Scandinavian Journal of Surgery 100: 243–249, 2011

Modern Treatment of Hirschsprung’s disease

A. Gunnarsdóttir1, 2, 3, T. Wester1, 2
1 Section of Pediatric Surgery, Astrid Lindgren Children’s Hospital, Karolinska University Hospital,
Stockholm, Sweden
2 Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
3 Section of Pediatric Surgery, The Children’s Hospital, Landspitali, University Hospital, Reykavik, Iceland

Key words: Hirschsprung’s disease; transanal endorectal pull-through; laparoscopically assisted
pull-through; constipation; soiling; enterocolitis; quality of life

Definition, history, and etiology HD occurs in about 1/5000 live born babies and is
more common in boys than girls (4:1) (11). This to-
Hirschsprung’s disease (HD) is a congenital gastro- gether with the fact that about 30% of patients with
intestinal motility disorder characterized by an ab- HD have other abnormalities suggests a genetic etiol-
sence of neuronal cell bodies in both myenteric and ogy for HD (11, 12). Different animal and human
submucous plexuses in the intestinal wall (1). HD is studies have identified various gene defects in HD
named after Harald Hirschsprung, a pediatrician at (13). The most common mutations are located to the
Queen Louise Children´s Hospital in Copenhagen, RET proto-oncogene on chromosome 10, accounting
Denmark, who described 2 cases of children with for approximately 20% of sporadic cases of HD and
megacolon in 1887 (2). It was though not until the about 50% of familial cases (14–16).
beginning of the twentieth century that Tittel noted
the absence of ganglion cells in the distal colon of a
child with HD (3). This aganglionosis, pathogno- Clinical presentation and diagnostic
monic for HD, always starts distally and is limited to work-up
the rectum and the sigmoid colon in 80–85% of the
cases. Less frequently, the aganglionosis involves the The patients with HD are most often diagnosed in the
entire colon with or without a part of the small intes- neonatal period (17). The clinical presentation is dis-
tine. Functionally, this results in a sustained contrac- tended abdomen, delayed passage of meconium and
tion of the aganglionic segment causing obstructive vomiting. Older children more often present with
symptoms. The etiology of HD is heterogeneous and chronic constipation, which usually starts already
not fully understood. During embryonic develop- during the breastfeeding period. Most children who
ment, the neural crest cells migrate caudally where present later have short-segment aganglionosis. Ap-
they differentiate amongst other cell types to gangli- proximately 10% of patients with HD present with
onic cells of the enteric nervous system. Studies of enterocolitis, with fever, abdominal distension, ab-
mice suggest that there is a delay or arrest in this dominal pain, and in the most severe cases, septice-
migration, which results in the neural crest cells fail- mia. This may be a life-threatening condition (1).
ing to reach their correct positions in the distal intes- Plain abdominal radiographs usually show dilated
tine (4, 5). Other studies have indicated that neural bowel loops. Contrast enema is the preferred first
crest cells fail to survive, proliferate, or differentiate diagnostic procedure and shows a transition zone
due to abnormalities within their microenvironment between the normal (often dilated) and the narrow
after the migration has occurred (6–10). aganglionic bowel in about 70–90% of the cases (18,
19). For definite diagnosis a rectal biopsy is needed
for histological evaluation. The absence of ganglionic
Correspondence: cells in the myenteric and submucous plexuses and
Tomas Wester M.D. the finding of hypertrophic nerve trunks are pathog-
Department of Pediatric Surgery
Karolinska University Hospital
nomonic for HD. This is attained traditionally with a
SE - 17176 Stockholm full-thickness biopsy or more commonly nowadays,
Sweden with a submucosal rectal suction biopsy. Anorectal
Email: tomas.wester@karolinska.se manometry may aid in the diagnosis where the
244 A. Gunnarsdóttir, T. Wester

r­ ectoanal inhibitory reflex is absent in children with erably during the last decade and they are dominat-
HD (20). ing the modern treatment of HD today.The main op-
erative approaches used today are the total transanal
endorectal pull-through (TERPT) (27–29) and the
Operative management ­laparoscopic assisted pull-through (30, 31).

Transabdominal operations Total transanal endorectal pull-through
(TERPT)
Surgical management for HD aims at removing the
aganglionic bowel and reconstructing the intestinal The transanal endorectal pull-through is carried out
tract by bringing the normally innervated bowel with a circumferential incision in the rectal mucosa
down to the anus while preserving normal sphincter about 5 mm above the dentate line, to establish a
function. Swenson and Bill were the first to describe submucosal plane. The dissection is then carried out
an operation for HD by removing the aganglionic in that plane for variable length leaving an agangli-
bowel with a pull-through in 1948 (21). Traditionally, onic muscular cuff behind, minimizing the risk of
Swenson’s procedure was done in a three-stage man- injury to pelvic structures. The original description of
ner with diverting colostomy prior to the reconstruc- the TERPT method included leaving an approxi-
tive surgery. Duhamel, Soave, and Rehbein have also mately 6 cm long muscular cuff, which was split with
described techniques for reconstruction of HD, mod- a longitudinal myectomy in the posterior wall (27, 28,
ifications of which have been widely used (21–24). 32). During the last years, reports of TERPT opera-
The surgical approach changed gradually from tions using a shorter muscular cuff without myec-
three-stage procedures to one-stage pull-through tomy have been shown to be just as beneficial (33–36).
without colostomy in the 1980s. This has turned out After the appropriate length is achieved, the rectal
to be as favorable as the multistage procedures with muscular wall is divided circumferentially and the
benefits for the patients and reduction in health full thickness of rectum mobilized out through the
care costs due to shorter and fewer hospital stays anus, dividing the small vascular pedicles along the
(25, 26). rectum and colon (Fig 1). A full thickness biopsy is
There has been a continuous development over the taken from macroscopically normal ganglionic colon
years of both operative techniques and diagnostic for frozen section to determine the resection level of
tools used for HD, striving towards minimal invasive the colon before suturing the final anastomosis. Some
procedures for the benefit of the patients, without surgeons prefer to take biopsies from the sigmoid
compromising the results and diagnostic accuracy on colon through a small infra-umbilical incision to con-
the way. The term minimal invasive surgery is used firm the level of the transition zone before starting
for any procedure that is less invasive for the patient the transanal dissection (37).
than traditional open surgery. It most often involves Since first described in 1998, the TERPT has be-
laparoscopy, endoscopy or computer-assisted surgery come widely used because of many advantages. It
and usually implies less surgical trauma for the pa- does not require laparotomy or laparoscopy and is
tient, faster recovery and shorter hospital stay. It also especially useful for aganglionosis confined to the
includes superior cosmetic results for the patient. Be- rectosigmoid area (38). The risks of intra-abdominal
cause of the small size of our pediatric patients, com- contamination and adhesion formation are minimized
bined methods are often chosen, i.e. laparoscopic as- and the procedure reduces the risk of damaging the
sisted surgery. The development of these techniques pelvic structures. It is also less expensive and usually
has changed the surgical management of HD consid- includes faster recovery time postoperatively. The

Fig. 1a. Expose the anal canal. Fig. 1b. Incise the mucosa 5 mm Fig. 1c. Cut the muscular layers Fig. 1d. Mobilize until normo-
above the dentate line. Dissect be- once above the pelvis floor. Con- ganglionic colon is reached.
tween the submucosa and the cir- tinue the full-thickness dissection
cular muscle layer. to mobilize the rectum and sig-
moid colon.
Modern treatment of Hirschsprung’s disease 245

patients can be discharged from the hospital 2–3 days 47). The higher incidence reflects a wider definition
after surgery. TERPT results in excellent cosmetic ap- of Hirschsprung-associated enterocolitis, but also an
pearance of the abdominal wall with no visible scar- increased awareness of the condition. Soiling has
ring without compromising the bowel function been a concern in the discussion of the TERPT be-
(27–29, 32–35, 38–41). cause stretching of the sphincters during the proce-
The TERPT method has, however, its limitations dure may potentially result in permanent sphincter
and is mostly recommended for patients with agan- injuries. However, studies have shown that the mano-
glionosis limited to the rectosigmoid colon. With a metric sphincter pressures are similar after transanal
longer or undefined aganglionic segment, a combina- and transabdominal surgery and also that the mano-
tion of a laparoscopic assisted pull-through or an metric findings are similar before and after a trans­
infra-umbilical mini-laparotomy for segmental biopsy anal procedure (48, 49). Another concern that has
is recommended (36, 41, 42). been raised is that the anal canal may be damaged if
the mucosal incision is done too low, injuring the
Laparoscopic assisted pull-through dentate line. This could impair discrimination be-
tween gas, fluid and solid stools and result in soiling
The first report of primary laparoscopic-assisted en- after transanal pull-through (50).
dorectal pull-through for HD was published by The overall outcome in patients with HD appears
Georgeson et al in 1995 (30). The procedure is done to be similar after transabdominal procedures, lap-
by inserting a 4–5 mm 30° scope in the right upper aroscopically assisted pull-through, and TERPT.
quadrant just below the liver edge after gaining a 12 There is a lack of both adequately controlled long-
cm H2O pneumoperitoneum with a Varess needle in term follow up studies and prospective controlled
the umbilicus. Two 4–5 mm trocars are then inserted, studies. In adolescence and adulthood many studies
one in the lower right quadrant and one in the left have shown that the bowel function is impaired to a
upper quadrant of the abdomen. Sometimes an ad- variable degree (51–55).The bowel function has been
ditional trocar is needed supra-pubically for better considered to improve with time after open Duhamel
traction of the colon during the laparoscopic dissec- procedure (56).On the other hand, more recently, it
tion of the rectum (30). After full mobilization of the was shown that the bowel function deteriorates with
aganglionic colon and rectum the procedure contin- increasing age (53).
ues from the perineum with transanal dissection of After laparoscopically assisted endorectal pull-
the rectal mucosa in a similar way as described above through with a transanal dissection, Georgeson
for the TERPT method. The main advantages of the showed a low incidence of early complications (42).
laparoscopic approach are the possibility to take the Most patients were too young to assess continence,
seromuscular biopsies for early identification of the but 18 of 20 older patients were reported to be conti-
ganglionic normal colon. It also provides better mo- nent. Langer et al reported 141 patients who had un-
bilization and dissection of the distal aganglionic dergone transanal one-stage pull-through with few
colon and rectum under direct vision, thereby mini- early complications (39). Eighty-one of those patients
mizing the transanal dissection. This might be an had normal bowel function at follow up. Elhalaby et
important factor as it minimizes the dilatation of the al. reported the outcome in 149 patients after trans­
anal canal often needed in the TERPT procedure (30, anal pull-through and found perianal excoriations in
42). The laparoscopic approach has, as the TERPT almost one third of the patients (32). Six of the pa-
method, shown faster recovery time with shorter tients had recurrent constipation and 7 of 42 patients
hospital stay compared to the open methods. It also older than 3 years had soiling. Comparing transab-
has shown better cosmetic results, less perioperative dominal Soave Boley procedure with laparoscopically
complications and superior functional results assisted pull-through with a transanal dissection,
(42–44). Mattioli et al showed that the complication rate was
similar between both groups, although the laparo-
scopically operated group had shorter hospital stay
(57). None of the patients older than 4 years of age
Functional outcome had fecal incontinence. Several studies have com-
pared total TERPT with transabdominal procedures
Long-term obstructive symptoms, such as constipa- and found similar complication rate and short-term
tion, abdominal distension, and enterocolitis are com- functional outcome between both groups, although
mon after procedures for HD. The most common the hospital stay was shorter after TERPT (35, 41, 58).
reasons for persistent obstruction are mechanical ob- On the other hand, El-Sawaf et al reported better con-
struction, recurrent or residual aganglionosis, motil- tinence score for open transabdominal endorectal
ity disorders of proximal bowel, internal sphincter pull-through than for TERPT, although the stool pat-
achalasia, and functional stool-holding behavior (45). tern and enterocolitis score was better in the TERPT
The patient with severe obstructive symptoms should group (59).
be evaluated with clinical examination to rule out Comparing laparoscopically assisted and total
stricture, rectal suction biopsies to exclude residual TERPT, both done with transanal endorectal dissec-
aganglionosis, and contrast enema to assess dilata- tion, Stensrud et al found similar high incidence of
tion of the proximal colon (45). Postoperative entero- soiling in both groups (60). Fifty-four percent of the
colitis has been reported to occur in 0–42% of the patients in the transanal group and 58% of patients
patients after one-stage pull-through procedures (46, in the laparoscopically assisted group reported soil-
246 A. Gunnarsdóttir, T. Wester

ing at follow up at the median age of 5.7 and 10.1 Redo pull-through
years respectively (60).
In a multicenter study from five large North Amer- Rarely patients with persistent obstructive symp-
ican institutions patients operated with transanal dis- toms, enterocolitis or soiling may benefit from a re-
section (total transanal or laparoscopically assisted) peat pull-through procedure. The indications are
and transabdominal technique (open or laparoscopic) residual or acquired aganglionosis, severe strictures,
were compared. The transabdominal approach re- and dysfunctional, sometimes severely dilated, prox-
sulted in more complications than the transanal tech- imal bowel. Conservative measures should have been
niques. Nineteen percent of the patients in the trans- attempted before considering a redo pull-through.
abdominal group had more than one late complica- The patients should undergo investigations with rec-
tion compared to 4 % of patients in the transanal tal biopsies and contrast enema. Different techniques
group. The transabdominal group had more episodes have been proposed for the redo procedure depend-
of enterocolitis and greater number of daily bowel ing on the previous operation the patient had and
movements. However, there were no differences be- also the preference of the surgeon. Langer reported
tween both groups for continence and stooling pat- 9 cases, 8 of who had a Duhamel procedure (68).
tern scores (61). Three of the patients had a normal stool pattern at
follow up, whereas four had persistent obstructive
symptoms, one had soiling, and one a stool-holding
Botulinum toxin injection
behavior. Teitelbaum et al. reported the experience
Mild obstructive symptoms can often be managed by with 26 redo pull-through procedures (69). Fourteen
dietary measures, laxatives or enemas. Occasionally patients were operated on with an endorectal pull-
the symptoms are more severe with recurrent bouts through, 9 with a Duhamel, and 3 with a Swenson
of enterocolitis and repeated admissions to the hos- procedure. At follow up all neurologically intact pa-
pital. Some children need rectal stimulation or irriga- tients older than 3 years of age were continent, ex-
tion to empty stools. If investigations do not reveal cept for two who had daily soiling. Redo pull-
any plausible reasons for the obstruction, the symp- through operations may be technically very difficult
toms are often caused by internal sphincter achalasia, and demanding due to scarring after previous op-
which could be an indication for intra-sphincteric in- erations or pelvic sepsis. However, in carefully se-
jection of botulinum toxin. This method was first de- lected cases, the reports indicate that the outcome
scribed by Langer et al in 1997 (62). Botulinum toxin can be good or excellent (68, 69).
A is injected into the internal sphincter under general
anesthesia. The administered doses vary widely, from
15 to 120 units, between different reports (63, 64). The Quality of life
injection of botulinum toxin frequently has to be re-
peated, usually after 3–4 months. An early prospec- Quality of life (QoL) is difficult to measure with no
tive study showed excellent results (63). The outcome real consensus regarding a gold standard definition
has been less favorable in other studies (65). A recent of QoL. There are many factors affecting individual
study reported that 80% of the patients responded to QoL and it has become an important endpoint in
the first injection but 69% required a second injection. evaluating results of medical treatment for chronic
The number of admissions to hospital for obstructive diseases. Most questionnaires for QoL rely on self
symptoms decreased significantly (64). Chumpitazi judgment of health and are dependent on different
et al reviewed a group of patients referred for defeca- internal and external factors such as employment,
tion disorders after surgery for HD. Sixty-nine per- education, leisure time, social belonging, physical
cent of their patients received botulinum toxin injec- and mental health which differ greatly and are ­valued
tions. A short-term response was shown in 89.2% of differently between individuals.
the patients (66). Measurements of QoL should be multi-dimensional
and include at least three broad domains that can be
Myectomy affected by one´s disease or treatment, including
physical, mental and social functioning (70). One en-
In patients who do respond to botulinum toxin, but counters problem when valuing different studies re-
do not want to continue with repeated injections, my- garding QoL for patients with HD in the heterogene-
ectomy is an option. Wildhaber et al reported the ity of the questionnaires used (70). It is therefore im-
outcome after posterior myectomy or myotomy in 32 perative to use validated questionnaires when esti-
patients with obstructive symptoms after pull- mating QoL for comparison of results. For adults, the
through. The operation was performed at a mean SF-36 health survey is a well established generic
time of 3.1 years after the pull-through and the aver- health survey and has been used in several studies
age time to follow up was 8.6 years. The response rate for adults with HD which found that general QoL of
depended on the indication to do the myectomy. Sev- adults operated for HD in childhood were overall
enty-five percent of the patients with recurrent en- good (70–72). Hartman et al showed that adults oper-
terocolitis became symptom-free and 60% of patients ated for HD scored significantly lower on the physi-
with chronic constipation responded to the myec- cal health scale (PCS) compared to control group,
tomy/myotomy. On the other hand, only 17 % of whereas Gunnarsdóttir et al found that adults with
those with residual aganglionosis and constipation HD scored higher than expected for role-physical
improved (67). function (RP) and PCS; this was found particularly
Modern treatment of Hirschsprung’s disease 247

noted in men, who also had higher mean scores for also be involved. TCA has been described to differ
physical function (PF) and bodily pain (BP) than ex- clinically, radiologically, and histologically from rec-
pected. This supports Hartman’s conclusion that it is tosigmoid Hirschsprung’s disease, which may lead
not the physical symptoms that mostly affect the QoL to misdiagnosis (82).
of adult HD patients (71). Gender subdivision, how- TCA has been associated with a higher mortality
ever, showed that the QoL outcome for women with and morbidity than short segment disease. Several
HD was poorer than for men in all subgroups and surgical methods have been proposed for TCA, such
women scored significantly lower in general- (GH) as the Martin-Duhamel procedure, Duhamel proce-
and mental health (MH) compared to the control dure, Swenson’s procedure, and endorectal pull-
group (71, 72). through with and without a J-pouch. A recent system-
Most follow-up studies after pull-through opera- atic review concluded that no single method is supe-
tions for HD focus on functional results and early rior to the others with respect to mortality, morbidity,
complications after the pull-through operation in enterocolitis or functional outcome. An increased
children with HD are well known as previously morbidity was shown in those who underwent a
shown (1, 73, 74). Follow-up studies for HD are gen- Martin-Duhamel operation using the descending co-
erally limited to 5–15 years postoperatively and indi- lon (83). The Martin-Duhamel procedure has previ-
cate an improvement in bowel symptoms by the time ously been associated with a 75% incidence of entero-
the children reach adolescence and this improvement colitis (84).
up to adolescence has also been noted in the general Early complications include anastomotic leakage,
QoL of patients with HD (52, 73–78). anal strictures, and perineal excoriations. Late com-
Bowel function alone is though not necessarily a plications are frequent bowel movements, inconti-
good indicator of QoL for adult individuals with HD nence, soiling, and recurrent enterocolitis. A few re-
(52, 79, 80). On the contrary, Hartman et al showed in cent studies have reported enterocolitis to occur post-
their study of 320 patients operated on for anorectal operatively in as many as approximately 55% of the
malformations and HD that generic QoL is particu- patients (85, 86). In their meta-analysis, Marquez et
larly affected by psychosocial function but not phys- al showed that the mean incidence of enterocolitis
ical symptoms, such as fecal incontinence and consti- was 22% (only seven of the studies reported the inci-
pation (71). In children with HD, however, Mills et al dence of enterocolitis) (83). Occasional patients need
found that fecal continence was an important predic- anal dilatations, myectomy, or botulinum toxin injec-
tor of overall QoL (78). tions to treat recurrent enterocolitis (86).Soiling is
When looking at disease-specific functioning and very common and occurs in 38–48% of the cases (86,
QoL the diversity of questionnaires used varies 87). Fecal incontinence is also common, particularly
greatly between studies and between different age during night-time, and has been reported in one third
groups. Gastrointestinal Quality of Life Index (GIQLI) of the patients (87). A considerable number of pa-
is a 36-item instrument concerning gastrointestinal tients end up with a permanent ileostomy (84, 86).
disease-related symptoms, physical status and psy-
chosocial dysfunction in adults and has been gaining
popularity for usage in adults born with congenital References
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