reevaluating the sonographic criteria for acute appendicitis in children

Reevaluating the SonographicCriteria for Acute Appendicitis

in Children:

A Review of the Literature and a Retrospective Analysis of 246 Cases

Andrew T. Trout, MD, Ramon Sanchez, MD, Maria F. Ladino-Torres, MD

Ac

FrCCCCAd

ªht

13

Rationale and Objectives: There has been little rigorous evaluation of the sonographic criteria for acute appendicitis in children. Our clin-

ical experience has called the traditional diagnostic criteria into question. We set out to review the literature, evaluate the most commonly

applied diagnostic criteria for acute appendicitis, and identify those criteria that best predict the presence of disease.

Materials and Methods: A critical review of the literature concerning the sonographic diagnosis of acute appendicitis was performed.

Based on diagnostic criteria identified in that review, two independent, blinded pediatric radiologists retrospectively reviewed 246 right

lower quadrant ultrasound examinations in which the appendix was identified with attention to commonly described diagnostic criteriafor acute appendicitis. Multivariate and classification and regression tree analysis were performed to identify criteria that predict

appendicitis.

Results: In a multivariate analysis, inflammation of the periappendiceal fat is the only finding that statistically significantly predicts acute

appendicitis (OR = 68.93,P< .0001). Other criteria such as diameter, noncompressibility, hyperemia, the presence of an appendicolith, andloss of stratification of the appendiceal wall do not independently predict appendicitis.

Conclusion: Periappendiceal fat infiltration is themost important diagnostic criterion for acute appendicitis in children. Strict application of

other criteria such as diameter should be avoided.

Key Words: Appendix; ultrasound; diagnosis.

ªAUR, 2012

Sonographic evaluation of the appendix was originally

described in 1986 in a population of adults (1). Since

that time, the technique has been adopted in children

and due to the lack of ionizing radiation has largely become

the technique of choice in this population (2). In the 25 years

since the original article, there have been numerous analyses

of the performance of ultrasound in diagnosing acute appen-

dicitis in children. Interestingly, the diagnostic criteria that are

applied for acute appendicitis are largely based on the adult

population and these criteria, as they apply to children, have

received significantly less analytic attention over that same

25-year period. A few studies have evaluated the diagnostic

value of specific sonographic findings (3–7) and a recent

analysis has called into question the diagnostic criteria as

ad Radiol 2012; 19:1382–1394

om the Department of Radiology, Section of Pediatric Radiology, C.S. Motthildren’s Hospital, University of Michigan Medical Center, 1500 East Medicalenter Drive, 3-228, Ann Arbor, MI 48109-4252 (A.T.T., R.S., M.F.L.-T.);incinnati Children’s Hospital Medical Center, Department of Radiology,incinnati, OH (A.T.T.). Received February 3, 2012; accepted June 23, 2012.dress correspondence to: R.S. e-mail: [email protected]

AUR, 2012tp://dx.doi.org/10.1016/j.acra.2012.06.014

82

historically defined in the literature (8). This recent publica-

tion resonated with our clinical experience as we have anec-

dotally noted the limited value of some of the traditional

diagnostic criteria. Specifically, we hypothesized that appen-

diceal diameter >6 mm and lack of compressibility of the

appendix are poor diagnostic criteria for acute appendicitis

and that secondary findings such as periappendiceal fat infil-

tration better predict the presence of appendicitis.

Based on our clinical experience and this hypothesis, we set

out to critically review the literature and to evaluate the diag-

nostic performance of common sonographic criteria for acute

appendicitis in children.

MATERIALS AND METHODS

Institutional review board approval was obtained for this ret-

rospective analysis, which represents an analysis of a subset of

patients from a cohort previously reported (9) in the literature.

Sonographic examinations of the appendix between May

2005 and May 2010 were identified through a search of the

Radiology Informatics System. The following search criteria

were used:

Delta:1_given name

Delta:1_given name

Delta:1_given name

Delta:1_surname

Delta:1_given name

Delta:1_given name

Delta:1_given name

Delta:1_surname

Delta:1_given name

mailto:[email protected]

http://dx.doi.org/10.1016/j.acra.2012.06.014

TABLE 1. Diagnostic Criteria Assessed by Independent Reviewers and the Specific Definitions of these Criteria

Parameter Definition

Maximal appendiceal diameter Maximum anteroposterior dimension of the appendix measured in millimeters from

serosal to serosal surface while imaging the appendix in the transverse plane

Compressibility (Figure 6) Measurable, reproducible change in the caliber of the lumen of the appendix or

noticeable deformation of the adjacent or overlying soft tissues

1. Yes

2. No

3. Inadequate compression

Appendiceal wall signature (Figure 7) 1. Three concentric hyperechoic rings (normal (17)): Five distinct layers of bowel

wall that are alternately hyperechoic and hypoechoic (hyperechoic mucosal

surface, hypoechoic mucosa, hyperechoic submucosa, hypoechoic muscularis

and hyperechoic serosa)

2. Two concentric hyperechoic rings: Preservation of the outer two hyperechoic

rings (serosa and submucosa), with nonvisualization of the inner hyperechoic

ring (mucosa)

3. One hyperechoic ring: Preservation of the outer most hyperechoic ring (serosa)

with nonvisualization of the inner two hyperechoic rings (mucosa and submucosa)

Appendiceal vascularity (Figure 8) Assessed with color or power Doppler, relative to adjacent normal soft tissue

1. Normal

2. Increased

3. Decreased or absent

4. Not assessed

Periappendiceal fat

infiltration (Figures 3 and 4)

Increased echogenicity of the periappendiceal fat relative to normal intraabdominal

fat with associated thickening

1. Absent: Very minimal (noncircumferential) or no echogenic fat adjacent to

the appendix

2. Present: Echogenic periappendiceal fat with ill-defined margins that

circumferentially surrounds the appendix

Presence of appendicolith (Figure 9) Echogenic, well-defined focus within the appendix with posterior acoustic shadowing

1. Yes

2. No

Presence of fluid Simple or complex fluid without a defined wall

1. Yes

2. No

Fluid characteristics 1. Simple: Anechoic

2. Complex: Echogenic components, including septations

Presence of organized fluid collection Loculated fluid collection surrounded by a definable wall with associated mass effect

1. Yes

2. No

Academic Radiology, Vol 19, No 11, November 2012 PEDIATRIC APPENDICITIS: ULTRASOUND CRITERIA

1. Patient demographics: <18 years of age

2. Referral source: outpatient or emergency room

3. Exam types: right upper quadrant, right lower quadrant,

abdominal ultrasound

4. Exam/clinical indications: abdominal pain, right lower

quadrant pain, pelvic pain, appendicitis, fever

Of the approximately 4000 records identified that met these

search criteria, only those in which the appendix was identified

by the initial interpreting radiologistwere included in the analysis.

Two pediatric radiologists with 11 and 4 years of clinical

experience (R.S., M.LT.) independently reviewed each ultra-

sound examination in which the appendix was identified.

These reviews were performed using Siemens KinetDx

WS3000 workstations (Siemens Medical Solutions USA

Inc., Mountain View, CA) and were independent of the

clinical interpretation of the ultrasound examinations that

had been previously provided by another radiologist. Research

reviewerswere blinded to patient outcomes andwere provided

with only the clinical history recorded by the technologist at

the time of the examination. Each reviewer recorded data

related to sonographic criteria for acute appendicitis previ-

ously reported in the literature (Table 1). These criteria were

derived from a review of the literature and included those cri-

teria that had been previously reported to have diagnostic

value. Diagnostic criteria were standardized between the two

reviewers before independent review of the data. In addition

to recording diagnostic criteria, each reviewer provided an

impression of ‘‘normal appendix,’’ ‘‘acute appendicitis,’’ or

‘‘perforated acute appendicitis’’ for each case.

The electronic medical records for each patient were

reviewed by a third study team member for demographic

1383

TABLE 2. Summary of Diagnostic Parameters as Recorded by Both Readers

Parameter n (%)

Pathology Conclusion

Normal Appendicitis Perforated Appendicitis

Mean maximal diameter

Reader 1: 5.9 � 1.8 mm 10.2 � 3.1 mm 10.1 � 4.1 mm

Reader 2: 5.7 � 1.6 mm 10 � 2.9 mm 10.3 � 3.1 mm

Compressibility

Yes

Reader 1: 40 (18.2%) 26 9 5

Reader 2: 42 (19%) 36 6 0

No

Reader 1: 17 (7.7%) 1 11 5

Reader 2: 58 (26.2%) 6 17 35

Inadequate compression

Reader 1: 163 (74.1%) 90 56 17

Reader 2: 121 (54.8%) 76 35 10

Appendiceal wall signature

3 rings (normal)

Reader 1: 155 (70.5%) 108 38 9

Reader 2: 154 (69.7%) 112 34 8

2 rings

Reader 1: 59 (26.8%) 9 34 16

Reader 2: 58 (26.2%) 6 36 16

1 ring

Reader 1: 6 (2.7%) 0 4 2

Reader 2: 9 (4.1%) 0 6 3

Appendiceal vascularity

Normal

Reader 1: 78 (53.4%) 59 14 5

Reader 2: 61 (41.8%) 49 9 3

Increased

Reader 1: 55 (37.7%) 7 38 10

Reader 2: 67 (45.9%) 12 43 12

Decreased/absent

Reader 1: 13 (8.9%) 0 10 3

Reader 2: 18 (12.3%) 2 12 4

Periappendiceal fat infiltration

Absent

Reader 1: 120 (52.4%) 110 10 0

Reader 2: 119 (51.5%) 110 9 0

Present

Reader 1: 109 (47.6%) 15 66 28

Reader 2: 112 (48.5%) 18 67 27

Presence of appendicolith

Yes

Reader 1: 38 (17.3%) 3 25 10

Reader 2: 32 (14.5%) 3 21 8

No

Reader 1: 182 (82.7%) 114 51 17

Reader 2: 189 (85.5%) 115 55 19

Presence of fluid

Yes

Reader 1: 135 (58.7%) 67 46 22

Reader 2: 104 (45.2%) 49 38 19

No

Reader 1: 95 (41.3%) 59 30 6

Reader 2: 124 (53.9%) 77 38 9

TROUT ET AL Academic Radiology, Vol 19, No 11, November 2012

1384

TABLE 2. (continued) Summary of Diagnostic Parameters as Recorded by Both Readers

Parameter n (%)

Pathology Conclusion

Normal Appendicitis Perforated Appendicitis

Fluid characteristics

Simple

Reader 1: 105 (78.4%) 65 34 6

Reader 2: 80 (75.5%) 44 26 10

Complex

Reader 1: 29 (21.6%) 1 12 16

Reader 2: 26 (24.5%) 5 12 9

Presence of organized fluid collection

Yes

Reader 1: 8 (3.4%) 0 2 6

Reader 2: 5 (2.1%) 0 1 4

No

Reader 1: 225 (96.6%) 129 74 22

Reader 2: 228 (97.9%) 129 75 24


information (age, sex, and body mass index) and outcomes

(surgery, surgical pathology, and discharge diagnosis). Dis-

charge diagnosis and pathologic diagnosis were considered

the gold standard for diagnosis and outcomes.

Statistical Analysis

Assessment of interrater agreement and reader agreement

with outcomes was performed using the kappa (k) statistic

with 95% confidence interval as well as frequency of agree-

ment. Individual parameters were assessed for diagnostic value

for acute appendicitis using Fisher’s exact test and calculation

of odds ratios for discrete parameters, and logistic regression

with resulting odds ratios for continuous parameters. Multiple

explanatory variables were assessed using logistic regression

using stepwise elimination of parameters. P < .05 was consid-

ered significant for all analyses. To determine if combinations

of criteria better predict appendicitis, Classification and

Regression Tree (CART) analysis was performed with nodes

restricted to a minimum of 20 patients. This type of analysis

creates a decision tree in which variables with the greatest dis-

criminatory efficacy are placed earlier in the tree. By restrict-

ing node size to n = 20, diagnostic criteria that subdivide

patients into groups smaller than 20 are excluded. Accepting

smaller node sizes allows more accurate subdivision of the

patient population but also complicates the diagnostic tree

making it less clinically useful. All analyses were performed

for data from both readers. Statistical analysis was performed

with SAS version 9.2 (SAS Institute Inc., Cary, NC), except

for the CART analysis, which was performed using S-PLUS

version 7.0 (Insightful Corp., Seattle, WA).

RESULTS

The appendix had been reportedly identified by the initial inter-

preting radiologist in 246 examinations. In 13 of these examina-

tions, the reviewers felt that the appendixhadnot beenaccurately

identified. Of the 233 patients with a visualized appendix, out-

comes data were available in 220, with the other 13 lost to

follow-up. A total of 125 (53.6%) of the examinations were in

female patients and 108 (46.4%) were in males. The mean age

for the patient population was 10.7 � 4.1 years. Raw data

with findings for each of the variables are detailed in Table 2.

Based on pathologic and clinical conclusions, 76 patients

were diagnosed with nonperforated acute appendicitis and

27 were diagnosed with perforated (gross and microscopic

perforation) appendicitis. A total of 117 patients (53.2% of

220) did not have appendicitis. Readers 1 and 2 correctly cate-

gorized patients into the three groups (appendicitis, perfo-

rated appendicitis, and normal) 82.9% (k = 0.70, 95% CI:

0.62–0.79) and 79.2% (k = 0.64, 95% CI: 0.55–0.73) of the

time, respectively. When patients were subdivided based on

the presence of acute appendicitis alone (combining perfo-

rated and nonperforated cases), readers 1 and 2 correctly diag-

nosed appendicitis in 88.7% (k = 0.77, 95% CI: 0.69–0.86)

and 89.1% (k = 0.78, 95% CI: 0.78–0.87) of cases. Diagnostic

agreement between the two readers was present 87.3% of the

time (k = 0.77, 95% CI: 0.7–0.85) when three diagnostic cat-

egories were used (appendicitis, perforated appendicitis, and

normal) and 93.2% (k = 0.86, 95% CI: 0.8–0.93) of the

time when distinguishing appendicitis from normal.

Appendiceal Diameter

Mean appendiceal diameter for each of the diagnostic catego-

ries is detailed for both readers in Table 2. Table 3 details the

observed frequency of acute appendicitis for each millimeter

of appendiceal diameter in this patient population. This table

also lists diagnostic performance results including sensitivity,

specificity, positive predictive value, negative predictive value

and accuracy for a diagnostic cut-off of 6 mm as commonly

1385

TABLE 3. Frequency of Acute Appendicitis (Perforated and Nonperforated) Based on Maximal Appendiceal Diameter

Diameter n

Appendicitis

(Perforated, Nonperforated) Normal Sensitivity Specificity PPV NPV Accuracy

2–4 mm

R1: 22 (10%) 2 (1, 1) 20

R2: 25 (11.3%) 1 (0, 1) 24

5 mm

R1: 32 (14.5%) 3 (3, 0) 29 95.1% 41.9% 59% 90.7% 66.8%

R2: 36 (16.3%) 2 (1, 1) 34 97.1% 49.2% 62.5% 95.1% 71.5%

6 mm

R1: 45 (20.5%) 10 (3, 7) 35 85.4% 71.8% 72.7% 84.8% 78.2%

R2: 43 (19.5%) 7 (2, 5) 36 90.3% 79.7% 79.5% 90.4% 84.6%

7 mm

R1: 23 (10.5%) 11 (1, 10) 12 74.8% 82.1% 78.6% 78.7% 78.6%

R2: 21 (9.5%) 12 (2, 10) 9 78.6% 87.3% 84.4% 82.4% 83.3%

8 mm

R1: 16 (7.3%) 5 (2, 3) 11 69.9% 91.5% 87.8% 77.5% 81.4%

R2: 14 (6.3%) 7 (2, 5) 7 71.8% 93.2% 90.2% 79.1% 83.3%

$9 mm

R1: 82 (37.3%) 72 (17, 55) 10

R2: 82 (37.1%) 74 (20, 54) 8

NPV, negative predictive value; PPV, positive predictive value; R1, reader 1; R2, reader 2.

Sensitivity, specificity, PPV and NPV results are based on using that diameter as a diagnostic cutoff.


described in the literature and 7 mm as recently proposed by

Goldin et al (8). Receiver operating characteristic curves for

the range of appendiceal diameters as measured by each reader

are shown in Figures 1 and 2. The area under the curve is

0.874 and 0.915 for readers 1 and 2, respectively.

Other Diagnostic Parameters

Based on univariate analysis which looks at each variable

isolated from the others, the statistical significance of indi-

vidual diagnostic parameters as predictors of acute appendi-

citis with associated odds ratios are detailed in Table 4. As a

continuous variable, appendiceal diameter is not a signifi-

cant predictor of acute appendicitis (P = .1286 and P =

.0933 for readers 1 and 2, respectively). Specific cutoffs of

6 mm, 7 mm, and 8 mm, however, are significant predictors

(Table 4).

On multivariate regression which accounts for interactions

between variables, the only diagnostic parameter that statisti-

cally significantly predicted the presence of acute appendicitis

for both readers was the presence of infiltration of the periap-

pendiceal fat (P < .0001 for both; Figs 3, 4). The diagnostic

value of infiltration of the periappendiceal fat is as follows

(listed reader 1/reader 2): sensitivity 90.4%/91.3%, specificity

88%/85.9%, positive predictive value 86.2%/83.9%, negative

predictive value 91.7%/92.4%, accuracy 89.1%/88.3%. For

reader 2 only, bowel wall signature (specifically two vs. three

rings) was also a significant predictor or acute appendicitis

(P = .0132). For reader 1, bowel wall signature approached

but did not reach statistical significance (P = .0561). The

remainder of the diagnostic criteria were not statistically sig-

nificant predictors of appendicitis on multivariate analysis.

1386

Classification and regression tree analysis demonstrates that

combinations of diagnostic criteria do not change, to a great

extent, the classification of a given case beyond that assigned

by the presence or absence of infiltration of the periappendi-

ceal fat (Fig 5).

DISCUSSION

Despite 25 years of experience with the use of sonography in

the evaluation of acute appendicitis, there has been little

refinement of the diagnostic criteria in a pediatric population.

Most of the data concerning the use of this modality in chil-

dren focus on the overall diagnostic performance of sonogra-

phy as it relates to clinical management and as it compares to

computed tomography. Few articles have rigorously evaluated

the specific criteria for a sonographic diagnosis of acute

appendicitis in children.

Currently, the most commonly used diagnostic criteria are

a noncompressible appendix with an outer diameter >6 mm

(7,10–12). Other criteria that have been described include

hypervascularity, periappendiceal fat infiltration, loss of the

normal bowel signature in the appendiceal wall, and the

presence of an appendicolith (13–18).

Appendiceal Diameter

An appendiceal diameter of >6 mm is the most commonly

described diagnostic criterion for acute appendicitis. This cut-

off was first described in 1988 by Jeffrey et al who prospec-

tively evaluated 250 adult patients with suspected acute

appendicitis (19). In this population, 78/84 (93%) patients

with an appendix measuring >6 mm had appendicitis. Based

Figure 1. Receiver operating characteristic

curve for appendiceal diameter for reader 1.

Figure 2. Receiver operating characteristiccurve for appendiceal diameter for reader 2.


on their findings, the authors stated that ‘‘.maximal appen-

diceal diameter may be an additional useful parameter in guid-

ing clinical management’’ but qualified this by saying ‘‘.our

criteria regarding appendiceal diameter are not absolute and

are presented merely as guidelines’’ (19).

Although the 6 mm cutoff was originally described in an

adult population, descriptive studies have since defined the

diameter of both the normal and acutely inflamed appendix

in children. Results of these studies are detailed in Table 5.

Although there is a broad range of measurements for normal

appendices, studies have shown no association between

appendiceal diameter and patient specific factors such as

height, weight, or body mass index (6,20). Some of the

observed variation in appendiceal diameter may reflect

differences in measurement. In our review of the literature,

we have been unable to identify an agreed-on measurement

method, and most authors do not define how they are

measuring the appendix. Differences are introduced by

measuring anterior to posterior versus transversely as well as

measuring under different degrees of compression, particu-

larly if the appendix is compressible (6,20). Additionally,

human variation introduces measurement differences.

Between our two reviewers, the mean difference in diameter

measurement over all patients was 0.7 � 1.3 mm.

1387

TABLE 4. Statistical Significance of Individual Diagnostic Parameters for a Diagnosis of Acute Appendicitis Based upon UnivariateAnalysis of Findings Recorded by Readers 1 and 2

Parameter

Reader 1 Reader 2Interrater Agreement

(95% Confidence Interval)Odds Ratio P Value Odds Ratio P Value

Sex (male) 1.99 .0120 –

Age 1.03 .0914 –

Body mass index 2.43 .0262 –

Appendiceal diameter

Continuous variable 1.02 .1286 1.02 .0933 0.9*

6-mm cutoff 14.12 <.0001 32.22 <.0001

7-mm cutoff 14.93 <.0001 36.43 <.0001

8-mm cutoff 13.54 <.0001 25.28 <.0001

Compressibility (no) 0.03 <.0001 0.02 <.0001 0.675 (0.469–0.882)

Appendiceal wall signature 0.741 (0.645–0.836)

1 ring vs. 3 rings NA .0010 NA <.0001

2 rings vs. 3 rings 12.77 <.0001 23.09 <.0001

Vascularity 0.755 (0.653–0.857)

Decreased vs. normal NA <.0001 NA <.0001

Increased vs. normal 21.29 <.0001 18.72 <.0001

Periappendiceal fat infiltration (yes) 68.93 <.0001 63.83 <.0001 0.886 (0.825–0.946)

Appendicolith (yes) 19.56 <.0001 15.02 <.0001 0.898 (0.818–0.979)

Free fluid (yes) 1.66 .0801 1.91 .0173 0.674 (0.579–0.769)

Fluid characteristics (complex vs. anechoic) 45.5 <.0001 5.13 .0015 0.713 (0.552–0.873)

Organized fluid collection NA .0014 NA .0168 0.763 (0.497–1)

Interrater agreement for each parameter is also provided expressed as kappa statistics with Pearson correlation (*) reported for appendiceal

diameter as a continuous variable. Odds ratios indicated as ‘‘NA’’ are a result of inability to calculate the odds ratio in situations in which there is

a frequency of zero in any one of the diagnostic categories.

Figure 3. Periappendiceal fat infiltration.

(a) A 2 year old with abdominal pain. Ultra-

sound showsa normal appendixwith normalperiappendiceal fat. The fat is intermediate in

echogenicity and without mass effect. (b) A10yearoldwith right lower quadrantpain.Ul-trasound shows circumferential echogenic

fat (asterisks) around a distended, abnormal

appendix in a patient with acute appendici-

tis. Note the increased thickness and poordefinition of the fat in addition to the altered

echogenicity.


Despite the difficulties inherent in measurement, several

studies in both children and adults have looked at the diagnos-

tic performance of a diameter cutoff in acute appendicitis.

Those studies that evaluated diameter as an independent var-

iable are summarized in Table 6. Much of the attention has

focused on the 6 mm cutoff described by Jeffrey et al, which

has been shown to be variably predictive in both children

and adults. Although some results support the use of a

6 mm cutoff (4,5), there is evidence that this cutoff may not

be ideal. The diameter measurement of the appendix

depends on wall thickness and luminal content. Normal

physiologic processes such as lymphoid hyperplasia leading

1388

to wall thickening as well as fecal impaction resulting in

distention of the appendiceal lumen have been shown to

increase the diameter of the appendix to >6 mm (14,21). In

their recent pediatric study, Goldin et al found that using

the traditional 6 mm cutoff would have only correctly classi-

fied 84% of appendicitis cases and would have resulted in 26

unnecessary surgeries (8). Based on their findings, the authors

recommend a 7 mm cutoff (8).

Studies in adult patients have also called a 6 mm cutoff into

question as up to 23% of normal patients and 14%–32% of

patients with right lower quadrant pain but without acute

appendicitis have appendices >6 mm in diameter (22,23).

Figure 4. A 10 year old with right lower quadrant pain and periap-

pendiceal fat infiltration resulting from acute appendicitis. In this im-age, the appendix is oriented longitudinally. Note the echogenic,

thickened periappendiceal fat (asterisks) surrounding the abnormal

appendix (A). The signature of the appendiceal wall is abnormal

with only a single echogenic layer visible.


Based on a high sensitivity (100%) but low specificity (68%),

Rettenbacher et al concluded that a 6 mm cutoff was more

appropriately suited to exclude appendicitis than to diagnose

it (22).

In our population, appendiceal diameter as a continuous

variable was not statistically significantly associated with a

diagnosis of acute appendicitis. While cutoff diameters of

6 mm, 7 mm, and 8 mm were all significant predictors in

the univariate analysis, the accuracy of these cutoffs was

only moderate (Table 3) and was not as good as described

by Goldin et al (8). This is difficult to explain, but might be

attributed to population or measurement differences. Median

appendiceal diameters were a full millimeter larger in both

normals and patients with acute appendicitis in our popula-

tion than in the population described by Goldin et al (5 vs.

6 mm for normal; 9 vs. 10 mm for appendicitis).

In multivariate analyses, diameter cutoffs were no longer

statistically significant predictors of acute appendicitis in our

population. To date, the only other multivariate analysis of

diagnostic criteria for acute appendicitis in the literature is a

study of adult patients by van Randen et al that did find a

diameter of 6 mm as a statistically significant predictor of

appendicitis (OR = 9.4) (24). This discrepancy is difficult to

explain but could relate to study design or possibly differences

between adult and pediatric patients.

Although statistically our data do not support the use of a

diameter cutoff, if one were to be used, an 8 mm cutoff would

provide greater diagnostic accuracy than a 6 mm cutoff

(Figs 1, 2; Table 3).

Compressibility

In the original description of the use of ultrasound for the

diagnosis of acute appendicitis, Puylaert described the diag-

nostic criteria for acute appendicitis as a noncompressible

appendix with a faint or invisible echogenic layer (Fig 6)

(1). These criteria were simply stated by the authors and not

evaluated for their specific diagnostic performance. Noncom-

pressibility is one of the diagnostic criteria that is most com-

monly accepted but has received little evaluation in isolation

of other diagnostic parameters. The only studies that have

evaluated this criterion in isolation are in adults and the results

are conflicting. Kessler et al found that the identification of a

noncompressible appendix in a population of 125 adults had a

sensitivity and specificity of 96%with an accuracy of 96% (12).

van Randen et al however found that a noncompressible

appendix was not a significant predictor of appendicitis in a

population of 942 adults (OR = 0.8) (24).

This discrepancy may be explained by methodological dif-

ferences. To the best of our understanding, it appears that

Kessler et al evaluated their data in a univariate fashion

whereas van Randen et al performed a multivariate analysis.

The importance of this difference is apparent in our findings.

Based on a univariate analysis, identification of a noncompres-

sible appendix is significantly associated with the presence of

acute appendicitis. Under multivariate analysis, however, a

lack of compressibility does not predict the presence of appen-

dicitis, suggesting interplay of diagnostic variables.

It is our opinion that compressibility is one of the most

operator dependent factors assessed in a right lower quadrant

ultrasound. As we were designing this study, we struggled to

define ‘‘adequate compression.’’ Although the concept seems

simple, there are many hindrances to adequate compression.

These include:

� Depth of the appendix: it is difficult to exert compressive

force on an appendix that is at depth within the abdomen

� Overlying/adjacent tissues: a subhepatic, perirenal, or ret-

rocecal appendix can be difficult to compress

� Patient guarding: adequate compression cannot be

achieved in a patient who is tensing their abdominal

musculature

� Patient body habitus: adequate compression can be difficult

to achieve in obese patients because of intervening body fat

(subcutaneous or intraabdominal)

� The presence of fluid, particularly loculated: fluid is non-

compressible and thus may not allow compression of an

underlying appendix

� Decompressed appendix: if the appendix is collapsed it may

not compress further

� Mobile appendix: a normal appendix is mobile and may be

displaced rather than compressed

Based on our definition of adequate compression which

required a measurable change in the diameter of the

appendiceal lumen or clear deformation of the adjacent soft

tissues, our reviewers felt that compression was inadequate

1389

TABLE 5. Diameters of Normal and Acutely Inflamed Appendices Reported in the Pediatric Literature

Study Study Type n Mean Normal Diameter Mean Appendicitis Diameter

Goldin, 2011 Retrospective 204 5.0 mm (range 2.0–11.0)* 9.0 (range 1.3–20.0 mm)*

Hahn, 1998 Prospective 542 suspected appendicitis

54 healthy

3.9 (�1.2) mm 10.9 (�3.1) mm

Ozel, 2011 Prospective 142 4.2 (�0.9) mm –

Park, 2007 Prospective 51 – 9.7 mm (range 6.7–21.2 mm)

Wiersma, 2005 Prospective 118 3.9 mm (range 2.1–6.4 mm) –

Our data Retrospective 216 5.9 (�1.7) mm 10.5 (�3.1) mm

*Diameters reported are median diameters.

Figure 5. Classification and Regression Tree (CART) analysis based on reader 1. Each decision point in the tree is the result of application of

one of the diagnostic criteria. Criteria with the greatest discriminatory efficacy are placed earlier in the tree. Percentages indicated in parenthe-

ses are the rate of appendicitis in that subgroup. Note that periappendiceal fat strandingmost effectively classifies patients (highest percentage

of appendicitis in the positive group and lowest percentage in the negative group). Application of additional diagnostic criteria change thediagnostic probability as indicated but do not substantially change the classification of patients to ‘‘appendicitis’’ or ‘‘not appendicitis.’’


in 74% and 55% of the examinations they reviewed (reader 1,

reader 2).

Altered Appendiceal Wall Signature

The appendix has been described as having five distinct echo

layers including (Fig 7) (18,25):

Echogenic mucosal surface

Hypoechoic mucosa

Echogenic submucosa

Hypoechoic muscularis propria

Echogenic serosal fat

In pathologic specimens of acute appendicitis, the integrity

and stratification of these layers is lost (25). Similar changes

were noted in vivo in a multicenter trial in which alteration

of the normal mural stratification was the only ultrasound

finding that in isolation had adequate sensitivity for a diagnosis

1390

of acute appendicitis (26). Other than these studies, there are

few data in the literature to support the use of this diagnostic

criterion. Our data show that loss of the normal appendiceal

wall signature is a statistically significant predictor of acute

appendicitis in univariate analysis for both readers but only

for reader 2 in multivariate analysis. The odds ratio for this

parameter, however, is much lower than that for periappendi-

ceal fat infiltration and CART analysis shows that the most

important criteria to stratify patients is periappendiceal fat

infiltration (Fig 5).

Vascularity

Doppler flow within the appendiceal wall that is greater than

that in normal adjacent soft tissues (which have little to no

detectable flow) has been described as a finding diagnostic

of acute appendicitis (Fig 8) (16). Quillin et al showed that

in children, increased Doppler flow had a sensitivity of 87%,

specificity of 97%, and accuracy of 93% for acute appendicitis

Figure 7. Appendiceal wall signature. In this 4 year old with right lower quadrant pain, the normal appendix (a) has three concentric hyper-

echoic rings formed by the serosa, submucosa, and mucosa. Progressive inflammation results in loss of these concentric rings beginningwith the mucosa. (b) In this 15 year old with right lower quadrant pain, the appendix has a two-ring appearance with the echogenic submucosal

and serosa still visible. (c) In this 10 year old with acute appendicitis, ultrasound shows loss of all but the outer serosal echogenic ring.

Figure 6. Compression of a normal appen-dix. In this 15 year old with right lower quad-

rant pain, the normal appendix is indicated

by the arrows. (a) With gentle pressure theappendix is more round in configuration.

During compression (b), there is a notable

change in diameter of the appendix which

is now more ovoid in configuration.

TABLE 6. Performance of Specific Diameter Cutoffs in the Diagnosis of Acute Appendicitis as Reported in the Literature

Study Study Type Population Total n n Used for Analysis Diameter Cutoff Sens Spec Acc OR

Je, 2009 Retrospective Pediatric 160 160 >5.7 mm 89.6 93.2

Peletti, 2006 Prospective Pediatric 107 100 >6 mm 100 98

Goldin, 2011 Retrospective Pediatric 304 204 >7 mm 89.7 95.4 93.2

Kessler, 2004 Prospective Adult 125 104 >6 mm 98 98 97

Rettenbacher, 2001 Prospective Adult 710 518 >6 mm 100 68 79

van Randen, 2010 Prospective Adult 942 528 >6 mm 9.4

Worrel, 1990 Prospective Adult 200 200 >6 mm 66 93

Sens, sensitivity; spec, specificity; acc, accuracy; OR, odds ratio.

Although diameter is commonly used as a diagnostic criterion, these were among the few studies that looked at diameter as an independent

predictor in the sonographic evaluation of appendicitis.


(16). Results in adults were less convincing with Kessler et al

showing a sensitivity of 52%, specificity of 96%, and accuracy

of 73% for color Doppler and Incesu et al showing a sensitivity

of 74%, specificity of 93%, and accuracy of 80% for Power

Doppler (12,27). More recently, studies in both children

and adults have found that vascularity is not a significant

predictor of acute appendicitis (3,8,24). Our findings

support the latter conclusion. Although vascularity was a

significant univariate predictor of appendicitis, this effect did

not persist in the multivariate analysis.

Assessment of the vascularity of the appendix is inherently

limited because it is dependent on Doppler settings and user

technique. Additional difficulty is introduced by the fact that

the assessment of hyperemia is subjective and the development

of appendiceal necrosis has been shown to result in decreased

or absent vascularity, clouding the diagnostic picture (14).

1391

Figure 8. Hypervascularity in acute appendicitis. Normally, flow

greater than that of normal adjacent soft tissue should not be detect-able within thewall of the appendix. In this 10 year old with right lower

quadrant pain, there is increased blood flow in the wall (arrowheads)

and within the echogenic periappendiceal fat.


Periappendiceal Fat Infiltration

In our population, infiltration of the periappendiceal fat had

the highest odds ratio of all diagnostic criteria in the univariate

analysis and was the only diagnostic criterion that was statisti-

cally significantly associated with the presence of acute appen-

dicitis in multivariate analysis for both readers (Figs 3, 4). The

diagnostic performance statistics for periappendiceal fat infil-

tration are higher than the diagnostic statistics for any of the

evaluated appendiceal diameters (6, 7, or 8 mm) and higher

than the 70.5% sensitivity and 88.9% accuracy described by

Goldin et al, who found that fat infiltration was an insensitive

indicator of acute appendicitis (8).

In children, there have been no other studies that have stat-

istically evaluated the diagnostic value of periappendiceal fat

stranding but descriptive studies have shown an association

between fat infiltration and acute appendicitis. Wiersma

et al identified echogenic fat in 97.2% of the 71 patients

with appendicitis in their series (7). Park et al also showed

that the presence of periappendiceal fat infiltration can help

to distinguish appendicitis from a dilated, fecally impacted

appendix because this was present in 50/51 cases of appendi-

citis but none of the fecal impaction cases (21).

Findings in studies of adult appendicitis also support the use

of periappendiceal fat infiltration as a diagnostic criterion.

Kessler et al found that this had a sensitivity of 91%, specificity

of 76%, and accuracy of 83% (11). Fat infiltration was one of

the few variables that remained statistically significantly pre-

dictive of appendicitis in the multivariate analysis by van Ran-

den et al where it had an odds ratio of 3.2 (24). The degree of

fat infiltration has also been shown by Noguchi et al to signifi-

cantly correlate with the severity of acute appendicitis (28).

Periappendiceal fat infiltration is not a perfect diagnostic

criterion for acute appendicitis. Echogenic fat has been

reported to be present in rare cases in normal individuals

and was seen in a small number of normal patients in our pop-

ulation (6,20). Echogenic fat can also be the result of an

1392

adjacent inflammatory process such as infectious or

inflammatory terminal ileitis, omental infarction, epiploic

appendagitis, or Meckel diverticulitis. Generally these

processes will result in adjacent but not circumferential

periappendiceal fat infiltration. These diagnoses, however,

must be excluded before a diagnosis of acute appendicitis is

made. Finally, some would argue that the identification of

infiltration of the periappendiceal fat is subjective with

potential confusion arising from misidentification of normal

periappendiceal fat. It is for this reason that we strictly

defined this criterion as ‘‘circumferential echogenic

periappendiceal fat.’’ We contend that using a strict

definition will maximize the diagnostic value of this criterion.

Appendicolith

The association of an appendicolith with acute appendicitis

was initially described with plain radiography (Fig 9) (29).

Despite the fact that many authors use the presence of an

appendicolith as one of several diagnostic criteria for acute

appendicitis, this has not been well evaluated as an isolated cri-

terion (13,14,30,31). In children, Goldin et al found a

sensitivity of 33%, specificity of 96%, and accuracy of 72%

for appendicoliths (8). In our population, although rarely

seen in normal appendices, the presence of an appendicolith

was not a significant predictor of appendicitis on multivariate

analysis. Similar findings were described in adults by van Ran-

den et al (24).

Presence of Fluid

According to the literature, the diagnostic value of periappen-

diceal fluid is variable. Both Goldin et al and Franke et al

found periappendiceal fluid to be highly specific (99%) but

not sensitive for acute appendicitis (20% Goldin, 14% Franke)

and both authors described poor accuracy for free fluid as a

diagnostic criterion (<70% Goldin, 77% Franke) (8,26). In

their analysis, van Randen et al showed that periappendiceal

free fluid had one of the lowest odds ratios for acute

appendicitis (0.9) in univariate analysis and was not a

significant predictor in multivariate analysis (24). Our results

are similar in that the presence of fluid was a significant pre-

dictor in univariate analysis (OR < 2) but was not a predictor

in multivariate or CART analysis.

The literature describes several diagnostic criteria that pre-

dict the presence of acute appendicitis and yet most of these

show no statistically significant associationwith acute appendi-

citis in our population. One possible explanation for this is that

prior articles predominately represent univariate analyses of

diagnostic criteria that do not account for the interaction

between variables. In our population, many of these same var-

iables are statistically significant predictors of acute appendicitis

in univariate analyses but when multivariate modeling and

CARTanalysis are performed, periappendiceal fat infiltration

is shown to be themost valuable predictorof acute appendicitis.

Figure 9. Longitudinal (a) and transverse(b) images of appendicoliths. In this 11 year

old with right lower quadrant pain, appendi-

coliths appear as echogenic foci (arrows)

with associated posterior acoustic shadow-ing (arrowheads) within the appendiceal

lumen. Note the normal appendiceal wall in

(a) with three discrete echogenic layers.


This study has several limitations. This is a retrospective

analysis, and the reviewers were limited to the images that

had been saved to the picture archiving and communications

system over the study period. These images may not have

adequately assessed all of the diagnostic parameters of interest

or provided sufficient imaging of an area of interest. Addition-

ally, this analysis concerns sonographically apparent criteria

and does not incorporate clinical data. The findings of this

analysis will need to be confirmed with prospective studies

and in clinical practice. These data are also limited by the

gold standard we used for a diagnosis of acute appendicitis.

In cases where surgery was not performed, appendicitis is

assumed to be absent. False-negative clinical diagnoses or

patients with mild appendicitis that resolved may have conta-

minated these data. Finally, these data are limited by sample

size. Larger samples might identify diagnostic criteria that

reach statistical significance that are not identified in this

analysis.

Approach to Ultrasound in Suspected AcuteAppendicitis

As a means of summarizing our results and review of the liter-

ature, we propose the following possible approach to inter-

preting right lower quadrant ultrasounds in acute appendicitis.

First evaluate for circumferentially thickened, echogenic

periappendiceal fat. If this is present, appendicitis should be

highly suspected (present in 87% of patients in our popula-

tion). Additional findings such as increased appendix diameter,

loss of normal appendiceal wall architecture, or the presence of

an appendicolith can further support the diagnosis. The

absence of any or all of these findings should not deter diagno-

sis unless another explanation for inflamed right lower quad-

rant fat is elicited. If, however, circumferentially thickened,

echogenic periappendiceal fat is absent, the likelihood of

appendicitis is low (present in 9% of patients in our popula-

tion). In this setting, the presence of a single diagnostic crite-

rion should not be considered diagnostic of acute appendicitis.

Appendiceal diameter $7 mm can be helpful to segregate

patients in this group, identifying those with a slightly higher

rate of appendicitis in the absence of periappendiceal fat

inflammation (20% rate of appendicitis in our population),

but even this criterion should not be applied in isolation.Mul-

tiple abnormal findings, however, may suggest the presence of

appendicitis even in the absence of abnormal periappendiceal

fat. Other criteria that should be given particular weight

include loss of normal mural stratification in the appendix

and the presence of an appendicolith. In all cases of suspected

acute appendicitis, we caution against overreliance on user-

dependent factors such as compressibility of the appendix or

appendiceal vascularity.

In conclusion, based on our findings and a review of the lit-

erature, periappendiceal fat infiltration appears to be the most

important single diagnostic criterion for acute appendicitis.

Strict application of other diagnostic criteria such as appendi-

ceal diameter, which is recently being called into question,

should be avoided.

ACKNOWLEDGMENT

The authors thankMike D. Smith, PhD, for statistical support.

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