The Journal of Emergency Medicine, Vol. 46, No. 2, pp. 157164, 2014 Copyright 2014 Elsevier Inc.

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http://dx.doi.org/10.1016/j.jemermed.2013.08.027

Original Contributions

ACUTE APPENDICITIS: INVESTIGATING AN OPTIMAL OUTER APPENDICEAL DIAMETER CUT-POINT IN A PEDIATRIC POPULATION
Patrick M. Prendergast, MD,* Naveen Poonai, MD,* Tim Lynch, MD,* Scott McKillop, MD,* and Rodrick Lim, MD*
*Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada, Department of Pediatrics and Medicine, Childrens Hospital at London Health Sciences Centre, London, Ontario, Canada, and Department of Medical Imaging and Radiology, Childrens Hospital at London Health Sciences Centre, London, Ontario, Canada Reprint Address: Rodrick Lim, MD, Department of Pediatric Emergency Medicine, Childrens Hospital, London Health Sciences Centre, 800 Commissioners Road West, London, ON N6K 0A9, Canada; E-mail: rod.lim@lhsc.on.ca

, AbstractBackground: Acute appendicitis is the most common cause of abdominal pain in children requiring operative intervention. Among a number of sonographic criteria to aid in the diagnosis of appendicitis, an outer diameter >6 mm is the most objective and widely accepted. However, there is a lack of evidence-based standards governing this consensus. Study Objectives: The aim of this study was to determine the outer appendiceal diameter that maximizes sensitivity and specicity in a pediatric population. Methods: A retrospective review of all urgent diagnostic ultrasounds (US) was performed over 2 years in children aged <18 years. The diagnostic accuracy of various cut-points was assessed by calculating the sensitivity and specicity and plotting a receiver operating characteristic (ROC) curve. Results: The study sample consisted of 398 patients in whom the appendix was visualized on US. The median outer appendiceal diameter was signicantly higher in the surgical group compared to the nonsurgical group (9.4 mm; range = 8.112.0 vs. 5.5 mm; range = 4.46.5, p < 0.01). The optimal cut-point with the greatest area under the ROC curve was determined to be an outer appendiceal diameter of 7.0 mm. Conclusions: In our patients, adopting a 7-mm rather than a 6-mm appendiceal diameter threshold would balance a greater number of missed cases of acute appendicitis for a reduction in the number of unnecessary surgeries. 2014 Elsevier Inc. , Keywordsultrasound; diagnosis pediatric; appendicitis;

INTRODUCTION Acute appendicitis is an important diagnosis in an emergency department (ED) and is the most common cause of abdominal pain requiring surgical intervention. Acute appendicitis has a lifetime risk of 7% and is particularly important in the pediatric population, given that it is primarily a diagnosis of adolescents and young adults (19). In the ED, an estimated 70,000 pediatric cases of acute appendicitis are observed per year in the United States (10). An accurate and timely diagnosis by the clinician is crucial due to the risk of perforation, abscess formation, peritonitis, sepsis, bowel obstruction, infertility, and death (1113). A number of imaging criteria have been established to aid in the preoperative evaluation of suspected appendicitis with ultrasonography. Major ultrasound (US) ndings of acute appendicitis in the right lower quadrant include: an aperistaltic, noncompressible, blind-ended, sausageshaped structure that arises from the base of the cecum, distinct appendiceal wall layers, a target appearance, appendicolith(s), periappendiceal uid collection, echogenic prominent pericecal fat, and an outer diameter > 6 mm (1417). There is no evidence-based standard governing the sonographic criteria used to diagnose appendicitis. Accordingly, large interrater variability exists as different

RECEIVED: 3 November 2012; FINAL SUBMISSION RECEIVED: 25 April 2013; ACCEPTED: 14 August 2013
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radiologists and experimental protocols have used various constellations of ndings to arrive at a diagnosis of acute appendicitis (1820). Potentially, the most important criterion is the outer diameter of the vermiform appendix. Studies in adult populations have found that this criterion provides high sensitivity but low specicity (21). One small study of 70 children concluded that the diagnosis of acute appendicitis could be made with the same accuracy in children as in adults (22). Another small Korean study reported an optimal maximal outer diameter of 5.87 mm for pediatric patients (23). This study has not been repeated in a larger sample and thus, a paucity of evidence-based support for the 6-mm criterion exists in a pediatric population. Because a diagnostic radiologist may need to guide an emergency physician and surgeons management using only an outer appendiceal diameter, a clearer description as to the sensitivity and specicity of different outer appendiceal diameters may help the clinician and radiologist in real time understand how to best interpret US results. The aim of this study was to determine the optimal value of the outer appendiceal diameter that maximizes the trade-off between sensitivity and false positives in a pediatric population. MATERIALS AND METHODS A retrospective review was conducted of all urgent abdominal and pelvic USs performed between July 1, 2008 and June 30, 2010 at the pediatric ED of an urban, tertiary care pediatric teaching hospital. The pediatric ED has a census of approximately 40,000 visits per year. The hospital serves as a referral center covering a catchment area with a population of 1.5 million. All urgent abdominal and pelvic USs assessing the appendix in patients < 18 years of age performed at the pediatric ED were included. Patients with cystic brosis were excluded from the present study because the appendiceal lumen in these children is often lled with mucoid content, resulting in an outer appendiceal diameter up to 14 mm when not inamed. Repeat examinations were also excluded. All US examinations were performed by US technicians and interpreted by a pediatric radiologist. To visualize the appendix on US, Puylaerts graded compression technique was performed using commercially available US equipment (24). Puylaerts technique applies graded compression and high-frequency transducers to visualize the appendix. It has become the standard in sonographic studies of appendicitis due to its high sensitivity and specicity (2531). The outer appendiceal diameter was measured as the distance between the outer boundaries of the hypoechoic tunica muscularis by radiologists using electronic

Figure 1. Sonographic image of an enlarged, noncompressible appendix with concentric layers suggestive of acute appendicitis.

calipers. Outer appendiceal measurements (in mm) were reported to two decimal places. The reporting radiologist was blinded to the nal pathology report. Sample positive and negative US images are presented in Figures 1 and 2, respectively. Data were analyzed using StatsDirect (Cheshire, UK) statistical software package. The mean and SD were used to summarize normally distributed continuous variables, whereas the median and range were used for skewed continuous variables. Categorical outcomes were reported as percentages. A chi-squared test was used to compare categorical outcomes between the surgical and nonsurgical groups, and the independent samples t-test or Mann-Whitney U-test was used to compare continuous outcomes between groups. A p value < 0.05 was considered statistically signicant. In patients where the appendix was visualized and the outer appendiceal diameter was measured, children were divided into two groups: patients who underwent surgery for possible appendicitis (surgical group) vs. patients not

Figure 2. Sonographic image of a normal appendix.

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688 US performed

664 exams

24 repeat exams excluded

398 appendix seen

242 appendix not seen

174 surgical group

224 non-surgical group

143 pathology positive

224 patients did not return

31 pathology negative

0 patients diagnosed with appendicitis

Figure 3. Flow of patient charts evaluated. US = ultrasound.

operatively managed (nonsurgical group). A pathological diagnosis was available for all members of the surgical group to identify pathology-positive appendicitis. For the nonsurgical group, all patient records were reviewed to ensure they did not return to the hospital for an appendectomy within 3 months. The diagnostic utility of various appendiceal outer diameters was assessed by calculating the sensitivity, specicity, and accuracy. A receiver operating characteristic (ROC) curve was constructed from these data to obtain the value of the outer appendiceal diameter of the vermiform appendix that optimized sensitivity and falsepositive rate using the area under the curve (32). This study received ethics approval by the local Ethics Review Board. RESULTS In a total of 688 pediatric pelvic and abdominal ultrasounds to diagnose appendicitis, an attempt was made to visualize the appendix. Twenty-four repeat examinations were excluded, leaving 664 children. The appendix was visualized and the outer appendiceal diameter was measured in 398 children (60%), and not seen in the remaining patients. The children with a visualized appendix made up the study sample and were divided into two groups: a surgical (n = 174) and a nonsurgical group
Table 1. Demographic Characteristics of the Surgical and Nonsurgical Groups n Surgical Nonsurgical 174 224 Mean Age, Years (SD) 12.3 (3.3) 11.9 (4.1) Males (%) 99 (56.9) 77 (34.4) Females (%) 75 (43.1) 147 (65.6)

(n = 224). A pathological diagnosis was available for all members of the surgical group, which conrmed appendicitis in 143 patients. Pathology reports were negative for acute appendicitis in 31 surgical patients. For the nonsurgical group, all patient records were reviewed to ensure that they did not return to the hospital for an appendectomy. There were no patients who returned with subsequent appendicitis from this group (Figure 3). The diameters for patients with missed or perforated appendices were not falsely low for this population studied (range 6.6, 21 mm, median = 10 mm). Demographic characteristics of the surgical and nonsurgical groups are provided in Table 1. The two groups were similar in age, although the surgical group had a greater proportion of males than the nonsurgical group (56.9% vs. 34.4%, p < 0.01). The age distribution of patients with and without acute appendicitis is presented in Figure 4. The median outer appendiceal diameter (Figure 5) was signicantly higher in the surgical group

40 35
Number of Patients

30 25 20 15 10 5 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Age (years) Non Surgical Surgical

SD = standard deviation.

Figure 4. Age distribution of patients with and without acute appendicitis.

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ROC plot from Appi Data Oct Vis ualized w No Repeats 23 2010~2.xls Sensitivity 1.00 E(+ve), E(-ve) 0.75

0.50

0.25

Figure 5. Median outer appendiceal diameter in the surgical and nonsurgical group.

0.00

0.00

0.25

0.50

0.75

1.00 1-Specificity

compared to the nonsurgical group (9.4 mm; range = 8.1 12.0 vs. 5.5 mm; range = 4.46.5, p < 0.01). The sensitivity, as well as the accuracy of the ultrasound for diagnosing appendicitis based on various outer appendiceal diameter values is provided in Table 2. As illustrated by Table 2, at a higher value, specicity and positive and negative likelihood ratios increase. At a lower value, sensitivity increases. Figure 6 provides the ROC curve using various values of sensitivity and 1-specicity to obtain an optimal value for the outer appendiceal diameter. The determination of this value reects the optimal sensitivity and falsepositive rate (33). The optimal value of the outer appendiceal diameter as determined by the greatest area under the ROC curve is 7.0 mm. DISCUSSION Acute appendicitis in children is a life-threatening surgical diagnosis in an ED. Hence, timely diagnosis and management is important. Numerous adult studies have evaluated the merits of various imaging modalities that may assist in diagnosing acute appendicitis (10,13,34).
Table 2. Evaluating the Outer Appendiceal Diameter as a Diagnostic Criterion for Acute Appendicitis Using US Sen (Sensitivity), Spec (Specicity), LR (Likelihood Ratio) Diameter Cut-off Point (mm) $4.5 $5.0 $5.5 $6 $6.5 $7.0 $7.5 $8.0 $8.5 US = ultrasound. Sen (%) 99.3 98.6 98.6 97.9 93.7 91.6 86.0 75.6 69.2 Spec (%) 25.1 33.7 47.1 63.1 73.3 83.9 91.4 93.3 94.5 Accuracy (%) 51.8 57.0 65.6 75.6 80.7 86.7 87.1 86.9 85.4 LR (+) 1.32 1.49 1.86 2.65 3.51 5.69 10.03 11.3 12.61 LR () 0.03 0.04 0.03 0.03 0.09 0.1 0.15 0.26 0.33

Figure 6. Receiver operating characteristic (ROC) curve demonstrating optimal value for the outer appendiceal diameter.

The two most common tests to aid in the diagnosis are computed tomography (CT) and US. A meta-analysis comparing CT and US in the diagnosis of acute appendicitis in children found CT to have greater sensitivity and specicity (94%, 95% CI 9297%; and 95%, 95% CI 94 97%, respectively); US pooled sensitivity and specicity were 88% (95% CI 8690%) and 94% (95% CI 9295%) (34). However, because US is a low-cost option, free of ionizing radiation, anesthesia, or contrast injection and involves less patient preparation, a common approach is to use US as the primary means of imaging children with suspected appendicitis. Furthermore, avoidance of radiation exposure is of crucial importance due to the greater lifetime radiation risk associated with the use of CT in the pediatric population (3541). One of the limitations of US is that there are many challenges to providing a denitive result. For example, US is operator dependent, and frequently, the appendix is not visualized or the results are equivocal. Not surprisingly, the sensitivity and specicity of US in children have been shown to be poorer in the community (42,43). Equivocal results can be common, as demonstrated by an American study in which quoted rates were as high as 68% (44). Consequently, despite the availability of numerous individual imaging criteria, surgeons frequently ignore imaging results that are not in keeping with their clinical impression (18). Potentially, the most important objective criterion is the outer diameter of the vermiform appendix. A potential advantage of the outer appendiceal diameter is that it is easier to measure, and is less subjective when compared to other criteria such as periappendiceal uid collection or echogenic prominent pericecal fat. This becomes increasingly important as point-of-care US in the ED continues to evolve. Our study is important in that it provides a range of outer appendiceal diameter cut-points in

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an attempt to determine the optimal cut-point for acute appendicitis in a pediatric population, and can assist emergency physicians, diagnostic radiologists, and surgeons in the management of acute appendicitis in children presenting to the ED. Although some debate exists, an outer appendiceal diameter > 6 mm is believed to be consistent with acute appendicitis and an outer appendiceal diameter < 6 mm is suggestive of a normal appendix. One important study concluded that the outer appendiceal diameter of 6 mm or more provides high sensitivity but limited specicity. This diagnostic criterion is more useful in excluding acute appendicitis than in conrming it (32). A few small studies applying this criterion to children have been performed, but the evidence is sparse. Establishing an optimal cut-point in a pediatric population could have a signicant impact on the management of pediatric patients. Applying a higher cut-point requires balancing the risks associated with missing an acute appendicitis with the benets of fewer unnecessary surgeries. Conversely, applying a lower cut-point requires balancing the benets of fewer missed cases of acute appendicitis with greater numbers of unnecessary surgeries. This study allows clinicians to assess the risks and benets of applying various cut-points (Table 2). Comparing extremes, a cut-point of 4.5 mm yields a sensitivity of 99.3% and a specicity of 25.1%, and a cut-point of 8.5 mm provides sensitivity and specicity of 69.2% and 94.5%, respectively. A cut-point of 4.5 mm would be unrealistic in that, although it would lead to a very low false-negative rate, the high false-positive rate could potentially result in unnecessary surgery with attendant risks, and the unnecessary resource allocation would be unacceptable. Conversely, a cut-point of 8.5 mm provides a higher false-negative rate than the 4.5 mm cutpoint, meaning that more cases will be missed and greater morbidity and mortality may be observed by adopting this cut-point. This must be balanced, of course, with a lower false-positive rate provided by 8.5 mm and fewer unnecessary surgeries. Examining the various outer appendiceal diameters and their respective sensitivities and specicities, the changes are relatively linear as one moves across the size criteria. Hence, no ideal cut-point exists, as an analysis of the data does not identify a value in which there is not an exchange of decreasing sensitivity for increasing specicity. If one were to weight sensitivity and specicity equally at 1:1, the optimal cut-point would be 7.0 mm (Table 2). Adopting a 7-mm cut-point rather than a 6-mm cut-point in clinical practice would balance a greater number of missed cases of acute appendicitis for a reduction of the number of unnecessary surgeries

and would reduce unnecessary resource allocation. Given the analysis of our data, this would be the most logical cut-point for designating the test as positive. It can be argued that the front-line practitioner needs to know the various sensitivities and specicities for outer appendiceal diameter. Due to the linear relationship previously described, patients presenting close to the cut-point of 7 mm still have a clinically worrisome chance of having appendicitis. Clinically, if the patient were to have an outer appendiceal diameter < 6 mm, where our data would suggest a sensitivity close to 98%, a clinician would be comfortable to designate the test as negative. Therefore, perhaps a more useful framework would be to designate outer appendiceal diameter < 6 mm as negative, outer appendiceal diameter 67 mm as equivocal, and an outer appendiceal diameter > 7 mm as positive. Although only one cut-point for a test can be designated as ideal given our sensitivity and specicity weightings, this graduated approach more accurately reects clinical practice. More specically, patients who approach but do not exceed a threshold may be observed clinically, further investigated, or managed according to ancillary information such as clinical examination ndings that may be used to guide the next course of action. The proportion of children who are imaged via US and go on to receive surgery is similar to known incidence rates (4547). The USs examined in this study were based on examinations ordered by practicing emergency physicians who were clinically suspicious of acute appendicitis. This is likely representative of the population of children that physicians face when considering the diagnosis of appendicitis. Limitations Several limitations were inherent in this study design. Firstly, the retrospective nature of the study meant that complete follow-up was neither practical nor possible. Moreover, numerous ultrasonographers conducted the abdominal and pelvic examinations, and ultrasonography is known to be highly operator dependent. Consequently, there may be considerable variation in an operators ability to: 1) visualize the appendix; and 2) accurately acquire an image of the appendix that can be measured. In this study, US was compared to the diagnostic standard surgery. Patients not undergoing surgery were followed, and charts were reviewed to ensure that they did not undergo future presentations for appendicitis. Although unlikely, patients may have presented out of our region for future complications, and may have been lost to follow-up. As well, we did not study patients with appendicitis who did not have an US, which may be a source of bias.

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CONCLUSION In the largest pediatric study to date, we found that the optimal cut-point for appendectomy using only the outer appendiceal diameter in a pediatric population to be 7.0 mm. However, because the sensitivity and specicity changes are relatively linear as one moves across the size criteria, other cut-points are very similar.
AcknowledgmentSpecial thanks to Jamie Seabrook, his assistance in the preparation of this manuscript.
PHD,

for

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ARTICLE SUMMARY 1. Why is this topic important? At present, there exists no evidence-based standard governing the sonographic criteria used to diagnose appendicitis. Therefore, a clearer description of the sensitivity and specicity of the outer appendiceal diameters may help the clinician optimize detection and minimize unnecessary surgical intervention. 2. What does this study attempt to show? This study attempts to provide the sensitivity and specicity of different outer appendiceal diameters to enable the clinician understand how to best interpret ultrasound results in the diagnosis of acute appendicitis in children. 3. What are the key ndings? The optimal cut-point for appendectomy using only the outer appendiceal diameter in a pediatric population was found to be 7.0 mm. However, because the sensitivity and specicity changes are relatively linear as one moves across the size criteria, other cut-points are very similar. 4. How is patient care impacted? A higher appendiceal cut-point would allow for fewer false positives and potentially unnecessary surgical interventions. The trade-off is a decrease in sensitivity for the diagnosis of acute appendicitis. We propose a more useful framework based on a range of outer appendiceal cutpoint values.