Background
Hirschsprung disease (HSCR) is caused by the migration failure of
neural crest cells during intestinal development, resulting in an aganglionic colon
and causing a functional obstruction in children [
1,
2]. According to the
length of aganglionosis, HSCR can be classified as follows: 1) short-segment, 2)
long-segment, and 3) total colonic aganglionosis (TCA), with a male-to-female ratio
of approximately 4:1 [
1].
The goal of HSCR treatment is surgical resection of the aganglionic
bowel and pulling the ganglionated bowel through to a point just above the dentate
line [
3]. Several pull-through
procedures have been described for Hirschsprung disease (HSCR) with varying
functional outcomes [
4‐
8].
There is currently some debate over which pull-through technique offers the best
outcome [
9]. The voluntary bowel
movement (VBM) and the absence of soiling or constipation following pull-through
remain the most important markers of good outcome [
9]. This study aimed to compare the functional outcomes including
VBM, soiling and constipation in HSCR patients following the Soave and Duhamel
procedures.
Methods
Patients
A retrospective study was conducted with children < 18 year of
age with HSCR at Dr. Sardjito Hospital, a University Teaching Hospital
[
10] in Yogyakarta, Indonesia from
January 2012 to December 2016. Fifty-three patients were ascertained (Soave: 23
males and 2 females vs. Duhamel: 22 males and 6 females,
p = 0.26), corresponding to a sex ratio of 5.6:1 (Table
1).
Table 1
Clinical characteristics of HSCR patients who underwent Soave
and Duhamel procedures
Gender |
▪ Male | 23 (92) | 22 (79) | 0.26 |
▪ Female | 2 (8) | 6 (21) | |
Aganglionosis type | | | 0.67 |
▪ Short-segment | 23 (92) | 24 (86) | |
▪ Long-segment | 2 (8) | 4 (14) | |
Age of HSCR diagnosis | 24 mo (0.5–218 mo) | 22.5 mo (1–163 mo) | 0.93 |
Age of pull-through | | | 0.66 |
▪ ≥3 years old | 11 (56) | 14 (50) | |
▪ < 3 years old | 14 (44) | 14 (50) | |
Length of follow-up | 17.0 ± 14.3 mo | 15.5 ± 14.6 mo | 0.71 |
Nutritional status | | | 0.38 |
▪ Undernourished | 18 (72) | 23 (82) | |
▪ Well-nourished | 7 (28) | 5 (18) | |
Diagnosis of HSCR in our hospital was established according to the
clinical manifestation, contrast enema, and histopathology findings. The
pathologist utilized the hematoxylin and eosin staining and/or S100
immunohistochemistry for the histopathology diagnosis of HSCR [
11‐
16].
The two-staged Soave and colonic Duhamel pull-through were
conducted at our hospital based on our previous study [
15]. The definitive surgical procedures were
performed by two experienced pediatric surgeons in our institution, and one
surgeon only performed one of the techniques. All HSCR patients showed the level
of the aganglionic zone at the sigmoid colon, except with six patients which was
at the descending colon. Furthermore, there were no TCA patients in our
study.
We defined the age of pull-through with the following criteria:
≥3 years old and < 3 years old since surgery in older children presents
specific perioperative challenges that might impact the outcomes [
17].
In addition, we classified the nutritional status of HSCR patients
as follows: undernourished and well-nourished since the peri-operative
malnutrition was associated with the functional outcomes following pull-through
[
3]. Undernourished was defined as
weight-for-age Z score < − 2 [
18].
This study was approved by the Institutional Review Board of the
Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr.
Sardjito Hospital, Yogyakarta, Indonesia (KE/FK/1356/EC/2015). Written informed
consent was obtained from all parents for participating this study.
Functional outcomes
Krickenbeck classification was used to evaluate the functional
outcomes, including VBM, soiling and constipation, according to previous studies
[
19‐
21]. VBM was
determined as feeling an urge to defecate, the capacity to verbalize this feeling,
and the ability to hold the bowel movement. Soiling was classified into 3 grades
as follows: a) grade 1, occasionally soiling (up to once or twice per week); b)
grade 2, soiling every day but no social problems; and c) grade 3, constant
soiling with social problems, whereas constipation consists of 3 grades: a) grade
1, manageable by changes in diet; b) grade 2, requires laxatives; and c) grade 3,
resistant to laxatives and diet [
19].
The functional outcomes were assessed by the pediatric surgeons in children
≥3 years old since toilet training is expected by this age [
9].
To further investigate the functional outcomes in our HSCR patients
after pull-through, we performed a contrast enema to visualize the anatomy after
the initial surgery and give insight into the colon motility and any structural
defect, or if necessary, a rectal biopsy to rule out a transition zone
pull-through or retained aganglionosis, as suggested by previous study
[
22].
Statistical analysis
Data were presented as number/percentages and median/mean for
categorical and continuous variables, respectively. The Fischer exact, chi-square,
Mann-Whitney U, and t tests were used to evaluate the differences between
groups.
Results
We used ICD-10 codes (International Statistical Classification of
Diseases and Related Health Problems, 10th Revision) (Q43.1: Hirschsprung disease)
to identify patients diagnosed with HSCR and examined 65 medical records. We
excluded 12 subjects due to incomplete medical records, thus, we further analyzed 53
infants.
Fifty-three HSCR patients (Soave = 25 vs. Duhamel = 28) had complete
data for final analysis (Table
1). Most
patients were having short-segment HSCR (89%) and were undernourished (77%). None of
the clinical characteristics of HSCR patients showed any difference between the two
surgical methods (Table
1).
The VBM rates were 93% and 88% in the Duhamel and Soave groups,
respectively, but the differences did not reach a significant level (
p = 0.66) (Table
2). The soiling frequency was not statistically significant between
the Duhamel and the Soave groups (21% vs. 8%,
p = 0.26) (Tables
2 and
4). In contrast, the constipation rate was
significantly higher in the Soave than the Duhamel groups (24% vs. 4%,
p = 0.04) with OR of 8.5 (95% CI = 1.0–76.7)
(Tables
2 and
5). Furthermore, four patients underwent a contrast enema and
showed a dilated (hypomotile) colon, a nondilated (hypermotile) colon and an
anatomic stricture in one, two and one patients, respectively, while none of the
patients underwent a rectal biopsy.
Table 2
Functional outcomes in HSCR patients after Soave and Duhamel
procedures according to Krickenbeck classification
Voluntary bowel movements | 22/25 (88) | 26/28 (93) | 0.66 |
Soiling |
√ Grade 1 | 2/25 (8) | 5/28 (18) | 0.26 |
√ Grade 2 | 0 | 1/28 (3) | |
√ Grade 3 | 0 | 0 | |
Constipation |
√ Grade 1 | 1/25 (4) | 1/28 (4) | 0.04* |
√ Grade 2 | 5/25 (20) | 0 | |
√ Grade 3 | 0 | 0 | |
Next, we analyzed the impact of the gender, aganglionosis type,
nutritional status, and age at pull-through on the VBM, soiling and constipation
(Tables
3,
4 and
5, respectively).
None of the factors affected the functional outcomes after pull-through, but an
almost significant effect was observed in the Soave group: the female patients had
~ 21.7-fold higher risk to have constipation after surgery than the male patients
(
p = 0.05) (Table
5).
Table 3
Voluntary bowel movements in HSCR patients after Soave and Duhamel
pull-through
Voluntary bowel movements | 26/28 (93) | 22/25 (88) | 0.66 | | 1.7 (0.3–11.1) | |
Gender |
√ Male | 20/26 (77) | 20/22 (91) | 0.78 | 0.92 | 0.6 (0.03–14.9) | 1.2 (0.05–29.9) |
√ Female | 6/26 (23) | 2/22 (9) | | | | |
Aganglionosis type |
√ Long-segment | 3/26 (11.5) | 2/22 (9) | 0.19 | 0.92 | 0.1 (0.01–2.7) | 0.9 (0.03–21.8) |
√ Short-segment | 23/26 (88.5) | 20/22 (91) | | | | |
Nutritional status |
√ Undernourished | 21/26 (81) | 17/22 (77) | 0.88 | 0.15 | 0.8 (0.03–18.8) | 6.8 (0.5–91.5) |
√ Well-nourished | 5/26 (19) | 5/22 (23) | | | | |
Age of pull-through |
√ ≥3 years old | 14/26 (54) | 11/22 (50) | 0.27 | 0.21 | 5.8 (0.3–132.6) | 7.0 (0.3–151.4) |
√ < 3 years old | 12/26 (46) | 11/22 (50) | | | | |
Table 4
Soiling frequency in HSCR patients after Soave and Duhamel
pull-through
Soiling frequency | 6/28 (21) | 2/25 (8) | 0.26 | | 3.1 (0.6–17.2) | |
Gender |
√ Male | 6/6 (100) | 2/2 (100) | 0.29 | 0.75 | 5.1 (0.3–104.6) | 0.6 (0.02–15.9) |
√ Female | 0 | 0 | | | | |
Aganglionosis type |
√ Long-segment | 0 | 0 | 0.46 | 0.75 | 0.3 (0.01–6.7) | 1.7 (0.06–46.9) |
√ Short-segment | 6/6 (100) | 2/2 (100) | | | | |
Nutritional status |
√ Undernourished | 5/6 (83) | 2/2 (100) | 0.93 | 0.61 | 1.1 (0.1–12.3) | 2.2 (0.1–53.4) |
√ Well-nourished | 1/6 (17) | 0 | | | | |
Age of pull-through |
√ ≥3 years old | 4/6 (67) | 2/2 (100) | 0.36 | 0.21 | 2.4 (0.4–15.9) | 7.6 (0.3–177.2) |
√ < 3 years old | 2/6 (33) | 0 | | | | |
Table 5
Constipation rate in HSCR patients after Soave and Duhamel
pull-through
Constipation frequency | 6/25 (24) | 1/28 (4) | 0.04* | | 8.5 (1.0–76.7) | |
Gender |
√ Female | 2/6 (33) | 1/1 (100) | 0.05 | 0.14 | 21.7 (0.9–534.1) | 12.2 (0.4–344.1) |
√ Male | 4/6 (67) | 0 | | | | |
Aganglionosis type |
√ Long-segment | 0 | 0 | 0.70 | 0.75 | 0.5 (0.02–12.8) | 1.7 (0.1–49.9) |
√ Short-segment | 6/6 (100) | 1/1 (100) | | | | |
Nutritional status |
√ Undernourished | 5/6 (83) | 1/1 (100) | 0.49 | 0.87 | 2.3 (0.2–24.3) | 0.8 (0.03–21.5) |
√ Well-nourished | 1/6 (17) | 0 | | | | |
Age of pull-through |
√ ≥3 years old | 4/6 (67) | 0 | 0.21 | 0.49 | 3.4 (0.5–23.8) | 0.3 (0.01–8.3) |
√ < 3 years old | 2/6 (33) | 1/1 (100) | | | | |
Discussion
We clearly show that the VBM and soiling frequencies are similar
between the Duhamel and Soave groups, but the constipation rate is higher in the
Soave than Duhamel groups. The risk of constipation following the Soave procedure is
increased ~ 8.5-fold higher than the Duhamel procedure. This finding might be caused
by an anastomotic stricture or “rolling down” of the rectal muscular cuff following
the Soave procedure [
23]. If there was
an anatomic stricture identified in our patients after evaluation by a contrast
enema, we managed them with serial dilatation. Also, the constipation rates
following the Soave and Duhamel procedures in our study were similar (24% vs. 25%)
and lower than (4% vs. 25%) previous study [
20].
It has been reported that the HSCR patients who underwent Duhamel
procedure will have less soiling [
22].
The soiling in the Duhamel group might be caused by the “overflow” incontinence
secondary to constipation since the Duhamel technique results in less possibility
for the anal canal damage [
21,
22,
24]. However, our study showed that the soiling frequency was
similar between the Duhamel and the Soave groups. Furthermore, our study focused on
the development of soiling and constipation following pull-through, while the
enterocolitis after surgery in our cohort patients has been previously reported
[
15]. As for the VBM, its frequency
in this series reached ~ 90% HSCR patients after pull-through and was higher than
previous study (67%) [
20].
Interestingly, in the Soave group, the female patients had 21-fold
higher risk to have constipation following the Soave procedure than the male
patients. In the general population without any other gastrointestinal disorders, it
has been shown that females have higher constipation rate due to hormonal factors
[
25]. Unfortunately, we do not have
any data on the constipation rate in HSCR children after pull-through who were going
through or already had passed puberty. Therefore, it is interesting to conduct a
cohort study to compare the constipation frequency between adolescent females and
male HSCR patients.
The functional outcomes after pull-through were also associated with
the peri-operative malnutrition [
3]. Our
study showed that there was no association between nutritional status of HSCR
patients and their functional outcomes following pull-through. It should be noted
that the small sample size, which was a weakness of our study, suggests that a
larger sample of patients needs to be ascertained to clarify our findings.
Our study utilized the Krickenbeck classification to evaluate the
functional outcomes following pull-through procedure according to previous studies
[
19‐
21]. However, it
should be noted that the Krickenbeck classification was originally established for
patients with anorectal malformation (ARM). There are different anatomies and
associated anomalies between HSCR and ARM patients. The patients with HSCR possess
normal anal canal and sphincter, and usually do not have any anomaly in the spinal
cord and vertebrae. Therefore, our results should be interpreted with some caution
given those differences. Caution should be also taken when generalizing about the
findings since this is a mono-institutional study.
The algorithm has been proposed to improve the outcome of HSCR
patients with soiling and constipation after pull-through [
22]. The pediatric surgeon should begin with a
detailed history and physical examination focused on the patient’s bowel habits and
the method of the first pull-through, followed by several examinations, such as:
contrast enema and rectal biopsy. Once the etiology of the symptoms after
pull-through is established, it will be followed by specific treatment accordingly
[
22]. Moreover, our study also
implies that the pediatric surgeon should monitor and evaluate closely the
functional outcomes of their HSCR patients after pull-through to determine
appropriate follow-up and management.
Conclusions
The constipation rate is higher in patients who underwent Soave than
Duhamel procedure, but the VBM and soiling frequencies are similar. The constipation
risk following Soave pull-through might be increased by the female gender.
Furthermore, a multicenter study with a larger sample of patients is necessary to
clarify and confirm our findings.
Acknowledgements
We are thankful to Harini Natalia for ethical clearance management. We are
also grateful for the English Services Center, Faculty of Medicine, Public Health
and Nursing, Universitas Gadjah Mada, for editing the grammar and proofreading of
our manuscript. We are also thankful to Dian Nirmala Sirait, Alvin Santoso Kalim and
all those who provided excellent technical support and assistance during the
study.
Open AccessThis article is distributed
under the terms of the Creative Commons Attribution 4.0 International License (
http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in
any medium, provided you give appropriate credit to the original author(s) and the
source, provide a link to the Creative Commons license, and indicate if changes
were made. The Creative Commons Public Domain Dedication waiver (
http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless
otherwise stated.