Proximal jejunostomy with or without myectomy-myotomy modification in five infants with total intestinal aganglionosis: An experience with surgical treatments in a single institution.

Abstract

Total intestinal aganglionosis is characterized by the absence of intramural ganglion cells, in which the disease's involvement extends from the stomach to the anorectum. This disease was suggested previously to be incompatible with life, but recently an extended small bowel myectomy-myotomy has achieved some prolonged survivors.
Five patients with total intestinal aganglionosis underwent laparotomy at 1 to 5 days of age. Surgery was performed as a simple jejunostomy 60 to 70 cm below the ligament of Treitz in the initial 2, jejunustomy 30 cm below the ligament of Treitz in 1, and jejunostomy with myectomy-myotomy modification 30 to 35 cm below the ligament of Treitz in the remaining 2 infants.
The initial 2 patients died of sepsis, possibly derived from frequent enteritis and bacterial translocation at 7 and 8 months of age. Another patient had prolonged survival but died of hepatic failure at 1 year, 4 months. The remaining 2 children have survived beyond 2 years of age without any liver dysfunction, receiving a combination of enteral and parenteral nutrition.
The more proximal site (30 to 35 cm below the ligament of Treitz) of jejunostomy with myectomy-myotomy modification appeared to be preferable for prolonged survival in these 5 patients with total intestinal aganglionosis.

Full text

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Proximal Jejunostomy With or Without Myectomy-Myotomy
Modification in Five Infants With Total Intestinal Aganglionosis:
An Experience With Surgical Treatments in a Single Institution
By Takashi Shimotake, Seitetsu Go, Hideki Tomiyama, Shigeyoshi Aoi, and Naomi Iwai
Kyoto, Japan
Background: Total intestinal aganglionosis is characterized
by the absence of intramural ganglion cells, in which the
disease’s involvement extends from the stomach to the ano-
rectum. This disease was suggested previously to be incom-
patible with life, but recently an extended small bowel my-
ectomy-myotomy has achieved some prolonged survivors.
Methods: Five patients with total intestinal aganglionosis
underwent laparotomy at 1 to 5 days of age. Surgery was
performed as a simple jejunostomy 60 to 70 cm below the
ligament of Treitz in the initial 2, jejunustomy 30 cm below
the ligament of Treitz in 1, and jejunostomy with myectomy-
myotomy modification 30 to 35 cm below the ligament of
Treitz in the remaining 2 infants.
Results: The initial 2 patients died of sepsis, possibly derived
from frequent enteritis and bacterial translocation at 7 and 8
months of age. Another patient had prolonged survival but
died of hepatic failure at 1 year, 4 months. The remaining 2
children have survived beyond 2 years of age without any
liver dysfunction, receiving a combination of enteral and
parenteral nutrition.
Conclusions: The more proximal site (30 to 35 cm below the
ligament of Treitz) of jejunostomy with myectomy-myotomy
modification appeared to be preferable for prolonged sur-
vival in these 5 patients with total intestinal aganglionosis.
J Pediatr Surg 37:835-839. Copyright 2002, Elsevier Science
(USA). All rights reserved.
INDEX WORDS: Hirschsprung’s disease, total intestinal
aganglionosis, myectomy-myotomy.
T
opment.1-2The aganglionosis involves the entire colon,
small intestine, duodenum and stomach.3Treatments for
infants with total intestinal aganglionosis previously re-
sulted in uniformly fatal outcomes, but recently extended
myectomy-myotomy of the proximal jejunum (Ziegler)
has achieved some prolonged survivors.4-5However, the
extreme rarity of the disease appears to make it difficult
to assess the significance of this recently recognized
surgical alternative for extensive aganglionosis without
biases from differences in institutional equipment, clin-
ical experience, or the practice of parenteral nutritional
support.
Here, we describe the results of the surgical treatments
for 5 such patients in a single institution.
OTAL INTESTINAL aganglionosis is an extremely
severe form of enteric nervous system maldevel-
MATERIALS AND METHODS
We treated 5 patients who had total intestinal aganglionosis between
1990 and 2000. Of the 5 children, 4 were sporadic cases and 1 had
familial occurrence. In each case, the diagnosis of congenital agangli-
onosis was made based on histopathology, and the levels of involve-
ment of aganglionic segments were determined by intraoperative lev-
eling biopsies from the stomach, duodenum, jejunum, ileum, colon, and
rectum.
Case 1
A male newborn baby, delivered after a 34-week gestation with a
2,100 g birth weight, underwent a laparotomy at the age of 1 day. His
elder sister had total colonic aganglionosis and had been treated in our
hospital. Intraoperative biopsy specimens all showed an absence of
intramural ganglion cells from the stomach to the rectum. We made a
jejunostomy 70 cm distal from the ligament of Treitz and treated with
total parenteral nutrition (TPN). The volume of ostomy outputs re-
mained less than 10 mL per day, and he repeatedly showed severe
enteritis. He died of sepsis at the age of 7 months. Two years later, his
younger sister was born. She had total colonic aganglionosis with
extensive involvement of the ileum. She was treated uneventfully with
a modified Martin’s procedure.
Case 2
The second patient, delivered after a 39-week gestation with a birth
weight of 2,540 g, underwent a laparotomy at the age of 3 days.
Intraoperative histopathology of the gut wall biopsy specimens con-
firmed total intestinal aganglionosis. We performed a jejunostomy at a
site 65 cm distal from the ligament of Treitz, and treated with TPN. The
ostomy did not function, and his abdomen was persistently distended.
He died of sepsis complicated with liver failure at 8 months of age.
From the Division of Surgery, Children’s Research Hospital, Kyoto
Prefectural University of Medicine, Kyoto, Japan.
Supported by grants from the Scientific Research Fund of the
Ministry of Education, Science and Culture of Japan (Nos. 11470369 &
13671870).
Address reprint requests to Takashi Shimotake, MD, Division of
Surgery, Children’s Research Hospital, Kyoto Prefectural University
of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-
0841, Japan.
Copyright 2002, Elsevier Science (USA). All rights reserved.
0022-3468/02/3706-0004$35.00/0
doi:10.1053/jpsu.2002.32883
835Journal of Pediatric Surgery, Vol 37, No 6 (June), 2002: pp 835-839

Page 2

Case 3
The third patient, delivered after a 41-week gestation with a 3,884 g
birth weight, underwent a laparotomy at 5 days of age. Histopathology
confirmed total intestinal aganglionosis during surgery. In this case, we
performed a jejunostomy at 30 cm distal from the ligament of Treitz.
His early postoperative course was favorable, and enteral feeding was
started using an elemental diet (20 mL of 8 times a day; Elental-P,
Morinaga-Lucel Co, Tokyo, Japan). The volume of ostomy output
measured between 50 and 100 mL per day. He gained weight up to
6,500 g until 7 months of age. However, his liver dysfunction worsened
at 8 months, and he died of liver failure at 1 year, 4 months.
Case 4
The fourth patient, of 2,270 g birth weight, underwent a laparotomy
at the age of 4 days. Histology findings showed a small number of
ganglion cells at 3 cm from the ligament of Treitz; but the distal gut
was completely aganglionic. A jejunostomy was made 35 cm below the
ligament of Treitz. At 8 weeks of age, he underwent myectomy-
myotomy modification of a 30 cm proximal jejunal segment. A 10-cm
myectomy with 5-mm width starting at the histology-proven transition
zone was coupled with a 20 cm antemesenteric myotomy of the
subsequent jejunum. The depth of the myectomy/myotomy incision
was kept within the submucosa, and the cut edge was spread to a width
of 8 to 10 mm. The final length of the treated jejunum was 30 cm, and
it ended as a stoma. Enteral feeding was soon started orally using breast
milk and an elemental diet (20 mL at 8 times a day; Elental-P,
Morinaga-Lucel Co), and the volume of daily ostomy output measured
between 50 and 110 mL. Antibiotics and medications for hepatic
protection were used to prevent cholestatic liver disease after the
treatment for parenterally fed infants with short bowel syndrome. His
growth consistently remained between the 5th and 95th percentile of
the standard for weight and height. He currently is 8 years old using a
combination of home parenteral nutrition and oral intake of elemental
diet. He receives 60% of his calories by the enteral feeding and the
other 40% from the parenteral nutritional support, respectively.
Case 5
A female newborn baby, delivered vaginally after a 39-week gesta-
tion with a 3,698 g birth weight, was referred to our hospital because
of abdominal distension and bilious vomitus. At laparotomy at the age
of 4 days, histopathology confirmed total intestinal aganglionosis. We
performed a jejunostomy 30 cm distal from the ligament of Treitz. On
the 8th postoperative day, we performed a myectomy-myotomy for the
proximal jejunal loop. A 10-cm myectomy with 5-mm width starting at
the ligament of Treitz was coupled with a 20 cm antemesenteric
myotomy. The depth of the seromuscular incision was the submucosa
and the cut edge was spread to a width of 10 mm. The treated jejunum
was 30 cm and ended as a stoma. Her postoperative course was
favorable, and enteral feeding soon was started using breast milk (20
mL at 8 times per day). The volume of enterostomy output remained
between 40 and 100 mL per day. During early postoperative care, she
showed no episode of enteritis, and no prophylactic antibiotics were
used. She currently is in good condition at 2 years and 8 months of age
using a combination of parenteral nutrition and continuing oral intake
of an elemental diet (Elental-P, Morinaga-Lucel Co,). She receives
20% of her calories by oral intake and the other 80% via the parenteral
route, respectively. She consistently remains within the 5th to 95th
percentile of the standard for height and weight. She has not shown any
signs or symptoms of liver dysfunction.
RESULTS
Intraoperative Findings
All 5 patients underwent laparotomy aged 1 to 5 days.
At the initial surgery, gut caliber changes were found at
a site between 90 and 110 cm distal from the ligament of
Treitz in each case (Fig 1). The average ratio of the
proximal bowel caliber to the distal one was 3.01 (Table
1). However, a histology-based transition zone was con-
firmed only in case 4 and was only 3 cm distal from the
ligament of Treitz. Therefore, there was no correlation of
the observed transition with the presence or absence of
intramural ganglion cells in these 5 infants.
Surgical Outcomes
In cases 1 and 2, proximal enterostomy was not
successful. The volume of ostomy output remained less
Fig 1.
tive findings in 5 patients with total and
near-total intestinal aganglionosis. Intes-
tinal caliber changes were found at a site
between 90 and 110 cm distal from the
ligament of Treitz, but the histopathology
based transition zone was confirmed only
in case 4. In the remaining 4 infants, the
gastrointestinal tract was aganglionic
throughout.The myectomy-myotomy
procedure was performed in cases 4 and 5
at 7 weeks and 8 days of age, respec-
tively. LOT, ligament of Treitz.
Schematic description of opera-
836 SHIMOTAKE ET AL

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than 10 mL per day. They suffered from intraluminal
stasis and cholestatic liver disease. Liver function mea-
surements progressively deteriorated after repeated en-
teritis, and they died of sepsis at 7 and 8 months of age,
respectively. In case 3, the output volume from ostomy
measured between 50 and 100 mL per day. He grew up
to the age of 7 months with enteral feeding and parenteral
nutrition support. However, his liver function worsened
after enteritis at 8 months of age, which led to a fatal
result at 1 year, 4 months of age. The remaining 2
patients with myectomized proximal jejunal loop sur-
vived beyond 2 years of age without any liver dysfunc-
tion. They receive a combination of enteral and paren-
teral nutrition, in which cases 4 and 5 receive 60% and
20% of their calories by the enteral route (oral intake),
respectively. Both of them remain within the 5th to 95th
percentile of the standard for height and weight after the
age of 1 year (Fig 2).
DISCUSSION
The majority of enteric ganglion cells are derived from
the neural crest and migrate into the intestinal wall in a
caudal direction between the 5th and 12th gestational
weeks.6,7Total intestinal aganglionosis is a rare condi-
tion in which the neural crest–derived cell development
is disrupted severely.8-10This type of congenital agan-
glionosis is estimated to occur in less than 0.1% of
patients with Hirschsprung’s disease.11,12The extreme
rarity of the disease makes it difficult to assess the
detailed pathophysiologic conditions. The pathology of
total intestinal aganglionosis may be different from that
of near-total intestinal aganglionosis, in which the gan-
glionated bowel often extends distally from the ligament
of Treitz.13In total intestinal aganglionosis, a lack of
peristaltic propulsion by the ganglionated bowel theoret-
ically is expected.14In such pathologic conditions, the
intraluminal stasis of the gastric, bile, and pancreatic
juice may be harmful to the sphincter function of the
papilla of Vater and the surrounding region resulting
in severe cholestatic liver injury or dysfunction. An
extended myectomy-myotomy for the aganglionic prox-
imal small bowel produced encouraging results in chil-
dren with both total and near-total intestinal aganglio-
nosis.5However, the questions of whether and how
surgery for total intestinal aganglionosis should be mod-
ified from that for near-total intestinal aganglionosis
have not been answered clearly.
Here we described the results of surgical treatment for
5 infants with total or near-total intestinal aganglionosis,
4 of whom had no ganglionated bowel below the liga-
ment of Treitz (Table 1). In the initial 2 patients, we
performed a jejunostomy 60 to 70 cm distal from the
ligament of Treitz during the neonatal period, but could
Table 1. Results of Surgical Treatments for Five Infants With Total and Near-Total Intestinal Aganglionosis
Patient
No.
Diagnosis
Gender
Age at
Diagnosis
Age at Myectomy-
Myotomy
Ganglionated Bowel
Below LOT
Gut Caliber Change
Below LOT
(dilated 3 narrow)
Jejunostomy
Below LOT
Extent of Myectomy-
Myotomy
Episode of
Sepsis
Outcome
1
Total intestinal aganglinosis
Male
1 d
-
0 cm
90 cm
(25 mm 3 8 mm)
70 cm
—
7
Dead at 7 mo
2
Total intestinal aganglinosis
Male
3 d
-
0 cm
100 cm
(20 mm 3 8 mm)
65 cm
—
3
Dead at 8 mo
3
Total intestinal aganglinosis
Male
5 d
-
0 cm
100 cm
(15 mm 3 7 mm)
30 cm
—
2
Dead at 1 yr,
4 mo
4
Near-total intestinal aganglionosis
Male
4 d
7 wk
3 cm
95 cm
(24 mm 3 8 mm)
35 cm
30 cm
1
Alive at 8 yr,
10 mo
5
Total intestinal aganglinosis
Female
4 d
8 d
0 cm
110 cm
(30 mm 3 7 mm)
30 cm
30 cm
0
Alive at 2 yr,
8 mo
Abbreviation: LOT, ligament of Treitz.
837SURGERY FOR TOTAL INTESTINAL AGANGLIONOSIS

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perform no additional myectomy-myotomy surgical in-
tervention because of their deteriorating general condi-
tion. Severe enteritis and intraluminal stasis in the prox-
imal jejunum could not be controlled because the
proximal jejunal loop was too long to be effectively
irrigated and also because antibiotics could not relieve
the overwhelming bacterial overgrowth. In previous
studies, a jejunostomy with myectomy-myotomy modi-
fication 50 to 70 cm below the ligament of Treitz was
reported to function in several cases with near-total
intestinal aganglionosis.13,15However, we performed it
30 to 35 cm below the ligament of Treitz in the subse-
quent 3 infants because a jejunostomy 60 to 70 cm below
the ligament of Treitz appeared to us excessively long for
total intestinal aganglionosis. Theoretically, myectomy
can relieve the resistance to the entry of luminal contents
into that segment of the intestine, but the resistance is
never zero and will cause obstruction if the segment is
too long.13At an aganglionic segment with a length
greater than 20 to 40 cm, the small bowel passive conduit
length would be too long to permit proximal propulsive
forces to push the luminal contents through, resulting in
a functional obstruction and intraluminal stasis.5
In these 5 infants, we found a gut caliber change at a
site between 90 and 110 cm distal from the ligament of
Treitz. However, the histologically proven transition was
confirmed only in case 4. There was no correlation of the
observed transition with the distribution of enteric gan-
glia in these patients. Based on most previous descrip-
tions, the presence of gut caliber change may be inex-
plicable in the totally aganglionic gastrointestinal tract.
This unique phenomenon may be derived from a passive
fluid retention in the proximal gut during embryogenesis,
which was aggravated from fetal amniotic fluid ingestion
and functional obstruction of the distal gut. Attention
should be paid to possible discrepancies between mac-
roscopic and microscopic transition zones because the
presence of a gut caliber change does not always indicate
a location for which an ostomy should be made in this
rare disease.
The absorptive capability of the myectomized agan-
glionic bowel remains to be assessed in children with
total and near-total intestinal aganglionosis. In cases 3
through 5, we decided to perform a jejunostomy 30 to 35
cm distal from the ligament of Treitz for patients with
total intestinal aganglionosis after the difficult clinical
course in the initial 2 cases. A more proximal jejunos-
tomy, as performed in the current patients, may be
advantageous for the control of enteritis and intraluminal
stasis, but may lead to poor absorptive activity.16,17In
cases 4 and 5, who had a 30- to 35-cm jejunal segment
myectomized, body weight and height both remain be-
tween the 5th and 95th percentile of the standardized
curve (Fig 2). However, they can receive only 20% to
60% of their calories by oral feeding, and the parenteral
nutrition support has not been discontinued. Considering
the findings reported on infants with short bowel syn-
drome, a 30- to 35-cm proximal jejunal loop must be too
short eventually to support adequate enteral absorption to
predict a TPN-free related survival.15,17Alternatively, a
second myectomized 30 cm of more distal jejunoileum
with a second stoma, which could be fed, may be a
feasible and attractive option for such patients.12Pursuit
of the potential to be fully nourished enterally in infants
with total intestinal aganglionosis remains a challenge
for pediatric surgeons.18,19Intestinal absorption/adapta-
Fig 2.
infants with total and near-total intestinal
aganglionosis. Cases 1 and 2 suffered
from enteritis and intraluminal stasis and
died of sepsis at 7 and 8 months of age,
respectively. Patient
longed survival, but died of hepatic failure
at 1 year, 4 months. Cases 4 and 5, with
the jejunal segment myectomized, have
survived without any liver dysfunction,
receiving a combination of enteral and
parenteral nutrition. The shaded area in-
dicates the range of the 5th to 95th per-
centile of age-matched infants.
Postoperative body weight of 5
3achieved pro-
838 SHIMOTAKE ET AL

Page 5

tion of the aganglionic bowel segment, the patient’s
growth, and possible TPN-associated liver injury should
be investigated further based on a greater number of
children with total intestinal aganglionosis.20,21How-
ever, considering that the outlook for gut nutritional
absorption is hardly optimistic in many patients with
total intestinal aganglionosis, this disease entity remains
a candidate for intestinal transplantation.
REFERENCES
1. Caniano DA, Ormsbee HS III, Polito W, et al: Total intestinal
aganglionosis. J Pediatr Surg 20:456-460, 1985
2. MacKinnon AE, Cohen SJ: Total intestinal aganglionosis, an
autosomal recessive condition? Arch Dis Child 52:898-899, 1977
3. Di Lorenzo M, Yazbeck S, Brochu P: Aganglionosis of the entire
bowel: Four new cases and review of the literature. Br J Surg 72:657-
658, 1985
4. Talwalker VC: Aganglionosis of the entire bowel. J Pediatr Surg
11:213-216, 1976
5. Ziegler MM, Royal RE, Brandt J, et al: Extended myectomy-
myotomy a therapeutic alternative for total intestinal aganglionosis.
Ann Surg 218:504-511, 1993
6. Okamoto E, Ueda T: Embryogenesis of intramural ganglia of the
gut and its relation to Hirschsprung’s disease. J Pediatr Surg 2:437-443,
1967
7. Jacob-Cohen RJ, Payette RF, Gershon MD, et al: Inability of
neural crest cells to colonize the presumptive aganglionic bowel of ls/ls
mutant mice: Requirement for a permissive microenvironment. J Comp
Neurol 255:425-438, 1987
8. Schuchardt A, D’Agati V, Larsson-Blomberg L, et al: Defects in
the kidney and enteric nervous system of mice lacking the tyrosine
kinase receptor Ret. Nature 367:380-383, 1994
9. Inoue K, Shimotake T, Iwai N: Mutational analysis of RET/
GDNF/NTN genes in children with total colonic aganglionosis with
small bowel involvement. Am J Med Genet 93:278-284, 2000
10. Chalazonitis A, Pham TD, Rothman TP, et al: Neurotrophin-3 is
required for the survival-differentiation of subsets of developing enteric
neurons. J Neurosci 21:5620-5636, 2001
11. Martin LW: Surgical management of Hirschsprung’s disease
involving small intestine. Arch Surg 97:183-189, 1968
12. Attie T, Pelet A, Edery P, et al: Diversity of RET proto-
oncogene mutations in familial and sporadic Hirschsprung’s disease.
Hum Mol Genet 4:1381-1386, 1995
13. Zerella JT, Ingebo KR: A 3-year survivor of near-total intestinal
aganglionosis. J Pediatr Surg 28:1589-1591, 1993
14. Nemeth L, Yoneda A, Kader M, et al: Three-dimensional
morphology of gut innervation in total intestinal aganglionosis using
whole-mount preparation. J Pediatr Surg 36:291-295, 2001
15. Ziegler MM, Ross AJ, Bishop HC: Total intestinal agangliono-
sis: A new technique for prolonged survival. J Pediatr Surg 22:82-83,
1987
16. Andorsky DJ, Lund DP, Lillehei CW, et al: Nutritional and other
postoperative management of neonates with short bowel syndrome
correlates with clinical outcomes. J Pediatr 139:27-33, 2001
17. Georgeson KE, Breaux CW Jr: Outcome and intestinal adapta-
tion in neonatal short-bowel syndrome. J Pediatr Surg 27:344-350,
1992
18. Bianchi A: Intestinal loop lengthening—A technique for in-
creasing small intestinal length. J Pediatr Surg 15:145-151, 1980
19. Coran AG, Teitelbaum DH: Recent advances in the management
of Hirschsprung’s disease. Am J Surg 180:382-387, 2000
20. Moss RL, Das JB, Raffensperger JG: Total pareteral nutrition-
associated cholestasis: Clinical and histopathologic correlation. J Pe-
diatr Surg 28:1270-1275, 1993
21. Farmer DG, McDiarmid SV, Yersiz H, et al: Outcome after
intestinal transplantation: Results from one center’s 9-year experience.
Arch Surg 136:1027-1031, 2001
839 SURGERY FOR TOTAL INTESTINAL AGANGLIONOSIS