Computed Tomography Diagnostic Values of Acute Appendicitis in Different Patient Subgroups

J Radiol Sci 2013; 38: 9-14 Computed Tomography Diagnostic Values of Acute Appendicitis in Different Patient Subgroups Chih-Chen Chang Yon-Cheong Wong Li-Jen Wang Cheng-Hsien Wu Huan-Wu Chen Chen-Chih Huang Yung-Liang Wan Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan Abstract To determine the diagnostic values for computed tomography (CT) in acute appendicitis in different subgroups of patients presenting with right lower abdominal pain at emergency room (ER). This was a retrospective study on 226 patients (105 men and 121 women) with mean age of 44.0 ± 16.7 years (age range, 16-88 years) who presented with right lower abdominal pain at ER from January 2008 to December 2009. All were suspected of having acute appendicitis and underwent CT examinations before therapy was instituted. Their medical charts were reviewed for initial CT report, surgical report, pathology report and final diagnosis. Subgroup analyses of CT diagnostic values of acute appendicitis were performed in patients with different gender (men or women) and age ( 45 years or > 45 years). Of 226 patients, 114 (50.4%) had a final diagnosis of acute appendicitis. Overall, CT accuracy of acute appendicitis was 94.7%. In subgroup analyses, CT accuracy was 94.7% (men 45 years), 93.8% (men > 45 years), 97.1% (women 45 years), 92.5% (women > 45 years), respectively. The likelihood ratio (LR) of positive CT for acute appendicitis ranged from 37.7 in women 45 years to 7.0 in men > 45 years. Overall, CT diagnosis of acute appendicitis at ER is accurate. Women 45 years benefit most from preoperative CT because positive CT in this subgroup is associated with a large chance in the LR for appendicitis. However, in elderly patients, appendiceal tumors and chronic appendicitis may mimic acute appendicitis on CT scan. Acute appendicitis is one of the most common causes of right lower quadrant abdominal pain in emergency room (ER) and the most common indication for emergency abdominal surgeries [1]. The typical clinical presentation of appendicitis is initial periumbilical abdominal pain, which is progressively localized to a point in the right lower quadrant (RLQ), where the inflamed appendix irritates the parietal peritoneum. The pain is usually associated with vomiting, fever, and leukocytosis. Therefore, American College of Radiology (ACR) Appropriateness Criteria demonstrates that acute appendicitis should be suspected in the patient with RLQ pain associated with fever or leukocytosis. However, the clinical diagnosis of appendicitis has both false-positive and false-negative rates of approximately 20%; thus, clinical diagnosis based on history taking and physical examination remains challenging [2]. Imaging diagnostic tests such as ultrasound and computed tomography (CT) have been employed to reduce misdiagnosis. Evaluation of the diagnostic performance of CT for acute appendicitis has revealed a sensitivity of 87-100%, a positive predictive value of 94-97%, a negative predictive value of 93-100%, and an accuracy of 93-98% [3]. The high accuracy of the CT scan has led to increased use of this modality for suspected cases of acute appendicitis. Correspondence Author to: Yon-Cheong Wong Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taoyuan, Taiwan No. 5, Fu-Hsing Street, Guei-Shan, Taoyuan 333, Taiwan J Radiol Sci March 2013 Vol.38 No.1 9

In recent years, the negative appendectomy rate (NAR), defined as the proportion of pathologically normal appendices removed surgically in patients suspected of having acute appendicitis, has been used to evaluate the quality of diagnosis of acute appendicitis. Historically, an acceptable NAR has been set between 15% and 25% [4]. Several previous investigations have demonstrated a decrease in the NAR with use of preoperative CT [4]. McGory and colleague s study demonstrated that the increased use of CT only reduced NAR in women [5]. However, some studies demonstrated that the use of CT significantly reduces the NAR in women 45 years of age but only subtle decline for men and women >45 years which may be owing to initially low NAR [6, 10]. Due to these inconsistent NAR reductions in the literature and the existence of only a few studies that have tried to analyze the discrepancies, we undertook this project to address the issues of the effects of age and gender on CT diagnostic values. Materials and methods Subjects This retrospective study was approved by our institutional review board. Informed consent was waived. We included patients > 16 years of age with RLQ pain, fever and/or leukocytosis who had undergone abdominal CT examination at ER under a clinical suspicion of acute appendicitis. The CT data between January 1, 2008, and December 31, 2009, were retrieved from our radiological information system. Patients with an appendectomy history were excluded. A total of 226 patients were identified within this 2-year period. In total, 105 men and 121 women with a mean age of 44.0 ± 16.7 years (age range, 16-88 years) were included. Among them, 57 men (57/105, 54.3%) and 68 women (68/121, 56.1%) were 45 years. Their medical charts were reviewed for surgical records, pathology reports, and discharge diagnosis. CT data All intravenous contrast-enhanced CT examinations were obtained at the portal venous phase after administration of 100 ml of iodinated contrast material with 4-detector MDCT scanner (LightSpeed QX/i Scanner, General Electric Medical Systems, Milwaukee, WI, USA). No oral or rectal contrast was given for opacification of the bowels. All images were reconstructed with a 5-mm slice thickness and a 5-mm interval and were then sent to a Picture Archiving Communication System for viewing. Coronal and sagittal reconstructions were available if the radiologists had made a request at the time of reporting. All official CT reports were reviewed for the CT diagnosis of RLQ pain. In our department, positive diagnosis of acute appendicitis of CT is defined as a distended appendix (> 6 mm wall-to-wall diameter), appendicolith, fluid-filled lumen, enhancing appendiceal walls, and/or inflammatory changes around the appendix (Fig. 1, 2) [7]. If acute appendicitis was excluded, we recorded the alternative diagnosis provided by the CT report. Pathology records All pathology records were reviewed to determine whether the removed appendices were acutely inflamed. All acutely inflamed appendices were categorized as positive for acute appendicitis, whereas all other findings were categorized as negative. Figure 1 Figure 1. Axial contrast-enhanced CT scan demonstrates dilatation of appendix, enhancing appendiceal walls, and periappendiceal fat stranding (black arrow). Tip of appendix is also shown (white arrow). 10 J Radiol Sci March 2013 Vol.38 No.1

Final diagnosis of acute appendicitis The final diagnosis of acute appendicitis or alternative diagnosis (not acute appendicitis) was concluded based on pathological diagnosis in patients who had undergone surgery. For patients who had not undergone surgery, the discharge diagnosis based on clinical course and outcome served as the final diagnosis. Analyses and statistics The CT diagnosis was compared with the final diagnosis of acute appendicitis for sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and the likelihood ratio (LR) of a positive CT test. The overall CT performance in all patients as well as the CT performances in the subgroups stratified by gender (men and women) and age ( 45 years and > 45 years) were computed. Figure 2 Results Of the 226 patients, 122 (53.9%) had a CT diagnosis of acute appendicitis, and 14 patients (6.1%) had a normal CT scan. Ninety patients (39.8%) had an alternative CT diagnosis. Gastrointestinal system disorders were the most common and were attributed to 48 patients, followed by gynecological and urological disorders. The alternative CT diagnoses are summarized in Table 1. A total of 135 (59.7%) of 226 patients underwent surgery. Of these, 108 were diagnosed with acute appendicitis based on surgery and pathology, 16 had a gastrointestinal disorder, eight had a gynecological disorder, and three had another condition. The alternative surgical diagnoses are summarized in Table 2. Of the 226 patients, 114 (50.4%) had a final diagnosis of acute appendicitis. Among these, 108 final diagnoses were made based on the surgical pathology report, and six were based on the discharge diagnosis. Of these six patients, three underwent CT-guided drainage of a periappendiceal abscess. These periappendiceal abscesses were resulted from ruptured appendicitis because they contained a segment of a perforated appendix [8]. The other three Table 1. The classification and types of CT alternative diagnoses in 90 patients CT alternative diagnoses 90 Gastrointestinal system 48 Diverticulitis/diverticulosis 29 Colitis/ enteritis 9 Colon/ appendix tumor 5 Small bowel ileus 3 Periappendicitis 1 volulus 1 Gynecological disorder 25 Pelvic inflammatory disease 18 Adenxal disorder 5 Endometriosis/adenomyosis 2 Urinary tract disorder 4 Mesenteric adenitis 4 Intraperitoneal and retroperitoneal abscess 3 Biliary tree disorder 3 Figure 2. Reconstructed oblique coronal image of contrastenhanced CT scan demonstrates dilated appendix (black arrow) owing to appendicolith impaction at the base of appendix (white arrowhead). Pancreatitis 1 CAPD Peritonitis 1 Fat necrosis 1 J Radiol Sci March 2013 Vol.38 No.1 11

patients who refused surgery had a discharged diagnosis of acute appendicitis based on clinical presentation such as right lower abdominal pain, fever, leukocytosis as well as typical CT findings. Their condition was improved on discharge after receiving antibiotic treatment. Of the remaining 112 patients, 97 had a specific alternative final diagnosis, 15 had a final diagnosis of non-specific abdominal pain. All of the 15 patients did not receive any specific treatment and were discharged with an improved condition. The alternative final diagnoses are summarized in Table 3. The overall CT sensitivity, specificity, accuracy, PPV, and NPV for acute appendicitis were 98.2%, 91.1%, 94.7%, 91.8 %, and 98.1%, respectively. The CT diagnostic performance for appendicitis in male versus female patients and in patients > 45 years versus 45 years is summarized in Table 4. In subgroup analyses (Table 5), the PPVs of the CT diagnosis for acute appendicitis in decreasing order from the highest to lowest were 96.6% for women 45 years, 91.2% for men 45 years, 90.0% for men > 45 years, and 89.7% for women > 45 years. The NPV in decreasing order was 100.0% for men 45 years, 100.0% for men > 45 years, 97.4% for women 45 years, and 95.8% for women > 45 years. The accuracies in decreasing order were 97.1% in women 45 years, 94.7% in men 45 years, 93.8% in men > 45 years, and 92.5% in women > 45 years. Overall, a positive CT for acute appendicitis in a woman 45 years had the largest LR (37.7) for a final diagnosis of appendicitis compared with those of other subgroups. Discussion High diagnostic values of CT in diagnosing acute appendicitis have been widely reported. Our results are comparable to those of prior studies. Rhea and colleagues revealed a similar accuracy in male and female patients of 93% [9]. In the present study, the accuracies in women (95%) and men (94.3%) are quite similar. Some studies have evaluated the likelihood ratio of a positive CT examination for acute appendicitis. The positive LR for CT ranges from 4.61 to 13.5 [10]. However, no gender subgroup analysis was found in the literature against which to compare these results. In our study, the overall positive LR was 11.0. The positive LR for male and female patients was 7.8 and 15.7, respectively. In our study, CT diagnostic performance for acute appendicitis was poorer in patients > 45 years than in Table 3. The classification and types of final alternative diagnoses in 112 patients Final alternative diagnoses 112 Gastrointestinal system 57 Diverticulitis/diverticulosis 31 Colon/ appendix tumor 8 Colitis/ enteritis 8 Chronic inflammation of appendix 4 Small bowel ileus 3 Table 2. The classification and types of surgical alternative diagnoses in 27 patients Surgical alternative diagnoses 27 Gastrointestinal system 16 Colon/ appendix tumor 8 Chronic inflammation of appendix 4 Diverticulitis/diverticulosis 2 Ischemic bowel 1 Periappendicitis 1 Gynecological disorder 8 Pelvic inflammatory disease 6 Ovary torsion 1 Endometriosis/adenomyosis 1 Retroperitoneal abscess 1 Biliary tree disorder 1 CAPD Peritonitis 1 Ischmic bowel 1 PPU with intraperitoneal abscess 1 Periappendicitis 1 Gynecological disorder 24 Pelvic inflammatory disease 17 Adenxal disorder 4 Endometriosis/adenomyosis 2 Ovary torsion 1 Urinary tract disorder 4 Mesenteric adenitis 4 Biliary tree disorder 3 Retroperitoneal abscess 2 CAPD peritonitis 1 Pancreatitis 1 Fat necrosis 1 Non-specific abdominal pain 15 12 J Radiol Sci March 2013 Vol.38 No.1

younger patients, particularly in men > 45 years. By contrast, the accuracy for patients > 65 years reported by Rhea et al. was 100% [9]. This discrepancy could be attributed to an appendiceal tumor (e.g., mucinous cystadenoma or adenocarcinoma) and chronic appendicitis, both of which can mimic acute appendicitis in elderly patients. Most patients with an appendiceal tumor present with clinical symptoms of acute appendicitis; therefore, this diagnosis is usually not suspected preoperatively [11]. In the literature, the median age of patients with an appendiceal tumor is 69 years. In our study, four of 226 patients with a final diagnosis of appendiceal tumor had a median age of 60 years, including two men and two women. Of these four patients, two had a preoperative CT diagnosis of an appendiceal tumor. However, the other two, both men, were diagnosed with acute appendicitis on preoperative CT. Chronic appendicitis is a relatively rare disease and could result from recurrent inflammation of the appendix. Chronic appendicitis is usually indistinguishable from acute appendicitis on CT [12]. In our study, four of 226 patients, including two men and two women, had final diagnoses of chronic appendicitis, and their median age was 49 years. None had a correct diagnosis of chronic appendicitis on preoperative CT. In general, the differential diagnosis list for right lower abdominal pain in women of reproductive age is plentiful because of the multiple possible gynecologic diseases in pelvis. Furthermore, pelvic inflammatory disease, gastroenteritis, and urinary infections may mimic the clinical presentation of acute appendicitis [13]. Thus, the clinical diagnosis of acute appendicitis in young women is more challenging. However, in our study, the highest PPV and positive likelihood ratio of CT diagnosis for acute appendicitis occurred in women 45 years. This is due to the high diagnostic performance of CT in distinguishing pelvic inflammatory disease from acute appendicitis in young female patients in the current study. Our CT examination helped us to correctly diagnose 16 of 17 patients who were having pelvic inflammatory disease rather than acute appendicitis. In our study, two female patients with a final diagnosis of acute appendicitis were diagnosed with pelvic inflammatory disease on CT scan. Both patients had a large ovarian cyst and regional inflammatory fat stranding on CT that may have overlapping CT findings with acute appendicitis. Pelvic inflammatory disease was the most common alternative diagnosis for right lower abdominal pain in women, whereas the most common alternative diagnosis in men was diverticulitis. With liberal use of preoperative CT, Fuch and colleagues found that NAR for women could be reduced from 23.5 to 5.3% [3]. Rao and colleagues also found that the most salient improvement of CT in decreasing NAR occurred in women, with NAR decreasing from 35 to 11% [14]. Courtney also reported that NAR decreased from 42.9% in 1998 to 7.1% for women 45 years and younger [6]. These findings are similar to our results in which women 45 years benefit most from preoperative CT. Thus, Antevil J. and colleagues also suggested that a CT scan should be considered for all women with suspected appendicitis before surgery [15]. Our study had several limitations. The study was retrospective, and a number of important parameters could not be controlled. The discharge diagnosis based on clinical Table 4. CT diagnostic performance for appendicitis in all patients, men, women, adults 45 years and > 45 years Patients Number Sensitivity (95% CI) Specificity (95% CI) Accuracy (95% CI) PPV NPV LR(+) All N=226 98.2 (95.8, 100.7) 91.1 (85.8, 96.4) 94.7 (91.8, 97.6) 91.8 98.1 11.0 Men N=105 100 (100.0, 100.0) 87.2 (77.7, 96.8) 94.3 (89.8, 98.7) 90.6 100.0 7.8 Women N=121 96.4 (91.6, 101.3) 93.8 (88.0, 99.7) 95 (91.2, 98.9) 93.1 96.8 15.7 Adults 45 years N=125 98.3 (95.1, 101.6) 93.8 (88.0, 99.7) 96 (92.6, 99.4) 93.7 98.4 16.0 Adults >45 years N=101 98.1 (94.6, 101.7) 87.2 (77.7, 96.8) 93.1 (88.1, 98.0) 89.8 97.6 7.7 Table 5. CT diagnostic performance for acute appendicitis in different subgroups Patients Number Sensitivity (95% CI) Specificity (95% CI) Accuracy (95% CI) PPV NPV LR(+) Women 45 years N=68 96.6 (89.9, 103.2) 97.4 (92.5, 102.4) 97.1 (93, 101.1) 96.6 97.4 37.7 Women >45 years N=53 96.3 (89.2, 103.4) 88.5 (76.2, 100.7) 92.5 (85.3, 99.6) 89.7 95.8 8.3 Men 45 years N=57 100.0 (100.0, 100.0) 88.5 (76.2, 100.7) 94.7 (88.9, 100.5) 91.2 100.0 8.7 Men >45 years N=48 100.0 (100.0, 100.0) 85.7 (70.7, 100.7) 93.8 (86.9, 100.6) 90.0 100.0 7.0 J Radiol Sci March 2013 Vol.38 No.1 13

course and outcome, which served as the final diagnosis for comparisons in patients who did not undergo surgery, is imperfect. However, this is the preferred way of diagnosing most patients who did not require surgery. We arbitrarily stratified female patients into groups < 45 years or > 45 years in age based on reproductive age. The definition of reproductive age could vary in different developed and developing countries. In conclusion, overall, the CT diagnosis of acute appendicitis is generally accurate. A positive CT is strongly associated with the LR for appendicitis in women < 45 years. For women < 45 years with ambiguous RLQ pain at the ER, a CT scan can be very helpful for emergency physicians to make a clinical decision about patients disposition. However, we must be cautious in reading CT scans of elderly patients because appendiceal tumors and chronic appendicitis may mimic findings of acute appendicitis. Reference 1. Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol 1990; 132: 910-925 2. Wijetunga R, Tan BS, Rouse JC, Bigg-Wither GW, Doust BD. Diagnostic accuracy of focused appendiceal CT in clinically equivocal cases of acute appendicitis. Radiology 2001; 221: 747-753 3. Fuchs JR, Schlamberg JS, Shortsleeve MJ, Schuler JG. Impact of abdominal CT imaging on the management of appendicitis: an update. J Surg Res 2002; 106: 131-136 4. Raja AS, Wright C, Sodickson AD, et al. Negative appendectomy rate in the era of CT: an 18-year perspective. Radiology 2010; 256: 460-465 5. McGory ML, Zingmond DS, Nanayakkara D, Maggard MA, Ko CY. Negative appendectomy rate: influence of CT scans. Am Surg 2005; 71: 803-808 6. Coursey CA, Nelson RC, Patel MB, et al. Making the diagnosis of acute appendicitis: do more preoperative CT scans mean fewer negative appendectomies? A 10-year study. Radiology 2010; 254: 460-468 7. Rao PM, Rhea JT, Novelline RA, et al. Helical CT technique for the diagnosis of appendicitis: prospective evaluation of a focused appendix CT examination. Radiology 1997; 202: 139-144 8. Marin D, Ho LM, Barnhart H, Neville AM, White RR, Paulson EK. Percutaneous abscess drainage in patients with perforated acute appendicitis: effectiveness, safety, and prediction of outcome. AJR Am J Roentgenol. 2010;194(2):422-429 9. Rhea JT, Halpern EF, Ptak T, Lawrason JN, Sacknoff R, Novelline RA. The status of appendiceal CT in an urban medical center 5 years after its introduction: experience with 753 patients. AJR Am J Roentgenol 2005; 184: 1802-1808 10. van Randen A, Bipat S, Zwinderman AH, Ubbink DT, Stoker J, Boermeester MA. Acute appendicitis: metaanalysis of diagnostic performance of CT and graded compression US related to prevalence of disease. Radiology 2008; 249: 97-106 11. Bucher P, Mathe Z, Demirag A, Morel P. Appendix tumors in the era of laparoscopic appendectomy. Surg Endosc 2004; 18: 1063-1066 12. Chalazonitis AN, Tzovara I, Sammouti E, et al. CT in appendicitis. Diagn Interv Radiol 2008; 14: 19-25 13. Rothrock SG, Green SM, Dobson M, Colucciello SA, Simmons CM. Misdiagnosis of appendicitis in nonpregnant women of childbearing age. J Emerg Med 1995; 13: 1-8 14. Rao PM, Rhea JT, Rattner DW, Venus LG, Novelline RA. Introduction of appendiceal CT: impact on negative appendectomy and appendiceal perforation rates. Ann Surg 1999; 229: 344-349 15. Antevil J, Rivera L, Langenberg B, Brown CV. The influence of age and gender on the utility of computed tomography to diagnose acute appendicitis. Am Surg 2004; 70: 850-853 14 J Radiol Sci March 2013 Vol.38 No.1