MINISTRY OF HEALTH OF TH REPUBLIC OF MOLDOVA [601343]

MINISTRY OF HEALTH OF TH REPUBLIC OF MOLDOVA
STATE OF MEDICAL AND PHARMACEUTICAL
UNIVERSITY “NICOLAE TESTEMITANU”

FACULTY OF MEDICINE

CATEDRA: CHIRURGIE, ORTHOPEDIE & ANESTHESIO LOGY OF PEDIATRIC
DIPLOMA THESIS IN GENERAL MEDICINE

License thesis : Appendicitis In Children

Student: [anonimizat] : Amran Abu Moch
Year,grup:6th year ,1638
Scientific coordinator name :
dr. hab. med.prof. univ. Bernic Jana

Chisinau
2015

aim of the rescarch(scopul) :
Aim of this study is to determine the frequency of Appendicitis In Children children
through literature and data analysis to demonstrate anatomical features, diagnosis
and treatment.
The rescarchobjective :
1. conducted an analysis of causal factors Appendicitis In Children.
2. variants studied etiology and pathology of Appendicitis In Children.
3. Examination of morphological changes in Appendicitis In Children.
4. To establish methods of diagnosis, differential diagnosis and on their basis to
establish a medical treatment, and weaker response to determine indications
palliative surgical treatment.
In addition the thesis chapter clinical diagnostics, laboratory (imaging, functional,
urography, scintigraphy.Methods of conservative and surgical
treatment.Histopathology. Complications)

STATEMENT
I here declare that the license thesis titled (Appendicitis In Chil dren) is writte by me
and has never been submitted to another university or inst itution of higher education
in the country or abroad. Also that all sources used including those on the internet, are
given in the paper with the rules for avoiding p;giarims :
-all the fragment soft extreproducedexactly , even his own translation from aother
language are written betwee quotation marks and have a detailed reference source .
-reformulation of the texts in owwordswritten be othervauthors have detailed
reference :
-summarizing the ideas of other authors havedetaildreferenceto the orginal te xt.

Amran Abu Moch
______________________

ABSTRACT

Suspected appendicitis is the most common cause of emergency abdominal surgery in children .
Because of the often atypical clinical findings, the diagnosis of appendicitis is difficult and may be
delayed. Perforation has been reported to occur in 23-73% of children with acute appe ndicitis.
The negative appendectomy rate has been reported to be 15-25%. Since the complication rate is
not negligible, it is desirable to avoid unnecessary laparotomies.

The diagnostic accuracy of ultrasonography (US) and additional abdominal computed t omography
(CT) was studied in a prospective study that included 600 children. It was found that US is a
valuable and highly specific tool in the diagnosis of appendicitis in children. The sensitivity can be
increased significantly by performing abdominal CT in addition to US. A negative appendectomy
rate of 3.7% and a perforation rate of 21% were achieved.

The diagnostic accuracy of different CT techniques, namely non-enhanced helical CT l imited to the
lower part of the abdomen, CT of the entire abdomen after intravenously administer ed contrast
medium, and the combination of both, were studied in a retrospective review of p rospectively acquired
data including 306 CT examinations. It was found that the limited non-enhanced CT ha d a significantly
lower sensitivity than the contrast-enhanced CT, while the combination of both sequence s did not
further improve the diagnostic accuracy. Hence, the limited non-enhanced scan can be e xcluded, which
results in a reduction of the radiation dose.

The negative appendectomy rate and the perforation rate were studied in a retrospective study including
600 children who underwent appendectomy because of suspected appendicitis during the past decade.
A gradual and substantial decrease in the negative appendectomy rate was found during the years
studied. The overall perforation rate remained stable, while the rate of perfora tions after admission
appeared to decrease over time. Since nothing was changed in the management of suspect ed
appendicitis apart from the increasing use of US and CT, it may be assumed that the fi ndings result from
the preoperative radiologic imaging.

The impact of radiologic imaging procedures, including US only or US and abdominal CT, on the
surgeon’s decision -making process in the management of suspected appendicitis was studied in a
prospective study including 600 children. Radiologic imaging was found to provide valuable
guidance as to whether a child with suspected appendicitis should be discharged, observed, or
given surgical treatment. Following this guidance may lead to beneficial changes in the
management plan. False negative imaging results are infrequent but may still occur and
therefore, a close clinical re-examination and communication with the radiologist is of utmo st
importance for the appropriate final decision.

Key words: appendicitis, appendix, ultrasonography, computed tomography, appendectomy,
perforation, diagnostic accuracy, decision analysis

4

LIST OF PUBLICATIONS

This thesis is based on the following four papers, which are referred
to in the text by their Roman numerals:

I. Kaiser S, Frenckner B, Jorulf HK.
Suspected appendicitis in children: US and CT – a
prospective randomized study

Radiology 2002; 223:633-638

II. Kaiser S, Mesas-Burgos C, Söderman E, Frenckner B.
Appendicitis in children – impact of US and CT on the
negative appendectomy rate
European Journal of Pediatric Surgery 2004;14 (in press)

III. Kaiser S, Finnbogason T, Jorulf HK, Söderman
E, Frenckner B.
Suspected appendicitis in children: Diagnosis with
contrast-enhanced versus nonenhanced helical CT
Radiology 2004; 232 (in press).
Published online before print March 18, 2004

IV. Kaiser S, Jorulf H, Söderman E, Frenckner B.
Impact of radiologic imaging on surgical decision-making
process in suspected appendicitis in children
2004, Submitted .

5

ABBREVIATIONS

US = ultrasonography
CT = computed tomography
ROC = receiver operating characteristic
CRP = C-reactive protein
WBC = white blood cell count

6

TABLE OF CONTENTS
Abstract 1
List of publications 5
Abbreviations 6
Introduction 9
Background 9
History of appendicitis 9
Embryology, anatomy and histopathology 11
Etiology 12
Epidemiology 14
Clinical management 15
Negative appendectomies 15
Clinical course 16
Diagnostic methods 17
History 17
Physical examination 18
Laboratory findings 18
Urinalysis 18
Laparoscopy 19
Radiologic imaging 19
Treatment of appendicitis 24
Appendectomy 24
Conservative treatment 24
Histopathologic analysis 25
Aims of the thesis 26
Material and methods 27
Prospective study 27
Study setting 27
US and CT Scan Interpretation 27
Final disposition, final diagnosis and follow- up 28
Retrospective study 29
Statistical analysis 29
Paper I 29
Paper II 30
Paper III 30
Paper IV 30
Results 31
Diagnostic accuracy of US and CT 31
The rates of negative appendectomies and perforations 32
Diagnostic accuracy of different CT techniques 32
Changes in the rates of negative appendectomies and perforations 33
Impact of radiologic imaging on surgical decision-making process 34
Discussion 34
Ultrasonography 35
Computed tomography 35

7

Negative appendectomy rate 37
Perforation rate 37
Decision analysis 38
Conclusions 39
Acknowledgements 40
References 41

8

INTRODUCTION

Background

Appendicitis is one of the most common surgical diseases in western
countries [1]. It accounts for 25% of hospital admissions due to abdominal
pain [2] and for more than 40% of all emergency laparotomies. The lifetime
cumulative risk of having appendicitis is approximately 7-9% in the US [3]. In
Sweden, roughly 30,000 patients are admitted for observation in hospitals
and 12,500 emergency laparotomies are performed annually because of
suspected appendicitis [4]. There is a high peak in the second decade, and
about 50% of patients with appendicitis are between 15 and 35 years of age
[5]. In children, suspected appendicitis is the most common cause of
emergency abdominal surgery [6].

The treatment of choice in the vast majority of patients is appendectomy, i.e.
surgical removal of the inflamed appendix, although conservative treatment
with antibiotics has also been used in adults [7]. However, appendicitis can
mimic several other diseases and is a possible differential diagnosis in almost
all patients with acute abdominal symptoms. In the youngest and in the oldest
age groups, it is more likely that appendicitis will present with atypical history
and clinical findings, and hence the diagnosis is often difficult and may be
delayed. Therefore, the complication rates are highest in these populations
[8]. In children, perforation has been reported in 23-73% [9].

The difficulties in differentiating the patients with appendicitis needing
surgical intervention from the patients with non-surgical or spontaneously
resolving abdominal pain, together with the aim to prevent complications, i.e.
perforation of the appendix and peritonitis, has led to the traditional
acceptance of a relatively high frequency of unnecessary surgery and removal
of a healthy appendix (hereafter, negative appendectomy). In children, a
negative appendectomy rate of 15-25% has been reported [9-11]. Since
unnecessary surgery is a waste of medical resources, and the complication
rate after negative appendectomy is not negligible [12-14], this practice is
being increasingly questioned [15-17]. A more restrictive surgical approach is
supported by the development of modern imaging techniques, in particular
ultrasonography and computed tomography.

History of appendicitis

There are indications that appendicitis was present already in 3000 B.C., as
adhesions in the right lower abdominal quadrant, strongly suggestive of

9

appendicitis, were detected in one Egyptian mummy [18, 19]. However, it is
not clear whether the appendix was recognized by the Greek anatomists,
since there are some uncertain descriptions by Soaranos from Ephesos
around year 100 and Aretaios around year 200 [20].

From the late 15th century, the vermiform appendix has been described as an
anatomical structure in autopsy reports, but the pathogenesis of appendicitis
was not understood. In 1554, a French court physician to Catherine de Medici,
Jean Fernel, provided the earliest documented description of appendicitis in a
7-year-old girl, who died of perforated appendicitis, although he called the
disease “passion iliac” [21]. From the 18th century, there are several reports on
both the appendix and appendicitis. The first known written description of the
appendix in detail was done by Morgagni in 1719 [22]. During the following
decades, several authors report cases of inflammation or gangrene of the
appendix and pain in the right iliac fossa, but the connection was still not
completely understood [19, 20]. The condition was believed to begin with an
inflammation of the caecal mucosa, called stercoral typhlitis, which could be
complicated by paratyphlitis (a retro-caecal abscess) or perityphlitis (an intra-
abdominal abscess). In 1812, James William Keys Parkinson described a
perforated appendix and recognized it as a cause of death in a 5-year old boy
[19]. Several other reports followed, e.g. by Wegeler [20], Prescott [20] and
Louyer-Villermay [23, 24], who seem to have understood the pathogenesis of
appendicitis, although the typhlitis theory still predominated in contemporary
reports by Melièr [20], Goldberg [25] and Dupuytren [19, 26].

The treatment of acute appendicitis was non-operative in almost all patients
until the end of the 19th century and consisted of bed-rest, enemas,
purgatives, venesectio, opium drops etc [20, 27]. The surgical treatment was
limited to incision of abscesses [27]. In 1827, Melièr proposed a more radical
treatment with early appendectomy before the complications occurred, but as
this was prior to the aseptic and anaesthetic era, abdominal surgery was not
possible [27]. In 1880, Robert Lawson Tait became the first to perform a
successful appendectomy [28]. During the following years, appendectomy
was performed by several surgeons in different countries with variable and
not always successful results, e.g. Groves in Canada 1883 [20], Krönlein in
Zürich 1884 [20, 27], Mikulicz-Radecki in Krakow 1884 [20, 24], and Barton
Sands in New York 1888 [19, 24].

Charles McBurney, who had been an assistant to Barton Sands, delivered one
of the better known early reports on appendectomy in 1889 [29], where he
also described the point of maximal tenderness, now known as the point of
McBurney. He was also the first to describe the classical muscle-splitting grid-
iron incision [30], although this had already been used by others before
McBurney’s publication [19, 31].

10

In Sweden, appendectomy was introduced as treatment for acute appendicitis
by Karl Gustaf Lennander in Uppsala in 1889. The number of appendectomies
performed in Sweden increased rapidly from 618 in 1901 to 10,449 in 1913
[32].

The indication for appendectomy, however,
was still a subject of conflict. In 1895, the
majority of appendicitis cases were thought
to be self-limiting and spontaneously
resolving [33]. There was a fear that the
operative mortality would exceed that of
conservative treatment and hence, surgery
was avoided until signs of perforation or
abscess were at hand [21]. McBurney and
others proposed that an exploratory incision
should be performed in all patients with
suspected appendicitis [29, 34], but early
surgery did not become common practice
until the morbidity of unoperated perforated
appendicitis greatly exceeded the morbidity
of laparotomy. Due to modern anaesthetic
techniques, treatment became predominantly
surgical in less than 20 years. It became a
principle to perform appendectomy early, on the slightest suspicion of
appendicitis.

At this time, the cost of a negative laparotomy was felt to be low compared to
the risk of a delayed operation [27]. A negative appendectomy was even
regarded as a benefit, eliminating for the patient the risk of a serious and
potentially life-threatening disease [35]. Interval appendectomies were also
strongly recommended after an attack of appendicitis because of the risk for
recurrence [36].
In Western Europe, the frequency of appendectomies reached a peak in mid-
century and has steadily declined since then [37].

Embryology, anatomy and histopathology

The vermiform appendix and the caecum develop from the caecal bud, which
arises from the antemesenteric border of the caudal limb of midgut loop
around the beginning of the sixth gestational week [27]. It remains at the tip
of the caecum until birth but reaches its final position on the posteriomedial
wall below the ileocaecal valve [38] due to the lateral caecal wall growing
faster than the medial. Both the anterior [38] and the retrocaecal position

11
Karl Gustaf Lennander (1857-
1908). Painting by J. A. Drougge
(Museum of Medical History,
Stockholm)

[39] have been described as most frequent by different authors. Different
degrees of malrotation may result in more ectopic locations of the appendix,
e.g. subhepatic [40] and intracaecal [41].
The average appendix length is 9 cm (range 2-25 cm) [39]. The appendix has
the same basic structures as the colon: serosa, muscularis propria,
submucosa, muscularis mucosae, and large intestinal-type mucosa, and the
mucosal features are similar to those of the colon [37]. However, development
of lymphoid tissue resembling the arrangement in the distal small intestine
occurs soon after birth and persists through childhood, until approximately
the age of 25 years. The maximum transverse diameter is reported to be
reached by 4 years of age and decreases gradually thereafter, due to the
involution of the lymphoid tissue and increasing fibrosis [38, 42].

The commonly accepted view is that the appendix is a vestigial organ with no
function. It has been suggested that there is a connection with food habits,
since an appendix-like structure is found in other omnivores than man [43].
The appendix has also been proposed to play a role in the motility of the colon
[44, 45] or for the immunological system, but these theories remain
unproven.

The classical histopathological criterion of acute appendicitis is
polymorphonuclear leucocytic infiltration of the muscularis [46, 47]. In more
advanced stages of inflammation, necrosis of the muscular layer occurs and
may be complicated by perforation, abscess formation or peritonitis. It has
been proposed that simple appendicitis and advanced appendicitis are two
different diseases with different etiologies [48, 49].

Etiology

The etiology of appendicitis remains unknown. The most favoured theory
today is that appendicitis starts with an obstruction, due to swelling of the
mural lymphoid tissue during an acute infection, a faecolith or stenosis, with
subsequent increase of the luminal pressure, leading to mucosal ischemia and
secondary bacterial infection [27]. However, obstruction can only be
demonstrated in approximately one third of surgically removed appendices
[50, 51]. Still, it appears to be more frequent in advanced appendicitis
compared to simple, phlegmonous appendicitis, which may indicate that
obstruction is an aggravating factor when appendicitis is present [49].

Faecoliths or appendicoliths, regarded as possible causes of obstruction, are
more frequently detected when using modern imaging techniques, especially
CT [52, 53]. They appear more frequently associated with perforated
appendicitis and may therefore represent a possible risk for perforation [52,

12

53]; faecoliths may also be an incidental finding when inflammation is absent
[50, 54].

Several alternative causes of appendicitis have been suggested, i.e. primary
infection of the appendix, either hematogenous or originating from a breach
of the mucosal barrier [49, 55], or a consequence of a previous breakdown of
the mucosal barrier with a subclinical infection, leading to a stricture [56]. A
seasonal variance in incidence and cluster outbreaks of appendicitis, as well
as the age distribution with an incidence peak in adolescence, resemble that of
many infectious diseases, especially tonsillitis and influenza [57-59], but a
causal relation has not been verified. There are series of specific infections of
the appendix reported impossible to differ from common acute appendicitis.
Although rare, they may be coincidental findings as well as predisposing
factors: actinomyces [50], Helicobacter jejuni [60], pinworm [61-68],
tuberculosis [50] and Yersinia enterocolica [50, 69, 70] among others. Other
rare reported causes of appendicitis are foreign bodies [38, 71-73] and trauma
[74-80].
Most probably, the etiology of appendicitis is multifactorial.

13

Epidemiology

The diagnosis of appendicitis is not always verified by histopathology and
hence, a review of the epidemiology of appendicitis is difficult. It is generally
assumed that the incidence of appendectomy reflects the incidence of
appendicitis, but this assumption is disputable [27].

Appendectomy is more common in industrialized countries than in
developing countries, and there are also regional differences within the
industrialized countries [81-84]. The highest incidence is reported from Japan
with an incidence of 750 per 100,000 inhabitants annually [85] and from
France with 564 per 100,000 inhabitants [86]. In Sweden, incidences of 120-
210 per 100,000 inhabitants have been reported [87-89]. The cause of
regional variations in incidence is unclear. Hereditary as well as dietary
factors have been suggested [90-95]. The relatively high incidence of
appendectomy in Japan and France is thought to be related to the type of
insurance systems, qualification regulations for surgeons and patient
expectations [27].

Acute appendicitis occurs in all ages but there is a marked increase in the second
decade [3, 21, 37]. About 10% of all patients are younger than 10 years and about
10% are older than 50 years [49]. Acute appendicitis occurs also in neonates
[96-101], although the disease is rare under the age of two years.

Appendicitis is 15% to 48% more common in men and the gender difference is
seen in all ages [3, 57, 87-89, 102]. From the United States, racial differences
have been reported with a 50% lower incidence in blacks and Asians
compared to Caucasians [3, 57]. A family history of appendicitis appears to be
a significant risk factor [90, 91, 103, 104]. Synchronous appendicitis in first-
degree relatives has been reported, indicating both a genetic susceptibility and
an environmental cause [105-107]. Breastfeeding in infancy may have a
protective effect since children who were breastfed for more than 7 months
had a 40% lower risk of appendicitis than children who were never breastfed
[108].

The lifetime risk of having appendicitis, based on data from the United States
1970-1984 [3] is approximately 9% for males and 7% for females. The lifetime
risk of appendectomy is 12% for males and 23% for females [3].

14

CLINICAL MANAGEMENT

Epidemiological research during the last decades has demonstrated different
incidence patterns of perforated and non-perforated appendicitis, and it has
been suggested that these are two different entities [109]. There is a constant
incidence of perforation in all age groups [102, 110], and there are indications
that most perforations occur before admission to hospital [111, 112]. Since
obstruction is more common in advanced appendicitis, it has been proposed
that simple and complicated appendicitis have different etiology and
pathogenesis [48, 49].
The overall incidence of perforation is 16%-39%, with a median of 20% [3, 12,
16, 27, 52, 111-114].

The perforation rate is higher in children (23-73%) [9, 114-118] and in elderly
patients (55-70%) [54, 112, 113, 116], who are thought to have a lower
resistance to perforation or a more rapidly progressive disease [119]. Patients
who have a delayed diagnosis have a high perforation rate [120-123]. These
patients often have concurrent diseases and unclear clinical symptoms [124].

In children, there is often a delay before being brought to medical attention
[125]. Approximately one third of patients are regarded to have atypical
clinical findings [9]. Furthermore, children may be difficult to examine and
may be unable to communicate their complaints [126]. It has also been
suggested, that the thinner appendiceal wall in children may result in a more
rapid progression of appendicitis to perforation [127].

Negative appendectomies

An inverse relationship between the rate of perforations and the rate of
negative laparotomies has been demonstrated [16, 128]. It has been argued
that “a proportion of normal appendices should appropriately be removed to
avoid perforations” [16]. The reported negative appendectomy rate ranges in
various studies from 14 to 25% [9-11, 129, 130] and even higher rates have
been reported in selected populations with diagnostic difficulties and a higher
risk of perforation, i.e. in children, women and elderly patients [12, 131]. A
negative appendectomy rate of approximately 20% generally has been
considered acceptable [11, 54].

The necessity of the inverse relationship between the perforation rate and the
negative appendectomy rate was questioned already during the seventies
[132]. In a study from Germany 1971, the high rate of negative explorations
was associated with increased mortality [83]. Studies performed during the
last decades have shown that most perforations probably have occurred

15

before the patient’s admission to hospital, and the rate of explorations has not
been found to influence the incidence of perforation [110, 111, 133, 134].

Avoiding unnecessary laparotomies has become increasingly desirable, since
the complication rate is not negligible and is even higher with negative
laparotomy, compared to positive [12-14, 135]. The increased risk of
developing small bowel obstruction after a negative appendectomy may be
attributable to both the surgical technique [12, 13] and to patient-related
factors, i.e. increased inflammatory response [136]. Economic aspects on the
negative appendectomy rate have also become increasingly important, since
unnecessary surgery is a waste of medical resources. The death and
complication rates following perforated appendicitis have decreased over the
years as a result of improved perioperative routines and postoperative care,
including treatment with modern antibiotics [137, 138].
Since the introduction in recent years of modern imaging techniques in the
evaluation of suspected acute appendicitis, namely ultrasonography 1986
[139] and computed tomography [9, 52, 140-143], several studies have
demonstrated that the negative appendectomy rate can be reduced without
an increase of the perforation rate [10, 144-146].

Clinical course

In typical cases, the disease begins with a visceral pain located to the
epigastrium. After a variable time interval, but usually within 6-18 hours, the
pain migrates to the right lower quadrant of the abdomen and a constant,
distinct tenderness develops, due to the peritoneal engagement. Rebound
tenderness, as well as voluntary and involuntary muscular contraction, may also
be present. Associated symptoms may include anorexia, nausea, vomiting,
constipation or, especially in children, diarrhoea.
Untreated appendicitis is thought to proceed to perforation in the vast
majority of cases. Perforation may result in short-lasting pain relief, but is
then followed by a gradual increase in severity of the symptoms [37].
Associated complications include peritonitis and septicaemia.

In approximately 2-3% of patients with acute appendicitis, perforation is
followed by the development of a demarcated appendiceal abscess [33, 147].
The appendiceal abscess formation is also believed to occur without an
obvious rupture of the appendiceal wall, since bacteria may readily permeate
a damaged appendiceal wall [46].

The disease progression proceeds usually during 8-48 hours; if the diagnosis of
appendicitis is not made within this time interval, the probability that it actually
is appendicitis is progressively reduced [37]. A developed appendiceal

16

abscess may, however, have a history of less distinct symptoms during several
weeks. As mentioned before, spontaneously resolving appendicitis has been
reported [148-150]. Recurrent and chronic forms of appendicitis have also
been recognized [151-154].

The typical presentation described above, however, occurs in only two thirds
of the patients with appendicitis, and patients with other abdominal
conditions may have similar symptoms [121, 155]. The variability in the
precise anatomical location of the appendix affects the localized symptoms
[155]. Children are more often believed to have an atypical presentation [9].

Table 1. Diagnostic accuracy in acute appendicitis at Massachusetts
General Hospital 1937-1959. Modified after Barnes et al. [156]

Incidence of diagnosis when Incidence of postoperative
Diagnosis appendicitis was diagnosed diagnosis when appendicitis was
peroperatively (%) diagnosed preoperatively (%)

Mesenteric lymphadenitis 0.2 4.6
Ovarian cyst pathology 0.3 2.0

Pelvic inflammatory disease 0.2 1.3
Gastroenteritis 0.9

Small bowel pathology 0.3 0.5
Meckel’s diverticulitis 0.4
Diverticulitis 0.1 0.3
Cholecystitis 0.2 0.3

Renal or urethral pathology 0.2
Regional ileitis 0.2

Endometriosis 0.2
Colon carcinoma 0.3 0.1
Pancreatitis 0.1

Diagnostic methods

History

Knowledge of the clinical course of appendicitis is mandatory for adequate
history taking. In children, there are considerable difficulties involved;
young children, especially, may be incapable of understanding and
answering questions meaningfully [126], which may contribute to a delay
before being brought to medical attention [125].

17

Physical examination

The basis for the diagnosis of appendicitis is the induction of abdominal
tenderness in the right iliac fossa due to the local inflammation of the
appendix. With further progress, the tenderness becomes more severe. A
local muscle guarding develops as a response to peritoneal involvement. After
a rupture and free peritonitis, the abdomen becomes distended with a
general, pronounced tenderness and generalized muscular guarding [37].
Rectal examination may yield tenderness anteriorly or to the right. Some
patients have a positive psoas stretch test; i.e., raising the right leg causes
pain. Due to the dynamic character of the disease, repeated examinations are
strongly recommended [157-160].

Laboratory findings

Appendicitis is often accompanied by a systemic inflammatory response, as
seen by the presence of fever, leukocytosis, and an increase in the
concentration of the C-reactive protein (CRP) [27]. The diagnostic efficacy of
laboratory tests, however, depends on the stage of appendicitis [161].

The total white blood cell count (WBC) is usually increased to more than 9.0 x
109 per litre. Repeated measurements have shown that WBC may decrease
and even be normalized despite the continuous process of inflammation
[162].

CRP values exceeding 10 mg/l may be useful in clinical managements of
acute infections, including appendicitis [8, 163-165]. In evaluating the CRP
results, however, the duration of symptoms is important since patients with a
short history of symptoms (less than 12 hours) may not have developed an
increase of CRP values. Therefore, repeated measurement may be valuable
[162]. In children, CRP values are less reliable in the evaluation of suspected
appendicitis, than in adults [166].

Urinalysis

Bacteriuria can be detected in 15% of patients with appendicitis [167].
Haematuria and leukocyturia may occur, and are more frequent when
the appendix is localized retrocaecally or in the pelvis [168]. A normal
urine sample, however, does not rule out appendicitis.

18

Laparoscopy

Laparoscopy has been described as a cost-saving procedure in the diagnosis
and treatment of abdominal pain in patients with unclear etiology [169, 170]
and especially when appendicitis is suspected [171-174]. Still, laparoscopy is
an invasive procedure requiring anaesthesia, and is associated with a risk for
complications [175, 176].

Radiologic imaging

PLAIN RADIOGRAPHS AND BARIUM ENEMA

Plain abdominal radiographs and barium enema are non-specific and of little
value. Radiographs were reported to be normal or misleading in 75% of cases
of pediatric appendicitis in one study [177], whereas other authors found
radiographs helpful in only 6% of cases [178]. Filling of the appendix to the
tip with contrast virtually excludes appendicitis, whereas non-filling of the
appendix with mass effect on the caecum suggests appendicitis [179].
However, the appendix does not fill completely in 8% of normal cases [179].
Furthermore, determination of complete filling can be difficult because of the
variation in the length of normal appendices and variation in the level of
obstruction in appendicitis [180]. Other conditions than appendicitis can
produce mass effect on the cecum [181]. Nowadays, plain radiographs and
barium enema have been replaced by modern imaging techniques with
higher sensitivity and specificity.

ULTRASONOGRAPHY (US)

The graded-compression ultrasonographic technique was originally
introduced by Puylaert 1986 [139]. Since then, numerous studies have
demonstrated the usefulness of US in the evaluation of suspected appendicitis
[182-188]. The overall sensitivity of US varies in different studies, but usually
lies within the range of 75-95% [183]; however, values as low as 44% have
been reported [142]. The specificity of US is usually reported to lie within the
range of 90-95% [183], although substantially lower values have been
reported [189, 190]. The diagnosis of appendicitis is based on the detection of
a blind-ending, non-compressible tubular structure with a maximal diameter
exceeding 6 mm, with or without an appendicolith, and with no peristaltic
activity. Color Doppler imaging may demonstrate hyperemia in the
appendiceal wall which is regarded as a finding of high specificity [191];
however, detectable hyperemia may be absent in early and in advanced,

19

gangrenous appendicitis [9]. Currently, there are no reports on the use of
contrast-enhanced ultrasonography in the evaluation of appendicitis.

Ultrasonographic images of a phlegmonous appendicitis.
Longitudinal (left) and transverse (right) image.

The major limitation of US is its high
operator dependency, as illustrated by the
wide range of sensitivity and specificity
values in different studies. The lowest
values are generally achieved in studies
when US is performed by sonographers
with limited experience of imaging of the
gastrointestinal tract [192], while
substantially higher values are achieved
when US is performed by a limited
number of experienced specialists [187,
193]. A further limitation of US in
diagnosing appendicitis is the fact that
non-
visualization of the appendix does not rule out appendicitis. Well-known
difficulties in identifying the appendix may occur in patients with pain,
obesity, overlying gas, or in perforated appendicitis. Several recent studies
have demonstrated that a normal appendix can be visualized in a large
number of patients with symptoms suggestive of appendicitis [182, 191, 193-
196]; this finding is regarded as highly specific in excluding appendicitis [191].
In children, however, the smaller amount of intraabdominal fat compared to
that in adults may affect the ability to identify the normal appendix and also
to distinguish it from bowel loops.

20
Phlegmonous appendicitis. Color
Doppler ultrasonographic image
demonstrating mural hyperemia.

The outer diameter of the appendix has
been a subject of discussion. Rettenbacher
et al [193] demonstrated a marked overlap
of outer appendiceal diameter in normal
and inflamed appendices, and concluded
that an outer diameter of 6 mm or more as a
sign of acute appendicitis provides high
sensitivity but limited specificity. Hahn et al
[187] reported lymphoid hyperplasia as a
cause of a sonographically abnormal
appendix. In children, the mucosa and

submucosa are physiologically thicker
[197], which might explain the relatively
high number of false-positive US
examinations reported by some authors
[198]. Some cases regarded as false-positive in different studies may also
represent spontaneously resolving appendicitis [148-150].

The great advantage of US as the primary imaging modality is the fact that
it is relatively quick to perform and does not involve the use of ionizing
radiation, which is of special importance in children [199].

COMPUTED TOMOGRAPHY (CT)

Helical computed tomography with use of a variety of techniques has been
shown to be highly sensitive and specific for the diagnosis of appendicitis [10,
52, 54, 140-142, 144, 200-204]. The reported overall sensitivity lies usually
within the range of 90-100%, and the specificity within 91-99% [142, 144, 178,
201, 202, 205, 206], although different techniques have been used in the
various studies. Several institutions have now accepted CT as the method of
first choice because of its advantages over US, including less operator
dependence, more confident visualization of the appendix, and better
delineation of the extent of phlegmon and abscess in complicated appendicitis
[207]. The disadvantages of CT include higher cost, potential risks of contrast
media, and ionizing radiation exposure, which is especially critical in children
[199]. There is considerable controversy in the literature regarding the use of
oral, rectal or intravenous contrast agents, as well as the question of whether
the area scanned should be limited or not.
The diagnosis of appendicitis is based on the visualization of an enlarged
appendix with a maximum diameter exceeding 6 mm, with contrast
enhancement in the thickened appendiceal wall (in contrast enhanced CT

21
Ultrasonographic longitudinal
image of a gangrenous
appendicitis.

studies), and/or pericaecal inflammatory changes, or on the visualization of
an abscess, with or without an appendicolith. The pericaecal inflammation
may be absent, as reported by some authors [203, 204, 208], especially in
patients with mild and incipient forms of appendicitis [52].

Transverse contrast-enhanced abdominal CT scan
demonstrating an inflamed, curved appendix (arrows).

Transverse contrast-enhanced abdominal CT scan
demonstrating a gangrenous appendicitis with an
appendicolith (arrow) and pericaecal inflammation.

Accurate identification of the normal appendix in patients whose symptoms
are caused by alternative conditions is of great value; however, the
relatively small volume of intraperitoneal fat, which is generally seen in
children, especially younger than 10 years, has been shown to decrease the
rate of identification of a normal appendix [209].

22

Two consecutive contrast-enhanced abdominal CT scans demonstrating
a normal air-filled appendix (arrows).

In recent years, it has been suggested that ionizing radiation from diagnostic
imaging carries a risk of later development of malignancy [199, 210, 211].
Children are at greater risk from ionizing radiation than adults, both because
of a longer life span during which cancer can develop, and also because of the
increased radiation sensitivity of developing tissues. Because of its frequent
use, a major area of concern is the risk of radiation from CT scanning. Mettler
et al. found that CT scans were responsible for 67% of the effective dose to the
population from all diagnostic imaging studies, and 11% of these CT scans
were performed in children [212]. Paterson et al. reported that the majority of
CT studies performed at different institutions did not use techniques
appropriate for children, which included both factors resulting in increased
radiation dose and factors decreasing diagnostic accuracy [213]. An example
of a non-medical activity that increases radiation exposure is high altitude
airline flight. It has been estimated that 10,000 miles of long distance airline
travel result in an increase in the cancer risk rate for children of 1 in 5,000
[214], which is similar to the single CT risk calculated, using the modern lower
dose techniques.

Therefore, CT scanning should be ordered with attention to both the risk and
the benefit. In most cases, the benefit greatly outweighs the risk [215]. All CT
scans should be performed using the lowest dose that provides the radiologist
with the necessary information [215]. Donnelly et al. described a table that
can be used to choose the single-detector CT scanning technique for adjusting
the radiation dose, depending on the part of the body scanned and on the
patient’s size. Th e use of this technique in young children provided a decrease
in radiation dose of up to 75% without loss of diagnostic confidence [216].
Models for dose reduction for multidetector CT are also being increasingly
discussed [217]. Still, the greatest possible decrease in risk occurs when an
unnecessary study is not performed.

23

MAGNETIC RESONANCE IMAGING (MRI)

Magnetic resonance imaging offers the advantages of excellent soft tissue
contrast, multiplanar imaging capability, and no ionizing radiation exposure.
There are, however, only a small number of studies regarding evaluation of
possible appendicitis in selected populations [218-220]. The method has
several limitations; i.e., high cost, it is time-consuming and therefore
frequently requires sedation in children, and is rarely available on an
emergency basis. Furthermore, since faecoliths and intestinal gas produce
similar signal voids on MRI, they may be difficult to distinguish. There is a
need for further studies, but currently MRI cannot be advocated over US or
CT for the evaluation of appendicitis, especially not in children.

Treatment of appendicitis

Appendectomy

Open appendectomy is the treatment of choice in the vast majority of patients
with appendicitis. The surgical technique used today has evolved from
tradition and experience during several decades. Detailed descriptions are
available in textbooks of surgery, e.g., P. Myers description from 1994 [23].
Laparoscopic appendectomy was performed for the first time in 1983 [221],
and is now performed routinely at numerous institutions, in both adults and
children.

Conservative treatment

Conservative treatment with antibiotics only (combined intravenous and oral
treatment) has been used in acute appendicitis in small adult populations [ 7]
but, to my knowledge, there are no studies restricted to children. Antibiotic
treatment that may or may not be followed by an interval appendectomy,
however, is frequently used in the management of appendiceal abscesses;
sometimes combined with percutaneous drainage of the abscess. Prophylactic
antibiotic treatment, preceding an appendectomy, is recommended especially
in cases of advanced appendicitis [138].

24

Histopathologic analysis

The generally accepted histologic criterion for the diagnosis of acute
appendicitis is polymorphonuclear leukocytic infiltration of the
muscularis layer [46]. Usually, neutrophils and ulcerations are also
present within the mucosa. The different stages of appendicitis are usually
referred to as phlegmonous, gangrenous or perforated appendicitis.
However, the histopathological examination has been stated to be an
“imperfect gold standard” [27], since the cr iteria for the diagnosis of
appendicitis are not set and may vary between different institutions and
interpreters.

Histological section of an acute appendicitis with
ulceration of the mucosa and intense
inflammatory infiltration of neutrophile
granulocytes through the appendiceal wall.

(Section provided by Edneia Tani, MD, PhD, Dept.
of Cytology, Karolinska Hospital).

25

AIMS OF THE THESIS

The main aims of the present investigation were

฀ To evaluate the diagnostic accuracy of ultrasonography (US) and of
abdominal computed tomography (CT) performed in addition to US in
the diagnosis of appendicitis in children 



฀ To compare the diagnostic accuracy of different CT techniques, namely
non-enhanced helical CT limited to the lower part of the abdomen, CT
of the entire abdomen after intravenously administered contrast
medium, and the combination of both, in order to optimize the CT
technique and possibly reduce the radiation dose 



฀ To evaluate how the negative appendectomy rate and the perforation
rate have changed during the past decade with the introduction of and
increased use of US and CT 



฀ To evaluate how the radiologic imaging procedures, including US
only or US and CT, affect the surgeon’s decision making process in
the management of suspected appendicitis in children 

26

MATERIAL AND METHODS

Prospective study

Study setting

The evaluation of suspected appendicitis was analysed in a prospective
randomized study that constituted the basis for papers I, III and IV. The study
was performed during a period of 9 months, from December 1999 to
September 2000, and was approved by the local ethics committee at
Karolinska Hospital. All children who were clinically suspected of having
acute appendicitis and were admitted to the emergency department of Astrid
Lindgren Children’s Hospital, Stockholm, received oral and written
information about the study. Patients with abdominal pain that was
considered to be due to obstruction without inflammation were excluded.
Informed consent was obtained from each child’s parents. The vast maj ority
of the consecutive patients chose to participate in the study. The study
population consisted of 600 children, including 312 girls and 288 boys
(average age, 10.4 years; age range, 2-15 years).

The initial examination was performed by a pediatric surgeon or a surgical
resident on duty, who estimated the likelihood of each child having
appendicitis on a scale from 0% to 100%. The initial clinical impression before
performing radiologic investigation was recorded, designating the patient for
operation, observation, or discharge, with or without a planned new visit for
re-examination.
After this protocol, all patients were randomized to undergo US only (283
patients) or US and additional abdominal CT (317 patients).

US and CT Scan Interpretation

The US studies were performed and interpreted by either one of 12 pediatric
radiologists or one of 9 senior residents who had completed rotations in
general US and at least 2 months in pediatric radiology. All studies were
performed by using a 7-MHz linear- array transducer (Sequoia; Acuson,
Mountain View, Calif) and the graded compression technique described by
Puylaert [139]. The criteria for the diagnosis of appendicitis were previously
established [139, 193].

Helical CT scanning was performed on a single detector-row CT scanner (CT
HiSpeed Advantage; GE Medical Systems, Milwaukee, Wis). Each CT study
consisted of two scans. Initially, a limited scan of the lower part of the
abdomen was performed without any contrast medium administration. After

27

that, a nonionic contrast medium was administered intravenously, and the
entire abdomen was scanned. The injected dose was 2 mL per kilogram of
body weight, with an upper limit of 100 mL. Patients with a history of asthma
or possible previous reactions to contrast medium were excluded. There were
no severe adverse drug reactions to the intravenous administration of contrast
medium. No oral or rectal contrast medium was administered. All CT scans
were analysed at a workstation, i.e. on computer monitors, and interpreted by
either one of 12 pediatric radiologists or one of 9 senior residents. The
diagnosis of appendicitis was based on criteria established in prior studies
[54, 208, 222-224]. The CT study was always performed after the US study,
and the time interval between the US and CT examinations was kept as short
as possible. The interpreter of the CT study had access to the results of the US
study.
Both the US scan interpreter and the CT scan interpreter stated whether
appendicitis was present or not, and estimated their level of confidence
in their finding on a scale from 0% to 100%.
These statements form the basis for the analysis performed in papers I
and IV.

In paper III, a retrospective review of prospectively acquired data from the
CT examinations referred to above was performed. All CT examinations were
divided into three groups, which were evaluated by three pediatric
radiologists, working independently: group A, all non-enhanced limited CT
studies; group B, all contrast enhanced CT studies; group C, both all the non-
enhanced and the enhanced sequences together. To avoid any recall bias, the
readers evaluated the sequences in different order, and the patients appeared
in different order within the groups. In this study, the readers were blinded to
all clinical information and to the results of previous US and CT studies.

Final disposition, final diagnosis and follow -up

After the radiologic imaging was completed, the patient was re-examined by
the surgeon, who made the final disposition for the patient as to operation,
observation, or discharge. The final clinical outcomes were determined at
surgery and histopathologic analysis in the patients who underwent
laparotomy (n = 252). The nonsurgically treated patients (n = 348) were
followed up with a questionnaire, which was sent to the child’s parents 6
months after their emergency department admission. The questions about
their state of health and possible treatment at other facilities, if any, after
discharge from our hospital were designed to track any false-negative
diagnoses. The questionnaire was completed by 327 (94%) of the 348
patients who were treated nonsurgically. The medical records of all patients
were also reviewed.

28

Retrospective study

The changes in the negative appendectomy rate and the perforation rate
during the past decade were studied in a retrospective study, which
constituted the basis for paper II.
In the greater Stockholm area, pediatric surgery is centralized such that the
vast majority of pediatric surgical cases up to 15 years of age have been
provided care at St. Göran Children’s Hospital until 1998, when it was closed
and replaced by Astrid Lindgren Children’s Hospital , located at the
Karolinska Hospital area. The pediatric population in the greater Stockholm
area has gradually increased during the past decade, and at present, the
hospital has a referral area of approximately 350,000 children.

We retrospectively reviewed the medical records of the first 150 children
during the years 1991, 1994, 1997 and 2000 who underwent appendectomy.
Hence, the study population consisted of totally 600 children (343 boys, 257
girls; mean age 10 years, age range 0 – 15 years). The years were chosen with
consideration to the time when US and CT were introduced as diagnostic tools
in the evaluation of suspected appendicitis at St. Göran Children’s Hospital.
The total number of appendectomies and the total number of cases of
appendicitis were recorded. In perforated appendicitis, the perforation was
considered to have occurred after admission if the time interval between the
first contact between the patient and any health professional (i.e., primary
physician or surgical consultant at admission) and surgery exceeded 12 hours.
Any performance of US and/or CT in order to investigate suspected
appendicitis, as well as the results of the investigation, were recorded.

The study was scrutinized by the local ethics committee and considered
quality assurance and therefore exempted from further ethical review.

Statistical analysis

Paper I

Measures of imaging examination validity – namely sensitivity, specificity,
diagnostic accuracy, and positive and negative predictive values – in the
diagnosis of appendicitis were calculated in each randomly selected group,
and also for the diagnosis of appendicitis with US only in all 600 patients, and
for the diagnosis of appendicitis with CT only in 317 patients. The standard
Pearson χ2 test was performed to compare the calculated values of US and CT

29

in each group. A P value of .05 or lower was considered to indicate a
significant difference.

Paper II

The contingency tables were analysed by standard Pearson χ2 test and tested
for trend by Spearman correlation. Fisher’s exact test was used for
comparison of the negative appendectomy rates for the years studied. The
computations were done with SPSS procedure crosstabs, release 10.0.1 (SPSS
Inc., Chicago, Ill.). A P value of .05 or lower was considered to indicate a
significant difference. The incidence of appendicitis for the years studied was
correlated to the population statistics and an overall incidence was calculated.

Paper III

Individual and pooled sensitivity and specificity values for the three
interpreters were calculated for the diagnosis of appendicitis for the limited
non-enhanced CT, for the contrast enhanced CT of the entire abdomen, and
for the combination of both. The standard Pearson χ2 test was performed to
compare the values between groups. A P value of .05 or less was considered to
indicate a statistically significant difference. Receiver operating characteristic
(ROC) curves were calculated by group for each reader.

Paper IV

Receiver operating characteristic (ROC) curves were calculated for the
radiologist and for both the initial and the final surgical decision in the two
randomized groups. The computations were done with SPSS for Windows,
release 10.0.1 (SPSS Inc., Chicago, Ill.).

30

RESULTS

The main results are summarized below. For further details, see paper I – IV.

Diagnostic accuracy of US and CT

Of the 600 patients, 244 (41%) had a final diagnosis of appendicitis. US had an
overall sensitivity of 80% (196 of 244 patients), an overall specificity of 94% (336
of 356 patients) and diagnostic accuracy of 89% (532 of 600 patients). In the
group assigned to undergo US only, US had a sensitivity of 86% (94 of 109
patients), a specificity of 95% (165 of 174 patients) and diagnostic accuracy of
92% (259 of 283 patients). In the group of patients who were randomly assigned
to undergo US and CT, CT had a sensitivity of 97% (131 of 135 patients), a
specificity of 93% (170 of 182 patients) and diagnostic
accuracy of 95% (301 of 317 patients).
The combination of both US and CT had
a sensitivity of 99% (133 of 135 patients),
a specificity of 89% (162 of 182 patients)
and diagnostic accuracy of 93% (295 of
317 patients). Positive and negative
predictive values were also calculated. All
values and clarifying data are listed in
Tables 1-3, paper I.
Ultrasonographic image of a
phlegmonous appendicitis with
an appendicolith (arrow).

Table 2. The most common differential diagnoses in patients who did not have
a final diagnosis of appendicitis.

Diagnosis Number of patients %
(of the total of 356)

Non-specific abdominal pain 192 54

Mesenterial lymphadenitis 100 28

Gastroenteritis 20 5.6

Ovarian cyst 8 2.3

Urinary tract infection 8 2.3

Pneumonia 4 1.1

Ovarian torsion 3 0.8

Miscellaneous* 21 5.9

* The ”miscellaneous” group included patients (n = 1 in each condition) with pancreatitis,
intussusception, hematokolpos, small bowel obstruction, Wilms’ tumor etc.

31

The rates of negative appendectomies and perforations

Of the total of 244 patients with appendicitis, 235 patients underwent
appendectomy, and 8 were treated conservatively with antibiotics only for
appendiceal abscess. One patient with an appendiceal abscess was
identified at follow-up and treated by means of drainage.

A total of 252 patients underwent laparotomy. Eight patients underwent
laparotomy because of diagnoses other than appendicitis, and all of
these diagnoses were made using preoperative radiologic imaging.

In 9 patients, the results of appendectomy were negative for appendicitis.
Of these, 6 patients had negative radiologic findings and appendectomy was
performed on the basis of clinical symptoms. Consequently, the negative
appendectomy rate in this study was 3.7%.

Perforated appendicitis was diagnosed in 52 of 244 patients, including 11
cases of appendiceal abscess. Consequently, the perforation rate was 21%. In
88% (46 of 52 patients), a correct diagnosis of appendicitis was made with US
and/or CT. One patient had a false- negative diagnosis with both US and CT,
but surgery was performed because the clinical findings were convincing for a
diagnosis of perforated appendicitis.

Two consecutive contrast-enhanced abdominal CT scans
demonstrating perforated appendicitis. Pus in the peritoneal cavity
(white arrow). An appendicolith surrounded by pus (black arrow).

Diagnostic accuracy of different CT techniques

From the original 317 patients who underwent CT, 11 were excluded from the
retrospective review of the prospectively acquired data (paper III) because of
technical difficulties in obtaining both CT sequences in each patient when the
PACS software was upgraded. Hence, the study population consisted of 306
patients.

32

Of these, 129 (42%) had appendicitis. Interpreters diagnosed appendicitis
with 66% pooled sensitivity and 96% pooled specificity with limited, non-
enhanced CT. With contrast-enhanced CT of the entire abdomen, appendicitis
was diagnosed with 90% pooled sensitivity and 94% pooled specificity. With
the combination of both sequences together, readers diagnosed appendicitis
with 90% pooled sensitivity and 94% pooled specificity. The individual results
for each reader, by CT technique, are listed in Table 2 (paper III).

Transverse non-enhanced
abdominal CT scan. The appendix,
although visible, cannot be
distinguished from bowel loops.

Transverse contrast-enhanced
abdominal CT scan at the same
leve as the image above. The
inflammed appendix clearly visible
due to contrast enhancement of the
thickened appendiceal wall (arrow).

Changes in the rates of negative appendectomies
and perforations over time

The retrospective study (paper II) revealed that the total number of
appendectomies performed because of presumed acute appendicitis during
the years 1991, 1994, 1997 and 2000 varied from 334 to 406 (Table 1). Th e
negative appendectomy rate for the years studied decreased gradually from
23% to 4.0%. During the same years, the use of US and CT increased
gradually from 1.3% and 0.0% to 98% and 59%, respectively. In appendicitis,
the overall perforation rate remained stable between 29% and 34%. The
perforation rate after admission decreased from initially 12% to 2.1%. For
details, see Fig 2-3 (paper II).

33

Because of the very low incidence of appendicitis below the age of 3 years (Fig.
1), the overall incidence of appendicitis was calculated for the age interval of 3
to 15 years. After adjusting for age, the population-based incidence of
appendicitis for the years studied has not changed.

Impact of radiologic imaging on surgical decision-
making process

The initial disposition called for 88 operations, 338 observations, and 167
discharges. In total 347 patients had their treatment plan changed from the
initial disposition, resulting in 252 operations, 65 observations, and 276
discharges. A total of 7 patients were initially designated for “other
treatment”, such as medical treatment, referral to other departments etc, and
were thus excluded from further analysis. In 11 patients, an unnecessary
operation was possibly avoided. In 28 patients who turned out to have
appendicitis, a possible inappropriate discharge was avoided. Eighteen
patients had a false negative radiological diagnosis. Of these, 17 underwent
surgery due to convincing clinical findings. For further details, see Fig. 2a- c
(paper IV).
CT provided additional information for the surgeon only when the results
of US and CT were discordant, which occurred in 16% (50 of 317 patients).

DISCUSSION

Suspected appendicitis is the most common cause of emergency abdominal
surgery in children [225]. Despite its common occurrence, accurate diagnosis
remains challenging. Appendicitis may be missed at initial clinical
examination in 28-57% of children aged 12 years or younger and in nearly
100% of children younger than 2 years [226]. Delay in treatment increases the
risk of perforation and its complications, including abscess formation,
peritonitis, sepsis, bowel obstruction, tubal sterility in girls, and death [207].

Diagnostic imaging of appendicitis with graded-compression US and helical
CT has steadily improved over the past decades, but the effect of radiologic
imaging on negative appendectomy rates, perforation rates and management
outcome has been a subject of discussion [11, 135, 227]. A minority of studies
are prospective and focused on children [11, 142, 143, 178, 201, 206, 228-
230].

The ideal diagnostic test should be safe, fast, non-invasive, highly accurate,
inexpensive and readily available. Several studies have demonstrated that
higher sensitivity can be achieved when using helical CT compared to US, and

34

it has been recommended as the method of first choice by several authors
[231-233]. During recent years, however, concern over the risks of ionizing
radiation generated by CT has increased, especially in the pediatric
population [199, 210, 211].

Ultrasonography

The results of our prospective study demonstrate that both US and CT are
excellent tools for making the diagnosis of appendicitis in children, and that
CT outperforms US with respect to sensitivity, negative predictive value and
overall diagnostic accuracy. It has also been shown, however, that CT provides
additional information to the surgeon only when the results of the US and CT
studies are discordant.

US is a generally available, relatively inexpensive and safe procedure, that
does not involve the use of ionizing radiation, and requires no patient
preparation. Although it is well known that US is highly operator-dependent,
the fact that senior residents were included among the staff members who
performed US in our study demonstrates that an acceptable value of
sensitivity can be reached. The major disadvantage of US is the fact that a
negative US examination does not exclude appendicitis unless a normal
appendix is confidently visualized. Visualization rates vary widely in the
published literature from 22 to 98% [142, 234]. Our studies demonstrated
even lower visualization values; however, although a normal appendix has
been seen occasionally, the possibility of mistaking a bowel loop for a normal
appendix, and thus giving the surgeon the false impression that appendicitis
has been ruled out, has led to some underreporting of this finding. Patient-
dependent difficulties include body constitution and meteorism; bypassing an
initial ultrasonogram in obese children has even been suggested [209, 235].

US should remain the method of first choice in the evaluation of suspected
appendicitis in children. CT should be added to the imaging protocol for
patients who have negative US findings but clinical presentations strongly
suggestive of appendicitis, in inconclusive cases, and/or when the radiologist
lacks experience with US.

Computed tomography

The additional CT study should be performed with intravenous contras t
material. Our results of the retrospective review of the prospectively acquired
CT studies have demonstrated a significant improvement in sensitivity values

35

with contrast-enhanced CT compared to non-enhanced. Our results do not
support the need of rectal contrast administration since our sensitivity and
specificity values are consistent with other studies performed both with and
without rectal contrast [144, 178, 201, 202, 206]. Partial opacification of the
appendix occurs frequently when contrast material is administered rectally
[179, 180] and hence, distal appendicitis may not be excluded.

Our results have led to a modification of the previous CT protocol and the
non-enhanced limited scan has been excluded at our department. The present
protocol includes scanning of the entire abdomen similar to the scanning
model used in the study. Previous studies have shown that limiting the
scanning field may result in not including the appendix in the CT study and
also adversely affect the interpreter’s ability to diagnose alternative conditions
[200, 236]. However, in our study, the total number of patients with
substantially pathological conditions in the upper abdomen was low,
representing approximately 2.6% (8 of the 306 patients). Hence, over 97% of
the CT studies could have been limited to the lower abdomen without clinical
consequence. There is a need for further studies regarding the extent of the
scanning field.

The exclusion of the first, limited non-enhanced CT study from the imaging
protocol has reduced the total radiation dose by approximately 31%, and the
exposure to the gonads by approximately 50% compared to the original
protocol that included two scans. As previously postulated, CT should be
performed using the lowest dose that is reasonably achievable but still
providing the radiologist with the necessary diagnostic information [199,
207], and scanning parameters should be optimized for children [217, 237-
240]. Communication between the radiologist and the clinician is crucial for
avoiding unnecessary CT studies (especially repeat examinations) and
provides the greatest possible potential to minimize unnecessary ionizing
radiation.

The sensitivity values achieved by the three interpreters in the retrospective
CT review (paper III) were lower than those achieved in the prospective study
(paper I), probably due to several reasons which are discussed in the paper.
Still, the sensitivity and specificity values achieved are high enough to
consider CT useful for long distance consultations between radiologists
without access to clinical data or the results of an US study, if performed; e.g.,
using an inter-hospital teleradiology system.

36

Negative appendectomy rate

The results of our retrospective study have demonstrated a gradual decrease
in the negative appendectomy rate during the past decade, and a
contemporaneous increase of the use of US and CT in the evaluation of
suspected appendicitis in children. Since the management of appendicitis has
not changed apart from the increased preoperative use of imaging modalities,
it may be assumed that the decrease in the negative appendectomy rate is
attributable to the increased use of preoperative radiologic imaging.

The negative appendectomy rate of 3.7% achieved in our prospective study is
very low compared with that in most studies, but rates of 4% [145, 241] and
6% [142] have been reported. Still, false negative imaging results may occur,
and the final decision to operate or not remains the surgeon’s. Thus, a small
number of negative laparotomies cannot be completely avoided.

Perforation rate

It has been repeatedly shown in prior studies that the rates of perforated
appendicitis are higher in children than in adults, probably due to several
reasons that have been discussed previously. The majority of appendiceal
perforations in children appear to occur before the patient’s admission to the
surgical service [112] limiting the possibility to affect the number of these
perforations. The results of our retrospective study have demonstrated a
stable overall perforation rate during the years studied, but a decreasing
perforation rate after admission, from initially 12% to 2.1%. It has been
suggested that preoperative imaging might contribute to an increase in
perforation rate [11]. Our results do not support this hypothesis. Other
authors have reported decreased perforation rate after implementation of an
imaging protocol rather similar to ours [146]. On the basis of our results, it
may be assumed that a decrease in the rate of perforations after admission
may be achieved when preoperative radiologic imaging is used.

The radiological diagnosis of perforated appendicitis may be difficult. The
results of our studies have demonstrated that the vast majority of cases with
perforated appendicitis can be correctly diagnosed by means of CT, although
occasional false negative results may occur. Therefore, a careful clinical
examination is of utmost importance, as well as close communication between
the radiologist and the surgeon.

37

Decision analysis

Despite the numerous studies that have demonstrated significantly improved
diagnostic accuracy in detecting appendicitis [10, 139, 142, 143, 145, 185, 187,
200, 206, 242, 243], relatively little is known about the impact of various
radiological investigati ons on the physician’s diagnostic and therapeutic
thinking. A hierarchical model for assessing the effectiveness of a radiological
investigation has been described by Fineberg [244] and further developed by
Fryback and Thornbury [245] and Dixon [246, 247]. In these models, the first
two levels refer to technical and diagnostic-accuracy efficacy, respectively
[245], or technical and diagnostic performance, respectively [248]. Most
studies concentrate on these two levels [248]. A minority of studies are
focused on the third and fourth levels, namely diagnostic thinking efficacy and
therapeutic efficacy [245], or diagnostic and therapeutic impact [248]. The
number of studies concerning the impact of radiologic imaging on the
surgeon’s decision -making process in suspected appendicitis in particular is
relatively small [142, 186, 228, 249]. Previously, US has been reported to
change initial treatment plans in 30-46% of patients [186, 228], and CT in up
to 73% of patients [142, 249]. The results of our prospective study are in
accordance with these reports, demonstrating that imaging findings have a
high level of efficacy in level 3 and 4, according to Fryback and Thornbury
[245], concerning diagnostic thinking and therapeutic efficacy. Radiologic
imaging may guide whether a patient should be discharged home, admitted
for observation, or given surgical treatment, which may lead to beneficial
changes in management plans. The greatest influence on the surgeon’s
decision-making process was achieved in the group of patients initially
designated for observation, since a large number of patients were discharged
from the hospital after performing radiologic imaging which was negative for
appendicitis. In minor groups of patients, unnecessary operations as well as
unfortunate discharge were possibly avoided. Since the costs of radiologic
imaging are minor compared to the cost of observation on a pediatric ward,
unnecessary surgery or delayed diagnosis, the improvement in diagnosis
provided by radiologic imaging can be obtained in a cost-effective manner.

38

CONCLUSIONS

฀ US is a valuable, highly specific tool in the diagnosis of appendicitis in
children. The sensitivity of US is lower than that of CT but a positive
US examination greatly helps rule in the diagnosis of appendicitis,
making further imaging unnecessary. The well-known advantages of
US make it suitable as the primary imaging modality in the evaluation
of suspected appendicitis in children. 

฀ Diagnostic accuracy can be increased significantly by performing
abdominal CT in addition to US. Therefore, abdominal CT should be
added to the imaging protocol when the US study fails to visualize the
appendix but the patient has a clinical presentation strongly suggestive
of, but not totally convincing for, appendicitis, when the US study is
inconclusive, or when the radiologist lacks experience with US. 

฀ Additional abdominal CT should be performed with intravenous
contrast material administration. A limitation of the scanning field can
probably be considered for the majority of patients but there is a need
for further studies. 

฀ During the past decade, the introduction and gradually increased use
of US and CT in the evaluation of suspected appendicitis in children
has led to a substantially decreased negative appendectomy rate. The
overall perforation rate has remained stable. The rate of perforations
after admission appears to decrease over time. 

฀ Following the imaging protocol described above, the negative
appendectomy rate can be reduced to a level of approximately
4% without an increase of the perforation rate. 

฀ Radiologic imaging with US and/or CT provides valuable guidance as
to whether a child with suspected appendicitis should be discharged,
observed, or given surgical treatment, which may lead to beneficial
changes in the management plan. The high diagnostic accuracy
achieved by CT makes it an alternative for long distance consultations
between radiologists, e.g., using an inter-hospital teleradiology system.
Still, false negative results may occur and a close clinical re-
examination is of utmost importance for the appropriate final decision. 

39

ACKNOWLEDGEMENTS

I wish to express my sincere gratitude to all persons who have
contributed to this work and made it possible for me to complete
this thesis. In particular, I want to thank

Associate professor Håkan Jorulf , my supervisor, for his
continuous support. Without his dynamic vision and never ending
enthusiasm, this project would never have gotten off the ground.

Professor Björn Frenckner , my supervisor, for his continuous
support. Without his constructive encouragement and
professional supervision, this project would never have landed.

Erik Söderman, PhD , statistician and co-author of papers II, III
and IV, for valuable help with statistical calculations.

Carmen Mesas-Burgos, MD and Thröstur Finnbogason,
MD , my co-authors of papers II and III, respectively, for their
positive attitude despite the large number of cases to be reviewed.

Peter Radell, MD, PhD, for skilful linguistic assistance.

Lars Johanson, MD , head of the Department of Pediatric
Radiology, Astrid Lindgren Children’s Hospital, for continuous
support and encouragement.

All my collegues and all nurses at the Department of Pediatric
Radiology, Astrid Lindgren Children’s Hospital, who have contributed to
the completion of the first prospective study by performing the US and
CT investigations, for their patience and positive attitude.

All the surgeons and nurses at the Emergency Department, Astrid
Lindgren Children’s Hospital, who have contributed to the
completion of the first prospective study by performing the clinical
examinations and filling in the study forms, for their positive attitude
and encouragement.

Ulla Svahn , research assistant, for valuable help with collecting
the data regarding papers I and III.

My family , for love and encouragement. Sten , my husband, for
appreciated discussions and continuous IT-support. Ylva , my
daughter, for always telling me that I am the best.

40

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