatric Surgery, Children's Hospital
of Fudan University, Shanghai 200032, China (Basnet A and Zheng S)
Corresponding Author: Shan Zheng, MD, Department of Pediatric Surgery,
Children's Hospital of Fudan University, Shanghai 200032, China (Tel: 86-
21-54524666 ext 2042; Fax: 86-21-64038992; Email: szheng@shmu.edu.cn)
©2006, World J Pediatr. All rights reserved.
equal. Eighty percent of patients are encountered in
the neonatal period with delayed passage of meconium,
abdominal distention, constipation, and bilious
vomiting.[3] Few patients are present in childhood and
Review article
adulthood. The diagnosis and treatment of the disease
are known to be difficult and more difficult in the latter.
Many surgical techniques have been developed for the
radical treatment of this disease,[4] but none of them
has been proved effective. The disease is considered
fetal in infancy. Chronic intestinal obstruction and
long-term total parenteral nutrition (TPN) would result
in higher morbidity and mortality rates than segment
aganglionosis.[5] Although the survival rate of infants
with TCA has improved markedly, problems in the
surgical treatment remains unsolved and long-term
consequences for growth and continence are poorly
documented.[6] In recent years, early and accurate
diagnosis and improved supportive care of TCA have
increased the survival rate of patients,[7] and improved
the prognosis.
97
Advances in diagnosis
Radiographic features
Although the presence of a radiographic transition zone
(RTZ) shown by barium enema may aid in the diagnosis
of HD, it is not correlated with TCA. A false transition
zone was found in 15% of patients with TCA.[8] De
Campo et al[9] reviewed the radiological findings in 13
TCA patients and concluded that there were no specific
pathognomonic findings on barium enema examinations.
In their study, normal caliber colon was found in 77%
of patients, microcolon in 23%, shortened colon in 23%,
colonic wall irregularity in 46%, and significant ileal
reflux in 33%. Irregular muscular contractions in the
hepatic flexure, normal caliber colon, and small bowel
dilatation suggested a diagnosis of TCA. The narrow
descending colon showed a marked change of caliber
at the splenic flexure as well as evidence of neonatal
functional immaturity of the large bowel.[10] In 2000
Narla and Hingsbergen found that evaluation of the
caliber of the colon is essential to the elucidation of
low intestinal obstruction. A microcolon has a caliber
World J Pediatr, Vol 2 No 2 . May 15, 2006 .
 World Journal of Pediatrics

less than 1 cm in diameter owing to disuse of the colon
from a more proximal obstruction. Microcolon is seen
in patients with meconium ileus; distal jejunal, ileal, or
proximal colonic atresia; and megacystis-microcolon-
intestinal hypoperistalsis syndrome. It is seen in less
than one-fourth of patients with TCA.[11]
Radiological manifestations of TCA and allied
disorders are more or less similar. In TCA, radiographic
studies may show dilated bowel loops, and contrast
enema may show a question mark-shaped colon owing
to rounded edges of the splenic and hepatic flexure.
However radiographic findings are not diagnostic
Review article
nerve fibers were absent in all layers of the bowel wall,
which suggested that an abnormality in the preganglionic
cholinergic fiber or extrinsic neuron is involved in the
pathogenesis of this unusual form of TCA.
Apart from the differences in AChE activities
in parasympathetic nerve fibers, histopathological
differences have been found in other neurotransmitters,
such as nitric oxide (NO), NADPH-diaphorase and
C-kit+ interstitial cell of cajal (ICC), which may assist
the diagnosis of TCA. In 2003, Solari and colleagues[18]
found shortage or absence of neuronal nitric oxide
synthase (nNOS) in the sparse, short nerve trunks of the

and ultimately a diagnosis of TCA has to rely on myenteric and submucous plexuses and muscle layers
histopathological confirmation. in TCA in contrast to normal nNOS in the weakly
positive nerve trunks in rectosigmoid HD. The number
Histopathological features of peripherin immunoreactivity and NADPH-positive
nerve trunks was reduced more markedly in TCA
Proper histopathological diagnosis will prevent the
than in rectosigmoid HD.[18] No NADPH-D-positive
loss of bowel length caused by inadvertent resection
fibers was found in the myenteric muscles in patients
and will be helpful in selecting an optimal procedure
with TCA and hypertrophic nerve trunks stained
for the patient. Until the advent of new molecular
weakly.[19] The whole-mount preparation technique
biological techniques, histopathology remains the gold
used by Nemeth et al[20] showed the absence of typical
standard diagnostic method for HD.[12] The cases of
architecture of the myenteric plexus and the presence
TCA show more diagnostic problems associated with
of hypertrophied nerve trunks running in a haphazard
higher morbidity and mortality than classic HD cases.
manner and frequently crossing each other in classic
Clinical and radiological features can be useful in the
HD. At the same time, the hypertrophied never trunk
diagnosis of the disease but they are not pathognomonic.
in TCA pursued a straight course, running parallel to
The diagnosis of TCA is confirmed by intraoperative
longitudinal muscle fibers without crossing each other.
seromuscular biopsies of the rectum, colon and ileum.
In TCA specimens, lack of c-kit+ ICCs was noted in
98 Therefore, laparotomy and open frozen biopsies are
the smooth muscle layer, whereas in rectosigmoid HD
always required for a correct diagnosis of TCA.[13]
specimens, ICCs were markedly reduced.[18] Hence
Although laparoscopic colonic biopsies are either
attention should be paid to regional differences of
minimally invasive or valuable for the investigation of
distribution, and identical regions of affected and
children with chronic constipation,[14-16] it is unsuitable
unaffected intestine must be differentiated in detecting
for a particular case of TCA. Patients with TCA usually
the relationship between the abnormality of c-Kit-
present with lower intestinal obstruction which needs
positive cells and motility disorders in HD including
emergency laparotomy with ileostomy.
TCA.[21]
Histological findings of TCA are similar to those
Hence, preoperative determination of the length
of classic HD. No absolute histomorphological criteria
of aganglionic segment in TCA is still a diagnostic
are available for the diagnosis of TCA, except the lack
challenge. Although the diagnosis of TCA is based
of ganglia in the whole colonic segment. Only a few
on ACTH enzyme activity in colic and ileal biopsies,
articles focused on the dissimilarity between TCA
recognition of the differences of other neurotransmitters
and classic HD cases. An important diagnostic test
may be helpful in confirming the diagnosis and the
involves histochemical staining for acetylcholinesterase
length of involvement, and further preventing multiple
(AChE). In TCA, AChE activity presents an atypical
laparotomy and resection of massively ditated ileum.
pattern different from the classic one. In rectosigmoid
Therefore it is helpful to preserve the length of the
HD, positive fibers can be found in the lamina propria
intestine at premium in TCA.
as well as in the muscularis mucosae. In TCA, however,
cholinergic fibers present with a lower density in the
lamina propria and muscularis mucosae.[4] Sun et al[17]
studied 8 segments of the aganglionic colon, including 2 Advances in treatment
cases of TCA, in whom hypertrophied and AchE-positive Since the report of a successful pull-through procedure
. World J Pediatr, Vol 2 No 2 . May 15, 2006
 Total colonic aganglionosis: diagnosis and treatment
for TCA in 1953, major advances have been made in
the management of TCA.[2] In recent years, several
surgical techniques have been utilized in the treatment
of TCA, but optimal management of recurrent
complications or failed procedures is not available.
Some of the techniques are derived from the operations
for the treatment of classic HD, others are specifically
designed.[4] Although the features of TCA are similar to
those found previously, substantial improvement in the
treatment of TCA has been noted.
Surgical procedures
Modified Martin-Duhamel is a procedure of choice for
most cases of TCA. Swenson's operation with ileoanal
anastomosis and Soave procedures are also advisable.
Some doctors hold that although modified Martin-
Duhamel is the most widely employed technique, the
Swenson procedure results in few complications in
cases of TCA associated with distal ileal involvement.[22]
With the introduction of the endo-GIA stapling
device, the one-stage Duhamel-Martin procedure has
become feasible for neonates and infants.[23] Aslan
et al[24] reported that in infants, the Martin-Duhamel
procedure using an endo-GIA stapler transanally for
colo-ileal anastomosis without protective ileostomy
may be an alternative for the treatment of patients with
TCA. Others[25] have treated cases of TCA with ileal
involvement by the Boley procedure or the Rehbein
procedure using a GIA stapler. The result of this
operation includes high survival rate, low morbidity,
rapid recovery of bowel function and continence, and
normal physical development.[25] Bonnard et al[26]
considered that the laparoscopic procedure for TCA is
safe and feasible, because of absence of soiling or stool
incontinence and constipation.
The ileoanal S pouch (IASP) technique has
been used for TCA patients with poor results from
total colectomy and Soave pull-through.[27] In 1998,
Nishijima et al[28] used colon patch graft (CPG) in the
treatment of patients with extensive aganglionosis.
The CPG effectively reduces "ileostomy diarrhea",
while shortening the period of intravenous nutrition,
improving bowel habit patterns with the advancement
of time, and normalizing body weight for age. Sharif
et al[29] affirmed that subtotal resection of the intestine
at the time of diagnosis must be avoided. Conservative
management with TPN may be related to long-term
good outcome. Bowel transplantation is an option
for TCA with unadapted short bowel syndrome
(SBS). Hence, intestinal transplant is promising in the
management of TCA involving the long segment of the
small intestine.
Complications
Surgical treatment of TCA is associated with a number
of complications including recurrent enterocolitis and
anal strictures. Long-term outcome is quite favorable.[30]
Primary endorectal pull-through and the Martin-
Duhamel procedure or Swenson's operation may
induce some postoperative complications including
enterocolitis, anal stricture, and perineal excoriation.
Approximately 89% of the patients can be free from
recurrent enterocolitis after the operation. The
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frequency of bowel movement is 1-5 per day, 18% of
the patients have 6 or more bowel movements per day.
Occasional soiling is noted, and the rate of functional
recovery approaches 83%.
In 27 children with TCA treated by N-Fekete, 11
underwent the modified Martin-Duhamel operation,
and one received the Swenson's operation with ileoanal
anastomosis, and one had the Kimura procedure. The
results of these cases proved that the essential problem
in TCA is not the surgical management of the condition,
but rather its prompt diagnosis and the handling of
neonatal intestinal obstruction.[31] Early management
of neonatal intestinal occlusion seems to decrease
the incidence of enterocolitis. Normally, diarrhea and
intestinal occlusion occur during the first postoperative
year.[32]
99
Long-term outcome
After reviewing 36 patients with TCA, Escobar et al[33]
concluded that the highest morbidity may be induced
by the Martin-Duhamel or Soave procedures. During
the long-term follow-up, the patients must be evaluated
for the deficiency of iron and folic acid. It was reported
that ileoendorectal pull-through with a right colon patch
is associated with few early and late postoperative
complications. This method of reconstruction provides
a best opportunity for TCA patients for normal
growth, development, and long-term recovery of
bowel function.[34] The use of the aganglionic bowel
of extensive length to maximize fluid absorption is
frequently met with substantial morbidity.[35] Despite
the occurrence of some common postoperative com-
plications, most children with TCA may get well as
shown by long-term follow-up.[36] Obstructive symptoms
and incontinence may be resolved with time, and that
the risk of enterocolitis is almost eliminated after first
5 years of life. Sexual function, social satisfaction, and
life quality all appear to be normal in the vast majority
of patients.
World J Pediatr, Vol 2 No 2 . May 15, 2006 .
 World Journal of Pediatrics
Conclusion
TCA with or without involvement of the ileal segment
constitutes a small proportion of all cases of HD. The
clinical and radiological features of TCA can be useful
in the diagnosis but they are not pathognomonic and one
finally has to depend on histopathological evaluation for
confirming the diagnosis and the length of involvement.
No surgical method has been confirmed clearly to be
superior for TCA. Although the features of TCA are
similar to those reported previously, a substantial
improvement in the treatment of TCA has been noted.
Improvements in supportive care, early recognition and
Review article
appropriate treatment have led to a drastically increased
rate of survival in patients with TCA.
Funding: None.
Ethical approval: Not needed.
Competing interest: No benefits in any form have been received
or will be received from any commercial party related directly or
indirectly to the subject of this article.
Contributors: BA wrote the main body of the article under the
supervision of ZS. ZS is the guarantor.
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Received October 24, 2005
Accepted after revision March 9, 2006
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World J Pediatr, Vol 2 No 2 . May 15, 2006 .