W. A.

Meier-Ruge1
E. Bruder1
A. M. Holschneider2
H. Lochbühler3
G. Piket4
Diagnosis and Therapy of Ultrashort H. G. Posselt5
Hirschsprung’s Disease G. Tewes4
Original Article

Abstract was ineffective. UHD is either limited to the anal ring, or extends
3 – 4 cm into the distal rectum. Over the past 15 years, UHD had
Background: Although ultrashort Hirschsprung’s disease (UHD) in our series an incidence of 13.4 % of all aganglionoses. The gen-

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was enzyme-histochemically characterised about 35 years ago,
its existence is still often ignored. The aim of this study is to sum-
marise the clinical diagnostic, incidence, gender ratio, morpho-
logical characteristics, and therapy over 15 years.
Methodology: The reliable diagnosis of suspected UHD requires
a minimal enema of contrast medium to exclude Hirschsprung’s
disease (HD). In UHD during pressing or crying no reflux of con-
trast medium is observed. Final proof of UHD is an enzyme-his-
tochemical biopsy examination of distal rectal mucosa. The biop-
sies must demonstrate submucosa and be taken from the den-
tate line and 1 cm, 2 cm, 4 cm and 6 cm above the dentate line.
The cryostat sections must be cut 15 μm thick; this thickness is
reduced to 4.5 μm by the thawing, spreading and drying of the
sections on microscope slides. A reliable diagnosis of UHD needs
392 an enzyme-histochemical acetylcholinesterase reaction of native
sections of rectal mucosa.
Results: UHD develops with first symptoms of chronic constipa-
tion in the second half of the first year of life. The chronic consti-
pation proves to be therapy resistant. In HD constipation occurs
in the first weeks of life or after weaning. In contrast to HD, no
nerve fibres with increased AChE activity are observed in the
lamina propria mucosa. Nets of nerve fibres with increased AChE
activity can be found only in the muscularis mucosa and the
musculus corrugator cutis ani (MCCA).
The therapy of choice has proven to be a partial myectomy of the
distal internal sphincter if dilatation of the internal sphincter
der ratio of girls to boys was 1 : 2.
Conclusion: UHD is reliably diagnosed by an AChE reaction in
native biopsy sections from the anocutaneous transitional zone
and, potentially, from 3 – 4 cm above the pectinate line. As UHD
is always accompanied by aganglionosis of the distal internal
sphincter, an increase in AChE activity is observed in the nerve
fibres of the MCCA. The therapy of choice is a partial myectomy
of the distal internal sphincter.
Key words
Hirschsprung’s disease · aganglionosis · internal sphincter · ultra-
short Hirschsprung’s disease
Résumé
But: Bien que le Hirschsprung ultra court (UHD) soit histolo-
giquement caractérisé depuis 35 ans, son existence est encore
souvent ignorée. Le but de cette étude est de résumer le diagnos-
tic clinique, l’incidence, le sex-ratio, les caractéristiques morpho-
logiques et le traitement sur 15 ans.
Méthodes: Le diagnostic de UHD nécessite au minimum un lave-
ment opaque pour éliminer une maladie de Hirschsprung (HD).
Dans UHD, durant la poussée ou la crise, aucun reflux du
contraste n’est observé. La preuve finale de UHD est une biopsie
avec étude histochimique de la muqueuse du rectum distal. Les

Affiliation
1
Institute of Pathology, University Medical School Basel, Basel, Switzerland
2
Department of Paediatric Surgery, Children’s Hospital Köln, Köln, Germany
3
Department of Paediatric Surgery, Paediatric Hospital, Olgaspital, Stuttgart, Germany
4
Department of Paediatric Surgery, Paediatric Hospital, Hamm, Germany
5
Department of Gastroenterology, Center of Paediatrics, University Frankfurt, Frankfurt, Germany

Correspondence
Prof. Dr. W. A. Meier-Ruge · Institute of Pathology · University Medical School Basel · Schönbeinstraße 40 ·
4003 Basel · Switzerland · E-mail: elisabeth.bruder@unibas.ch

Received: September 3, 2003 · Accepted after Revision: March 1, 2004

Bibliography
Eur J Pediatr Surg 2004; 14: 392 – 397 © Georg Thieme Verlag KG Stuttgart · New York ·
DOI 10.1055/s-2004-830354 ·
ISSN 0939-7248
biopsies doivent comporter de la sous muqueuse et être prises
depuis la ligne pectinée jusqu’à 1, 2, 4 et 6 cm au-dessus. Les sec-
tions au cryostat doivent être coupées à 15 μm d’épaisseur, cette
épaisseur réduite à 5.5 μm par la préparation. Un diagnostic
fiable de UHD nécessite une réaction acétylcholinestérasique de
la muqueuse rectale.
Résultats: Les premiers symptômes d’une constipation chro-
nique liée à UHD apparaissent dans la seconde moitié de la pre-
mière année de vie. La constipation s’avère être particulièrement
résistante. Dans la maladie de Hirschsprung, la constipation ap-
paraît dans les premières semaines de vie ou après sevrage. Par
opposition au HD, aucune fibre nerveuse avec une activité AChE
augmentée n’est observée dans la lamina propria mucosa. Des
filets de fibres nerveuses avec une augmentation de l’activité
AChE peuvent être retrouvés seulement dans la musculaire mu-
queuse et le musculus corrugator cutis ani (MCCA).
Le traitement de choix peut être une myomectomie partielle de
la partie distale du sphincter anal si les dilatations du sphincter
interne sont inefficaces. L’UHD est, soit limité à l’anneau anal, ou
s’étend sur 3 à 4 cm sur la partie distale du rectum. Durant les 15
dernières années, UHD a dans notre série une incidence de 13.4 %
de toutes les aganglionoses. Le sex-ratio fille/garçon est de 1/2.
Conclusion: UHD est diagnostiqué de manière fiable par une ré-
action à l’acétylcholinestérase sur des biopsies de la zone transi-
tionnelle ano-cutanée et potentiellement 3 à 4 cm au-dessus de
la ligne pectinée. Comme l’UHD est toujours accompagnée d’une
aganglionose de la partie distale du sphincter interne, une aug-
mentation de l’activité AChE est observée dans les fibres ner-
veuses du MCCA. Le traitement de choix est une myomectomie
partielle du sphincter interne.
Mots-clés
Maladie de Hirschsprung · aganglionose · sphincter interne ·
forme ultracourte de maladie de Hirschsprung
Resumen
Antecedentes: Aunque la enfermedad de Hirschsprung ultracor-
ta (UHD) fue caracterizada histoenzimológicamente hace alrede-
dor de 35 años su existencia es a menudo ignorada. El objetivo de
este estudio es resumir el diagnóstico clínico, la incidencia y la
características morfológicas así como el tratamiento de la UHD
en los últimos 15 años.
Métodos: El diagnóstico fiable de la UHD requiere un enema con
pequeña cantidad de contraste para excluir la Enfermedad de
Hirschprung (HD). En la UHD durante la compresión o el llanto
no se observa reflujo del material de contraste. Una prueba final
del UHD es una biopsia histoenzimática de la mucosa rectal dis-
tal. Éstas deben contener submucosa y deben ser tomadas a 1, 2,
4 y 6 cm por encima de línea pectínea. Los cortes de criostato de-
ben ser de 15 μm que se reducen a 4.5 μm tras descongelar y ex-
tenderlos y secarlos sobre los portas. Para un diagnóstico fiable
de UHD se necesita una reacción inmunohistoquímica de AchE
en la mucosa rectal.
Resultados: En la UHD los primeros síntomas de constipación
crónica se desarrollan en la segunda mitad del primer año de la
vida y son resistentes al tratamiento mientras que en la HD este
estreñimiento ocurre en las primeras semanas de la vida o tras el
destete.
Meier-Ruge WA et al. Diagnosis and Therapy … Eur J Pediatr Surg 2004; 14: 392 – 397
En contraste con la HD, no había fibras AchE positivas aumen-
tadas en la lámina propia mucosae. Se apreció una red de fibras
nerviosas con actividad AchE aumentada solamente en la
muscular y mucosa y en el músculo corrugator cutis ani (MCCA).
El tratamiento de elección ha sido la miectomía parcial del esfín-
ter distal interno si la dilatación de dicho esfinter es ineficaz. La
UHD es o limitada al anillo anal o se extiende a 3 a 4 cm del recto
distal. En los últimos 15 años la UHD constituyó el 13.4 % de todas
los aganglionismos en nuestra serie. La relación mujer/varón fue
de 1/2.
Conclusion: La UHD se diagnostica fiablemente con una reacción
de AchE en los cortes de la biopsia tomada en la zona transicional
anocutánea y potencialmente en los 3 o 4 cm por encima de línea
pectínea. Como la UHD siempre se acompaña de aganglionismo
Original Article
del esfínter interno se observa un aumento de la actividad ACHE
en las fibras nerviosas del MCCA. El tratamiento del elección es la
miectomía parcial del esfínter interno.
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Palabras clave
Enfermedad de Hirschsprung · aganglionismo · esfínter interno ·
Hirschsprung ultracorto
Zusammenfassung
Hintergrund-Information: Obwohl das ultrakurze Hirsch-
sprung-Segment (UHD) bezüglich seines morphologischen Er-
scheinungsbildes bereits vor rund 35 Jahren eindeutig beschrie-
ben wurde, gibt es immer wieder Stimmen, welche die Existenz
dieses Krankheitsbildes infrage stellen. Das Ziel der vorliegenden
Studie besteht darin, die in den letzten 15 Jahren beobachtete
Häufigkeit, Geschlechtsverteilung, histopathologische Charakte-
ristika sowie die klinische Diagnostik und Therapie aufzuzeigen. 393
Methodik: Eine zuverlässige Diagnose eines vermuteten UHD
erfordert zunächst einen minimalen Kontrasteinlauf, um einen
klassischen Hirschsprung (HD) auszuschließen.
Im Gegensatz zum klassischen Hirschsprung findet sich bei UHD
kein längerer spastischer Enddarm-Abschnitt. Es kommt aber
auch durch Pressen oder Schreien zu keinem Kontrastmittel-Re-
flux. Zur Sicherung der Diagnose eines UHD bedarf es einer en-
zymhistochemischen Acetylcholinesterase-Darstellung an nati-
ven Schnitten einer Rektumschleimhaut-Biopsie. Diese Biopsie
muss Submucosa aufweisen und aus der Linea dentata sowie
1 cm, 2 cm, 4 cm und 6 cm darüber entnommen sein.
Die Kryostatschnitte müssen 15 μm dick geschnitten werden.
Diese Dicke der Gewebeschnitte kollabiert zu 4,5 μm durch das
Auftauen, Aufziehen und Trocknen der Schnitte auf Objektträ-
gern. Die morphologische Diagnose einer UHD erfordert in nati-
ven Schnitten eine Acetylcholinesterase(AChE)-Reaktion.
Ergebnisse: Eine UHD entwickelt in der Regel erste Symptome
einer chronischen Obstipation in der zweiten Hälfte des ersten
Lebensjahres. Die chronische Obstipation zeigt eine progressive
Therapieresistenz. Im Gegensatz zum UHD entwickelt der klassi-
sche HD eine Obstipations-Symptomatik in den ersten Lebens-
wochen oder nach dem Abstillen. Im Vergleich zum HD fehlt
beim UHD die Erhöhung der AChE-Aktivität in Nervenfasern der
Lamina propria mucosae. Es finden sich lediglich Netze parasym-
pathischer Nervenfasern mit gesteigerter AChE-Aktivität in der
Muscularis mucosae und in Nervenfasern des Musculus corruga-
tor cutis ani (MCCA). Als Therapie der Wahl hat sich nach erfolg-
 loser Dehnung des Sphincter internus eine distale Sphinkter-
Myektomie bewährt. Die UHD ist oft auf den Analring beschränkt
oder zeigt eine Ausdehnung von 3 – 4 cm oberhalb des Analrin-
ges. Die UHD hatte in den letzten 15 Jahren in unserer Untersu-
chungs-Serie eine Häufigkeit von 13,4 % aller untersuchten
Aganglionosen und weist eine Geschlechtsverteilung weiblich
zu männlich von 1 : 2 auf.
Schlussfolgerung: Die UHD lässt sich an nativen Biopsien aus
der anokutanen Übergangszone mittels einer AChE-Reaktion zu-
verlässig diagnostizieren und ist auf 3 – 4 cm proximal der Linea
Introduction
Original Article
Ultrashort Hirschsprung’s disease (UHD) can only be reliably di-
agnosed by an enzyme-histochemical acetylcholinesterase
(AChE) reaction in native mucosal biopsies of the distal colon.
UHD cannot be diagnosed without this procedure. The enzyme-
histochemical diagnosis of UHD and its epidemiology has been
demonstrated in a number of investigations (2,15 – 18).
The aim of this paper is to discuss diagnostics, epidemiology and
therapy of UHD over the past 15 years. UHD is always accompa-
nied by aganglionosis of the distal internal sphincter.
A similar symptomatology to UHD is caused by aganglionosis of
the musculus corrugator cutis ani (MCCA), which can be diag-
nosed in anocutaneous biopsies taken 0.5 – 1.0 cm distal to the
dentate line.
394 Materials and Methods
Between 1986 and 2000, biopsies from 558 patients with agan-
glionosis of the distal colon were investigated. All biopsies from
the anocutaneous and distal rectal mucosa were cut by cryostat
(– 20 8C) into 15 μm thick sections. The sections were spread and
thawed on microscope slides and subsequently air-dried. The na-
tive cryostat section loses 60 – 70% of its volume through this
procedure and has a final thickness of 4 – 5 μm. From each biopsy,
164 serial sections were routinely prepared.
The section series were distributed in four to five ribbons on six
microscope slides. Five serial sections were prepared in four to
five ribbons for an AChE reaction (n = 20) and an AChE reaction
with hemalum counterstaining (n = 20).
Ten sections were cut in four to five steps for a lactic dehydroge-
nase (n = 40) and nitroxide synthase reaction (n = 40). Seven seri-
al sections were prepared for a succinic dehydrogenase reaction
(n = 24), and five for a picric acid/sirius red staining (n = 20). The
enzyme-histochemical reactions were performed according to
the laboratory manual of Lojda et al. (11).
The clinical diagnosis of a chronically constipated child is made
after a minimal enema. This makes it possible to exclude a longer
spastic HD segment. If no reflux of contrast medium occurs by
pressing, a manual dilatation of the internal sphincter is per-
formed under anesthesia. On this occasion biopsies are taken
Meier-Ruge WA et al. Diagnosis and Therapy … Eur J Pediatr Surg 2004; 14: 392 – 397
dentata beschränkt. Da die UHD stets mit einer Aganglionose des
distalen Sphincter internus einhergeht, zeigt der MCCA para-
sympathische Nervenfasern mit stark erhöhter AChE-Aktivität.
Die Therapie der Wahl ist nach einer erfolglosen Sphinkterdeh-
nung eine partielle Myektomie des Sphincter internus.
Schlüsselwörter
Morbus Hirschsprung · Aganglionose · Sphincter internus · ultra-
kurzer Hirschsprung
from the linea dentata and mucosal biopsies of the distal rectum.
A reliable diagnosis of UHD is only possible with an enzyme-his-
tochemical AChE reaction (10).
As the diagnosis of UHD is not known in advance, the whole pro-
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cedure mentioned above has to be performed. Biopsies must be
taken from the dentate line and 1 cm, 2 cm, 4 cm and 6 cm above
the dentate line. At 5 – 6 cm above the dentate line, a normal
muscularis mucosa is seen.
It is not possible to use immunohistochemical techniques be-
cause they do not permit Hirschsprung’s disease (HD) or any oth-
er aganglionosis of the distal colon (8) to be recognized in mu-
cosal biopsies. In particular, absence of nerve cells in the submu-
cosa is no proof of UHD, since in the very distal rectum and anal
segment, nerve cells or ganglia are rarely seen even in normal pa-
tients.
Results
Between 1986 and 2000, an incidence of 13.44 % was observed
for UHD in all 558 HD cases (Table 1). In the same period, 75 chil-
dren with UHD were diagnosed, i.e. about five children per year.
The gender ratio was two males to one female. Most cases with
UHD develop chronic constipation during the second half of the
first year of life. The chronic constipation has a progressively in-
creasing symptomatology. Similar to HD, UHD is always accom-
panied by aganglionosis of the distal internal sphincter. There-
fore the MCCA, which is the distal end of the longitudinal muscle
of the internal sphincter ending in the anal cutis, also shows the
characteristics of aganglionosis, with an increase in AChE activity
in parasympathetic nerve fibres (Figs. 1 and 2).
Table 1 Incidence of inborn aganglionosis of the colon diagnosed
between 1986 and 2000
n %
Hirschsprung’s disease 428 76.7
Total aganglionosis of the colon 55 9.8
Ultrashort Hirschsprung’s disease 75 13.4

Fig. 1 Aganglionosis of the distal internal sphincter musculus corru-
gator cutis ani with increased AChE activity in parasympathetic nerve
fibres accompanying the smooth muscle fibres (magnification: 6 ×).
Fig. 3 Ultrashort Hirschsprung’s disease with increased AChE activity
in nerve fibres of the muscularis mucosa and submucosa (magnifica-
tion: 90 ×).
A radiological examination shows no spastic rectum as in HD.
This can be clearly shown by irrigation with a minimal amount
of contrast medium. Due to the spastic internal sphincter a dila-
tation of the distal recto-sigmoid develops over time. A final
proof of an UHD is only possible by an enzyme-histochemical ex-
amination of acetylcholinesterase activity in the MMCA and/or
the distal rectal mucosa.
UHD can be distinguished from an aganglionic rest segment of a
Hirschsprung resection by the fact that, in Hirschsprung’s dis-
ease, nets of parasympathetic nerve fibres with increased AChE
activity are found in the lamina propria mucosa. UHD shows net-
works of parasympathetic nerve fibres with increased AChE ac-
tivity only in the muscularis mucosa (Fig. 3). In the submucosa,
many thick afferent nerve fibres with high AChE activity are ob-
served. Also smooth muscles that spread under the skin of the
dentate line show nerve fibres with increased AChE activity. In
contrast to UHD, classical Hirschsprung’s disease shows dense
Meier-Ruge WA et al. Diagnosis and Therapy … Eur J Pediatr Surg 2004; 14: 392 – 397
Fig. 2 Higher mag-
nification of Fig. 1
(magnification:
230 ×).
Original Article
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395
Fig. 4 Classical Hirschsprung’s disease with characteristic increase in
AChE activity in nerve fibres of the lamina propria mucosa (magnifica-
tion: 90 ×).
nets of parasympathetic nerve fibres in the lamina propria mu-
cosa (Fig. 4).
If a biopsy 6 cm above the dentate line still shows nets of nerve
fibres with increased AChE activity in the muscularis mucosa
and scarcely developed nets of nerve fibres in the lamina propria
mucosa, a long aganglionic colon segment or a total agangliono-
sis of the colon with a hypoplastic extramural parasympathicus
can be expected (Figs. 5 and 6).
From a therapeutic point of view, manual sphincter dilatation is
successful only in about 30 – 40 % of UHD children. A partial
sphincter myectomy of the internal sphincter is the therapy of
choice if sphincter dilatation was not successful. In about 10% of
children with UHD, a short resection of the rectum was neces-
sary. The final outcome in all cases was successful without any
recurrence.
Original Article
Fig. 5 Extended aganglionosis of the colon 8 cm above the pectinate
line with hypoplasia of the extramural parasympathicus. In contrast to
UHD, nerve fibres are observed in the lamina propria mucosa (magni-
fication: 90 ×).
Discussion
The diagnosis of UHD requires a minimal enema of contrast
medium to exclude HD. Sphincter spasticity is not specific for
UHD. A reliable proof of UHD is only possible with biopsies from
the area of the anal ring. The first biopsy must be taken from the
dentate line and others 1 cm, 2 cm, 4 cm and 6 cm proximal to
the dentate line. An additional biopsy from the MCCA, 0.5 cm dis-
tal to the dentate line, may be helpful in establishing the diagno-
sis of UHD. Aganglionosis of the internal sphincter can also be es-
396 tablished by a biopsy from the MCCA.
The old idea that it is difficult to distinguish between a so-called
“physiological aganglionosis” at the junction of anal canal and
rectum (1) and aganglionosis of the internal sphincter has to be
corrected (5, 20). The density of nerve cells in a normal internal
sphincter is low but AChE activity is within the normal range
and is always an important additional reaction because it gives
important information about the parasympathetic tonus. Agan-
glionosis of the internal sphincter always shows an increased
AChE activity as in HD (5, 20).
In this connection it may be worthwhile to discuss the old state-
ment that UHD and HD cannot be diagnosed in immature babies
or 1 – 2 weeks after birth (6, 7). This observation may be linked to
the fact that many investigators use 4 μm thick cryostat sections
which shrink after thawing and spreading on microscope slides
to a final thickness of 1.2 μm. This section thickness lowers the
total amount of AChE until it is below the level required for an
appropriate enzyme-histochemical reaction. With our technique
of using 15 μm thick cryostat sections a negative AChE reaction in
biopsies with HD or UHD from new-born or immature babies
was never seen. The reliability of the diagnosis of UHD has been
reported several times over the last 35 years (2, 4,15,16,18).
From a clinical point of view, absence of relaxation of the internal
sphincter and powerful propulsive waves in the more proximal
parts of the rectum are suggestive of UHD (3, 9). An enzyme-his-
Meier-Ruge WA et al. Diagnosis and Therapy … Eur J Pediatr Surg 2004; 14: 392 – 397
Fig. 6 The same section as Fig. 5 but with hemalum counterstaining
(magnification: 90 ×).
Downloaded by: Collections and Technical Services Department. Copyrighted material.
tochemical diagnosis using an AChE reaction, in the hands of an
experienced pathologist, is the most reliable technique. The
treatment of UHD is more or less the same as the management
of aganglionosis of the internal sphincter (9). If posterior myec-
tomy of the internal sphincter fails, hypoganglionosis proximal
to the aganglionic sphincter is probably present. Hypogangliono-
sis proximal to an aganglionic segment is a frequent observation
(12 – 14,17 – 19, 21). Hypoganglionosis or hypoplastic neuronal
dysganglionosis of the myenteric plexus necessitate further sur-
gical treatment.
It is useful to be aware that the rectum has a caudocranial growth
in the first months of life. A 3 – 4 cm long UHD diagnosed in the
first 2 months of life may grow into a short HD segment of 5 –
6 cm in length up to the first or second year of life, which renders
a resection of the rectum necessary. Therefore a control biopsy 2
years after the first diagnosis is recommended.
The 13.4 % incidence of UHD observed over the past 15 years,
with 8 % higher values, does not completely correspond to that
observed between 1975 and 1984 (17).
In rare cases total aganglionosis of the colon with a hypoplastic
extramural parasympathetic innervation shows the characteris-
tics of UHD in the AChE reaction, which are in contrast to the
classical UHD which can be observed up to 6 – 8 cm proximally
from the dentate line.
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