THIEME

Case Report e55

Pullthrough Operation for Hirschsprung’s Disease:

Importance of a Circumferential (Donut) Biopsy at the
Level of the Anastomosis
Susan Jehangir1,2 Soundappan Venkatraman Sannappa Soundappan2 Micheal Krivanek3
Susan Arbuckle3 Nicole Graf3

1 Department of Paediatric Surgery, Christian Medical College, Address for correspondence Soundappan Venkatraman Sannappa
Vellore, India Soundappan, MBBS, FRACS (Peads), Department of Paediatric
2 Department of Paediatric Surgery, The Children’s Hospital at Surgery, The Children’s Hospital at Westmead, Corner Hawkesbury
Westmead, Sydney, New South Wales, Australia Road and Hainsworth Street, Westmead, Sydney, NSW 2145, Australia

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3 Department of Anatomical Pathology, The Children’s Hospital at (e-mail: [email protected]).
Westmead, Sydney, New South Wales, Australia

Eur J Pediatr Surg Rep 2019;7:e55–e57.

Abstract Hirschsprung’s disease is characterized by the absence of ganglia in the distal colon,
resulting in a functional obstruction. It is managed by excision of the aganglionic segment
and anastomosis of the ganglionated bowel just above the dentate line. The level of
aganglionosis is determined by performing multiple seromuscular biopsies and/or full
Keywords thickness biopsy on the antimesenteric border of the bowel to determine the level of
► atypical pullthrough. The transition zone is described as being irregular, and hence a doughnut
aganglionosis biopsy is recommended so that the complete circumference can be assessed. Herein, we
► Hirschsprung’s described a child in whom there was a selective absence of ganglion cells in 30% of the
disease circumference of the bowel along the mesenteric border for most of the transverse colon.
► skip lesions This case defies the known concept of neural migration in an intramural and transmesenteric
► zonal aganglionosis fashion and emphasizes the importance of a doughnut biopsy of the pulled-down segment.

New Insights and the Importance for the Pediatric Surgeon

A careful doughnut biopsy of the pullthrough segment is essential to avoid missing unusual patterns of aganglionosis

Introduction ated by Coventry’s theory that vagal neural crest cells

colonize the gut by intra- and extramural migration.1 The
Hirschsprung’s disease (HSCR) is a disorder of migration of intramural progression is from cranial to caudal, whereas
neural crest cells during embryonic development charac- the extramural migration occurs along the mesentery
terized by the absence of ganglia in the distal colon, and circumferentially innervates the bowel from the
resulting in a functional obstruction. The principles of mesenteric side.1 Some authors also recommend the pres-
management involve excision of the aganglionic segment ence of ganglion cells and the absence of hypertrophies
and anastomosis of the ganglionated bowel above the nerves on a full-thickness biopsy to be adequate to deter-
dentate line. The level of aganglionosis is determined by mine the level of pullthrough.2 Herein, we describe a child
performing multiple seromuscular biopsies on the anti- in whom this practice would have failed because of the
mesenteric border of the bowel. This practice is substanti- selective absence of ganglion cells in 30% of the

received DOI https://doi.org/ © 2019 Georg Thieme Verlag KG

January 20, 2019 10.1055/s-0039-1693494. Stuttgart · New York
accepted after revision ISSN 2194-7619.
June 7, 2019
e56 Pullthrough Operation for Hirschsprung’s Disease Jehangir et al.

Fig. 3 Pictorial representation of the pattern of aganglionosis.

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history of HSCR. Plain abdominal X-ray showed free air
(►Fig. 1). He underwent emergency laparotomy with repair
of a perforation at the splenic flexure, ileostomy, multiple
seromuscular biopsies of the bowel, a rectal washout, and
full-thickness rectal biopsy. The biopsies showed the absence
of ganglion cells distal to the perforation at the splenic flexure
and ganglion cells present at and proximal to the perforation. He
underwent a pullthrough at 5 months of age. Frozen section of
the proximal doughnut showed ganglion cells and no hyper-
trophied nerves, but some parts of the circumference were
difficult to assess. It was decided to bring the splenic flexure
down to complete the pullthrough. The final biopsy completed
4 days later, however, found absent ganglion cells in 30% of the
circumference of the doughnut on the mesenteric side (►Fig. 2).
Findings were discussed with the family, and they wished for
Fig. 1 Supine plain abdominal film with evidence of free air in the normal bowel to be pulled through. A redo pullthrough was
peritoneal cavity. performed 9 days after the original operation. Intraoperative
biopsies at the revision pullthrough showed the absence of
circumference of the bowel along the mesenteric border for ganglion cells in 30% of the circumference along the mesenteric
most of the transverse colon. To the best of our knowledge, border in the entire transverse colon (►Fig. 3). The hepatic
this is the first report of such an occurrence and has flexure was tumbled down. The postoperative recovery was
significant diagnostic and therapeutic implications. uneventful, and the child remains well at follow-up except for
frequent stooling. The genetic work-up is pending.

Case Report
Discussion
A boy baby born at 37 weeks of gestation was transferred for
specialist care for abdominal distension and delayed passage of HSCR is thought to be the result of arrested enteric neural
meconium at 36 hours of life with a significant maternal family crest cell (ENCC) migration, which occurs rostrocaudally. The

Fig. 2 Histopathology of the doughnut showing (a) the presence of ganglion cells in 70% of the circumference on the antimesenteric side
(long arrows indicate the myenteric plexus, short arrows indicate the submucosal plexus) and (b) the absence of ganglion cells in 30% of the
circumference on the mesenteric side (arrowheads indicate the aganglionic myenteric plexus).

European Journal of Pediatric Surgery Reports Vol. 7 No. 1/2019

 Pullthrough Operation for Hirschsprung’s Disease Jehangir et al. e57

level of arrest determines the length of the aganglionic adhesion molecule (L1CAM), a protein that maintains such
segment. Rare variations in the pattern of aganglionosis cell–cell contacts, reduce ENCC contact and can retard ENCC
are well described and are categorized into “skip” lesions, migration.5 The microenvironment may no longer be per-
in which there is a segment of ganglionated bowel sur- missive to colonization by the time they arrive.
rounded proximally and distally by aganglionosis, occurring • Genetic factors provide the framework for patterning and
most commonly with total colonic aganglionosis.3 Another morphogenesis. However, it is now known that maternal
variant described is the “zonal” aganglionosis, in which a and placental factors such as hypoxia, inflammation, drug
segment of aganglionic bowel is surrounded by normal intake, and nutrition can affect the survival of ENCC.6 This
ganglionated bowel. The concept of “double zonal aganglio- concept shed new light on the existing theories of agan-
nosis” is applied to HSCR with a skip lesion.3 The presence of glionosis. The area of aganglionosis in our patient involved
skip lesions is explained by the mesenteric migration of the watershed area of the intestine. Did a hostile environ-
ENCCs that colonize a segment of bowel within the agan- ment due to transient hypoxia, inflammation, or nutrient
glionic segment ahead of the wavefront of distally migrating deficiency destroy the colonized ENCCs and cause the
ENCCs. However, the pattern of aganglionosis in our patient defect?

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is unique and defies the current understanding of the em-
bryogenesis of HSCR. The pattern of aganglionosis in the transition zone is
ENCC precursors originate in the vagal region (somites 1–7) unusual, and a proper doughnut biopsy will avoid a transi-
and to a lesser extent from the thoracic and sacral regions of tion zone pullthrough.2
the neural tube.3 They enter the gut mesenchyme by the third
week of gestation and migrate in a craniocaudal pattern, Funding
proliferate, differentiate, and colonize the gut completely by None.
the eighth week of gestation, forming the network of the
enteric nervous system. This theory, however, does not explain Conflict of interest
the defect in our patient. We hypothesize the following various None.
mechanisms that could cause the pattern of aganglionosis in
our patient.

• Failure of transmesenteric migration: in a mouse model, References

1 Coventry S, Yost C, Palmiter RD, Kapur RP. Migration of ganglion
Druckenbrod and Epstein studied the transmesenteric
cell precursors in the ileoceca of normal and lethal spotted
migration of ENCCs from the midgut to the hindgut during embryos, a murine model for Hirschsprung disease. Lab Invest
the time these organs are transiently juxtaposed.4 This 1994;71(01):82–93
migratory process requires glial cell derived neurotrophic 2 Ghosh DN, Liu Y, Cass DT, Soundappan SSV. Transition zone pull-
factor (GDNF) signaling. In the absence of this trans- through in Hirschsprung’s disease: a tertiary hospital experience.
mesenteric migration, the intramural migration may con- ANZ J Surg 2017;87(10):780–783
3 O’Donnell AM, Puri P. Skip segment Hirschsprung’s disease: a
tinue along the antimesenteric border and cause a defect
systematic review. Pediatr Surg Int 2010;26(11):1065–1069
such as in our patient. The failure of transmesenteric 4 Druckenbrod NR, Epstein ML. Age-dependent changes in the gut
migration could be because of a lack of juxtaposition, environment restrict the invasion of the hindgut by enteric neural
inadequate numbers of ENCCs due to a preexisting genetic progenitors. Development 2009;136(18):3195–3203
defect, or defects in GDNF signaling. 5 Newgreen DF, Dufour S, Howard MJ, Landman KA. Simple rules for
a “simple” nervous system? Molecular and biomathematical
• Delayed migration: ENCC colonization has been shown to
approaches to enteric nervous system formation and malforma-
be a timed process.5 Furthermore, ENCC migration is en-
tion. Dev Biol 2013;382(01):305–319
hanced when the cells are in contact with each other along 6 Heuckeroth RO, Schäfer KH. Gene-environment interactions and
the wavefront. Isolated ENCCs do not migrate as quickly or the enteric nervous system: Neural plasticity and Hirschsprung
as directionally as chains of cells. Mutations in L1 cell disease prevention. Dev Biol 2016;417(02):188–197

European Journal of Pediatric Surgery Reports Vol. 7 No. 1/2019