An Imaging Diagnostic Protocol in Children with

Clinically Suspected Acute Appendicitis

MATIAS EPIFANIO, M.D., PH.D.,* MARCO ANTONIO DE MEDEIROS LIMA, M.D., M.SC., PATRICIA CORREA, M.D.,
MATTEO BALDISSEROTTO, M.D., PH.D.*

From the *School of Medicine and Graduate School of Medicine, Pontifcia Universidade Catolica do Rio Grande
do Sul (PUCRS), Porto Alegre, Brazil; Graduate Program in Pediatrics and Child Care, Pontifcia
Universidade Catolica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Pontifcia Universidade Catolica
do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil

The objective of the present study is to evaluate a new diagnostic strategy using clinical findings
followed by ultrasound (US) and, in selected cases, MRI. This study included 166 children
presenting signs and symptoms suggesting acute appendicitis. Cases classified as suggesting
appendicitis according to clinical exams had to be referred to surgery, whereas the other cases
were discharged. Unclear cases were evaluated using US. If the US results were considered
inconclusive, patients underwent MRI. Of the 166 patients, 78 (47%) had acute appendicitis and
88 (53%) had other diseases. The strategy under study had a sensitivity of 96 per cent, specificity
of 100 per cent, positive predictive value of 100 per cent, negative predictive value of 97 per cent,
and accuracy of 98 per cent. Eight patients remained undiagnosed and underwent MRI. After
MRI two girls presented normal appendixes and were discharged. One girl had an enlarged
appendix on MRI and appendicitis could have been confirmed by surgery. In the other five
patients, no other sign of the disease was detected by MRI such as an inflammatory mass, free
fluid or an abscess in the right iliac fossa. All of them were discharged after clinical observation.
In the vast majority of cases the correct diagnosis was reached by clinical and US examinations.
When clinical assessment and US findings were inconclusive, MRI was useful to detect normal
and abnormal appendixes and valuable to rule out other abdominal pathologies that mimic
appendicitis.

A CUTE APPENDICITIS ISthe most common surgical

emergency in children and adolescents in the
1
United States, with an incidence of two to four cases
per thousand children.2 An accurate diagnosis of ap-
pendicitis in pediatric populations remains a challenge
for physicians due to the initial presentation of this
disease is often obscure or mimics other common pe-
diatric conditions.
The diagnosis of acute appendicitis can be defined
by findings in the patients history, physical exams,
and initial laboratory test performed during the clin-
ical evaluation.3 Imaging studies have traditionally
been performed in children when appendicitis is
suspected. Ultrasound (US) and CT have advanced
substantially in the last decades and presently provide
great accuracy for the diagnosis of appendicitis in
pediatric patients.410 The use of these imaging
Address correspondence and reprint requests to Matias
Epifanio, M.D., PH.D., Pediatric Gastroenterologist, Professor,
School of Medicine and Graduate School of Medicine, Pontifcia
Universidade Catolica do Rio Grande do Sul (PUCRS), Porto
Alegre, Brazil. E-mail: mepifanio@hotmail.com.
modalities is important to avoid appendix perfora-
tions or unnecessary appendectomies.11, 12 CT, which
is an operator-dependent imaging modality, is par-
ticularly useful for the evaluation of obese patients7;
however, it exposes the patient to ionizing radiation
and may require the use of contrast material, general
anesthesia, or sedation in selected cases.1014
Ionizing radiation is an extremely important
factor1517 because children are 10 times more sen-
sitive to radiation than adults, particularly girls. 17 In
1998, two pioneering studies proposed assessing
appendicitis by MRI.18 Since then, few similar
studies have been carried out.1924 Recently, some
authors proposed the use of MRI to diagnose acute
appendicitis.2428 These studies have different de-
signs and include only a small number of patients.
Thus, new investigations are necessary.
This study evaluated a diagnostic strategy for ap-
pendicitis that uses clinical findings, followed by US
and, for selected cases, MRI. This strategy is an in-
novative method and in some patients, MRI, which
does not expose patients to ionizing radiation, may be
an alternative to CT.

390
No. 5 ACUTE APPENDICITIS
Methods
From January 2007 to September 2009, we have
prospectively studied 166 patients with signs and
symptoms of possible acute appendicitis, who were
hospitalized to undergo diagnostic investigation in
a general university hospital. The Institutions Ethics
Committee, where this study was conducted, ap-
proved it and informed that consent was obtained
from the patients when able to understand it, and
parents or guardians when they are not.
Patients included in this study were admitted to the
pediatric emergency department of the hospital and
a pediatrician attended them in the first place, who later
requested a consultation with a pediatric surgeon. One
pediatric surgeon of the pediatric surgery team taking
into consideration symptoms, signs, and initial labora-
tory findings made the clinical evaluation. The follow-
ing signs and symptoms were evaluated: duration of
clinical signs and symptoms, physical examination
findings such as pain at palpation of right lower ab-
dominal quadrant and abdominal guarding, leukocyto-
sis, and left shift. Clinical findings were classified as
suggestive of appendicitis when the patient presented
abdominal pain at palpation of right lower abdominal
quadrant associated with guarding for any length of
time, with or without leukocytosis or left shift. Clinical
findings were classified as not suggestive of appendi-
citis when the patient presented abdominal pain if not
localized in the right lower abdominal quadrant for
longer than 48 hours and no guarding. In cases of
younger children not yet able to express themselves
well verbally, only the presence of guarding at pal-
pation was taken into consideration. Findings were
classified as inconclusive when 1) the patient pre-
sented abdominal pain at palpation of the right lower
abdominal quadrant without guarding, with or with-
out leukocytosis or left shift; or 2) patient presented
abdominal pain not localized in the lower right ab-
dominal quadrant for up to 48 hours and no guarding,
with or without leukocytosis or left shift. Total blood
count results (leukocytosis or left shift) were primarily
used to establish disease severity.
The surgeon first conducted a clinical evaluation in
the patients and, if necessary, the patients underwent
sequential and cumulative imaging studies (Fig. 1).
When the clinical evaluation and laboratory findings
yielded suggestive findings, the patient was referred to
surgery; in case of nonsuggestive findings, the patient
was discharged after prescription of specific treat-
ments for other diseases; and in case of inconclusive
findings, the patient underwent evaluation using US. If
findings were inconclusive, the patient was referred to
urgent US evaluation.
? Epifanio et al. 391
In this protocol, unclear cases of suspected appendi-
citis for which US findings are inconclusive routinely
undergo another US examination or CT after 6 to
12 hours under clinical observation.
After clinical and imaging evaluations, patients were
classified according to their findings: suggestive of
acute appendicitis, not suggestive (another disease) of
acute appendicitis, and inconclusive findings (di-
agnostic uncertainty). When the US evaluation yielded
suggestive findings, the patient was referred to surgery;
in case of nonsuggestive findings, the patient was dis-
charged after prescription of specific treatment for other
diseases; and in case of inconclusive findings, the pa-
tient underwent evaluation using MRI. When the MRI
evaluation yielded suggestive findings, the patient was
referred to surgery; in case of not suggestive findings,
the patient was discharged; and when findings were
inconclusive, the patient was hospitalized for 24 hours
for clinical observation. When clinical conditions de-
teriorated during observation, the patient was referred to
surgery, and if the patient improved or the clinical
condition remained stable, he was discharged.
Histopathological findings of the surgical specimens
confirmed the final appendicitis diagnosis. One expe-
rienced pathologist confirmed the histological changes
characteristic of appendicitis. The histopathological
picture of acute appendicitis is characterized by the
destruction of the mucosa, submucosa, and external
muscle layers. Final exclusion was based on possible
pathological findings of a normal appendix in patients
who underwent surgery or in patients who did not need
to undergo surgery during a 30-day clinical follow-up.
Patients who had previously undergone appendectomy
were excluded.
Sonography Technique
Complete abdominal US examination was per-
formed by one of the 14 general radiologists during
office hours using 5.0- or 7.5-MHz linear or 5.0-MHz
curved array transducers.
The US units were Philips HD11 XE, 2008 (Philips,
Bothell, WA), and Siemens G40, 2007 (Siemens,
Erlanger, Germany). Specialized radiologists with more
than five years of experience interpreted US exams, in-
cluding those performed during out-of-office hours. A
graded-compression technique was used, as described by
Puylaert.35 Negative US results (not suggestive) were
recorded when one of the following independent find-
ings were noticed: 1) visualization of blind-ending tu-
bular structure leaving the cecum with a maximum
transverse diameter of 6 mm, 2) no detection of the ap-
pendix and resolution of clinical signs and symptoms in
12 to 24 hours after US examination, and 3) clear and
unequivocal US definition of another disease. A positive
392 THE AMERICAN SURGEON
US finding (suggestive) was recorded when the following
independent results were seen: 1) a blind-ending tubular
structure leaving the cecum and with a transverse di-
ameter greater than 6 mm or 2) pericecal inflammation of
omentum and no detection of an abnormal appendix
(considered suggestive, but not specific for acute ap-
pendicitis). Inconclusive US results were recorded when
the appendix was not detected and the clinical conditions
remained the same for 12 to 24 hours after US.
May 2016 Vol. 82
FIG. 1. Algorithm for the clinical and
imaging diagnostic strategy. n, number of
patients.
MRI Technique
Full abdominal MRI study was performed by one of
the four general radiologists during office hours or at
other times 12 to 24 hours after the performance of
the US study, using the following units and specifi-
cations: Siemens Magnetom Vision Plus 1.5 Tesla,
1998 (Siemens, Erlangen, Germany). MRI scans were
interpreted by specialized and experienced radiolo-
gists with more than five years of experience. The
No. 5 ACUTE APPENDICITIS
FIG. 2. Algorithm for total abdominal US. n, number of patients.
sequences were the same as those used in a previous
study that evaluated the normal appendix in asymp-
tomatic children. 19 Scanning started with a T2-
coronal sequence to detect the position of the cecum.
Axial sections were defined according to the position
of the cecum. The most cranial section was obtained
at least 10 cm above the cecum, and the most caudal,
at the pubic symphysis. Four sequences were per-
formed according to the following imaging param-
eters: axial T1-weighted fast spin echo: T1/FSE;
TR/TE:700 ms/8.7 ms; 4.0 mm section thickness,
512 3 512; axial T2-weighted fast spin echo: T2/FSE;
TR/TE:1900 ms/957 ms; 4.0 mm section thickness,
256 3 256; axial T2-weighted fast spin echo with fat
suppression: T2/FSE fat saturation (FATSAT); TR/TE:
1800 ms/95.7 ms; 4.0 mm section thickness, 256 3 256;
coronal T2-weighted fast spin echo: T2/FSE; TR/TE:1800
ms/102.7 ms; 4.0 mm section thickness, 512 3 512.
Scanning was performed, ideally, without general
anesthesia or contrast media. When the cecal ap-
pendix was not identified in the initial sequences
carried out without constrast, we proceded to exam-
ine with gadolinium [0.2 mg/kg intravenously (IV) at
0.5 mmol/ml].
MRI evaluation consisted of the detection of ap-
pendix and measurement of its total transverse di-
ameter, of pericecal inflammation omentum without
? Epifanio et al. 393
detection of the appendix, and imaging investigation of
other possible diseases. Appendicitis diagnostic crite-
ria used in MRI studies were those suggested by
Horman et al.19
A negative imaging result for appendicitis was
recorded when the following independent findings were
seen: 1) visualization of a blind-ending tubular structure
leaving the cecum and with a maximum transverse di-
ameter of 6 mm or 2) clear and unequivocal imaging
definition of another disease. A positive imaging result
of appendicitis was recorded when the following in-
dependent findings were seen: 1) visualization of blind-
ending tubular structure leaving the cecum and with
a transverse diameter greater than 6 mm or 2) pericecal
inflammation of omentum and no detection of an ap-
pendix (considered suggestive, but not specific for acute
appendicitis). An inconclusive result was recorded
when the appendix was not detected.
Statistical Analysis
Quantitative variables are described as mean and
standard deviations. Categorical variables are de-
scribed as frequencies and percentages. Kappa statis-
tics was used to evaluate statistical agreement between
diagnostic test and disease and also to evaluate in-
terobserver agreement. The Student t test for
394 THE AMERICAN SURGEON May 2016 Vol. 82

independent samples was used to compare means. any statistically significant difference in mean age
The Pearson chi-squared test was used to evaluate (P 4 0.692) or sex distribution (P 4 0.464).
the association between categorical variables. The Seventy-five diagnoses of appendicitis were made
SPSS 13.0 (Chicago, IL) software was used for using the strategy under study: all results were true
statistical analyses. The level of significance was positive, and there were no false-positive results. The
set at 5 per cent (P # 0.05). general diagnostic strategy had a sensitivity of 96 per
cent, specificity of 100 per cent, positive and negative
predictive values of 100 and 97 per cent, and accuracy
Results
of 98 per cent (Table 1). Of all patients, 102 underwent
One hundred and sixty-six children with suspected US studies, 37 had negative results for appendicitis,
acute appendicitis were evaluated in this study. Mean and 57 were referred to surgery (100% probability of
age was 9.15 years 2.78 and age range was 1 to appendicitis) (Table 2). Three US results were false
13 years. For the 94 boys, mean age was 8.91 years negative, and as the clinical condition of these patients
2.51 and age range was 1 to 12 years, and for the (one boy and two girls) deteriorated, they were re-
72 girls, mean age was 9.47 3.08 and age range was ferred to surgery. A normal appendix was detected in
1 to 13 years. Appendicitis was confirmed by patho- 8 (22%) of the 37 patients with negative US results; in
logical examination of the surgical specimen in 78 3 (8%) an equivocally normal appendix was detected
(47%) of the patients: 47 were boys (60%) and 31 were (false-negative results); 10 (27%) patients the appen-
girls (40%), mean age was 9.25 years, and age range dix was not detected and their clinical condition im-
was 2 to 13 years. Other diseases were diagnosed in 88 proved in 12 to 24 hours after US studies; and
(53%) patients: 47 were boys (53%) and 41 were girls 16 (43%) had a diagnosis of other diseases, such as
(47%), mean age was 9.07 years, and age range was pancreatitis (n 4 1), inflamed Meckels diverticulum
1 to 12 years. The comparison between the groups of (n 4 1), pneumonia (n 4 2), ovarian cyst (n 4 2), and
patients with and without appendicitis did not reveal acute mesenteric lymphadenitis (n 4 10). None of
these patients, therefore, underwent MRI scanning.
The abnormal appendix was detected in 52 (91%) of
TABLE 1. Evaluation of the General Strategy for Suspected the 57 patients with positive US findings, and pericecal
Acute Appendicitis in Children inflammation but no abnormal appendix in 5 (9%).
Final Diagnosis Clinical and US findings remained inconclusive for
eight patients, and they were referred to MRI (age
Test Acute Appendicitis Another Disease Total range was 411 years). After MRI, one girl was di-
Positive 75 0 75 agnosed with acute appendicitis, confirmed by surgery.
Negative 03 88 91 Two girls were discharged after the normal appendix
Total 78 88 166
Sensitivity 96.1 (89.999.0) was detected and five patients were kept under clinical
Specificity 100 (96.7100) observation because of unclear MRI findings. Of the
PPV 100 (96.1100) eight patients who underwent MRI, seven received IV
NPV 96.7 (91.399.2) contrast material, one 4-year-old boy required sedation
Accuracy 98.2 (95.299.5)
IV, and only one 5-year-old girl required general
CI, confidence interval; PPV, positive predictive value; NPV, anesthesia. Total examination time, considering the
negative predictive value.
Diagnostic measures are described as proportions (95% con- four sequences in all cases, was 10 minutes. Kappa
fidence interval). Kappa statistics (statistical agreement between statistics between observers had the greatest value
test and disease) 4 0.96; 95% CI 4 0.90 to 0.99; P < 0.001. (k 4 0.80).

TABLE 2. Disease Probability According to Diagnostic Test

Patients with
Appendicitis/Not Patients with Patients with
Suggestive (n) Appendicitis/Inconclusive (n) Appendicitis/Suggestive (n)
Tests Number Per cent (95% CI) Per cent (95% CI) Per cent (95% CI)
Clinical evaluation 166 0/47 61/102 17/17
0.0 (06.18) 59.8 (50.169.0) 100 (83.8100)
Complete abdominal US 102 3/37 1/8 57/57
8.11 (2.1020.5) 12.5 (0.6348.0) 100 (94.9100)
Complete abdominal MRI 8 0/2 0/5 1/1
0.0 (077.6) 0.0 (042.1) 100 (5.0100)
CI, confidence interval; n, number of patients.
No. 5 ACUTE APPENDICITIS
Discussion
Clinical evaluation is an initial, fundamental stage in
the diagnosis of appendicitis, and its performance may
affect disease complications, economic costs, and
hospitalization time. Samuel3 conducted a study with
children using a clinical score (pediatric appendicitis
score) that reached 100 per cent sensitivity and 92
per cent specificity. In this study, 17 patients were re-
ferred to surgery after clinical evaluation, with a prob-
ability of 100 per cent for appendicitis. The criteria used
in this study, such as duration of clinical signs and
symptoms, pain at palpation of right lower quadrant,
guarding in right lower quadrant, and leukocytosis and
left shift had a very high positive true value. We used
fewer clinical criteria than another study, in which pain
migration, anorexia, nausea, vomits, fever, pain at pal-
pation of the right iliac fossa, guarding in the right lower
quadrant of the abdomen, and leukocytosis and left shift
were used.3 In that same study, the score obtained de-
termined whether the findings were compatible, not
compatible, or highly probable of appendicitis, and in
which inconclusive findings were not defined as
a category.
The first authors proposing MRI assessment of ap-
pendicitis were Incesu et al. in 1997 and Horman et al.
in 1998.18, 19 Both studies showed promising results,
when using MRI to diagnose appendicitis. In spite of
this till now, few studies to further clarify this issue
were performed.2024 These studies used different
imaging techniques and assessed different populations.
Although in some studies, patients were only assessed
by MRI,2528 others performed US and MRI in all
patients18 or only used MRI when US showed signs of
appendicitis.19 Our study used a different approach.
Patients with suggestive clinical signs and symptoms
were not submitted to imaging and were immediately
sent to surgery. Patients with doubtful clinical findings
did US. When US showed appendicitis, patients were
sent to surgery. Only the few cases not yet well di-
agnosed underwent MRI. Thus, despite an initial high
number (164), only nine children were sent to MRI.
Although this may be a limitation of our study, we
believe it to be the most rational algorithm to be used
in daily clinical practice. Thus, we optimized the use of
physical assessment and US and only used a more
complex imaging technique when really necessary.
Our approach showed sensitivity and specificity
similar to the other studies, but not using MRI in all
patients.
The aforementioned investigations also studied dif-
ferent populations. Some only assessed adults,18, 29, 34
others, children and young adults28, 31 or pregnant
women,23, 30 or only children.18, 23, 33 Our study only
assessed the pediatric population up to the age of 13.
? Epifanio et al. 395
In our eight patients that underwent MRI, this im-
aging study was useful to detect one inflamed appen-
dix, confirmed by surgery. MRI ruled out the disease in
two of the eight patients, because it provided direct
visualization of the normal appendix, and in the other
five patients, it was not possible to demonstrate the
normal appendix; however, no other sign of the disease
was detected, such as an inflammatory mass, free fluid
or an abscess in the right iliac fossa. In addition, MRI
ruled out other abdominal pathologies that could
mimic appendicitis. In the patient with appendicitis, in
which MRI detected an abnormal appendix, this im-
aging study was useful because it detected an enlarged
appendix and moderate amount of free fluid in the
right iliac fossa and the pelvis. These imaging findings
were valuable to establish the diagnosis and to refer the
patient to surgery.
Most of the children in our study received IV con-
trast material for the performance of MRI, in agree-
ment with other studies in the literature.21 Total
examination time, considering the four sequences in all
cases, was 10 minutes in our study. This duration was
shorter than those reported in two other studies,23 in
which mean times were 31 and 29 minutes. This dif-
ference in duration may be assigned to the different
MRI scanners used in the studies and to advances in
the application of techniques.
Our study had a limitation: the small number of
patients referred to MRI, which might have com-
promised a more accurate evaluation of this imaging
modality. As this study presents the initial results, the
analysis of a larger number of patients may mitigate
such limitation. In our institution, unclear cases of
suspected appendicitis for which US findings are
inconclusive routinely undergo another US exami-
nation after 6 to 12 hours under clinical observation.
During this study, US was replaced with MRI for the
second imaging exam, which might have added some
bias to our results because MRI exams were per-
formed at a time when the disease was at a more
advanced stage.
Conclusion
The combination of clinical assessment and US
evaluation of children with signs and symptoms sug-
gestive of acute appendicitis was a highly accurate
diagnostic strategy.
When clinical assessment and US findings were
inconclusive, MRI was useful to detect normal and
abnormal appendix and valuable to rule out other ab-
dominal pathologies that could mimic appendicitis. In
addition, MRI does not expose patients to ionizing
radiation and may, therefore, be an alternative to CT
when US findings are inconclusive.
396 THE AMERICAN SURGEON
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