Journal of Pediatric Surgery 53 (2018) 1351–1354

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Journal of Pediatric Surgery

journal homepage: www.elsevier.com/locate/jpedsurg

Comparison of Hirschsprung-associated enterocolitis following Soave

and Duhamel procedures☆,☆☆
Isidora Galuh Parahita, Akhmad Makhmudi, Gunadi ⁎
Pediatric Surgery Division, Department of Surgery, Faculty of Medicine, Universitas Gadjah Mada/Dr. Sardjito Hospital, Yogyakarta 55281, Indonesia

a r t i c l e i n f o a b s t r a c t

Article history: Background: Hirschsprung-associated enterocolitis (HAEC) represents the primary cause of high morbidity and
Received 17 April 2017 mortality in Hirschsprung disease (HSCR) patients. The most common surgical methods for HSCR are the
Received in revised form 21 June 2017 Soave and Duhamel procedures. Therefore, we aimed to compare the HAEC frequency following the Soave and
Accepted 10 July 2017 Duhamel procedures.
Methods: Medical records were retrospectively analyzed for patients who underwent the Soave and Duhamel
Key words:
pull-through at Dr. Sardjito Hospital, Indonesia from 2010 to 2015. The diagnosis of HAEC was determined
Duhamel
HAEC following pull-through
using a HAEC scoring system.
Hirschsprung Results: One hundred patients were involved (Soave: 52 males and 19 females vs. Duhamel: 23 males and 6 fe-
Pre-operative enterocolitis males, p = 0.62). There was significant difference in mean age at pull-through (Soave: 29.9 ± 45.2 vs. Duhamel:
Soave 50.8 ± 47.5 months, p = 0.04), whereas mean age of HSCR diagnosis and pre-operative enterocolitis frequency
did not differ significantly between groups (Soave: 25.4 ± 41.0 vs. Duhamel: 43.7 ± 48.1 months, p = 0.06, and
Soave: 7% vs. Duhamel: 14%, p = 0.44, respectively). The HAEC frequency after pull-through was significantly
higher in the Duhamel than the Soave group (28% vs. 10%, respectively, p = 0.03). Furthermore, pre-operative
enterocolitis showed a significant association with HAEC following pull-through (p = 2.0 × 10–4) and the risk
of HAEC after Soave pull-through was increased in long-segment aganglionosis compared to short-segment
HSCR (p = 0.015).
Conclusions: The frequency of HAEC was significantly higher after the Duhamel than the Soave procedure.
Moreover, patients with pre-operative enterocolitis are prone to have HAEC following pull-through.
Level of evidence: III
© 2017 Elsevier Inc. All rights reserved.

1. Background intestinal microbiome, compromised mucosal barrier function, changed

Hirschsprung disease (HSCR), which is characterized by the absence
of ganglion cells (Meissner and Auerbach) along variable lengths of the
intestines, is a common cause of functional intestinal obstruction in chil-
dren [1,2]. This disorder can be classified as follows: (1) short-segment,
(2) long-segment, and (3) total colonic aganglionosis (TCA), with an
overall male:female ratio of 4:1 [1].
Hirschsprung-associated enterocolitis (HAEC) represents the prima-
ry cause of high morbidity and mortality in HSCR patients [3]. There are
several hypotheses for the cause of HAEC involving: dysbiosis of the
☆ The authors declared no potential conflicts of interest with respect to the research, au-
thorship, and/or publication of this article.
☆☆ Author contributions: IGP, AM, and G conceived the study. IGP and G drafted the man-
uscript, and AM critically revised the manuscript for important intellectual content. AM
and G facilitated all project-related tasks.
⁎ Corresponding author at: Pediatric Surgery Division, Department of Surgery, Faculty
of Medicine, Universitas Gadjah Mada/Dr. Sardjito Hospital, Jl. Kesehatan No. 1, Yogyakarta
55281, Indonesia. Tel./fax: +62 274 631036.
E-mail address: drgunadi@ugm.ac.id (Gunadi).
innate immune responses, and translocation of bacteria [3]. HAEC might
occur prior to pull-through procedure or after definitive repair [3–5].
The current treatment for HSCR is surgical resection of the
aganglionic segment of the bowel. The most common operative
methods for HSCR are the Soave and Duhamel procedures [6–10].
Therefore, we aimed to compare the frequency of HAEC following the
Soave and Duhamel techniques.
2. Material and methods
2.1. Patient samples
We conducted a retrospective study of children b 18 years of age
with HSCR at the Pediatric Surgery Division, Department of Surgery,
Dr. Sardjito Hospital in Yogyakarta, Indonesia, from January 2010 to
October 2015. Dr. Sardjito Hospital is a University Teaching Hospital
and as a tertiary referral center, it serves urban and rural populations
not only from Yogyakarta province but also from the southern parts of
the Java Island [11].

http://dx.doi.org/10.1016/j.jpedsurg.2017.07.010
0022-3468/© 2017 Elsevier Inc. All rights reserved.
1352 I.G. Parahita et al. / Journal of Pediatric Surgery 53 (2018) 1351–1354

We diagnosed a patient with HSCR in our hospital based on the clin-
ical manifestation, contrast enema, and/or histopathology findings. The
hematoxylin and eosin staining and/or S100 immunohistochemistry
were utilized for the histopathology diagnosis of HSCR [12–15].
One hundred non-syndromic HSCR patients (Soave = 71 vs.
Duhamel = 29) had adequate data for analysis, consisting of 52 males
and 19 females, and 23 males and 6 females for the Soave and Duhamel
groups, respectively (p = 0.62), corresponding to a sex ratio of 3:1
(Table 1). The Soave and colo-Duhamel techniques were performed at
our hospital based on previous studies [7,16]. The pull-through proce-
dures were conducted by two experienced pediatric surgeons in our
hospital. Each definitive surgery was chosen based upon the pediatric
surgeon's preference. Any patients with a pull-through surgery per-
formed external to our Hospital were excluded.
The Ethical Committee of Faculty of Medicine, Universitas Gadjah
Mada/Dr. Sardjito Hospital gave approval for this study (KE/FK/787/
EC/2015).
2.2. HAEC
Diagnosis of HAEC was determined using a HAEC scoring system
[17]. HAEC scoring consists of 16 items that include: history, physical
examination, radiologic examination, and laboratory findings. A HAEC
score of 10 or greater indicates confirmed diagnosis of HAEC [17].
to left (100%), followed by lethargy (85.7%) and dilated loops of bowel
(85.7%) (Table 2).
Our first analysis involved comparing the HAEC frequency after the
Soave and Duhamel procedures (Table 3). The episodes of HAEC took
place at 5 ± 5.3 months and 8 ± 5.6 months after the Soave and
Duhamel procedures, respectively. For the Soave technique, the HAEC
frequency following pull-through occurred in 7/71 (10%) HSCR patients,
while for the Duhamel procedure, it was 8 (28%) of 29 HSCR patients.
These frequency differences were statistically significant with p-value
of 0.03 (Table 3). Furthermore, the risk of HAEC after Soave pull-
through was increased in long-segment aganglionosis compared to
short-segment HSCR (p-value = 0.015), with odds ratio (OR) of 24.4
(95% confidence interval (CI) = 1.9–318.1) but was not significantly
associated with gender (p-value = 0.44) (Table 3).
To determine the impact of pre-operative enterocolitis on the devel-
opment of HAEC following pull-through, we analyzed the observed
number of patients with pre-operative and post-operative enterocolitis
with respect to the Soave and Duhamel procedures. The results shown
in Table 4 clearly demonstrate that there was a strong association be-
tween the diagnosis of pre-operative and post-operative enterocolitis
in all groups (p-value = 0.041, 0.017, and 2.0 × 10 − 4 for Soave,
Duhamel, and total group, respectively) with OR of 8.1 (95% CI =
1.1–60.6), 43 (95% CI = 1.9–948.3), and 18.2 (3.9–85.6) for Soave,
Duhamel and total group, respectively (Table 4).

4. Discussion
2.3. Statistical analysis
We present new data on Indonesian HSCR patients that reveal a
Data are presented as number and percentages for categorical vari- similar frequency of short-segment aganglionosis and male patients as
ables. The chi-square test was used to evaluate the differences of
HAEC frequency between groups. IBM SPSS Statistics version 16 (SPSS
Chicago, IL, USA) was used for statistical analysis. Table 2
HAEC scoring system findings in Indonesian Hirschsprung patients following Soave and
Duhamel procedures.
3. Results
HAEC Score Soave Duhamel
n (%) n (%)
We analyzed 100 HSCR patients: 75 males and 25 females. The Soave
and Duhamel pull-through procedures were performed in 71 and 29 History
HCSR patients, respectively (Table 1). Diarrhea with explosive stool 2/7 3/8
(28.6) (37.5)
There was significant difference in mean age at pull-through proce- Diarrhea with foul-smelling stool 4/7 6/8 (75)
dure (Soave: 29.9 ± 45.2, Duhamel: 50.8 ± 47.5 months, p = 0.04), (57.1)
whereas the mean age of HSCR diagnosis and the pre-operative entero- Diarrhea with bloody stool 1/7 3/8
colitis frequency did not differ significantly between groups (Soave: (14.3) (37.5)
History of enterocolitis 7/7 8/8 (100)
25.4 ± 41.0, Duhamel: 43.7 ± 48.1 months, p = 0.06; and Soave: 7%
(100)
vs. Duhamel: 14%, p = 0.44, respectively. In addition, the follow-up Physical examination
time was equivalent in the two cohorts, of whom 17 ± 7.1 months Explosive discharge of gas and stool on rectal 5/7 5/8
and 25 ± 15.6 months for the Soave and Duhamel groups, respectively examination (71.4) (62.5)
(p = 0.24) (Table 1). Distended abdomen 7/7 7/8
(100) (87.5)
The most common findings of the HAEC score found in the Duhamel Decreased peripheral perfusion 3/7 1/8
group were history of enterocolitis (100%), followed by distended abdo- (42.9) (12.5)
men (87.5%), whereas for those in the Soave group findings showed: Lethargy 6/7 5/8
history of enterocolitis (100%), distended abdomen (100%), and shift (85.7) (62.5)
Fever 5/7 5/8
(71.4) (62.5)
Table 1 Radiologic examination
Baseline characteristics of Indonesian Hirschsprung patients Multiple air fluid levels 2/7 2/8 (25)
(28.6)
Characteristic Soave Duhamel P-value
Dilated loops of bowel 6/7 5/8
n (%) n (%)
(85.7) (62.5)
Gender Sawtooth appearance with irregular mucosal lining 1/7 1/8
▪ Male 52/71 (73) 23/29 (79) 0.62 (14.3) (12.5)
▪ Female 19/71 (27) 6/29 (21) Cutoff sign in rectosigmoid with absence of distal air 5/7 5/8
Aganglionosis type 0.09 (71.4) (62.5)
▪ Short-segment 68/71 (96) 25/29 (86) Pneumatosis 1/7 2/8 (25)
▪ Long-segment 3/71 (4) 4/29 (14) (14.3)
Age of HSCR diagnosis 25.4 ± 41.0 mo 43.7 ± 48.1 mo 0.06 Laboratory finding
Age of pull-through 29.9 ± 45.2 mo 50.8 ± 47.5 mo 0.04 Leukocytosis 6/7 6/8 (75)
Pre-operative HAEC 5/71 (7) 4/29 (14) 0.44 (85.7)
Length of follow-up 17 ± 7.1 mo 25 ± 15.6 mo 0.24 Shift to left 7/7 6/8 (75)
(100)
mo, months; HSCR, Hirschsprung diseases; HAEC, Hirschsprung-associated enterocolitis.
 I.G. Parahita et al. / Journal of Pediatric Surgery 53 (2018) 1351–1354
Table 3
Comparison of HAEC frequency following Soave and Duhamel pull-through.
Duhamel (n, %) Soave (n, %)
HAEC frequency 8/29 (28) 7/71 (10)
▪ Gender
✓ Male 7/8 (87.5) 6/7 (86)
✓ Female 1/8 (12.5) 1/7 (14)
▪ Aganglionosis type
✓ Long-segment 1/8 (12.5) 2/7 (29)
✓ Short-segment 7/8 (87.5) 5/7 (71)
reported in the literature [18,19]. Our study clearly shows that the HAEC
frequency was significantly higher in the Duhamel group (28%) than the
Soave group (10%). The incidence of enterocolitis following the Duha-
mel procedure in our study was higher than in previous studies
[7,18,20] but with similar results reported by Kim et al. [21], while
those of in the Soave group were comparable with other findings
[8,18,20]. HAEC after Duhamel pull-through may be attributed to rectal
achalasia secondary to retained aganglionic rectum, resulting in partial
obstruction [22]. It is important to note that the patients that suffer
from fecal incontinence after pull-through, a complication that happens
more often following Soave surgery [23], will not have HAEC. It implies
that HAEC is a more complex disease that will not be solely resolved by
the type of operation chosen. Furthermore, our study focused on the de-
velopment of enterocolitis following pull-through but did not deter-
mine the functional outcomes.
HAEC might occur in the immediate after definitive surgery, with the
greatest risk within the first year following pull-through [24]. In our
study, the HAEC appeared at 5 ± 5.3 months and 8 ± 5.6 months
after the Soave and Duhamel procedures, respectively.
The most frequent findings in our patients with HAEC were history
of enterocolitis and distended abdomen, followed by lethargy and dilat-
ed loops of the bowel. These results were similar with a previous study
[25]. The clinical manifestation of HAEC varies widely with the classic
findings that include abdominal distention, fever, and diarrhea [3]. It is
preferable to treat suspected HAEC cases since its high morbidity and
mortality are related to a delayed or missed diagnosis [3].
The incidence of HAEC following pull-through differs widely, rang-
ing from 25 to 45% [3,26]. The frequency of overall post-operative
HAEC in our series (15%) was lower than previous reports [3–5,26].
These results might be related to our protocol where our HSCR patients
were long-term administered with oral metronidazole during the post-
operative period. Frykman and Short [27] have proposed the implemen-
tation of routine use of rectal irrigations by trained parents, long-term
administration of oral metronidazole, and use of probiotic therapy pre-
ventive measures to prevent HAEC after pull-through. Notably, a larger
prospective study is necessary to clarify and confirm our results. In ad-
dition, since we only extracted data from the medical records (retro-
spective study), data of rectal washout by trained parents were
missing or incomplete, becoming a weakness of our study.
Nearly 10% of HSCR patients are diagnosed after 3 years of age and
usually suffer from less severe symptoms [28,29]. In our series, the diag-
nosis of HSCR was established at ~ 3 years old. It might relate with the
fact that the frequency of overall post-operative HAEC in our study
was lower than previous reports (15% vs. 25–45%) [3–5,26].
Table 4
Association between pre-operative enterocolitis and HAEC following pull-through procedures.
Pre-operative HAEC (n, %)
Soave 5/7 (71)
Duhamel 4/8 (50)
Total 9/15 (60)
1353
P-value OR (95% CI)
Duhamel Soave Duhamel Soave
0.03 3.5 (1.1–10.8)
0.51 0.44 2.2 (0.2–22.3) 2.4 (0.3–20.9)
0.90 0.015 0.9 (0.1–9.7) 24.4 (1.9–318.1)
The long-segment diagnosis has been associated with increased risk
of HAEC after pull-through [3]. In our series, long-segment
aganglionosis is a strong risk factor for post-operative HAEC in Soave
group with a relative risk of ~ 24 (Table 2). This value is consistent
with previous studies [3,26]. The cause of HAEC is presumed to be
dysbiosis of the intestinal microbiome, compromised mucosal barrier
function, changed innate immune responses, and translocation of bacte-
ria [3]. Therefore, the longer aganglionosis indicates a greater impair-
ment of the bowel immune system, leading to higher vulnerability of
intestinal stasis and production of putrefactive and potentially patho-
genic bacteria [26]. Furthermore, the presence of an anastomotic stric-
ture after Soave procedure has been associated with increased risk for
post-operative HAEC [30]. It should be noted that our results should
be interpreted with some caution given the small number of patients
being analyzed.
The risk of HAEC after pull-through was also increased in patients
with history of prior HAEC [3,26]. Our study shows that patients with
pre-operative enterocolitis have a possibility to suffer from HAEC after
pull-through with a relative risk of ~8 and ~43 for the Soave and Duha-
mel procedures, respectively. It has been proposed that prior HAEC ep-
isodes lead to the altered microbiome and resultant short chain fatty
acid changes, and it might contribute to further episodes of HAEC [31].
Another hypothesis proposes that the patients with prior HAEC show
significantly reduced Lactobacillus and Bifidobacteria species in their in-
testines, thus, decreasing the ability to initiate immunoglobulin A secre-
tion and the protease production that deactivates Clostridium difficile
endotoxin [32]. In addition, there was a significant reduction in the di-
versity of the fecal fungi composition with increased Candida sp., and
decreased Malassezia and Saccharomyces spp. in the intestines of HAEC
patients compared with non-HAEC patients [33].
The incidence of pre-operative HAEC in our study was 9% [Table 4]. It
was comparable with a previous report (6–60%) [3]. It should be noted
that our study determined the pre-operative HAEC incidence according
to the number of HSCR patients who underwent the Soave and Duhamel
pull-through procedures only. Further research with all definitive sur-
gery for HSCR patients is needed to determine more concisely the pre-
operative HAEC incidence in our Hospital.
In this series, we have 1 (1.4%) patient with recurrent episodes of
HAEC after Soave. It is important to evaluate an anatomic/pathologic
and functional obstruction in children with recurrent HAEC [3]. We
have eliminated the possibility of a transition zone pull-through or
retained aganglionosis since we have performed intraoperative histo-
pathological evaluations. There was no anatomic/pathologic cause iden-
tified in this patient after evaluation by a contrast enema using a water
Post-operative HAEC (n, %) P-value OR (95% CI)
2/5 (40) 0.041 8.1 (1.1–60.6)
4/4 (100) 0.017 43 (1.9–948.3)
6/9 (67) 2.0 × 10−4 18.2 (3.9–85.6)
1354 I.G. Parahita et al. / Journal of Pediatric Surgery 53 (2018) 1351–1354
soluble agent. The patient has been discharged uneventfully from the
Hospital after undergoing rectal washout and broad-spectrum antibi-
otics including metronidazole. Moreover, it has been proposed that
Clostridium botulinum toxin (Botox, Allergan, Plc.) injection into the
intersphincteric groove will alleviate the recurrent obstructive symp-
toms [34].
5. Conclusions
The frequency of HAEC was significantly higher after the Duhamel
than the Soave procedure. Moreover, patients with pre-operative en-
terocolitis are prone to have HAEC following pull-through.
Conflict of interest
The authors declare that they have no conflict of interest.
Acknowledgement
We are thankful to Harini Natalia for ethical clearance management.
This work was supported by a grant from the Directorate General of
Higher Education, Indonesian Ministry of Research, Technology and
Higher Education (“PUPT 2016” to G. and A.M.). We are also grateful
to a native speaker at English Services Center, Faculty of Medicine,
Universitas Gadjah Mada, for editing the grammar and proofreading of
our manuscript. We are also thankful to Alvin Santoso Kalim, Dian
Nirmala Sirait, Andi Lestiono, and all those who provided excellent tech-
nical support and assistance during the study.
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