Glass 2016
Glass 2016
Glass 2016
a r t i c l e in f o abstract
Appendicitis represents the most common abdominal surgical emergency in the pediatric age group.
Keywords: Despite being a relatively common condition, the diagnosis of appendicitis in children can prove to be
Appendicitis challenging in many cases. The goal of this article is to review the predictive utility for presenting signs
Diagnosis and management and symptoms, laboratory tests, and imaging studies in the diagnostic work-up of appendicitis.
Clinical pathway Furthermore, we sought to explore the predictive utility of composite measures based on multiple
sources of diagnostic information, as well as the utility of clinical pathways as a means to streamline the
diagnostic process.
& 2016 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1053/j.sempedsurg.2016.05.001
1055-8586/& 2016 Elsevier Inc. All rights reserved.
C.C. Glass, S.J. Rangel / Seminars in Pediatric Surgery 25 (2016) 198–203 199
Laboratory data specificities were found across the 26 component studies, ranging
from 44% to 88% and 90% to 97%, respectively, suggesting that the
White blood cell count and absolute neutrophil count pooled results may not necessarily be generalizable to individual
The utility of white blood cell counts (WBC) and absolute hospitals (Table 1).22–26
neutrophil counts (ANC) in the diagnosis of appendicitis has been Despite the benefits of US, the diagnostic utility of the modality
well studied. Elevated WBC and ANC counts can be found in may be greatly limited by operator experience and lack of avail-
several conditions associated with abdominal pain in children, and ability at many hospitals during nights, weekends and holi-
up to 20% of patients with pathology-proven appendicitis may days.22,27 Several studies have attempted to explore patient-
present without a leukocytosis.10 It is therefore not surprising that related factors that may contribute to the high variability in
the reported sensitivity and specificity for WBC in the diagnosis of diagnostic accuracy for US reported in the literature. In a pro-
appendicitis varies widely among studies, ranging from 70% to 80% spective study of 263 patients, Schuh et al.28 reported that obesity
and 60% to 68%, respectively.11–15 Similarly, the reported sensitivity and low clinical suspicion were independent predictors for a non-
and specificity for ANC in diagnosing appendicitis has also varied diagnostic ultrasound in children with abdominal pain. In a
widely, ranging from 59% to 97% and 51% to 90%, respectively.1,11,15 prospective study of 1810 children evaluated with abdominal pain
The wide range in reported predictive value for these laboratory in the emergency department (ED), Bachur et al.29 reported that
tests likely reflects the wide variation in pre-test probability the sensitivity of US increased with the duration of abdominal
among hospitals where these tests were performed. In this regard, pain, from 81% in patients presenting with less than 12 h of pain to
the predictive value of WBC for diagnosing appendicitis is likely to 96% in children with greater than 48 h of pain. The evolution of
be very different for all children evaluated in the ED vs. those pain (and therefore inflammatory change which may be visualized
where the WBC is only obtained after a surgeon evaluates a child on US) may underlie the reported efficacy of serial abdominal US
with RLQ pain and feels that the likelihood for appendicitis is high. as a strategy to increase its diagnostic accuracy.30 In a prospective
study of 294 children, Schuh et al. reported that interval ultra-
sound in patients with an equivocal initial study and ongoing
C-reactive protein
clinical suspicion was associated with a sensitivity and specificity
The reported sensitivity and specificity for C-reactive protein
of 97% and 91%, respectively, compared to 80% and 39%, respec-
(CRP) in the diagnosis of appendicitis ranges between 58% and 93%
tively, for the initial ultrasound. The authors reported a negative
and 28% and 82%, respectively.1,15,16 A total of 2 studies have
appendectomy rate of 4.8% and a mean time from the initial
reported an association between disease severity and CRP level. In
ultrasound to the interval study of 9.2 h.30
a prospective study of 78 patients, Chung et al.17 reported that
Other studies have attempted to explore operator-dependent
patients with perforated appendicitis had a significantly higher
factors associated with improved diagnostic accuracy. In a retro-
mean CRP compared to patients without perforated appendicitis
spective study of 1009 patients, Trout et al.31 reported that
(92 vs. 31 mg/L). In a retrospective study of 200 patients, Grönroos
dedicated pediatric sonographers were able to identify the appen-
et al.10 reported that higher levels of CRP were associated with
dix at a significantly higher rate compared to sonographers who
perforated appendicitis and abscess formation. While CRP may be
imaged both pediatric and adult patients (39% vs. 19%). In a
helpful in identifying patients who may have complicated disease
prospective multi-center study of 2625 patients, Mittal et al.
(and those who may benefit from additional cross-sectional
reported a pooled sensitivity and specificity for ultrasound of
imaging), its predictive value for appendicitis is limited as a sole
72.5% and 97%, respectively. When the investigators examined
diagnostic test. Furthermore, studies have not demonstrated any
ultrasound performance at the level of individual hospitals, they
additional predictive value when obtaining a CRP in addition to a
found that sensitivity was higher at hospitals with more frequent
WBC count compared with obtaining a WBC count alone.18
utilization (78% at hospitals that used ultrasound in Z 89% of cases
of suspected appendicitis vs. 35% at hospitals that used US in less
Imaging studies than 10% of cases), suggesting that increased utilization may be
important for negotiating the “learning curve” associated with
Ultrasound effective US utilization. In contrast, specificity was relatively high
Due to the relatively poor predictive value associated with across all hospitals (96–99%), suggesting improvement with expe-
clinical and laboratory data, imaging tests are often employed as a rience was most important for the ability to diagnose appendicitis
diagnostic adjunct for children with suspected appendicitis. In this when present, rather than avoiding a false positive (and operating
regard, abdominal ultrasound is relatively inexpensive in compar- on such findings) in the absence of appendicitis.26 In a prospective
ison to CT and magnetic resonance imaging (MRI), and requires no cohort study of 2337 patients, Nielsen et al.32 reported that the
sedation, ionizing radiation, or contrast agents.19–21 In a meta- sensitivity and specificity of ultrasound examinations for sus-
analysis of 26 studies including 7448 patients, Doria et al. reported pected appendicitis increased from 67% to 92% and 97% to 98%,
a pooled sensitivity and specificity for ultrasound of 88% and respectively, following implementation of a standardized ultra-
94%, respectively. However, a wide range of sensitivities and sound reporting template.
Table 1
Reported sensitivities and specificities associated with the use of abdominal ultrasound in the diagnosis of appendicitis in children.
Study Patients (n) Study design Sensitivity (95% CI) Specificity (95%)
Garcia Peña et al.23 139 Retrospective cohort 0.44 (0.29–0.59) 0.93 (0.89–0.99)
Doria et al.22,a 7448 Meta-analysis 0.88 (0.86–0.90) 0.94 (0.92–0.95)
Mittal et al.26 2625 Prospective cohort 0.73 (0.59–0.86) 0.97 (0.96–0.98)
Yu et al.24 2643 Meta-analysis 0.87 (0.86–0.88) 0.90 (0.89–0.91)
Weston et al.25 5060 Meta-analysis 0.88 (0.87–0.90) 0.92 (0.91–0.93)
Orth et al.44 81 Prospective cohort 0.90 (0.74–0.94) 0.86 (0.74–0.94)
a
Meta-analysis.
200 C.C. Glass, S.J. Rangel / Seminars in Pediatric Surgery 25 (2016) 198–203
When considering this collective body of literature, variation in terms of defining optimal imaging protocol as well as its role in the
reported predictive value is likely to depend on a complex inter- context of other available diagnostic adjuncts.
play of many factors, some modifiable and others less so. Opti-
mization of diagnostic performance for suspected appendicitis Pediatric appendicitis risk scores
may hinge upon adequate experience and a thorough under-
standing of the negative and positive predictive value of US Composite scores designed to estimate the risk of appendicitis
findings within the context of an institution's own patient pop- in children were developed with the premise that the combined
ulation and sonography experience. Finally, variability in the predictive value of clinical symptoms, physical exam findings, and
predictive value of ultrasound may also be in part due to a lack laboratory data is greater than any of these sources of diagnostic
of consensus around which ultrasound findings have the greatest information considered individually. The 2 most studied scoring
predictive value, as well as the lack of consensus regarding approaches are those reported by Samuel (Pediatric Appendicitis
definitions and criteria for these findings. Score, PAS) and Alvarado (Alvarado score).45,46 The PAS is a 10-
point score comprised of 8 elements which include symptoms,
physical examination findings and WBC data (Table 3A). In their
Computed tomography
original study of 1170 patients, Samuel45 reported a 100% sensi-
Computed tomography has several advantages over other
tivity and 92% specificity for the PAS in diagnosing appendicitis
imaging modalities including ready availability at most institu-
when using a scoring threshold of 6 points or higher. However,
tions, rapid acquisition time, lack of operator dependency, and a
other investigators have not found the PAS to be as reliable. In a
relatively high sensitivity and specificity.33 In a meta-analysis of 26
prospective study of 588 patients, Schneider et al.47 reported a
studies including a total of 2506 patients, Doria et al.22 reported a
sensitivity of 82%, and a specificity of 65% using the same scoring
pooled sensitivity and specificity of 94% and 95%, respectively, with
threshold recommended by Samuel. In another prospective study
relatively little variation in these measures across the pooled
of 246 patients, also using the same scoring threshold, Bhatt
hospitals.34–37 Despite this relatively high diagnostic accuracy,
et al.48 reported a sensitivity of 93% and a specificity of 69%.
concern over ionizing radiation has prompted efforts to minimize
The Alvarado score uses a similar combination of symptoms,
use of CT as the initial diagnostic imaging test, and to explore the
physical examination findings and laboratory data to assign a score
efficacy of radiation-sparing protocols. In a retrospective cohort
on a 10-point scale, but differs from the PAS by the number of
study of 494 children, Callahan et al.38 reported that a 50% dose
points given for leukocytosis and in the assessment of abdominal
reduction in their imaging protocol (median effective dose of
pain on physical exam (Table 3B).46 Alvarado's original study of
4.4 mSv before protocol implementation vs. 2.7 mSv following
305 patients reported a mean score of 7.7 in patients with
implementation) was not associated with a decrease in either
appendicitis and 5.2 in patients without appendicitis. Based on
sensitivity or specificity of CT in the diagnosis of appendicitis (pre-
these mean values, Alvarado recommended patients with a score
implementation—98% and 93%, respectively, vs. post-implementa-
of a 5–6 should be observed and those with a score of 7 or higher
tion—97% and 94%, respectively). In another retrospective analysis
undergo surgery for appendicitis.46 In a prospective study of 588
of 98 patients with suspected appendicitis, Fefferman et al.39
patients, Schneider et al.47 reported a sensitivity of 72% and
reported that targeted CT imaging limited to the regions below
specificity of 81% for the diagnosis of appendicitis using the same
the lower pole of the right kidney significantly reduced radiation
threshold score for diagnosing appendicitis. In another prospective
exposure without compromising CT sensitivity or specificity.
analysis of 287 patients using the same threshold score, Mande-
ville et al.49 reported a sensitivity of 76% and specificity of 72%.
Magnetic resonance imaging The collective body of evidence to date would suggest that
Over the last decade, an increasing number of studies have appendicitis risk scores are neither sensitive nor specific enough to
reported on the use of MRI in the diagnosis of appendicitis. MRI be considered effective diagnostic tools in isolation. The finding of
does not expose the child to ionizing radiation and has a reported relatively low specificity found in many studies for both the PAS
accuracy greater than ultrasound and approaching that of CT. In and Alvarado score is particularly noteworthy as many children
the largest published experience to date which included 510 without appendicitis will meet the scoring threshold and poten-
patients, Kulaylat et al.40 reported a sensitivity and specificity of tially be at risk for a negative appendectomy. With this consid-
96.8% and 97.4%, respectively, and a negative appendectomy rate of eration, many have proposed the use of risk scores as a screening
3.1%. The sensitivity and specificity for MRI reported in other tool to identify patients who might benefit from further imaging or
studies have also been relatively high, ranging from 96% to 100% serial abdominal examinations prior to appendectomy.46–52
and 96% to 99%, respectively (Table 2).41–44 Despite its relatively
high diagnostic accuracy, MRI has several disadvantages including Predictive value of combining laboratory and ultrasound data
lack of availability at many hospitals, lengthy image acquisition
time, and relatively high cost compared to CT and US. Furthermore, In an attempt to explore the combined predictive value of
MRI is generally not considered appropriate for younger children laboratory and ultrasound data together, Anandalwar et al.53
and those who cannot lie still for the duration of the test.40 The retrospectively reviewed 845 patients who underwent surgical
role of MRI in the diagnosis of appendicitis is still evolving, both in consultation, laboratory evaluation (WBC) and US for suspected
Table 2
Reported sensitivities and specificities associated with the use of magnetic resonance imaging (MRI) in the diagnosis of appendicitis in children.
Study Patients (n) Study design Sensitivity (95% CI) Specificity (95%)
41
Moore et al. 208 Prospective cohort 0.98 (0.87–0.999) 0.97 (93–99)
Johnson et al.42 42 Prospective cohort 1 (0.93–1) 0.98 (0.94–1)
Koning et al.43 364 Retrospective Cohort 0.96 (0.91–0.98) 0.96 (0.92–0.098)
Orth et al.44 81 Prospective cohort 0.93 (0.78–0.99) 0.98 (0.89–1)
Kulaylat et al.40 510 Prospective cohort 0.97 (0.92–0.99) 0.97 (0.95–0.99)
C.C. Glass, S.J. Rangel / Seminars in Pediatric Surgery 25 (2016) 198–203 201
Pediatric Appendicitis Scorea Alvarado scoreb Predictive value of combining clinical scores with ultrasound findings
Cough/percussion/hopping tenderness Rebound pain (1 point) Other investigators have attempted to characterize the com-
in the right lower quadrant bined predictive value of appendicitis scoring systems with sono-
(2 points)
Anorexia (1 point) Anorexia (1 point)
graphic findings. In a retrospective study of 728 children
Pyrexia (1 point) Pyrexia (4 37.3) (1 point) undergoing US for suspected appendicitis, Bachur et al.54
Nausea/emesis (1 point) Nausea/emesis (1 point) used the pediatric appendicitis score as described by Samuel to
Right lower quadrant tenderness Right lower quadrant tenderness classify patients into low (0–3 points), medium (4–6 points) and
(2 points) (2 points)
high (7–10 points) risk groups. Ultrasound exams were categorized
Migration of pain (1 point) Migration of pain (1 point)
Leukocytosis (WBC Z 10,000) Leukocytosis (WBC as positive, negative or equivocal based on the final impression
(1 point) 4 10,000) (2 points) dictated by the radiologist. The positive predictive value of ultra-
Polymorphonuclear neutrophilia Left Shift (neutrophils sound was 73% in the low-risk group (27% false positive rate) and
(1 point) 4 75%) (1 point) 97% in the high-risk group, while the negative predictive value of
a
Score of 6 or above is considered diagnostic of appendicitis.
US decreased from 100% in the low-risk group to 81% in the high-
b
Score of 7 or above is considered diagnostic of appendicitis. risk group (19% false negative rate). Furthermore, 45% of patients
with equivocal ultrasound findings in the high-risk group were
confirmed to have appendicitis by pathology. Based on these
findings, the authors recommended that surgeons should proceed
appendicitis. The authors found that 51% of US exams were with caution in committing to an appendectomy when there is
equivocal as defined by both an inability to visualize the appendix discordance between clinical presentation (PAS score) and sono-
and a lack of secondary signs to suggest the presence of appendi- graphic findings.54
citis. The overall rate of appendicitis was 18% for equivocal studies,
but decreased to 3% in the absence of leukocytosis (defined as a Role of clinical pathways
WBC o9000/mL and relative polymorphonucleocyte distribution
o 65%), and increased to 48% when a leukocytosis was present. The goal of a clinical pathway is to standardize care, improve
Laboratory data also increased the diagnostic utility of US when outcomes and reduce resource utilization in carrying out a
primary and secondary findings were reported. The rates of diagnostic or treatment care plan. In the evaluation of a child with
appendicitis associated with primary and secondary findings were suspected appendicitis, clinical pathways have been used to
79% and 89%, respectively, but increased to 91% and 97%, respec- streamline the diagnostic process by incorporating appendicitis
tively, in the presence of a leukocytosis. In the absence of risk scores as a screening tool and providing a standardized
leukocytosis, the risk of appendicitis decreased to less than 50%, framework for selective diagnostic imaging based on initial risk
and represented a cohort where the risk of a negative appendec- assessment.55,56 In a prospective analysis of 196 patients, Saucier
tomy was particularly high (37%). The authors concluded that et al. reported the results of a clinical pathway using the PAS for
combining laboratory and US data could not only identify very initial risk screening and disposition. Patients deemed to be low
high and low-risk patients where further imaging and observation risk (PAS of 1–3 points) were discharged with a follow-up phone
was of low yield, but also patients at particularly high risk for call or admitted to general pediatrics with an alternative diagnosis.
negative appendectomy where further cross-sectional imaging or Patients designated as moderate risk (PAS of 4–7 points) under-
observation was warranted. However, the authors cautioned went ultrasound. If the ultrasound was positive, or if the ultra-
against the generalization of their results on the basis of their sound was negative or equivocal but clinical suspicion remained
reported WBC thresholds and US findings, which may carry high, surgical consultation was obtained for further management.
different risk profiles for appendicitis at different hospitals. Rather, If the ultrasound was negative and clinical suspicion for appendi-
the authors proposed that a similar approach could be adopted at citis was low, the patient was either discharged with a follow-up
Fig. 1. Risk stratification approach for appendicitis based on ultrasound findings and white blood cell count used at the author's institution. The approach is modeled after
that described by Anandalwar et al.53
202 C.C. Glass, S.J. Rangel / Seminars in Pediatric Surgery 25 (2016) 198–203
Fig. 2. Disposition guidelines used at the author's institution based on the risk stratification framework described in Figure 1.
phone call or admitted with an alternative diagnosis. Patients at While preliminary data in the use of MRI for suspected appendi-
high risk (PAS 8–10 points) received a surgery consult to deter- citis is promising, more data is needed to characterize ideal
mine further management. The authors reported that the stand- imaging protocols and the role MRI should play in the context of
ardization of their care pathway resulted in a CT utilization rate of other diagnostic adjuncts. Finally, clinical pathways have the
only 6.6% without compromising their relatively low negative potential to streamline the diagnostic process and reduce cost
appendectomy rate (4.4%).55 and radiation exposure. However, development of such pathways
At the author of this chapter's own institution, we have must take into account a hospital's available resources and
implemented a multi-disciplinary pathway which includes a PAS logistical considerations, and should involve a close collaboration
for initial risk assessment that has been modified to improve the between surgeons, radiologists, and emergency room physicians.
objectivity and consistency of scoring criteria among providers. For
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