Journal of Pediatric Surgery 53 (2018) 42–47

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Journal of Pediatric Surgery

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

Expanding the inclusion criteria for non-operative management of

uncomplicated appendicitis: Outcomes and cost
Steven L. Lee a,b,⁎, Lara Spence a, Kyle Mock a, James X. Wu b, Huan Yan a, Daniel A. DeUgarte a,b
a
Department of Surgery, Harbor-UCLA Medical Center, Torrance, CA
b
Department of Surgery, University of California–Los Angeles, Los Angeles, CA

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

Article history: Background: Carefully selected children with early appendicitis may be managed nonoperatively. However, it is
Received 27 September 2017 unknown whether nonoperative management (NOM) is applicable to all patients with uncomplicated appendi-
Accepted 5 October 2017 citis. The purpose of this study was to evaluate the outcomes of NOM of uncomplicated appendicitis with
expanded inclusion criteria.
Key words: Methods: A prospective, nonrandomized patient-preference study comparing NOM versus laparoscopic appen-
Appendicitis
dectomy (LA) was performed in children with radiographic/clinical evidence of uncomplicated appendicitis.
Nonoperative management
Appendectomy
Results: Demographics, laboratory values, and clinical presentation were similar between the NOM (n = 51) and
Cost-effectiveness LA (n = 32) groups. Initial failure rate was 31%. The outcomes were similar between groups, except that NOM
had fewer days of pain medication. Patients who failed NOM had a longer duration of symptoms prior to
admission. Patients with appendicolith had a failure rate of 50% compared to 24% without appendicolith. The
recurrence rate was 26%. Overall, 51% avoided appendectomy. Costs were similar between NOM and LA.
Conclusions: When expanding the inclusion criteria for children with presumed uncomplicated appendicitis,
NOM was associated with high failure and recurrence rates. These high rates may be because of the inclusion
of patients with complicated appendicitis and patients with an appendicolith. Even in this setting of less-
restrictive exclusion criteria, NOM remained cost neutral.
Level of evidence: LEVEL II (Treatment Study: Prospective Comparative Study).
© 2017 Elsevier Inc. All rights reserved.

Appendicitis is the most common disease requiring urgent surgery
in children [1,2]. For well over a century, appendectomy has been the
standard treatment [3,4]. Laparoscopic appendectomy has now re-
placed open appendectomy as the new standard of care for the treat-
ment of appendicitis [5,6]. Despite a minimally invasive approach,
laparoscopic appendectomy is invasive, requires general anesthesia,
and is associated with postoperative morbidity [7]. Recent studies
have shown that nonoperative management (NOM) for acute appendi-
citis is safe and effective in adults [8–12].
Studies have also shown that NOM for acute appendicitis is medical-
ly safe and effective in children, with a success rate ranging from 92% to
99% [7,13–18]. All of these studies carefully selected patients with early
appendicitis; however, it is unknown whether NOM is applicable to all
patients with uncomplicated appendicitis. The purpose of this study
was to prospectively evaluate the outcomes of NOM of uncomplicated
appendicitis with expanded inclusion criteria.
⁎ Corresponding author at: Harbor-UCLA Medical Center, Department of Surgery and
Pediatrics, Harbor-UCLA, 1000 W. Carson St., Box 461, Torrance, CA 90502. Tel.: +1 310
222 2700; fax: +1 310 533 1841.
E-mail address: slleemd@yahoo.com (S.L. Lee).
1. Materials and methods
A prospective patient-preference cohort study comparing NOM ver-
sus urgent laparoscopic appendectomy for nonperforated appendicitis
was conducted at a single institution, Harbor-UCLA Medical Center
(IRB# 30418-01). Patients presenting to this institution from April
2015 to December 2016 who met the following criteria were eligible
for enrollment: age 3–17 years; ≤ 5 days of abdominal pain; radiograph-
ic evidence of nonperforated appendicitis (ultrasound or CT); evalua-
tion by a surgeon confirming clinical suspicion of nonperforated
appendicitis; willingness to participate. Imaging confirmation of appen-
dicitis was not required if the attending pediatric surgeon diagnosed the
patient with nonperforated appendicitis (pediatric appendicitis
score ≥ 6). Exclusion criteria included: age b 3 years; positive pregnancy
test; history of immunodeficiency or cirrhosis; cognitive impairment;
inability to follow-up; diffuse peritonitis; evidence of severe sepsis/sep-
tic shock on clinical evaluation; intravenous antibiotics within 24 h of
presentation; evidence of intraabdominal abscess greater than 5 cm or
perforated appendicitis on imaging; or clinical concern for perforated
appendicitis. Informed consent was obtained from eligible patients/par-
ents by an attending surgeon or a research resident who was coached in

https://doi.org/10.1016/j.jpedsurg.2017.10.014
0022-3468/© 2017 Elsevier Inc. All rights reserved.
 S.L. Lee et al. / Journal of Pediatric Surgery 53 (2018) 42–47
the consent process using a standardized script to minimize bias. The
consent process was standardized and parents/legal guardians made
the final treatment choice and consented to participate in the study. As-
sent of all patients older than 7 years was also obtained.
Patients choosing NOM received intravenous antibiotics (ceftriax-
one/metronidazole or ciprofloxacin/metronidazole if penicillin allergic).
Patients with clinical improvement were started on liquids and had
their diet advanced. When tolerating a diet and having completed at
least one dose of intravenous antibiotics, patients were switched to
oral amoxicillin-clavulanate, ciprofloxacin/Flagyl, or cefdinir/Flagyl. Pa-
tients were subsequently discharged with oral antibiotics to complete a
10-day total course. Patients were instructed to resume activities as tol-
erated, with resumption of strenuous activities when desired.
A patient showing signs of clinical worsening or failure to show clin-
ical improvement within 24 h was considered treatment failure and re-
sulted in prompt laparoscopic appendectomy. After discharge, any
patient who returned with clinical findings consistent with recurrent
appendicitis was given the option of laparoscopic appendectomy or an
additional trial of intravenous antibiotics or change in antibiotics regi-
men. Follow-up was performed at 10 to 14 days, 30 days, 3 months,
and 1 year after discharge.
Surgical management consisted of prompt initiation of intravenous
antibiotics and timely laparoscopic appendectomy. Patients were
discharged based on clinical parameters: afebrile, tolerating a diet, and
pain adequately controlled. Patients were instructed to resume activi-
ties as tolerated, with resumption of strenuous activity 2 weeks postop-
eratively. All patients were scheduled for a 1 to 2 week follow-up in
clinic. Follow-up was performed at 30 days, 3 months, and 1 year by a
research resident by phone and electronic medical record.
The primary outcome was the initial failure rate of NOM. Secondary
outcomes included: the rate of complicated appendicitis; length of
hospitalization; days to normal activity; days of pain medication
(including acetaminophen, nonsteroidal inflammatory drugs, and
opioids); PedsQL™ quality of life score at 30 days; and recurrent appen-
dicitis during the follow-up period. Recurrence was defined as a diagno-
sis of appendicitis after completing initial course of antibiotics.
Complicated appendicitis was defined as the intraoperative finding of
gangrene, perforation, or abscess. Perforated appendicitis was defined
as the presence of a hole in the appendix or appendicolith present in
the peritoneal cavity.
The percentage of patients experiencing a complication was
compared. Complications included negative appendectomy, the need
for intraoperative drain placement, the development of an
intraabdominal abscess, postoperative ileus prolonging admission,
representation to the emergency department for pain control, readmis-
sion or reoperation, diarrhea resulting in termination of antibiotics at
7 days (instead of 10 days), superficial surgical site infection, or other
wound complication.
Variables were described with medians and interquartile ranges
(IQRs) or frequencies and percentages where appropriate and com-
pared using Fisher's exact test, χ 2 test, or Wilcoxon Rank-Sum test. All
tests were 2-sided with p b 0.05 used to determine statistical signifi-
cance. Multivariate analysis to identify predictors of initial failure of
nonoperative therapy was performed using logistic regression analysis.
Analysis was performed using JMP Pro 11.0.0 statistical software.
Using decision-tree software, we analyzed the cost-effectiveness of
NOM of nonperforated appendicitis without routine interval appendec-
tomy versus conventional management with laparoscopic appendecto-
my using a previously constructed model [19]. Early failure rate,
recurrence rate, length of stay after NOM, length of stay after routine
operative management, and quality of life scores were abstracted from
the results of the current study. Remaining clinical probabilities are
based upon review of the literature, as described previously [19]. Direct
medical costs were abstracted from the Healthcare Cost and Utilization
Project Kids Inpatient Database, Medicare Physician Fee schedule, and
wholesale costs of antibiotics obtained from UpToDate® drug
43
information. Areas of model uncertainty were assessed using one-way
sensitivity analysis.
2. Results
Since enrollment began, 83 patients were identified who met the
inclusion criteria and agreed to participate; 51 chose NOM and 32
chose surgery (Fig. 1). Baseline characteristics were similar between
the two groups (Table 1).
Table 2 summarizes the outcomes for all patients. Of the patients
who selected NOM, 16 (31%) failed to improve and underwent laparo-
scopic appendectomy. The median time to appendectomy for patients
who failed was longer than patients who preferred initial surgery
(31 h vs. 9 h, p b 0.001). Of the 16 patients who had an initial failure
of NOM, 8 had complicated appendicitis (2 with gangrenous appendici-
tis and 6 with perforated appendicitis). Those children failing NOM had
a longer hospital stay (3 [2, 5] vs. 2 [1, 2] days, p b 0.01) but the overall
length of index hospitalization was similar between the NOM and
surgery groups (2 [1, 3] vs. 2 [1, 4] days, p = 0.52). Overall length of
stay for the study period (including all readmissions) was also similar
between NOM and surgery groups (2 [1, 3] vs. 2 [1, 4] days, p = 0.94).
Return to normal activity was similar in the two cohorts despite failure
of NOM in some cases (5 [3, 8] vs. 6 [4, 11]) days, p = 0.32). Patients
undergoing NOM required fewer days of analgesic medication (3 [2, 5]
vs. 5 [4, 9] days, p b 0.001). Quality of life scores (PedsQL™) were similar
between the two groups at 30 days.
Data comparing initial successful versus failed NOM are summarized
in Table 3. Patients who failed NOM had a longer median duration of
symptoms (24 [24, 48] vs. 48 [24, 48] h, P = 0.02). There were no
differences in age, sex, and admission laboratory data between patients
who had initial success with NOM and those who failed. Patient who
had initial failure of NOM had a significantly longer hospital stay, longer
days of analgesic and longer return to normal activity than those who
had initial success with NOM (p b 0.005). Patients in the NOM cohort
with evidence of appendicolith on imaging had an initial failure rate of
50% (7/14) compared to 24% of patients (9/37) without an
appendicolith (p = 0.07). Multivariate analysis failed to identify any
significant predictors of failure.
Median follow-up period of electronic medical records for all pa-
tients was 13 months [IQR 7, 19]. The percentage of patients lost to
phone follow up was 5% (4/83) at 2 weeks, 13% (11/83) at 30 days,
33% (28/33) at 3 months, and 40% (21/52) at 1 year. The percentage of
patients with a complication was similar between the surgery group
(19%; 6/32) and the nonoperative group (18%; 9/51). In the surgery
group, one patient developed an intraabdominal abscess, had a
prolonged hospital course, and was readmitted for abdominal pain.
Two patients had a postoperative ileus. One patient was found to have
early appendicitis at the time of surgery, but final pathology demon-
strated a normal appendix. One developed a superficial surgical site
infection. Another patient was readmitted for constipation. In the non-
operative failure group, one underwent placement of an intraoperative
drain. One had a reoperation with lysis of adhesions for a small bowel
obstruction. One developed blisters along his incision. In the nonopera-
tive initial-success group, three patients returned to the emergency
room for better pain control. One was readmitted for constipation.
Two patients had their antibiotics stopped in follow up clinic because
they had diarrhea and had completed at least 7 days of antibiotics.
The recurrence rate for patients with initial success following
nonoperative therapy was 26% (9/35 patients) with a median time to
recurrence of 2 months [IQR: 1, 6]. One of the nine recurrences was
successfully treated with another course of antibiotics, and the remain-
ing 8 were treated with laparoscopic appendectomy. For those patients
who underwent a laparoscopic appendectomy, 1 was treated at an
outside hospital and 7 returned to our institution and were found to
have uncomplicated appendicitis. Overall, 26 of 51 patients who
44 S.L. Lee et al. / Journal of Pediatric Surgery 53 (2018) 42–47

Fig. 1. Flow diagram of the diagnosis and management of children treated for appendicitis.

underwent nonoperative therapy (51%) avoided appendectomy during 3. Discussion

our study period.
Based upon the clinical probabilities from our data set (initial failure The clinical severity of appendicitis varies greatly between patients
rate = 31%; recurrence rate = 26%), NOM without interval appendecto- with early acute appendicitis on one end of the spectrum and delayed
my had an expected cost of $9384/patient, which was similar to opera- presentation with perforation and phelgmon/abscess on the other.
tive management ($10,637/patient). When breaking down the cost of Patients presenting in delayed fashion with perforated appendicitis
NOM, successful initial NOM without recurrence cost $4008/patient, with associated phlegmon or abscess are generally managed
which was less than both initial failure of NOM ($14,646/patient) and nonoperatively with intravenous antibiotics and percutaneous drainage
successful initial NOM with recurrence ($15,589/patient). One-way of the abscess as indicated [20]. Patients with early perforated appendi-
sensitivity analysis revealed that operative management becomes the citis and diffuse peritonitis should be resuscitated with intravenous
preferred strategy if the recurrence rate of appendicitis after fluids, administered intravenous antibiotics, and undergo urgent appen-
nonoperative management exceeds 41.7%. dectomy [21]. Early appendicitis has traditionally been treated with ap-
pendectomy until recently where NOM has been shown to be highly
successful [13–18]. However, many patients with appendicitis fall in
the middle of this spectrum and do not present with early appendicitis
or clear evidence of perforation and it is uncertain whether these
Table 1 patients can be treated with NOM. The purpose of this study was to
Demographic data comparing patients treated with nonoperative management. prospectively evaluate the outcomes of NOM of uncomplicated appen-
NOM Appendectomy P-value dicitis with expanded inclusion criteria. We observed a high initial
(n = 51) (N = 32) failure rate when expanding the inclusion criteria for NOM. Other
Age (years) 10 [7, 13] 11 [8, 15] 0.28 studies enrolled relatively few patients of those evaluated and often
Male Sex (%) 30 (59%) 17 (53%) 0.65 applied strict exclusion criteria (e.g. WBC b 18; CRP ≤ 40, appendiceal
Body Mass Index (kg/m2) 19 [17, 24] 19 [16, 24] 0.61 diameter ≤ 1.1 cm) [Minecci] or only included patients with ill-defined
Latino (%) 44 (86%) 25 (78%) 0.33 ‘uncomplicated’ appendicitis [Tanaka, Steiner]. In our study, we
Hours of symptoms 24 [24, 48] 24 [24, 48] 0.72
observed successful NOM in patients with WBC count as high as 27.1
Pain score 7 [5, 8] 6 (4, 8) 0.31
Tmax 37.5 [37.1, 38.2] 37.2 [37, 38] 0.11 × 103 per μL, appendiceal diameter as large as 16 mm, and symptoms
WBC (×103 per μL) 13 [13, 18] 14 [11, 18] 0.47 as long as 96 h of pain. We also included patients without imaging
Neutrophil % 79 [73, 84] 80 [69, 84] 0.90 confirmation but a high clinical suspicion for appendicitis (pediatric
Sodium (mmol/L) 136 [134, 138] 136 [135, 138] 1.00
appendicitis score ≥ 6) as is routinely performed in practice. Our results
Appendix Diameter (mm)a 9 [7, 12] 10 [8, 14] 0.24
Appendicolith (%) 14 (27%) 12 (38%) 0.31 are thus more likely to be applicable to the general population including
Pediatric Appendicitis Score 7 [5, 8] 7 [6, 8] 0.12 settings other than children's hospitals.
Data are shown as median [interquartile range] or as number [percent].
Given our broad inclusion criteria, it is not surprising that our rates of
a
Data on appendiceal diameter were limited to only 41 patients in the NOM group and complicated appendicitis were higher than reported in other studies.
29 patients in the surgery group. While 50% (8/16) of patients who failed initial NOM had complicated
 S.L. Lee et al. / Journal of Pediatric Surgery 53 (2018) 42–47 45

Table 2
Outcome data comparing patients treated with nonoperative management (NOM) versus appendectomy.

Trial of Antibiotics Surgery p-valuea

Initial Success (n = 35) Initial Failure (n = 16) Total (n = 51) Total (n = 32)

Complicated n/a 8 (50%) 8 (16%) 10 (31%) 0.09

Perforated n/a 6 (38%) 6 (12%) 3 (9%) 0.41
Days of Index Hospitalization 2 [1, 2] 3 [2, 5] 2 [1, 3] 2 [1, 4] 0.52
Days of Pain Medicationb 2 [1, 3] 7 [4, 8] 3 [2, 5] 5 [4, 9] b0.0001
Days to Normal Activityc 4 [2, 6] 9 [7, 11] 5 [3, 8] 6 [4, 11] 0.32
PedQL QOL scored 100 [99, 100] 100 [99, 100] 100 [99, 100] 100 [95, 100] 0.45
Recurrence 9 (26%) n/a n/a n/a n/a
Time to Recurrence (months) 2 [1, 6] n/a n/a n/a n/a
Days of Overall Hospitalization n/a n/a 2 [1, 3] 2 [1, 4] 0.94
Cost per patient $4008 $14,646 $9384 $10,637 n/a

Data are shown as median [interquartile range] or as number [percent].

a
p-values are comparing the totals of each cohort.
b
Pain medication included acetaminophen, nonsteroidal inflammatory drugs, and opioids.
c
Number of days to normal activity was defined as the number of days from the time of discharge until patient was ready to return to school or work and resume physical education or
activity.
d
Quality of life score at 30 days utilizing PedsQL™ was limited to only 30 patients in the NOM group (11 patients in failure and 19 in the success) and 17 patients in the surgery group.

appendicitis, the overall rates of complicated appendicitis trended appendicolith, all were successfully managed nonoperatively but 3
lower in the NOM than the surgery group (16% and 31%; p = 0.09). (60%) ultimately had appendectomy (1 with recurrent appendicitis, 1
This finding suggests that some patients with complicated appendicitis with recurrent abdominal pain, and 1 owing to parent request). Con-
were successfully treated with antibiotics alone. Since complicated versely, we found that the presence of an appendicolith was not associ-
appendicitis is a diagnosis made at the time of appendectomy, we ated with an increased risk of recurrence. Unlike Mahida and colleagues
cannot confirm this statement nor can we determine how many who halted enrollment of children with an appendicolith owing to a
patients with complicated appendicitis were successfully treated with 60% (3/5) initial failure rate, we do not feel that the presence of an
NOM. Similar overall rates of complicated appendicitis between the appendicolith is an absolute contraindication for NOM [22]. Parents
two arms also suggested that patients likely presented with complicat- and patients, however, must be carefully counseled that the risk of fail-
ed appendicitis and did not progress to complicated appendicitis during ure may be higher and more than 50% of patients will likely require an
the period of observation on antibiotics. Another possibility is that the appendectomy.
patients and/or surgical team may have been biased to prefer surgery We found an overall recurrence rate of 26% (9 recurrences in 35 pa-
because the child had more pain or was more ill; however, objective tients with initial success), which is consistent with previous studies
baseline demographics were similar between groups. Furthermore, which range from 5% to 29%.[Minneci, Tanaka, Svensson]. We found
patients were offered nonoperative management utilizing a standard- that the median time to recurrence was 60 days. Long-term recurrence
ized approach that would minimize treatment bias. Incidentally includ- is not well known, although Tanaka and colleagues reported a 21% recur-
ing patients with complicated appendicitis in this study highlighted the rence rate with over 4-year follow-up [13]. They also found that the ma-
overlap in clinical presentation between complicated and uncomplicat- jority of recurrences occurred within the first 6 months after initial NOM.
ed appendicitis and the difficulty in distinguishing between the two There are several limitations to this study. The study was initially un-
diagnoses. Also, by including patients with complicated appendicitis, dertaken to determine whether patients with expanded criteria could
our study demonstrated that NOM for such patients had morbidity be safely and successfully managed with expanded inclusion criteria.
that was similar to the surgery group despite a delay in appendectomy. As many of our patients were accepting of higher failure rates with
Our results may have also been influenced by the inclusion of the hope of avoiding surgery, we did not have a threshold failure rate
patients with appendicoliths. The majority of prior studies excluded with which to carry out a power analysis at the inception of the study.
patients with appendicoliths. Svensson and colleagues enrolled 5 As this was our initial experience with nonoperative management of
patients with appendicoliths of 24 children that were randomized to patients with more expanded criteria, we may have been more reluc-
nonoperative management [14]. Of the 5 children with an tant to continue nonoperative management in patients who did not
demonstrate improvement. This may explain a higher failure rate than
reported by other centers, where patients were generally admitted for
Table 3 longer periods of time [Tanaka]. Svensson reported a lower failure rate
Comparison of patients with initial success versus failure of nonoperative management
of 8% in a pilot randomized controlled trial with more expanded inclu-
(NOM).
sion criteria, but their sample size was limited to 24 patients. Our higher
Initial Success Initial Failure p failure rates may also have been influenced by the selection of antibi-
of NOM (n = 35) of NOM (n = 16)
otics (intravenous ceftriaxone/metronidazole followed by and oral
Age 10 [7, 13] 10 [7, 13] 0.85 amoxicillin-clavulanate). Other studies with lower initial failure rates
Male Sex (%) 21 (60%) 9 (56%) 1.00 utilized piperacillin/taxobactam, meropenem/metronidazole, and/or
Body Mass Index 20 [16, 24] 18 [17, 24] 0.99
imipenem intravenously [Tanaka, Minecci, Svensson]; another utilized
Latino (%) 30 (86%) 14 (88%) 0.86
Hours of symptoms 24 [24, 48] 48 [24, 48] 0.02 ciprofloxacin/metronidazole orally [Svensson].
Pain score 7 [4, 8] 8 [6, 8] 0.20 Overall, our study showed that NOM is feasible in all pediatric
Tmax 37.9 [37.2, 38.2] 37.2 [37.0, 38.0] 0.05 patients with suspected uncomplicated appendicitis. However, with
WBC (×103 per μL) 15 [13, 18] 15 [11, 17] 0.28
expanded inclusion criteria only half of the patients were able to avoid
Neutrophil % 79 [76, 84] 79 [65, 86] 0.82
Sodium (mmol/L) 136 [134, 138] 136 [134, 139] 0.68 appendectomy. The high rate of failure and recurrence may be because
Appendix Diameter (mm) 10 [7, 12] 9 [7, 13] 0.64 of the inclusion of patients with complicated appendicitis and patients
Appendicolith (%) 7 (20%) 7 (44%) 0.07 with an appendicolith. Even in this setting of less-restrictive exclusion
Pediatric Appendicitis Score 7 [5, 8] 7 [5, 8] 0.80 criteria, our findings demonstrated no differences in length of hospital-
Data are shown as median [interquartile range] or as number [percent]. ization, quality of life measures at 30 days, morbidity, or cost.
46 S.L. Lee et al. / Journal of Pediatric Surgery 53 (2018) 42–47
Author contributions
Study conception and design: Steven L. Lee; Lara Spence; Kyle Mock;
James X. Wu; Huan Yan; Daniel A. DeUgarte
Acquisition of data: Steven L. Lee; Lara Spence; Kyle Mock; James X.
Wu; Huan Yan; Daniel A. DeUgarte
Analysis and interpretation of data: Steven L. Lee; Lara Spence; Kyle
Mock; James X. Wu; Daniel A. DeUgarte
Drafting of manuscript: Steven L. Lee; Lara Spence; James X. Wu;
Daniel A. DeUgarte
Critical revision of manuscript: Steven L. Lee; Lara Spence; Kyle
Mock; James X. Wu; Huan Yan; Daniel A. DeUgarte
Appendix A. Discussions
Steven Lee, Los Angeles CA
FRANCOIS LUKS (Providence, RI): Great, well, controversial thing.
Great presentation. Two questions. One, you said there was no
statistical significance in outcome between the two groups.
There was a power issue, though, right, so the nonoperative
treatment overall seemed to be a little cheaper but did not
reach statistical significance, so you need to expand that group.
To that effect, I am surprised that you had a low number of surgi-
cal, in the surgical group. Certainly when we did our study we
had a hard time convincing parents to undergo nonoperative
treatment, and so our control group was larger. Could you not
have expanded that? And then the other question is diagnosis.
If you have somebody with 4–5 days of abdominal pain, how
sure were you that they all had appendicitis?
STEVEN LEE: Great questions. Thank you very much. I think you
mentioned first of all cost. We actually ran a pretty extensive
sensitivity analysis. We actually presented the algorithm at last
year's AAP, and just to make a long story short, those costs
were similar overall. With respect to choosing nonoperative
management versus a surgical approach, we had more patients
choose the nonoperative approach, and we tried to do this and
present the data as equally as possible. I don't know where you
all practice, but where we practice a lot of patients are coming
in asking for this, so this is one of the reasons why we tried to
expand the inclusion criteria for nonoperative management.
We really just tried to exclude patients with clearly perforated
appendicitis, large fluid collections on imaging, or diffuse
peritonitis. Those were our main exclusion criteria. Then, as far
as the diagnosis, how sure were we? We had all but one patient
radiographically confirmed. In addition, as best we could, the
two pediatric surgeons involved in the study had to say we're
going to offer this patient an appendectomy. Once we made
that decision, we were pretty convinced the patient had
appendicitis, and then we approached that family for whether
they wanted to try nonoperative management versus
undergoing laparoscopic appendectomy.
YI-HORNG LEE (New Brunswick, NJ): Thank you for this interesting
study. Many of the studies have used the presence of
appendicolith as a criterion for doing operative or nonoperative
therapy, and you mentioned the use of ultrasound as an imaging
modality, and there is an overall trend to decrease the use of CT
scan in these patients. In my personal experience, ultrasound
usage in more than a third of the patients we can't even see the
appendix itself, and it can be nondiagnostic, so how do you tell
the presence or the absence of appendicolith in these patients?
STEVEN LEE: For the appendicolith it was really with imaging how
we determined the presence of appendicolith. In our study 90% of
patients underwent ultrasound findings, and only about
20%–30% had CT scans, so it is with that that we determined
the presence of an appendicolith.
UNIDENIFIED SPEARKER (Miami, FL): We send all our patients
home from the recovery room, and so since your cost analysis
includes a day in the hospital, would the equivalency change if
all your patients were sent home like ours?
STEVEN LEE: Great question. Regarding outpatient management,
we heard a little bit about that earlier with a couple studies.
We are starting to do that as well. We are a safety net hospital,
and we're also incorporating that, but the other thing that
we've also done is to have incorporated outpatient management
for nonoperative, for antibiotics alone, so we're trying to use the
same discharge criteria. That can easily be done. It takes a little
kind of coordinating with the emergency department and our
pediatrics department, but that's the next wave to try to treat
this as an outpatient, both with antibiotics alone or with surgery.
DIANE MCCARTHY (Spokane, WA): You say the cost is similar for
the nonoperative therapy and the laparoscopic therapy. I′m
curious if your nonoperative cost includes those patients who
failed because your cohort is pretty large, and if they went on
to have operation, it is kind of hard to think that the overall
cost is similar.
STEVEN LEE: Right. Our analysis did include those that failed, those
that recurred, and those that had interval appendectomy, so all of
the costs — it was an intention to treat cost analysis, and we used
the cost analysis — the data were used from this study. When we
used our previous studies, we showed similar results, but that's
why we had equal costs.
UNIDENTIFIED SPEAKER: In your opening slide you had a little brief
blurb on acute appendicitis with nonoperative management as if
it were a solved issue, and you went on. In your hospital is it like a
solved issue, and are you offering nonoperative management and
considering a high rate of nonoperative management in that
group, and are you telling families that you have a 50% recurrence
rate, and are they still buying into that for this nonoperative
management group? Because we don't do any operation that
has a 50% failure rate. I mean if I told families, I′m going to do
this operation and by the way it doesn't work 50% of the time, I
′d be run out of town.
STEVEN LEE: Well, first of all, we travel to multiple hospitals, and
we only do nonoperative management ….
UNIDENTIFIED SPEAKER: You'd have to get out of town quick with
a 50% failure rate.
STEVEN LEE: … where we offer a study and in all the other hospitals,
we still consider laparoscopic appendectomy the standard of care.
However, it's very difficult not to answer questions when families
are coming in asking for nonoperative management. We can't just
say that doesn't exist, so that's why we have a higher nonoperative
management rate. It's not a solved issue. That's why we are still
working on this. At our institution we are actually involved in an
adult multi-institutional randomized controlled trial, and part of
the leg work for that study as well as this study was a patient-
centered study. The questions to the patients were what success
rate would you be willing to accept in order to enroll in this
study and the answer was 50% or higher, so they had a 50% chance
of succeeding with antibiotics, they would be willing to participate
in the study, and that was kind of prospective data collection study
in preparation for these studies. I think we have to do a little bit
more adjustment now that we have these data that are all put to-
gether. We were collecting it so we did not have the exact num-
bers, but usually tell families there is about a 15%–20% failure
rate and about a 15%–20% recurrence rate. It's a little bit higher be-
cause we're including more patients than the other previous
studies.
UNIDENTIFIED SPEAKER: I compliment you on your work.
SHAILINDER SHING (Nottingham, UK): Patients who fail the nonoperative
management, did you see any correlation between the presence
of appendicolith and the failure? In other words, if I see on
 S.L. Lee et al. / Journal of Pediatric Surgery 53 (2018) 42–47
ultrasound or CT a big appendicolith, in my experience those are
the ones who perforate and are likely to fail. Do you have any
alternate management plan for those, or did you find any
correlation?
STEVEN LEE: Our numbers were too small to find a correlation.
There was a trend towards a higher failure rate with an
appendicolith versus not having an appendicolith. We did not
specifically look at the size, which is I think what we're alluding
to, which I think is a great idea, but we did not specifically look
at that.
SHAILINDER SINGH: Thank you.
UNIDENTIFIED SPEAKER: Excuse me, how far out have you followed
the nonoperative patients for recurrence of appendicitis? Would
you send your patient out on a safari for six months after you
declare that your nonoperative was a success, tell him he can go
to Africa, not to worry about it?
STEVEN LEE: At this point, I probably would not unless they invited
me to that safari (laughter), but that's a real question. We don't
have the long-term data, and I think with the work of the moder-
ators here up at the podium as well as ongoing trials we need to
figure that out. The one thing to note is most of the studies out
there show that the median recurrence rate is about 60 days, so
when they do recur they seem to recur earlier. In the previous
prospective pilot study in children, there were a number of
patients who did undergo interval appendectomies, and I think
it was like six out of seven that underwent interval appendecto-
my had an obliterated lumen on pathology, so those patients
probably would not have gotten appendicitis again in the future.
I think we still need more data and I think it's ongoing, but thank
you very much. I appreciate all the discussion.
References
[1] Wier LM, Yu H, Owens PL, et al. Overview of children in the emergency department,
2010. Rockville, MD: Agency for Healthcare Research &Quality; 2013.
[2] Barrett ML, Hines AL, Andrews RM. Trends in rates of perforated appendix,
2001–2010. Rockville, MD: Agency for Healthcare Research & Quality; 2013.
[3] McBurney C. Experience with early operative interference in cases of disease of the
vermiform appendix. N Y Med J 1889;50:676–84.
47
[4] Fitz R. Perforating inflammation of the vermiform appendix. Am J Med Sci 1886;92:
321–46.
[5] Jen HC, Shew SB. Laparoscopic versus open appendectomy in children: outcomes
comparison based on a statewide analysis. J Surg Res 2010;161:13–7.
[6] Lee SL, Yaghoubian A, Kaji A. Laparoscopic vs. open appendectomy in children: out-
comes comparison based on age, sex, and perforation status. Arch Surg 2011;146:
1118–21.
[7] Minneci PC, Mahida JB, Lodwick DL, et al. Effectiveness of patient choice in nonoper-
ative vs surgical management of pediatric uncomplicated acute appendicitis. JAMA
Surg 2015;16:1–8.
[8] Di Saverio S, Sibilio A, Giorgini E, et al. The NOTA study (non operative treatment for
acute appendicitis): prospective study on the efficacy and safety of antibiotics
(amoxicillin and clavulanic acid) for treating patients with right lower quadrant ab-
dominal pain and long-term follow-up of conservatively suspected appendicitis.
Ann Surg 2014;260:109–17.
[9] Hansson J, Körner U, Khorram-Manesh A, et al. Randomized clinical trial of antibiotic
therapy versus appendectomy as primary treatment of acute appendicitis in unse-
lected patients. Br J Surg 2009;96:473–81.
[10] Styrud J, Eriksson S, Nilsson I, et al. Appendectomy versus antibiotic treatment in
acute appendicitis: a prospective multicenter randomized controlled trial. World J
Surg 2006;30:1033–7.
[11] Vons C, Barry C, Maitre S, et al. Amoxicillin plus clavulanic acid versus appendecto-
my for treatment of acute uncomplicated appendicitis: an open-label, non-
inferiority, randomized controlled trial. Lancet 2011;377:1573–9.
[12] Varadhan KK, Humes DJ, Neal KR, et al. Antibiotic therapy versus appendectomy for
acute appendicitis: a meta-analysis. World J Surg 2010;34:199–209.
[13] Tanaka Y, Uchida H, Kawashima H, et al. Long-term outcomes of operative versus
nonoperative treatment for uncomplicated appendicitis. J Pediatr Surg 2015;50:
1893–7.
[14] Svensson JF, Patkova B, Almström M, et al. Nonoperative treatment with antibiotics
versus surgery for acute nonperforated appendicitis in children. A pilot randomized
controlled trial. Ann Surg 2014;261:67–71.
[15] Gorter RR, van der Lee JH, Cense HA, et al. Initial antibiotic treatment for acute
appendicitis in children is safe: short-term results from a multicenter prospective
cohort study. Surgery 2015;157:916–23.
[16] Steiner Z, Buklan G, Stackievicz R, et al. A role for conservative antibiotic treatment
in early appendicitis in children. J Pediatr Surg 2015;50:1566–8.
[17] Minneci PC, Sulkowski JP, Nacion KM, et al. Feasibility of a nonoperative manage-
ment strategy for uncomplicated acute appendicitis in children. J Am Coll Surg
2014;219:272–9.
[18] Steiner Z, Buklan G, Stackievicz R, et al. Conservative treatment in uncomplicated acute
appendicitis: reassessment of practice safety. Eur J Pediatr 2017;176:521–7.
[19] Wu JX, Sacks GD, Dawes AJ, et al. The cost-effectiveness of nonoperative manage-
ment versus laparoscopic appendectomy for the treatment of acute, uncomplicated
appendicitis in children. J Pediatr Surg 2017;52:1135–40.
[20] Zhang HL, Bai YZ, Zhou X, et al. Nonoperative management of appendiceal phlegmon
or abscess with an appendicolith in children. J Gastrointest Surg 2013;17:766–70.
[21] Blakely ML, Williams R, Dassinger MS, et al. Early vs. interval appendectomy for
children with perforated appendicitis. Arch Surg 2011;146:660–5.
[22] Mahida JB, Lodwick DL, Nacion KM, et al. High failure rate of nonoperative manage-
ment of acute appendicitis with an appendicolith in children. J Pediatr Surg 2016;51:
908–11.