The American Journal of Surgery (2014) -, --

Initial operative treatment of isolated ileal

Crohns disease in adolescents
Ann M. Kulungowski, M.D.a,b,*, Shannon N. Acker, M.D.a,b,
Edward J. Hoffenberg, M.D.c,d, Deborah Neigut, M.D.c,d,
David A. Partrick, M.D.a,b
a

Department of Pediatric Surgery, Childrens Hospital Colorado, 13123 E 16th Avenue, Aurora,
CO 80045, USA; bDivision of Surgery, University of Colorado, School of Medicine, Aurora, CO 80045,
USA; cDeparment of Gastroenterology, Hepatology, and Nutrition, Childrens Hospital Colorado,
13123 E 16th Avenue, Aurora, CO 80045, USA; dDepartment of Pediatrics, University of Colorado,
School of Medicine, Aurora, CO 80045, USA

KEYWORDS:
Crohns disease;
Intestine;
Inflammatory bowel
disease;
Surgery;
Pediatrics

Abstract
BACKGROUND: We hypothesize that in children with Crohns disease (CD) isolated to a single site,
resection leads to clinical improvement, decreased medication requirements, and improved growth.
METHODS: A retrospective review was conducted of children with CD isolated to the terminal ileum
undergoing operative intervention at Childrens Hospital Colorado between 2002 and 2013.
RESULTS: Twenty-six patients underwent ileocecetomy (mean age at diagnosis 14.1 6 2.6 years;
mean age at resection 15.7 6 2.5 years; median follow-up 2 6 1.5 years). Twenty-two (84.6%) patients
reported clinical improvement and 17 (65.4%) were able to decrease the number or dosage of medications. Average weight increased from the 29th to the 45th percentile (P 5 .09) at 1 year and to the 56th
percentile (P 5 .02) at 3 years post resection. Average body mass index increased from the 30th to the
48th and 49th percentile at 1 and 3 years (P , .05 for both), respectively. Height increased from the
39th percentile at the time of resection to the 51st percentile at 3 years (P 5 nonsignificant).
CONCLUSION: Surgical resection of an isolated ileal segment in adolescents with CD allows for
catch-up growth and reduction in medication requirements.
2014 Elsevier Inc. All rights reserved.

Crohns disease (CD) is a potentially debilitating chronic

inflammatory disorder of unknown etiology; however, genetics, environmental factors, and intestinal microflora are all
likely involved.1 The worldwide incidence of pediatric CD is

There were no relevant financial relationships or any sources of support

in the form of grants, equipment, or drugs.
* Corresponding author. Tel.: 11-720-777-6571; fax: 11-720-7777271.
E-mail address: Ann.kulungowski@childrenscolorado.org
Manuscript received March 24, 2014; revised manuscript June 20,
2014
0002-9610/$ - see front matter 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjsurg.2014.07.009

.2 to 8.5 per 100,000 and is on the rise.24 CD develops during

childhood or adolescence in up to 25% of patients with a peak
age of onset in late adolescence.5 The individual presentation
depends on the location and extent of disease involvement5
with the terminal ileum being the most common location in
older children and adolescents (50 to 70%), whereas children
less than 5 years of age have higher rates of colonic involvement.5 The natural history of CD is characterized by an unpredictable course of alternating periods of inactivity and
symptomatic flares leading to physical and social impairment.6 Manifestations of CD include both intestinal symptoms (such as abdominal pain, diarrhea, perianal fistulae/

2
abscesses) and extraintestinal features (such as arthritis, uveitis, nephrolithiasis, erythema nodosum). Because of the
chronic nature of CD, patients can experience inadequate
nutrition during critical periods of growth during childhood
and adolescence. Traditional treatment algorithms aim to
induce remission with medical management before the onset
of puberty. The primary goal of most treatment strategies is to
avoid surgery to preserve intestinal length and prevent surgical complications for as long as possible. Unfortunately, the
cumulative probability of surgery 5 years after a pediatric
diagnosis of CD is 47% and increases to 71% in adulthood.7,8
At our center, we offer operative resection to those patients
identified with symptomatic CD isolated to the terminal
ileum early in the course of their disease, while other centers
may opt for longer trials of medical management before
referral for surgical resection. We hypothesized that surgical
intervention would lead to clinical improvement, decreased
medication requirements, and improved growth.

Patients and Methods

After approval by the Colorado Multiple Institutional
Review Board, the records of patients with inflammatory
bowel disease were collected for all patients with CD
isolated to the terminal ileum undergoing surgical resection
from 2002 to 2013. Records were retrospectively reviewed to
delineate clinical presentation, anatomic location of CD,
surgical intervention, complications, treatment modalities
both pre- and postoperatively, pre- and postoperative growth
parameters, and outcome. Additionally, comparisons were
made between those patients who underwent emergent and
elective resection. Statistical analysis was conducted in
Prism 6.0b (GraphPad Software, Inc, La Jolla, CA). Categorical variables were compared between the groups using a
chi-square test. Continuous variables were compared using
the t test for normally distributed data or Wilcoxon twosample test for nonparametric data. Statistical analysis was
performed based on available data. Differences were considered significant when P value was less than .05.

Results
Twenty-six patients (male 5 65%, n 5 17) with isolated
CD of the terminal ileum underwent surgical resection from
2002 to 2013 (Table 1). The average age at the time of diagnosis of CD was 14.1 6 2.6 years and the average age at
resection was 15.7 6 2.5 years. Indications for surgical
intervention included stricture (n 5 23), abscess (n 5 8),
fistula (n 5 6), obstruction (n 5 3), and perforation (n 5
3); 16 patients had 2 or more of these indications. Elective
ileocecal resections were performed in 15 (57.7%) patients.
Four patients received total parenteral nutrition (TPN)
before operative resection; 3 of these children received
TPN during their in-patient hospitalization before operative
resection because of poor nutritional intake at the onset of
an acute illness requiring operative intervention. The fourth

The American Journal of Surgery, Vol -, No -, - 2014

Table 1

Patient and operative characteristics

Age at diagnosis of CD (mean 6 SD)

Female
Age at resection (mean 6 SD)
TPN preoperatively
Weight at resection (percentile 6 SD)
Height at resection (percentile 6 SD)
Indication for operation
Stricture
Abscess
Fistula
Obstruction
Perforation
Emergent procedure

14.1 6 2.6
9 (35%)
15.7 6 2.5
4 (15%)
29.45 6 30.9
39.0 6 32.3
23 (88%)
8 (31%)
6 (23%)
3 (12%)
3 (12%)
11 (42%)

CD 5 Crohns disease; SD 5 standard deviation; TPN 5 total

parenteral nutrition.

child received 2 months of home TPN because of weight

loss soon after her CD diagnosis, before referral for operative resection. Laparoscopic-assisted resection was accomplished in 17 (65.4%) patients. Two patients underwent
temporary fecal diversion with ileostomy (both in the emergent group). The remaining patients underwent primary
anastomosis with staples (n 5 21) or suture (n 5 3). The
average time to discharge was 6 (62) days; this did not
differ between the emergent and elective groups (median
6 vs 5 days; P 5 .3). All patients were seen at least one
time postoperatively. Two patients were readmitted within
30 days of discharge for wound infection (n 5 1) and
intra-abdominal abscess (n 5 1). There were 5 postoperative complications including wound infections (n 5 4)
and intra-abdominal abscess (n 5 1). Three of the wound
infections occurred in patients with enteroenteral fistula
(n 5 2) and intra-abdominal abscess (n 5 1); the remaining
2 complications (1 wound infection and 1 intra-abdominal
abscess) occurred in patients with strictures of the terminal
ileum. The intra-abdominal abscess was treated with percutaneous drainage and antibiotics. Preoperative biologic
therapy was not associated with a higher complication
rate compared with those patients who did not receive preoperative biologic therapy (P 5 1.0). Rates of postoperative
complications did not differ between the emergent and
elective groups (2 wound infections in the emergent group
vs 3 complications in the elective group; P 5 1.0). A single
patient experienced late disease recurrence 5 years after the
initial procedure in the form of an intra-abdominal abscess
and fistula. She was treated with segmental bowel resection
and fecal diversion with an ileostomy.
Weight and height percentiles based on developmental
age were obtained before CD diagnosis, at the time of
diagnosis, at the time of resection, and at 1 and 3 years
postoperatively. Mean weight-based percentile was 54.7
pre-CD diagnosis, 19.6 at the time of diagnosis, and 29.5 at
the time of operative resection. Compared with mean
percentile at the time of resection, following resection,
average weight increased from the 29th to the 45th

A.M. Kulungowski et al.

Operative treatment of ileal Crohns disease in adolescents

postoperatively; P , .0001) was observed. A reduction in

the number of patients managed on immunomodulators
was also observed from 14 patients preoperatively to 8 patients postoperatively (P 5 NS). There was no change in
the number of patients receiving biologics pre- (n 5 8)
and postresection (n 5 8). Salicylate use decreased only
slightly (preoperatively, n 5 8; postoperatively, n 5 5).
Medication requirements pre and postoperatively are shown
in Table 2. Subjective improvement in disease severity was
reported by 22 (84.6%) patients.

Comments

Figure 1 Changes in average age-based weight percentile

following operative resection. Mean weight was highest before
the diagnosis of CD and at its lowest at the time of diagnosis.
Weight began to increase slightly with medical treatment. However, weight-based percentile increased back to prediagnosis levels
only after operative resection.

percentile (P 5 .09) at 1 year, and continued to improve at

3 years to the 56th percentile (P 5 .02) (Fig. 1). Weight did
not differ between the emergent and elective groups at the
time of operation or at 3 years follow-up. Height also
increased from the 39th percentile at the time of resection
to the 42nd (P 5 nonsignificant [NS]) and 51st percentile
at 1 and 3 years (P 5 NS), respectively. Height did not
differ between the emergent and elective groups at either
the time of operation or at 3 year postoperatively. Body
mass indices (BMIs) were also positively affected by
segmental intestinal resection. The average BMI before
intervention was 18.7 6 3.5 (30th percentile). At 1 and
3 years, the BMI increased to 21.2 6 4.2 (48th percentile;
P , .05) and 22.5 6 3.9 (49th percentile; P , .01), respectively. BMI also did not differ between the emergent and
elective groups at the time of operation or at 3 years
follow-up.
Preoperatively, 23 (86.5%) patients were undergoing
medical management of the CD with corticosteroids (n 5
18), immunomodulators (n 5 14), biologics (n 5 8), and
salicylates (n 5 8). Average age at the time of initiation
of medical therapy was 14 (62.6) years. Follow-up clinical
information was available for all patients. Median followup was 2.5 years (range: 30 days to 6 years). Postoperatively, 17 (65.4%) patients experienced a reduction in the
number or dosage of their medications. A significant
decrease in the number of patients receiving corticosteroid
treatment following resection (18 preoperatively vs 3

The complications associated with CD in childhood and

adolescence include poor weight gain, altered linear
growth, a negative impact on self-esteem, and delayed
puberty.5,9 The treatment goals in children are to achieve
remission of active disease to promote growth and adequate
nutrition, to improve physical and social quality of life, and
to decrease the likelihood for surgical intervention.6 Surgical intervention, however, is not infrequent in children with
CD, with 15% to 20% requiring operative intervention
within 3 years of diagnosis.7 Our patients underwent surgical intervention only 1.5 years after their initial diagnosis of
CD. This rate is likely accelerated because of more severe
disease seen in this population. While medical therapy is
the mainstay of treatment for CD, all immunosuppressive
medications have potential adverse side effects and not
all patients respond favorably to these medications. We
theorized that patients with CD isolated to the terminal
ileum would benefit from operative resection of the
diseased segment by reduction in the number and/or dosage
of medication, subjective clinical improvement, and
improved growth. Our data support this hypothesis.
A number of medical therapies are effective in inducing
remission of symptoms including salicylates, immunomodulators, corticosteroids, and biologics. Biologic therapy has
been found to not only heal mucosal inflammation but also
induce remission 1 year after therapy in about 50% of
children aged 6 to 7 years.10,11 However, these medications
are not without risk. Despite the ability of corticosteroid to
often achieve rapid symptom control, this intervention does
not heal mucosal lesions and is of almost no benefit for
maintenance therapy.1214 We observed a high rate of preoperative corticosteroid use among our patients despite

Table 2

Medication requirements pre- and postoperatively

Preoperative,
n (%)

Salicylate
8 (31)
Biologic
8 (31)
Immunomodulator 14 (54)
Steroid
18 (69)
None
3 (12)

Postoperative,
n (%)

P value

5
8
8
3
7

.52
1
.16
,.0001
.29

(19)
(31)
(31)
(12)
(27)

The American Journal of Surgery, Vol -, No -, - 2014

the known deleterious effects on linear growth velocity,

cosmetic changes, bone loss, and development of dependency and resistance. In addition, acknowledging the
efficacy of immunomodulators for maintenance therapy,
these medications may cause serious treatment-limiting
adverse effects including myelosuppression, pancreatitis,
and hepatoxicity, and in young males, the risk of hepatosplenic T-cell lymphoma, a rare but uniformly fatal complication.15 Given the chronic nature of CD as well as the risks
associated with these medications, our series provides
promising evidence that early operative intervention is a
useful strategy in these children by decreasing long-term
medication requirements.
Although intestinal resection of inflamed bowel in
children and adolescents with CD is certainly not a cure,
resection of the affected isolated terminal ileum is considered
an integral part of our therapeutic armamentarium. The most
common indications for surgical intervention in our patients
included stricture, abscess, enteroenteral fistula, obstruction,
and perforation. Adherence to a treatment strategy that favors
surgical avoidance can lead to undue delay of surgical
intervention. This delay can result in increased rates of septic
and infectious complications in the setting of intestinal
perforation, enteroenteral fistula, and abscess.16 A large proportion (42.3%) of our study population underwent emergent
ileocecal resections. Based on previously published data, we
hypothesized that we would see lower complication rates
among those patients who underwent elective resection
before the development of perforation, fistula, or abscess.17
When evaluating a group of children with intra-abdominal
abscess, Garcia et al17 observed a significant reduction in
recurrent intra-abdominal abscesses among those patients
treated with surgical drainage and bowel resection (12%)
compared with treatment with medical therapy or percutaneous drainage alone (56%). In our series, we did not see
higher complication rates associated with emergent resection. This may be related to the small sample size; we had
only 11 patients in the emergent group and 15 in the elective
group. It would likely require a larger patient cohort to
demonstrate a true difference in complication rates.
The mechanism of growth failure in CD is multifactorial
with malnutrition, active inflammation, and corticosteroid
therapy all contributing.18 When considering that the pubertal growth spurt accounts for 16% of adult height and a
doubling of body weight,5 it becomes obvious that these
nutritional demands are difficult to meet in a patient with
CD and may lead to delayed puberty. In general, between
age 2 and puberty, children gain 2 kg/year. Growth is not
considered abnormal as long as a child remains on a given
growth curve. For example, if a child is born at the fifth
percentile for weight and stays at the fifth percentile
throughout childhood and adolescence then that childs
growth is considered normal. Our data demonstrate that in
children with CD, mean percentile was around the 50th
percentile before the onset of CD and decreased to the 19th
percentile at the time of diagnosis. These data suggest that
these children did not remain on a normal growth curve;

however, medical and surgical therapy helped to bring the

children back to their original percentile, suggesting they
were back on their normal growth curve. Active and relapsing
disease during the years preceding and following puberty can
arrest puberty. Inducing remission medically, surgically, or
through a combination of treatments is critical because of
the narrow window of opportunity for growth. Catch-up
growth will occur only when intervention is instituted before
epiphyseal closure; this frequently occurs later in CD
because of pubertal delays.19 Timely bowel resection has
been shown to induce remission and can be associated with
postoperative catch-up growth,18,19 similar to the data presented here. Surgical resection also affords these patients a
steroid-free interval, allowing for increases in weight and
height.20 We observed a statistically significant increase in
weight based on age in our patients from the 29th percentile
at resection to the 56th percentile 3 years later. We observed a
similar trend in height with our patients crossing from the
39th percentile to the 51st at 3 years. We attribute the
improvement in both weight and height primarily to surgical
intervention and elimination of corticosteroid therapy.
Despite intestinal resection of CD isolated to the terminal
ileum, concerns remain about recurrence. Postoperative
clinical recurrence rates have been reported to approach
60% at 5 years in pediatric CD patients.6,21 Despite these reported high recurrence rates, the majority of our patients reported sustained subjective improvement at least 2.5 years
after intestinal resection. Additionally, many patients experienced a reduction in number and/or dosage of medication;
however, some type of suppressive medical therapy was
continued in all but 4 patients who were able to stop all medications. While some patients likely had persistent symptoms
of their CD, others continued pharmacotherapy for maintenance therapy. Offering no therapy after resection results in
an unacceptably high rate of recurrence.21 As many as 25%
of adult patients undergoing bowel resection for CD require
reoperation for recurrent disease within 3 years of the initial
surgery.22 We observed a much lower rate of recurrent CD
requiring surgical reintervention in our adolescent population. Only 1 patient 5 years after her initial ileocolic resection
required reoperation for fistulizing disease involving the
prior operative site. This low rate of recurrence observed in
our series is likely the result of both our limited follow-up
time (median 2.5 years) as well as the continuation of suppressive medical therapy with salicylates, biologics, and immunomodulators postoperatively.
Limitations of this study include those inherent to
conducting a retrospective analysis at a tertiary referral
center. Data for some variables, particularly growth parameters, were not available for all patients at 3 years. The
study was also limited by the relatively short follow-up as
many of our patients transitioned to adult care. Recognizing
these limitations, these data offer some evidence to the
potential benefits of operative intervention.
We found that for adolescent patients presenting with
isolated CD involving the terminal ileum, segmental resection was associated with sustained subjective improvement

A.M. Kulungowski et al.

Operative treatment of ileal Crohns disease in adolescents

during a critical time of physical and psychosocial development. Surgical resection around the pubertal growth spurt
allowed our patients a period of catch-up growth in terms of
both height and weight. Medication reduction, specifically
providing a corticosteroid-free interval, likely contributed to
this improved growth. We also identified a very low percentage (3.8%) of patients who required an additional surgical
resection, differing from previously reported series, perhaps
related to the ongoing multidrug medical therapy postoperatively. Based on our experience, early operative intervention for isolated ileocecal CD may be a valid treatment
option in the pediatric population. We recommend that in
children with isolated ileocecal CD who do not experience
adequate growth with medical therapy alone, referral for
surgical resection should be made.

References
1. Beattie RM, Croft NM, Fell JM, et al. Inflammatory bowel disease.
Arch Dis Child 2006;91:42632.
2. Diefenbach KA, Breuer CK. Pediatric inflammatory bowel disease.
World J Gastroenterol 2006;12:320412.
3. Sandborn WJ, Present DH, Isaacs KL, et al. Tacrolimus for the treatment of fistulas in patients with Crohns disease: a randomized,
placebo-controlled trial. Gastroenterology 2003;125:3808.
4. Benchimol EI, Fortinsky KJ, Gozdyra P, et al. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international
trends. Inflamm Bowel Dis 2011;17:42339.
5. Kelsen J, Baldassano RN. Inflammatory bowel disease: the difference
between children and adults. Inflamm Bowel Dis 2008;14(Suppl 2):
S911.
6. Hyams JS, Markowitz J, Otley A, et al. Evaluation of the pediatric
Crohns disease activity index: a prospective multicenter experience.
J Ped Gastroenterol Nutr 2005;41:1621.
7. Benchimol EI, Guttmann A, To T, et al. Changes to surgical and hospitalization rates of pediatric inflammatory bowel disease in Ontario,
Canada (1994-2007). Inflamm Bowel Dis 2011;17:215361.

8. Langholz E, Munkholm P, Krasilnikoff PA, et al. Inflammatory bowel

diseases with onset in childhood. Clinical features, morbidity, and
mortality in a regional cohort. Scand J Gastroenterol 1997;32:13947.
9. Lamber B, Lemberg DA, Leach ST, et al. Longer-term outcomes of
nutritional management of Crohns disease in children. Dig Dis Sci
2012;57:21717.
10. Hyams J, Crandall W, Kugathasan S, et al. Induction and maintenance
infliximab therapy for the treatment of moderate-to-severe Crohns
disease in children. Gastroenterology 2007;132:86373.
11. Hyams JS, Lerer T, Mack D, et al. Outcome following thiopurine use
in children with ulcerative colitis: a prospective multicenter registry
study. Am J Gastroenterol 2011;106:9817.
12. Griffiths A, Koletzko S, Sylvester F, et al. Slow-release 5-aminosalicylic aid therapy in children with small intestinal Crohns disease.
J Pediatr Gastroenterol Nutr 1993;17:18692.
13. Modigliani R, Mary JY, Simon JF, et al. Clinical, biological, and endoscopic picture of attacks of Crohns disease. Evolution on prednisolone. Groupe dEtude Therapeutique des Affections Inflammatoires
Digestives. Gastroenterology 1990;98:8118.
14. Greenberg GR, Feagan BG, Marin F, et al. Oral budesonide as maintenance treatment for Crohns disease: a placebo-controlled, doseranging study. Canadian Inflammatory Bowel Disease Study Group.
Gastroenterology 1996;110:4551.
15. Sherlock ME, Griffiths AM. Medical therapy for pediatric inflammatory bowel disease. Curr Gastroenterol Rep 2012;14:16673.
16. Hulten L. Surgical treatment of Crohns disease of the small bowel or
ileocecum. World J Surg 1988;12:1805.
17. Garcia JC, Persky SE, Bonis PA, et al. Abscesses in Crohns disease:
outcome of medical versus surgical treatment. J Clin Gastroenterol
2001;32:40912.
18. Savage MO, Beattie RM, Camacho-Hubner C, et al. Growth in
Crohns disease. Acta Paediatr Suppl 1999;88:8992.
19. McLain BI, Davidson PM, Stokes KB, et al. Growth after gut resection
for Crohns disease. Arch Dis Child 1990;65:7602.
20. Besnard M, Jaby O, Mougenot JF, et al. Postoperative outcome of
Crohns disease in 30 children. Gut 1998;43:6348.
21. Baldassano RN, Han PD, Jeshion WC, et al. Pediatric Crohns disease:
risk factors for postoperative recurrence. Am J Gastroenterol 2001;96:
216976.
22. Heimann TM, Greenstein AJ, Lewis B, et al. Prediction of early symptomatic recurrence after intestinal resection in Crohns disease. Ann
Surg 1993;218:2948.