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1 Note: This copy is for your personal, non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at ORIGINAL RESEARCH n GASTROINTESTINAL IMAGING Ali S. Raja, MD, MBA Christopher Wright, BA Aaron D. Sodickson, MD, PhD Richard D. Zane, MD Gordon D. Schiff, MD Richard Hanson Pieter F. Baeyens, MD Ramin Khorasani, MD, MPH Negative Appendectomy Rate in the Era of CT: An 18-year Perspective1 Purpose: Materials and Methods: To estimate the correlation between the negative appendectomy rate (NAR) and the rate of preoperative computed tomography (CT) in patients suspected of having acute appendicitis who presented to the emergency department during an 18-year period. This retrospective institutional review board approved, HIPAA-compliant study was performed in a 719-bed tertiary care adult teaching hospital with annual emergency department visits. The authors obtained a waiver of informed consent and used the medical records system to compare patients suspected of having appendicitis who presented to the emergency department between 2003 and 2007 to those who presented between 1990 and 1994, the period just before CT became commonly used at the authors institution for the evaluation of appendicitis. Surgical and pathology reports were reviewed to determine the NAR, and the authors queried the radiology databases to determine the proportion of appendectomy patients who underwent preoperative imaging. Outcome measures included the NAR, the proportion of appendectomy patients who underwent preoperative CT, and the annual number of appendectomies performed. The x 2 test for trend was used to assess for changes in proportions, and linear regression was used to evaluate numeric trends. Results: Conclusion: From 1990 to 2007, the NAR decreased significantly from 23.0% to 1.7% ( P,.0001), the annual number of appendectomies decreased significantly from 217 per year to 119 per year ( P =.0003), and the proportion of patients undergoing appendectomy who underwent preoperative CT increased significantly from 1% to 97.5% ( P,.0001). There was a significant reduction in both the NAR and the number of appendectomies in patients who presented to the emergency department during an 18-year period, which was associated with a significant increase in the use of preoperative abdominal CT. 1 From the Center for Evidence Based Imaging (A.S.R., C.M.W., A.D.S., R.D.Z., R.H., P.F.B., R.K.) and Departments of Radiology (A.D.S., R.H., P.F.B., R.K.), Emergency Medicine (A.S.R., R.D.Z.), and General Internal Medicine (G.D.S.), Brigham and Women s Hospital, Harvard Medical School, 75 Francis St, Boston, MA Received August 26, 2009; revision requested October 12; revision received December 12; accepted January 12, 2010; fi nal version accepted February 1. Address correspondence to A.S.R. ( asraja@partners.org ). q RSNA, 2010 q RSNA, radiology.rsna.org n Radiology: Volume 256: Number 2 August 2010

2 Appendicitis is one of the most common causes of abdominal pain in emergency departments ( 1 ); however, its diagnosis remains challenging. Historically, an acceptable negative appendectomy rate (NAR) defined as the portion of pathologically normal appendices removed surgically in patients suspected of having acute appendicitis ( 2 ) has been between 15% and 25% ( 3 ), with an even higher rate considered acceptable in women, for whom making the diagnosis is thought to be more difficult ( 4,5 ). More recently, clinicians have increasingly relied on radiologic imaging in an effort to more accurately diagnose appendicitis preoperatively and to decrease both the number of unnecessary appendectomies and the rate of complications ( 6 8 ). Initially, it was hoped that the increased use of ultrasonography (US) might correlate with a decrease in the NAR ( 9,10 ). Despite initial expectations to the contrary, a previous study at our institution found no association between the NAR from 1990 to 1994 and the use of US ( 11 ). Subsequently, computed tomography (CT) became the imaging modality of choice for patients suspected of having appendicitis ( 12,13 ). Recent studies have reported mixed results with regard to the association between CT use and the NAR. One large statewide database study concluded that there was no decrease in the NAR following the introduction of CT and US ( 14 ), whereas another database study from the same state did demonstrate a reduction in the NAR associated with increased CT use ( 15 ). Other reports have similarly suggested ( ) and refuted ( 19 ) a correlation between a reduction in the NAR and the increasing use of CT, whereas one Advance in Knowledge n We describe a 93% reduction in our emergency department negative appendectomy rate during an 18-year period, which correlated with an increase in the proportion of patients undergoing preoperative CT from 1% to 97.5%. study demonstrated a reduction in the NAR associated with increased CT use only in women ( 20 ). Given these inconsistencies in the literature regarding the association between CT and the NAR as well as our access to data across an 18-year time span, we decided to evaluate this relationship at our institution. We sought to estimate the correlation between the NAR and the rate of preoperative CT in patients suspected of having acute appendicitis who presented to our emergency department during an 18-year period. We compared the NAR and the use of preoperative CT in a recent 5-year period to that in a historical cohort of patients evaluated before the common use of CT in emergency department patients suspected of having appendicitis. We tested the hypothesis that there would be a decrease in the NAR that correlated with an increase in the use of preoperative CT during this 18-year period. Materials and Methods Setting This retrospective institutional review board approved, Health Insurance Portability and Accountability Act compliant study was performed in a metropolitan, tertiary care adult-only academic emergency department with an annual patient census of approximately visits. The institutional review board waived the need to obtain informed consent. Imaging Technique A number of different CT scanners and protocols were used for the evaluation of appendicitis from 1990 to 2008 ( Fig 1 ). All scanners were manufactured by Siemens (Erlangen, Germany) Implication for Patient Care n It is now standard of care at our hospital to obtain preoperative CT scans before an appendectomy; this change in practice has been associated with a significant decrease in the negative appendectomy rate, especially in women. and scans were obtained at 120 kv, with milliampere seconds and rotation times changing with technology development. Axial section thickness evolved from 10 to 5 mm. Oral contrast material (barium sulfate except in cases of suspected perforation, when a diatrizoate meglumine/diatrizoate sodium solution would be used instead) was administered during the entire period except , when rectal contrast material (an iopromide/saline solution) was administered instead. Intravenous contrast material (diatrizoate sodium until 1993, after which nonionic agents like iopamidol and iopromide were used) has been routinely administered since 1996 and was used only intermittently before then. Routine coronal reformations were added in Study Design and Patient Population We searched our electronic medical records (including surgery and pathology records) to identify the cohort of all emergency department patients who underwent an appendectomy for suspected acute appendicitis in the 5-year periods between January 1990 and December 1994 and between March 2003 and February The earlier period was chosen because it corresponded with the beginning of the trend toward preoperative CT, and the later period (classified as ) was chosen because it was the 5-year period immediately after we Published online before print /radiol Radiology 2010; 256: Abbreviation: NAR = negative appendectomy rate Author contributions: Guarantor of integrity of entire study, A.S.R.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of fi nal version of submitted manuscript, all authors; literature research, A.S.R., A.D.S., G.D.S., R.K.; clinical studies, A.S.R., P.F.B., R.K.; statistical analysis, A.S.R., C.M.W., R.H., R.K.; and manuscript editing, A.S.R., C.M.W., A.D.S., R.D.Z., G.D.S., R.K. Authors stated no fi nancial relationship to disclose. Radiology: Volume 256: Number 2 August 2010 n radiology.rsna.org 461

3 Figure 1 Figure 1: Table 1 Timeline of scanners and protocol adjustments used for CT of suspected appendicitis. Demographics and Surgical Outcomes, Parameter Total ED appendectomies Male patients 103 (47.5) 92 (51.4) 88 (41.1) 93 (50.5) 80 (45.2) 456 (47.0) Female patients 114 (52.5) 87 (48.6) 126 (58.9) 91 (49.5) 97 (54.8) 515 (53.1) Appendicitis Male patients 87 (52.1) 83 (55.7) 78 (46.2) 79 (56.4) 69 (50.4) 396 (52.0) Female patients 80 (47.9) 66 (44.3) 91 (53.8) 61 (43.6) 68 (49.6) 366 (48.0) Normal fi ndings Male patients 16 (32) 9 (30) 10 (22) 14 (32) 11 (28) 60 (28.7) Female patients 34 (68) 21 (70) 35 (78) 30 (68) 29 (72) 149 (71.3) Note. Numbers in parentheses are percentages. ED = emergency department. implemented our computerized radiology order entry system a change that allowed us easier access to utilization data. The NAR during the earlier period had been previously published in a study analyzing the effect of US on NAR at our institution ( 11 ). Patients undergoing incidental appendectomy during an unrelated procedure or those with other intraabdominal findings thought to cause their pain at surgical or pathologic evaluation were excluded. We reviewed our medical records to determine how many of these patients underwent abdominal CT before their appendectomy. Outcome Measures The main outcome measure was the NAR. Our two secondary measures included the proportion of patients undergoing appendectomy who underwent preoperative CT and the annual number of appendectomies performed in emergency department patients. We determined the NAR by reviewing pathology records to determine whether removed appendices were acutely inflamed. All acutely inflamed appendices were categorized as positive, whereas all other findings were categorized as negative. The NAR was calculated as the ratio of all negative results to the total number of appendectomies performed. The proportion of appendectomy patients who underwent preoperative CT was determined by reviewing the medical records of all the emergency department patients who underwent appendectomies between 1990 and 1994 and between 2003 and For patients in the later group, we were able to access electronic medical records and find images obtained either at our hospital or at an outside hospital. The presence of images from outside hospitals was determined by searching admission, surgical, and discharge notes for documentation of imaging performed before transfer. For patients in the earlier group, we were only able to access billing records to determine whether abdominal CT had been performed at our institution. Statistical Analysis We used software (JMP 7.0; SAS Institute, Cary, NC) to perform x 2 tests for trend to assess for changes in the sex proportion of appendectomies per year, the annual NAR, and the proportion of appendectomy patients who underwent preoperative CT each year. We used linear regression to evaluate the trend in the number of annual appendectomies and the number of abdominal CT examinations ordered per year in the emergency department. Results During the study period, 971 appendectomies (456 [47.0%] in male patients) were performed in patients who presented to the emergency department. The mean patient age was 33.7 years (range, years). Overall, in 762 of the 971 patients (78.5%) there were pathologic findings consistent with appendicitis ( Table 1 ). During the study period, 637 appendectomies (299 [46.9%] in male patients) were performed in patients who presented to the emergency department. The mean patient age was 38.6 years (range, years). Overall, in 598 of the 637 patients (93.9%) there were pathologic findings consistent with appendicitis. There was no significant difference in the sex proportion of appendectomy patients from 1990 to 2007 ( P =.7354) ( Table 2 ). The NAR decreased significantly between 1990 and 2007, from 23.0% to 1.7% ( P,.0001) ( Tables 3, 4 ). In female patients, the NAR decreased from 29.8% to 1.6% ( P,.0001) and in male patients it decreased from 15.5% to 1.8% ( P,.0001). Preoperative CT for patients undergoing appendectomy increased from 1% of patients undergoing appendectomy in 1990 to 97.5% of patients undergoing appendectomy in 2007 ( P,.0001) ( Tables 5, 6 ). Although other imaging modalities (US and magnetic resonance [MR] imaging) were occasionally used preoperatively (37 patients underwent preoperative US and two underwent preoperative MR imaging from 2003 to 2007 ), use was too infrequent 462 radiology.rsna.org n Radiology: Volume 256: Number 2 August 2010

4 Table 2 Demographics and Surgical Outcomes, Parameter Total P Value ( ) ED appendectomies Male patients 63 (49.2) 66 (48.9) 61 (43.3) 53 (46.5) 56 (47.1) 299 (46.9).7354 Female patients 65 (50.8) 69 (51.1) 80 (56.7) 61 (53.5) 63 (52.9) 338 (53.1) Appendicitis Male patients 60 (51.3) 65 (53.3) 60 (45.1) 51 (46.8) 55 (47.0) 291 (48.7).2428 Female patients 57 (48.7) 57 (46.7) 73 (54.9) 58 (53.2) 62 (53.0) 307 (51.3) Normal fi ndings Male patients 3 (27) 1 (7.7) 1 (12) 2 (40) 1 (50) 8 (20).1013 Female patients 8 (73) 12 (92) 7 (88) 3 (60) 1 (50) 31 (79) Note. Numbers in parentheses are percentages. ED = emergency department. Table 3 NARs, Parameter All patients Male patients Female patients Note. Data are percentages. Table 4 NARs, Parameter 2003* 2004* 2005* 2006* 2007* P Value ( ) All patients ,.0001 Male patients ,.0001 Female patients ,.0001 * Data are percentages. and inconsistent to be included in the study. The correlation coefficients for the proportion of appendectomy patients undergoing preoperative CT and the NAR were and for the periods and , respectively ( Fig 2 ). Discussion During an 18-year period from 1990 to 2007, we observed a significant decrease in the NAR and number of appendectomies per year. This decrease in the NAR was associated with a significant increase in the proportion of emergency department appendectomy patients who underwent preoperative CT. Our findings support the most recently reported studies in the literature by Coursey et al ( 21 ), Kim et al ( 17 ), Raman et al ( 18 ), Chooi et al ( 16 ), and Cuschieri et al ( 15 ) and are in contrast to a report by Flum et al ( 14 ), who failed to show a significant effect on NAR during the era of CT, US, and laparoscopy, Table 5 Abdominal CT Use in the Emergency Department, Parameter All abdominal CT examinations Male patients* 121 (58.7) 299 (58.9) 349 (51.2) 400 (57.9) 390 (51.2) Female patients* 85 (41.3) 209 (41.1) 333 (48.8) 291 (42.1) 372 (48.8) Preoperative CT 2 (1.0) 4 (2.2) 5 (2.3) 10 (5.4) 19 (10.7) Male patients 2 (1.9) 3 (3.3) 2 (2.3) 4 (4.3) 9 (11.3) Female patients 0 1 (1.1) 3 (2.4) 6 (6.6) 10 (10.3) * Numbers in parentheses are percentages of patients. Numbers in parentheses are percentages of appendectomies. and Frei et al ( 19 ), who demonstrated a statistically insignificant ( P =.087) decrease in the NAR associated with an increase in CT use from 1998 to However, the former study ( 14 ) which used a statewide database did not look at imaging utilization but rather simply tracked NAR during an era of widespread availability of CT, US, and laparoscopy and the latter study ( 19 ) reviewed data from only 7 years. Measuring CT use specifically and extending the time period of data analysis may have altered the results of both of these studies. One explanation for the significant decreases in both the NAR and the number of appendectomies performed might be that the increased use of imaging has led to a decrease in the number Radiology: Volume 256: Number 2 August 2010 n radiology.rsna.org 463

5 Table 6 Abdominal CT Use in the Emergency Department, Parameter P Value ( ) of CT and the risks of radiation exposure to help define the appropriate use of CT in the setting of suspected appendicitis. All abdominal CT ,.0001 examinations Male patients* 1234 (38.6) 1453 (40.2) 1546 (40.3) 1708 (41.0) 1611 (39.9),.0001 Female patients* 1962 (61.4) 2157 (59.8) 2289 (59.7) 2459 (59.0) 2425 (60.1) Preoperative CT 114 (89.1) 119 (88.2) 133 (94.3) 110 (96.5) 116 (97.5),.0001 Male patients 57 (90.5) 56 (84.9) 54 (88.5) 49 (92.5) 53 (94.6),.0001 Female patients 57 (87.7) 63 (91.3) 79 (98.8) 61 (100.0) 63 (100.0),.0001 * Numbers in parentheses are percentages of patients. Numbers in parentheses are percentages of appendectomies. Figure 2 References 1. Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol 1990 ; 132 ( 5 ): Velanovich V, Satava R. Balancing the normal appendectomy rate with the perforated appendicitis rate: implications for quality assurance. Am Surg 1992 ; 58 ( 4 ): Detmer DE, Nevers LE, Sikes ED Jr. Regional results of acute appendicitis care. JAMA 1981 ; 246 ( 12 ): 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 ( 10 ): Körner H, Söndenaa K, Söreide JA, et al. Incidence of acute nonperforated and perforated appendicitis: age-specific and sex-specific analysis. World J Surg 1997 ; 21 ( 3 ): Kim K, Rhee JE, Lee CC, et al. Impact of helical computed tomography in clinically evident appendicitis. Emerg Med J 2008 ; 25 ( 8 ): Figure 2: Graph shows the NAR and preoperative CT rate for the and study periods. Data were derived from reference 11. of unnecessary appendectomies, which would support earlier results ( ). We also found that nearly all emergency department patients (97.5%) currently undergoing appendectomy at our hospital undergo preoperative CT. Our data also suggest that the use of preoperative CT has been associated with a decrease in the female-to-male NAR ratio from 1.9:1 in 1990 to 0.9:1 in 2007, implying that the use of CT may have been helpful in decreasing the number of negative appendectomies in women. There were a number of limitations in our study. It was performed at a single academic medical center, and our conclusions may not be generalizable. We do not have electronic or scanned information about outside imaging for the earlier of our two cohorts, and thus a small proportion of patients may have been transferred to our hospital after obtaining CT scans from referring hospitals. We did not evaluate the appropriateness of CT in the work-up of suspected appendicitis in our emergency department, nor did we capture the pretest likelihood of appendicitis in our cohort. Finally, we did not perform a cost-effectiveness analysis to estimate the value of the reduced NAR against the cost of CT and the associated potential long-term risks of radiation exposure ( 22 ). We observed a significant reduction in both the NAR and number of appendectomies in emergency department patients, which was associated with a significant increase in the rate of preoperative CT in patients undergoing appendectomy during an 18-year period. Additional studies are needed to assess the relative benefits of decreased NAR compared with the costs 7. Nathan RO, Blackmore CC, Jarvik JG. Therapeutic impact of CT of the appendix in a community hospital emergency department. AJR Am J Roentgenol 2008 ; 191 ( 4 ): Raman SS, Lu DS, Kadell BM, Vodopich DJ, Sayre J, Cryer H. Accuracy of nonfocused helical CT for the diagnosis of acute appendicitis: a 5-year review. AJR Am J Roentgenol 2002 ; 178 ( 6 ): Jeffrey RB Jr, Laing FC, Lewis FR. Acute appendicitis: high-resolution real-time US findings. Radiology 1987 ; 163 ( 1 ): Puylaert JB, Rutgers PH, Lalisang RI, et al. A prospective study of ultrasonography in the diagnosis of appendicitis. N Engl J Med 1987 ; 317 ( 11 ): Khorasani R, Cheng D, Bates D, et al. Has the use of appendiceal ultrasound been effective in reducing the negative appendectomy rate? J Clin Outcomes Manag 2003 ; 10 ( 1 ): Andre JB, Sebastian VA, Ruchman RM, Saad SA. CT and appendicitis: evaluation of correlation between CT diagnosis and pathological diagnosis. Postgrad Med J 2008 ; 84 ( 992 ): radiology.rsna.org n Radiology: Volume 256: Number 2 August 2010

6 13. Rao PM, Rhea JT, Novelline RA, Mostafavi AA, McCabe CJ. Effect of computed tomography of the appendix on treatment of patients and use of hospital resources. N Engl J Med 1998 ; 338 ( 3 ): Flum DR, Morris A, Koepsell T, Dellinger EP. Has misdiagnosis of appendicitis decreased over time? A population-based analysis. JAMA 2001 ; 286 ( 14 ): SCOAP Collaborative, Cuschieri J, Florence M, et al. Negative appendectomy and imaging accuracy in the Washington State Surgical Care and Outcomes Assessment Program. Ann Surg 2008 ; 248 ( 4 ): Chooi WK, Brown JA, Zetler P, Wiseman S, Cooperberg P. Imaging of acute appendicitis and its impact on negative appendectomy and perforation rates: the St. Paul s experience. Can Assoc Radiol J 2007 ; 58 ( 4 ): Kim K, Lee CC, Song KJ, Kim W, Suh G, Singer AJ. The impact of helical computed tomography on the negative appendectomy rate: a multi-center comparison. J Emerg Med 2008 ; 34 ( 1 ): Raman SS, Osuagwu FC, Kadell B, Cryer H, Sayre J, Lu DS. Effect of CT on falsepositive diagnosis of appendicitis and perforation. N Engl J Med 2008 ; 358 ( 9 ): Frei SP, Bond WF, Bazuro RK, Richardson DM, Sierzega GM, Reed JF. Appendicitis outcomes with increasing computed tomographic scanning. Am J Emerg Med 2008 ; 26 ( 1 ): McGory ML, Zingmond DS, Nanayakkara D, Maggard MA, Ko CY. Negative appendectomy rate: influence of CT scans. Am Surg 2005 ; 71 ( 10 ): 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 ( 2 ): Sodickson A, Baeyens PF, Andriole KP, et al. Recurrent CT, cumulative radiation exposure, and associated radiation-induced cancer risks from CT of adults. Radiology 2009 ; 251 ( 1 ): Radiology: Volume 256: Number 2 August 2010 n radiology.rsna.org 465