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DOI 10.1007/s00247-014-3232-5
ORIGINAL ARTICLE
addition to focused US examination of the right lower quad- abscess or appendicolith and the loss of the echogenic
rant, can improve sonographic diagnosis of perforated appen- appendiceal submucosal layer were associated with per-
dicitis in the pediatric population. forated appendicitis.
Several of these earlier studies evaluating the sono-
Keywords Perforated appendicitis . Acute appendicitis . graphic diagnosis of perforated and non-perforated ap-
Appendix . Ultrasound . Children pendicitis in the pediatric population were performed
more than a decade ago. Recent advances in US tech-
nology have allowed for acquisition of more detailed
Introduction and higher-resolution images. Although previous studies
have discussed the association of lower abdominal sono-
Appendicitis is the most common reason for abdominal sur- graphic findings with perforated appendicitis, no study
gery in children [1]. Rapid and accurate diagnosis of appen- has explored the utility of sonographic evaluation of the
dicitis, particularly with respect to the presence or absence of abdomen focusing on liver echotexture, intraperitoneal
perforation, is essential in guiding appropriate management. fluid and the value of combinations of specific sono-
Acute appendicitis is typically treated by appendectomy, graphic findings in the diagnosis of perforated appendi-
whereas perforated appendicitis can be managed conserva- citis. The purpose of our study was to identify sono-
tively with antibiotic therapy followed by delayed appendec- graphic findings that improve the specificity of US in
tomy. Children younger than 5 years are known to have a the diagnosis of perforated appendicitis and demonstrate
higher risk of perforated appendicitis [2]. Because the clinical the value of abdominal sonography in the setting of
distinction between perforated and non-perforated appendici- perforated appendicitis. Our assessment of hepatic
tis is often difficult, especially in the youngest children, im- periportal echogenicity, detailed analysis of the quantity
aging plays an integral role in diagnosis. and quality of intraperitoneal fluid, and formulation of
With concerns regarding childhood radiation expo- select constellations of sonographic findings expands
sure, US is frequently the diagnostic imaging modality upon the literature addressing this important diagnostic
of choice for the initial evaluation of suspected appen- challenge.
dicitis [3]. Ramarajan et al. [4] demonstrated that a
multidisciplinary approach with the staged use of US
supplemented by CT imaging, if necessary, can decrease Materials and methods
radiation exposure while maintaining diagnostic accura-
cy. Perforated appendicitis, however, has repeatedly Our institutional review board approved this study,
been recognized as a potential pitfall in the sonographic which was compliant with the Health Insurance Porta-
diagnosis of appendicitis [3, 5–7]. The perforated ap- bility and Accountability Act. Patient informed consent
pendix can decompress and lose its integrity such that it was waived for this retrospective investigation.
cannot be reliably identified. US visualization of the Pediatric Surgery departmental databases were uti-
normal appendix can also be difficult, with reported lized to retrospectively identify all pediatric patients
rates ranging from 2.4% to 86.2% [8–13]. The diagnosis ages 2–18 years who presented to our university hos-
of perforated appendicitis can be particularly challeng- pital pediatric radiology department between January
ing when the appendix is not visualized, which can 2008 and September 2011 with a chief complaint of
occur in the setting of both perforated appendicitis and abdominal pain and suspected diagnosis of appendici-
a normal appendix. Although many studies have ex- tis. Database A was generated by extracting all pediat-
plored sonographic findings associated with acute ap- ric appendectomy patients evaluated pre-operatively
pendicitis, few investigations discuss specific signs that with abdominal sonography from the Pediatric Surgery
can reliably differentiate perforated appendicitis from clinical database. Database A (n = 194) was used to
acute appendicitis prior to abscess formation. The find- create the two experimental groups of acute appendici-
ings of a loculated fluid collection and absence of the tis and perforated appendicitis. Using a second Pediat-
echogenic appendiceal submucosal layer have been ric Surgery database, database B was generated by
shown to be predictive of perforated appendicitis in extracting all patients evaluated by abdominal US for
children [14] and adults [15, 16]. The secondary sono- suspected appendicitis who were subsequently
graphic findings of echogenic mesenteric fat, fluid col- discharged without undergoing appendectomy. This
lections and dilated bowel were found to be helpful in second database was compiled from the hospital infor-
the diagnosis of acute appendicitis in children when the mation system and included all children presenting
appendix was not visualized [17]. More recently with abdominal pain and suspected appendicitis. Data-
Blumfield et al. [18] demonstrated that the presence of base B (n = 68) was utilized to create the control group
Pediatr Radiol
consisting of children without a sonographic diagnosis greater than 2 mm [19, 20], dilated bowel measuring
of appendicitis. The study population inclusion criteria greater than 2.5 cm [21], echogenic RLQ fat defined as
consisted of children presenting with abdominal pain an area of increased echogenicity greater than 1 cm in
and no known co-morbid conditions who had under- diameter [15], increased hepatic periportal echogenicity
gone abdominal US including dedicated images of the defined as the qualitative increased echogenicity of the
right lower quadrant (RLQ), right upper quadrant in- portal venule walls relative to the adjacent liver parenchy-
cluding at least one image of the liver, and at least one ma and referred to as the “starry sky” liver [22–24]
image of two additional abdominopelvic regions. The (Fig. 1), and bladder debris (mobile or layering echogenic
four abdominal quadrants and the pelvis composed the material within the bladder). The vascularity of the ap-
five abdominopelvic regions for our investigation. The pendix was also evaluated by presence or absence of
US studies were performed by radiology residents, US hyperemia. Appendiceal hyperemia is defined as
technicians, attending radiologists or a combination of hypervascularity in the wall of the appendix when com-
the three operators, using the Acuson Antares, S2000 pared with normal soft tissues showing absence or rare
and Sequoia US equipment (Siemens Medical Solu- scattered foci of color Doppler signal [25, 26]. The radi-
tions, Malvern, PA). All US examinations were ologists recorded specific characteristics of the intraperi-
interpreted by an attending pediatric radiologist. toneal fluid including quality (simple or complex) and
The patient age, gender, presence of co-morbid con- relative quantity as a function of the distribution of fluid
ditions and date of abdominal US were recorded from
the electronic medical record. We reviewed both the
operative and pathology reports for children who
underwent appendectomy following the abdominal US
for all children in database A. The diagnosis of acute or
perforated appendicitis in the study group was based on
review of the operative and pathology reports. In a
small number of children the operative and pathology
reports differed with respect to the presence or absence
of perforation (n=9); in these cases if either the surgical
report (n=7) or pathology report (n=2) included evi-
dence of perforation, the diagnosis was considered to
be perforated appendicitis. In the seven cases where the
surgical note reported perforation and the pathology
report did not mention perforation, it was presumed that
the site of perforation was not included in the patho-
logical specimen. The absence of appendicitis in the
control group was confirmed by follow-up verbal com-
munication with families and children by the surgical
service. The follow-up interval ranged from 3 months to
3 years after the US examination.
The US exams were randomized and assigned study
numbers. De-identification of the patient data was
achieved by exporting the anonymized US exam images
as secure jpeg files from the PACS workstation to a
password-protected institutional server for review. Each
US exam was independently reviewed on a PACS work-
station (Color Coronis 6MP monitor, Barco Inc., Duluth,
GA) by four pediatric radiologists with Certificates of
Added Qualification and experience ranging 2–12 years
(S.L., S.M., N.S., L.P.). The radiologists were blinded to
diagnosis and all clinical information, including prior and
subsequent imaging studies. The following data were Fig. 1 Normal liver vs. increased periportal echogenicity. a Longitudinal
US image of the normal liver in a 5-year-old boy with acute appendicitis.
recorded: presence of a normal appendix defined by a b Longitudinal US image of the liver in a 7-year-old boy with perforated
diameter measuring less than 6 mm [11], abnormal ap- appendicitis demonstrates the “starry sky appearance” of increased
pendix [6], appendicolith, thick-walled bowel measuring periportal echogenicity
Pediatr Radiol
(Fig. 2). The relative quantity of fluid was designated on a accuracy such that numerators and denominators represented
scale of 0–5 based on presence or absence of fluid in the four counts of evaluations rather than individual children. Varia-
abdominal quadrants and pelvis, reflecting a sum total of the tions in US protocols resulted in a small number of missing
five regions. The presence of abscess or loculated fluid was data points, which resulted in variations in the denominators
also recorded. used for some of the sonographic findings.
To further investigate the potential subjectivity of the sono- Logistic regression for correlated data was used to
graphic finding of increased hepatic periportal echogenicity evaluate the association of diagnosis (control, acute
and potential bias related to the presence of additional ultra- appendicitis or perforated appendicitis) with the pres-
sound findings, the US images of the liver were subsequently ence or absence of each individual sonographic finding.
separated from each of the original US examinations. At least For each individual sonographic finding, sensitivity and
6 months after the initial review, this subset of liver images specificity were calculated for the discrimination of
was presented to the reviewers in a blinded fashion for reas- appendicitis (acute and perforated) from the control
sessment of the presence of increased hepatic periportal group and discrimination of perforated appendicitis from
echogenicity. acute appendicitis. Exact Mann–Whitney tests were used
for pair-wise comparison of diagnostic groups in terms
of ordinal imaging measures represented for each sub-
Statistical analysis
ject as an average over the four readers.
Based on the statistical analysis of the individual findings
The data for each child consisted of sonographic findings from
in isolation, a multivariable analysis was conducted to identify
each of four independent readers. The results were summed
constellations of sonographic findings that were predictive of
over readers to generate overall estimates of diagnostic
perforated appendicitis. To minimize the false discovery rate,
the constellations tested were limited to those consisting of
findings individually showing a significant association with
perforated appendicitis. These findings included dilated bow-
el, echogenic RLQ fat, complex fluid, ≥2 regions of fluid,
increased periportal echogenicity and appendicolith. The
same logistic regression and exact Mann–Whitney tests were
used to analyze the constellations of findings and their asso-
ciation with the diagnosis.
Intra- and inter-reader agreement were assessed for the
evaluation of hepatic periportal echogenicity using simple
kappa coefficients. Kappa (K) was interpreted as an indication
of poor agreement when less than 0.2, as fair agreement when
0.2<K≤0.4, as moderate agreement when 0.4<K≤0.6 and as
substantial agreement when K>0.6 [27]. Inter-observer vari-
ability was assessed for all sonographic findings in our inves-
tigation by calculating the percentage concordance and kappa
coefficient. Results were pooled over the six distinct reader
pairs and the Fleiss multi-reader kappa was reported. All tests
were conducted at the two-sided 5% significance level using
SAS 9.3 (SAS Institute, Cary, NC).
Results
48) and US exam was limited by technique or patient body Table 1 Mean and standard deviation (SD) of patient age and the number
(percentage) of boys within each diagnosis group (controls, acute appen-
habitus (n=13). Children with co-morbid conditions were also
dicitis or perforated appendicitis)
excluded (n=10), including Wilms tumor (n=1), parasitic infec-
tion with Enterobius vermicularis (n=2), sickle cell disease (n= Diagnosis Control Acute Perforated
1), leukemia (n = 2), lymphoid hyperplasia (n = 3) and
Total subjects 43 51 22
appendiceal mass (n=1). Of these 61 children excluded from
Male 14 (32.6%) 33 (64.7%) 9 (40.9%)
database A with localized RLQ US exams or technically limited
Age±SD (yrs) 9.5±4.6 11.3±3.7 9.4±3.6
US exams, 45 had acute appendicitis and 13 had perforated
appendicitis and 3 did not have appendicitis. Among children yrs years
with appendicitis, the percentage with perforated appendicitis
was 30.1% (22/73) for those included in the study and 22.4% (Fig. 3). The mean age of the study patients was 9.5, 11.3
(13/58) for those excluded from the study. According to a Fisher and 9.4 years, respectively. Children with perforated appendi-
exact test, the included and excluded patients were not signifi- citis were significantly younger (P=0.04) than those with
cantly different (P=0.43) in terms of the percentage with perfo- acute appendicitis but did not have significantly different
rated appendicitis. There were no negative appendectomies in age than the control subjects (P=0.97). There was a trend
our study cohort and there were two negative appendectomies in for children with acute appendicitis to be older than the control
the subset of children excluded on the basis of co-morbid patients (P=0.09). The total study population consisted of 60
conditions. girls and 56 boys (Table 1).
Of the 68 children discharged without undergoing appen- The percentage and number of children with each individ-
dectomy (database B), 1 was excluded because the US images ual US finding are summarized in Table 2. With the exception
were not retrievable in PACS. Of the remaining cases, 24 were of appendiceal hyperemia, all individual sonographic findings
excluded because they did not fulfill the inclusion criteria; US were most commonly seen in children with perforated appen-
exam did not include images beyond the RLQ (n=16) and US dicitis. The individual US findings and select constellations of
exam was limited because of technique (n=6), suspected lym- findings had specificity for the diagnosis of appendicitis
phoid hyperplasia (n=1), and age younger than 2 years (n=1). (acute and perforated combined) ranging from 59.9% to
The final study population consisted of 116 children in 100%, the majority of which were greater than 95% compared
three diagnostic categories: control group (n=43), acute ap- with the control group. These results are summarized in
pendicitis (n = 51), and perforated appendicitis (n = 22) Table 3.
Fig. 3 Control and study groups. a Database A includes all children who underwent appendectomy to create the two experimental groups. b Database B
includes all children who were discharged after abdominal US without undergoing appendectomy to create the control group
Pediatr Radiol
The individual US findings of abscess/loculated fluid, constellations of US findings in the diagnosis of perfo-
appendicolith, dilated bowel and increased hepatic rated appendicitis compared with acute appendicitis
periportal echogenicity were significantly associated yielded higher specificity than that of each individual
with perforated appendicitis when compared with acute finding in isolation (Table 4). The constellation of di-
appendicitis (P<0.01). The presence of complex fluid lated bowel, RLQ echogenic fat, and complex fluid had
yielded a specificity of 87.7% for perforated appendici- the highest specificity of 99.5% for perforated appendi-
tis compared with the acute appendicitis group. The US citis (P<0.01) (Fig. 4).
finding of ≥2 regions or ≥3 regions with fluid had Abscess or loculated fluid was identified in only 23.1% of
specificity of 87.3% and 99.0%, respectively, for perfo- US examinations in the perforated appendicitis group. There
rated appendicitis compared with the acute appendicitis was a systematic increase in both the number of
group. Echogenic RLQ fat did not distinguish between abdominopelvic regions containing intraperitoneal fluid and
perforated appendicitis and acute appendicitis. Select the complexity of the fluid when comparing the three
diagnostic groups. Specifically, the number of regions con- generation US equipment, potentially limiting clinical appli-
taining fluid and the complexity of the fluid both increased cation. Using state-of-the-art US equipment, we investigated
from control to acute appendicitis and from acute appendicitis the novel association of increased hepatic periportal
to perforated appendicitis, with corresponding increasing echogenicity with perforated appendicitis in addition to the
specificity (Table 5). The presence of any fluid, simple or previously described sonographic findings of RLQ echogenic
complex, in any number of quadrants yielded a sensitivity of fat, dilated bowel and appendicolith; we also correlated the
86.6% for perforated appendicitis. quantity and quality of intraperitoneal fluid with respect to the
Percentage concordance and kappa among the readers for diagnosis of perforated appendicitis. We subsequently per-
the specific sonographic findings assessed in our investigation formed a detailed analysis of the association of specific con-
ranged from 74.9% to 95.3% and 0.42 to 0.66, respectively stellations of these sonographic findings in the setting of
(Table 6). There was moderate to high agreement for all of the perforated appendicitis, with the goal of improving the diag-
findings. In the focused assessment of increased hepatic nosis of perforated appendicitis.
periportal echogenicity averaged over reader pairs, the kappa The sonographic findings that define an abnormal appendix
for inter-reader agreement was 0.54, indicative of moderate are well described in the literature. However, these findings
agreement. Intra-reader agreement was fair for reader 1 (kap- located in the RLQ may not provide adequate information to
pa=0.28) and moderate-substantial for the other three readers distinguish non-perforated from perforated appendicitis, an argu-
(kappa=0.54–0.66). Percentage concordance between reader ment for the need to improve sonographic distinction between
pairs for increased periportal echoes ranged from 77.2% to these pathological entities. Individual sonographic findings
87.8% with an overall percentage concordance of 82.5%. yielded a broad range of specificity for perforated appendicitis
compared with acute appendicitis. Dilated bowel proved to be a
useful individual sonographic finding associated with perforated
Discussion appendicitis when compared with acute appendicitis. The finding
of dilated bowel likely reflects the presence of an ileus in response
Perforated appendicitis is a well-known diagnostic challenge to the marked RLQ inflammation in the setting of perforation.
in the sonographic assessment of abdominal pain in children. Increasing volume of intraperitoneal free fluid and the presence of
Reliable US imaging in this setting is fundamental in guiding complex fluid, as individual findings, were both suggestive of
patient management and minimizing radiation exposure. Al- perforated appendicitis. The increasing volume or complexity of
though studies have addressed the sonographic diagnosis of fluid associated with perforated appendicitis may reflect early
perforated appendicitis, several of these studies utilized older- purulent changes even prior to frank abscess formation. Not
Pediatr Radiol
Table 6 The percentage (fraction) of times that results from two readers
were concordant and the kappa to assess reader agreement in terms of
each finding
The fact that clinical factors were not considered in concert US examination of the RLQ, can improve sonographic diagnosis
with US findings may be viewed as a potential limitation. of perforated appendicitis in the pediatric population.
However, it is common for the clinical presentation of perfo-
rated appendicitis to be atypical. To that end, the clinical
management is based on both the imaging findings and the Conflicts of interest None
clinical presentation, including physical examination, labora-
tory studies and detailed history. Because the purpose of our
investigation was to specifically identify sonographic findings References
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