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Sonography in the Evaluation of
Acute Appendicitis
Are Negative Sonographic Findings Good Enough?
Preeyacha Pacharn, MD, Jun Ying, PhD, Leann E. Linam, MD, Alan S. Brody, MD, Diane S. Babcock, MD
Objective. The purpose of this study was to evaluate the negative predictive value (NPV) of sonogra- phy in the diagnosis of acute appendicitis. Methods. Right lower quadrant sonograms of 193 patients (158 female and 35 male; age range, 3–20 years) with suspected acute appendicitis over a 1-year peri- od were retrospectively reviewed. Sonographic findings were graded on a 5-point scale, ranging from a normal appendix identified (grade 1) to frankly acute appendicitis (grade 5). Sonographic findings were compared with subsequent computed tomographic (CT), surgical, and pathologic findings. The diagnostic accuracy of sonography was assessed considering surgical findings and clinical follow-up as reference standards. Results. Forty-nine patients (25.4%) had appendicitis on sonography, and 144 (74.6%) had negative sonographic findings. Computed tomographic scans were obtained in 51 patients (26.4%) within 4 days after sonography. These included 39 patients with negative and 12 with positive sonographic findings. Computed tomography changed the sonographic diagnosis in 10 patients: from negative to positive in 3 cases and positive to negative in 7. Forty-three patients (22.2%) underwent surgery. The surgical findings were positive for appendicitis in 37 (86%) of the 43 patients who had surgery. Patients with negative sonographic findings who, to our knowledge, did not have subsequent CT scans or surgery were considered to have negative findings for appendicitis. Seven patients with negative sonographic findings underwent surgery and had appendicitis; therefore, 137 of 144 patients with negative sonographic findings did not have appendicitis. On the basis of these numbers, the NPV was 95.1%. Conclusions. Sonography has a high NPV and should be considered as a reasonable screening tool in the evaluation of acute appendicitis. Further imaging could be per- formed if clinical signs and symptoms worsen. Key words: appendicitis; children; sonography.
Received December 3, 2009, from the Department of Radiology, Siriraj Hospital, Bangkok, Thailand (P.P.); Department of Radiology, University of Cincinnati, Cincinnati, Ohio USA (J.Y.); Department of Radiology, Arkansas Children’s Hospital, Little Rock, Arkansas USA (L.E.L.); and Department of Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio USA (A.S.B., D.S.B.). Revision requested December 22, 2009. Revised manuscript accepted for publication July 15, 2010. We thank Shelia Salisbury, PhD, for contributions to the paper. Address correspondence to Diane S. Babcock, MD, Department of Radiology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, MLC 5031, Cincinnati, OH 45229-3039 USA. E-mail: diane.babcock@cchmc.org
Abbreviations CI, confidence interval; CT, computed tomography; NPV, negative predictive value; PPV, positive predictive value
cute abdominal pain is a common presentation of children seeking medical care. Suspected acute appendicitis is the most common condition requiring abdominal surgery in the pediatric pop- ulation and must be differentiated from other conditions that may mimic its signs and symptoms.1–3^ A history of migrating abdominal pain, classically beginning in the periumbilical region and traveling to McBurney’s point, combined with leukocytosis and other associated symp- toms such as anorexia remains the best diagnostic clue.^4 However, diagnostic imaging plays an important adjunc- tive role in confirming the diagnosis when the clinical presentation is inconclusive.
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Multiple studies have evaluated the use of sonography and computed tomography (CT) for the diagnosis of appendicitis.1,5–14^ In these stud- ies, the sensitivity and specificity of sonography ranged from 67% to 88% and 78% to 100%, respec- tively, whereas the sensitivity and specificity of CT were 76% to 96% and 75% to 97%.1,5,7,9,10, The purpose of our study was to evaluate the neg- ative predictive value (NPV) of sonography and determine whether it can be used as a screening tool to exclude acute appendicitis.
Materials and Methods
The study was approved by the Institutional Review Board. An electronic medical record search at a large children’s hospital for patients referred for right lower quadrant sonography to rule out appendicitis between August 1, 2006, and July 31, 2007, identified 230 patients. Thirty- seven of these patients were excluded because of incomplete follow up information. The remain- ing 193 patients (158 female and 35 male; age range, 3–20 years) were included in our study. One hundred six patients were referred by the emergency medicine department, 56 from pediatric primary care sites, and 31 were inpatients. Each sonogram was retrospectively reviewed by 2 radiologists: 1 pediatric radiologist with a Certificate of Added Qualification and 1 pediatric radiology fellow. Sonograms were reviewed without patient identification or clini- cal information. Interobserver reliability was assessed using κ statistics. Sonographic findings were compared with subsequent CT, surgical, and pathologic findings to determine the sensi- tivity and specificity of the sonographic examina- tions. The original reports were reviewed and graded by a certified pediatric radiologist.
Sonographic and CT Techniques and Interpretation Sonographic examinations were performed by experienced sonographers using a linear array transducer (Acuson Sequoia; Siemens Medical Solutions, Mountain View, CA) and a standard- ized protocol involving graded compression lon- gitudinal and transverse images of the right lower quadrant as well as right lower quadrant cine clips. Doppler images were reviewed in available
cases. In questionable cases, additional images were acquired by a radiologist. Sonographic find- ings were retrospectively graded using a 5 point scale: 1 represented identification of a normal appendix; 2 indicated that the appendix was not seen, but no inflammatory changes or free fluid were evident; 3 indicated that the appendix was not seen, but secondary signs of appendicitis were present, such as a fecalith, pericecal fluid, or increased pericecal echogenicity consistent with infiltration of the mesenteric fat; 4 represented identification of an appendix of borderline enlarged size (5–6 mm); and 5 indicated acute appendicitis, defined as an enlarged noncom- pressible appendix with an outer diameter of greater than 6 mm. Findings graded 1 or 2 were classified as negative, and those graded 3 to 5 were classified as positive for acute appendicitis (Figure 1). Original reports were reviewed and graded using the same criteria. Computed tomographic scans were performed on a multidetector CT scanner (LightSpeed; GE Healthcare, Milwaukee, WI) using a standard acute abdomen protocol involving 5-mm axial images, weight-based low tube current, and intravenous administration of 2-mL/kg iodi- nated contrast material. Oral contrast material was also given in cases in which the history of abdominal pain was 24 hours or longer. No rec- tal contrast material was used. Radiologic crite- ria for the diagnosis of acute appendicitis included an appendix diameter of greater than 6 mm, periappendiceal fat stranding or inflam- matory changes, appendiceal wall thickening or enhancement, and periappendiceal abscesses. All CT studies were obtained within 4 days after the sonographic examinations.
Final Diagnoses The final diagnoses were established on the basis of surgical and histopathologic findings for cases that underwent surgery (n = 43). For nonsurgical- ly treated patients, medical records regarding postpresentation follow-up were reviewed to establish the diagnosis for use in this study. The hospital records for all study patients were reviewed for the 6-month period after their study entry sonograms. Because our institution is the only children’s hospital with the only pediatric surgeons in our metropolitan area, few patients
Sonography in the Evaluation of Acute Appendicitis
ratios, sensitivity, specificity, and their respective 95% confidence intervals (CIs). Frequency tables were generated using SAS version 9.1.3 software (SAS Inc, Cary, NC), and the 95% CIs were calcu- lated using VassarStats.^15 The CIs were calculated using the efficient-score method (corrected for continuity).^16 Inter-reader reliability was verified using Cohen weighted κ and Kendall tau β coeffi- cients. Values between 0.61 and 0.80 were consid- ered good agreement. Values are reported as estimated values and 95% CIs.
Results
Among the 193 patients who underwent sono- graphic examination for clinically suspected acute appendicitis, the sonographic findings were negative in 144 (74.6%) and positive in 49 (25.4%). The Cohen weighted κ and Kendall tau β coefficients showed good inter-reader reliabil- ity between the 2 reviewers (Cohen κ = 0. [95% CI, 0.682–0.845]; Kendall tau β = 0. [95% CI, 0.594–0.815]). Computed tomography was subsequently performed in 39 patients with negative and 12 with positive sonographic find- ings. Computed tomography changed the imag- ing diagnosis in 10 patients: from negative to positive in 3 cases and from positive to negative in 7 (Table 1). Forty-three patients (22.2%) underwent surgery. The surgical findings were positive for appen- dicitis in 37 patients (86%). Seven patients with negative sonographic findings did have acute appendicitis according to surgical and pathologic findings (Table 2). On the basis of the final diag- nosis, the sensitivity of sonography was 81.1% ( of 37); specificity, 87.8% (137 of 156); PPV, 61.2% (30 of 49; 95% CI, 46.2%–74.4%); and NPV, 95.1% (137 of 144; 95% CI, 89.8%–97.8%; Table 3).
Review of the original reports compared with the final diagnoses showed 147 patients with nega- tive sonographic findings, of which 7 had appen- dicitis. The sensitivity was 81.1% (30 of 37); specificity, 89% (140 of 156); PPV, 65% (30 of 46; 95% CI, 49%–78%); and NPV, 95.2% (140 of 147; 95% CI, 90%–98%; Table 4). Ovarian conditions were found in 13 patients, including 1 with a tubo-ovarian abscess and 12 with ovarian cysts; 3 patients had intrauterine pregnancy.
Discussion
Suspected acute appendicitis is one of the most common diagnostic dilemmas encountered in clinical pediatric practice. Although the diagno- sis is primarily based on clinical findings, the pre- sentation can be confusing, and classic features may be subtle or difficult to elicit in children.^17 Moreover, clinical signs and symptoms may overlap with other conditions such as viral gas- troenteritis, intussusception, and mesenteric adenitis. In female patients, ovarian conditions may also mimic appendicitis. Imaging plays an important role in the modern evaluation of abdominal pain, although a definitive consensus on the appropriate imag- ing workup protocol remains elusive. The ideal imaging test would be readily available, fast, inexpensive, reproducible, safe, and accurate.^18 Radiographic findings are not specific, and as such, conventional radiographs are not con- sidered cost-effective compared with CT. 19 A radiopaque appendicolith may suggest the specific diagnosis of appendicitis on convention- al radiography, but this finding is present in less than 5% of cases of appendicitis.^20 Several studies
Sonography in the Evaluation of Acute Appendicitis
Table 1. Sonographic Diagnosis Compared With CT in Patients Who Underwent CT CT Sonography Negative Positive Total Positive 7 5 12 Negative 36 3 39 Total 43 8 51 Sensitivity, 0.62 (95% CI, 0.25–0.89); specificity, 0.83 (95% CI, 0.68–0.92); PPV, 0.41 (95% CI, 0.16–0.71); and NPV, 0.92 (95% CI, 0.78–0.97).
Table 2. Sonographic Diagnosis Compared With Surgical/Pathologic Findings in Patients Who Underwent Surgery Surgery Sonography Negative Positive Total Positive 2 30 32 Negative 4 7 11 Total 6 37 43 Sensitivity, 0.81 (95% CI, 0.64–0.91); specificity, 0. (95% CI, 0.24–0.94); PPV, 0.93 (95% CI, 0.78–0.99); and NPV, 0.36 (95% CI, 0.12–0.68).
have reviewed the use of sonography and CT in the evaluation of acute appendicitis. Most stud- ies to date have focused on the appendiceal visu- alization rate and the sensitivity and specificity of the study.1,5– Sonography is part of the diagnostic algorithm at our institution and is relatively inexpensive, safe, and readily available. Sonography can be performed at the bedside, involves a short acqui- sition time, does not use ionizing radiation, and may show evidence of other causes of abdomi- nal pain such as ovarian cysts, tubo-ovarian abscesses, and mesenteric adenitis. It is particu- larly useful in evaluating young women, in whom the radiation dose to the reproductive organs should be minimized and for whom it is important to exclude ovarian and uterine condi- tions that might mimic appendicitis.^21 In our study, ovarian- and uterine-related findings were shown in 16 patients, and an alternative diagno- sis was made by initial sonography. The criteria for the diagnosis of acute appen- dicitis by sonography are well established and reliable.^22 The most specific sign is the identifica- tion of a noncompressible blind-ending struc- ture in the right lower quadrant with an outer diameter of greater than 6 mm, consistent with an abnormal appendix. In our study, we also considered findings positive when the appendix was not identified but when secondary signs of appendicitis were present. Prior studies have suggested that a normal appendix should be identified to exclude acute appendicitis.^20 Wiersma et al^23 reported identifi- cation of the normal appendix by sonography in 82% of asymptomatic children. In the evaluation of acute appendicitis, the visualization rate varies from institution to institution, from a high of 98% to a low of 22%.^18 This study sought rather
to determine whether appendicitis could be excluded on the basis of negative sonographic findings. In our study, if an appendix was not visualized and there were no secondary signs to suggest appendicitis, the findings were consid- ered negative. Using these criteria, the NPV was 95.1%, similar to results in prior studies.10, Seven patients with acute appendicitis in our study had false-negative sonographic findings. These patients were 12 to 15 years old. Four were referred for CT because of continued clinical concern for appendicitis. Three went directly to surgery. Factors likely contributing to a false- negative diagnosis were identified in 4 of the 7 patients. A retrocecal appendix was identified in 2 of the 4 patients who had CT scans. One of these patients was also obese. Two of the 3 patients taken directly to surgery had a grossly normal appendix at surgery with a pathologic diagnosis of appendicitis. Sonography can be limited by patient body habitus as well as the variable and at times inac- cessible position of the appendix. Retrocecal and retroileal appendixes are difficult to visualize, whereas anterior appendixes are relatively easy to identify. In our study, 1 patient who had false- negative sonographic findings was obese, tech- nically limiting the study. Subsequently, CT showed retrocecal appendicitis (Figure 2). Other indications for CT after sonography included nonvisualization of the appendix by sonography, an equivocal findings with secondary signs of appendicitis, and negative findings with clinical concern for appendicitis. The PPV in our study was relatively low compared with other studies10,24^ and can be explained by the study design. Because our study focused mainly on the screening value of sonog-
Pacharn et al
Table 3. Sonographic Diagnosis Compared With Final Diagnosis (Surgery/Pathologic Examination) Appendicitis Sonography No Yes Total Positive 19 30 49 Negative 137 7 144 Total 156 37 193 Sensitivity, 0.81 (95% CI, 0.64–0.91); specificity, 0. (95% CI, 0.81–0.92); PPV, 0.61 (95% CI, 0.46–0.74); and NPV, 0.95 (95% CI, 0.90–0.98).
Table 4. Sonographic Diagnosis From Original Report Interpretation Compared With Final Diagnosis (Surgery/Pathologic Examination) Appendicitis Sonography No Yes Total Positive 16 30 46 Negative 140 7 147 Total 156 37 193 Sensitivity, 0.81 (95% CI, 0.64–0.91); specificity, 0. (95% CI, 0.83–0.93); PPV, 0.65 (95% CI, 0.49–0.78); and NPV, 0.95 (95% CI, 0.90–0.98).
- Doria AS, Moineddin R, Kellenberger CJ, et al. US or CT for diagnosis of appendicitis in children and adults? A meta- analysis. Radiology 2006; 241:83–94.
- Assefa G, Meseret S, Nigussie Y. The role of ultrasound in diagnosing acute appendicictis. Ethiop Med J 2006; 44: 67–74.
- Kaiser S, Jorulf H, Söderman E, Frenckner B. Impact of radi- ologic imaging on the surgical decision-making process in suspected appendicitis in children. Acad Radiol 2004; 11:971–979.
- Incesu L, Yazicioglu AK, Selcuk MB, Ozen N. Contrast- enhanced power Doppler US in the diagnosis of acute appendicitis. Eur J Radiol 2004; 50:201–209.
- Poortman P, Lohle PN, Schoemaker CM, et al. Comparison of CT and sonography in the diagnosis of acute appen- dicitis: a blinded prospective study. AJR Am J Roentgenol 2003; 181:1355–1359.
- Lowe LH, Penney MW, Stein SM, et al. Unenhanced limit- ed CT of the abdomen in the diagnosis of appendicitis in children: comparison with sonography. AJR Am J Roentgenol 2001; 176:31–35.
- VassarStats. Utilities/convert to standard scores. VassarStats website. http://faculty.vassar.edu/lowry/VassarStats.html. Accessed November 2, 2009.
- Newcombe RG. Two-sided confidence intervals for the sin- gle proportion: comparison of seven methods. Stat Med 1988; 17:857–872.
- Rodriguez DP, Vargas S, Callahan MJ, Zurakowski D, Taylor GA. Appendicitis in young children: imaging experience and clinical outcomes. AJR Am J Roentgenol 2006; 186: 1158–1164.
- Taylor GA. Suspected appendicitis in children: in search of the single best diagnostic test. Radiology 2004; 231:293–
- Rao PM, Rhea JT, Rao JA, Conn AK. Plain abdominal radio- graphy in clinically suspected appendicitis: diagnostic yield, resource use, and comparison with CT. Am J Emerg Med 1999; 17:325–328.
- Old JL, Dusing RW, Yap W, Dirks J. Imaging for suspected appendicitis. Am Fam Physician 2005; 71:71–78.
- Siegel MJ, Carel C, Surratt S. Ultrasound of acute abdom- inal pain in children. JAMA 1991; 266:1987–1989.
- Puylaert JB. Acute appendicitis: US evaluation using grad- ed compression. Radiology 1986; 158:355–360.
- Wiersma F, Sramek A, Holscher HC. US features of the nor- mal appendix and surrounding area in children. Radiology 2005; 235:1018–1022.
- Chang YJ, Kong MS, Hsia SH, et al. Usefulness of ultra- sonography in acute appendicitis in early childhood. J Pediatr Gastroenterol Nutr 2007; 44:592–595.
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