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Gastrointestinal Imaging |
1 From the Department of Radiology, University of Pennsylvania Medical Center, 3400 Spruce St, Philadelphia, PA 19104 (J.E.J., B.A.B., D.D.M., A.M.A., C.P.L.); and Department of Radiology, New York University Medical Center, New York, NY (M.M., A.J.M., G.I.). From the 2000 RSNA scientific assembly. Received September 14, 2000; revision requested November 3; final revision received February 13, 2001; accepted February 26. Address correspondence to J.E.J. (e-mail: jacobs@rad.upenn.edu).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: After receiving oral contrast material, 228 patients with clinically suspected appendicitis underwent focused appendiceal CT (5-mm section thickness, 15-cm coverage in the right lower quadrant). Immediately thereafter, helical CT of the entire abdomen and pelvis was performed following intravenous administration of contrast material (abdomen, 7-mm section thickness; pelvis, 5-mm section thickness). Studies were separated and independently interpreted by three observers who were blinded to patient names. Diagnoses were established by means of surgical and/or clinical follow-up findings.
RESULTS: Fifty-one (22.4%) of 228 patients had acute appendicitis. Readers diagnosed appendicitis with 83.3%, 73.8%, and 71.4% sensitivity and 93.0%, 92.3%, and 97.9% specificity with focused nonenhanced appendiceal CT. Readers diagnosed appendicitis with 92.9%, 92.9%, and 88.1% sensitivity and 93.7%, 95.1%, and 96.5% specificity with nonfocused enhanced CT. Summary areas under the receiver operating characteristic curve estimates for focused nonenhanced and nonfocused enhanced CT were 0.916 and 0.964, respectively; the differences were statistically significant (P < .05) for two of three readers. All readers demonstrated higher sensitivities for detecting the inflamed appendix with nonfocused enhanced CT. Appendicitis was missed with focused CT in two patients whose inflamed appendix was not included in the imaging of the right lower quadrant. All readers were significantly more confident in diagnosing alternative conditions with nonfocused enhanced CT.
CONCLUSION: Diagnostic accuracy of helical CT for acute appendicitis improved significantly with use of intravenous contrast material.
Index terms: Appendicitis, 751.291 • Computed tomography (CT), comparative studies, 751.1211 • Computed tomography (CT), contrast enhancement, 751.12112 • Computed tomography (CT), helical, 751.12115 • Contrast media, comparative studies
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Traditional CT involves scanning the entire abdomen and pelvis following both oral and intravenous administration of contrast material (7–9). Newer imaging strategies include performance of nonenhanced CT of the abdomen and pelvis (1,2), nonenhanced CT focused over the right lower quadrant (10), focused right lower quadrant CT following both oral and intravenous administration of contrast material (4), and focused right lower quadrant CT following rectal administration of colonic contrast material (5).
The purpose of our study was to compare the diagnostic accuracy of focused right lower quadrant helical CT performed with oral contrast material alone and nonfocused helical CT with both oral and intravenous contrast material.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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CT examinations were performed with helical CT scanners (CTi or HiSpeed Advantage; GE Medical Systems, Milwaukee, Wis). All patients initially received 800–1,000 mL of diatrizoate meglumine (Gastrografin; Bristol-Myers Squibb, Princeton, NJ) diluted to a 2%–3% concentration and administered orally during an approximately 45-minute interval. If the cecum was not readily identified on the initial CT scout view, three transverse scans were obtained in the right lower quadrant to localize the cecum and to assess for adequate opacification of the terminal ileum and cecum with oral contrast material. If oral contrast material was not present within these bowel segments, CT scanning was delayed for an additional 15–30 minutes.
At our institution, emergency department personnel rapidly triage patients with acute lower abdominal pain who require a diagnostic CT study and immediately ask these patients to begin drinking oral contrast material. By the time these patients are seen by a physician in the emergency department and are ready for their CT examination, adequate ileocecal bowel opacification is achieved in most.
Bowel preparation times were not recorded for the purposes of this study. We nevertheless estimated that in the majority of patients adequate bowel opacification was achieved in approximately 50–80 minutes. Once adequate bowel opacification with oral contrast material was achieved, a focused nonenhanced helical CT series was performed, with scanning of a 15-cm region of the right lower quadrant centered over the inferior one-third of the cecum (5-mm section thickness, pitch of 1.5:1, 200–220 mAs).
Immediately thereafter, an intravenous contrast material–enhanced helical CT acquisition was performed through the entire abdomen (7-mm section thickness from the hepatic dome to the iliac crests, pitch of 1.3:1, 200–220 mAs) and pelvis (5-mm section thickness from the iliac crests to the ischium, pitch of 1.5:1, 200–220 mAs). One-hundred fifty milliliters of 60% iodinated contrast material (diatrizoate meglumine [Hypaque] or iohexol [Omnipaque 300]; Nycomed, Princeton, NJ) was administered by means of a calibrated power injector (PercuPump, E-Z-Em, Westbury, NY; or ECT, Medrad, Pittsburgh, Pa) at an injection rate of 2–4 mL/sec.
Although the majority of patients received an intravenous injection of contrast material at a rate of 3 mL/sec, the injection rate was not recorded for all patients at the time of CT. When the examinations were performed with one of the three CT scanners equipped with bolus-tracking software (Smart Prep; GE Medical Systems), the software was used to trigger scanning when hepatic enhancement reached a 45-HU threshold. In the remaining cases, fixed scanning delays of 55, 70, and 85 seconds were used for injection rates of 4, 3, and 2 mL/sec, respectively. All examinations were recorded on film without patient names with a 20:1 format, and the films were separated so that the readers first evaluated the nonenhanced scans and later evaluated the intravenous contrast-enhanced scans.
Three readers at another institution who were blinded to patient names independently interpreted the studies. The first reader (A.J.M.) was a senior gastrointestinal radiologist with more than 20 years experience reading abdominal CT scans, the second reader (M.M.) had 3 years experience reading abdominal CT scans after completing an abdominal imaging fellowship, and the third reader (G.I.) was a fellow in abdominal imaging who had received American Board of Radiology certification 1 month previously. Findings on the focused nonenhanced CT scans of the right lower quadrant were initially analyzed, followed by evaluation of the nonfocused intravenous contrast-enhanced studies of the abdomen and pelvis 3–4 weeks later. Interpretations of the nonenhanced and enhanced CT scans were separated according to this interval to minimize recall bias, and the study order was changed between the first and second readings.
Readers evaluated the scans for the presence of acute appendicitis with a five-point Likert scale according to the following scores: 1, definitely absent; 2, probably absent; 3, indeterminate; 4, probably present; and 5, definitely present. Criteria that readers used for the diagnosis of acute appendicitis included the presence of appendiceal distension (diameter, >6 mm); mural thickening; and mural enhancement (either homogeneous or heterogeneous [mural stratification or target sign pattern]), with or without periappendiceal inflammatory change. If the abnormal appendix was not definitively seen, readers diagnosed appendicitis if they identified a calcified appendicolith associated with pericecal inflammation or abscess.
Readers also recorded whether the appendix was identified, its diameter if seen (measuring from outer wall to outer wall), and the presence of periappendiceal inflammation. The scans were additionally evaluated for the presence of an alternative diagnosis with a similar five-point Likert scale. If the reader thought an alternative diagnosis was present, its presumed cause was recorded. Last, each scan was evaluated to determine if the entire length of the appendix was included on the scan during the acquisition.
Patient population information is given in Table 1. Proof of diagnosis could not be established in 18 (7.9%) of 228 patients who did not undergo surgical exploration and were lost to follow-up. These patients were excluded from further statistical data analysis. Final diagnoses in the remaining patients were established on the basis of surgical findings (n = 58) or clinical follow-up data (n = 152). The referring physicians’ decisions to perform surgery were based on a combination of their clinical assessment of the patient’s condition and CT examination results. Fifty-one (24.3%) of these 210 patients had acute appendicitis, while the remaining 159 (75.7%) patients had an alternative diagnosis.
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2 test. Appendiceal diameters in patients with acute appendicitis were compared with those in patients without acute appendicitis by using a two-tailed t test, where a P value of less than .05 was considered to indicate a statistically significant difference. Because the appendix might be identified with one sequence and not with another in the same patient, an unpaired test was used. Individual and pooled sensitivity and specificity values were determined for the diagnoses of acute appendicitis with a decision threshold of a Likert score of 4 or 5 as positive for the diagnosis of acute appendicitis. Binormal receiver operating characteristic (ROC) curves were constructed for both the nonenhanced and enhanced data sets.
The nonenhanced and enhanced data were compared with use of a subroutine (laboratory multiple readers, multiple cases, or LABMRMC) of an ROC analysis program (ROCKIT; C. Metz, University of Chicago, Chicago, Ill) (11). The subroutine is an analysis of variance of areas under the ROC curve, or Az, that account for variability among modalities (here, nonenhanced vs enhanced CT), among readers (here, three different readers), and among cases. This program provides CIs rather than P values. A 95% CI for the difference in areas under the ROC curve that does not overlap zero is equivalent to a P value of less than .05. The effect of intravenous administration of contrast material on the confidence of establishing alternative diagnoses was assessed with the 2 test and ordinal logistic regression. For all analyses, a P value of .05 or less was considered statistically significant.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The appendix was not scanned in two patients examined with focused nonenhanced CT. The inflamed appendix of one patient with acute appendicitis was not included in the 15-cm field of view because it was located deep within the pelvis, while the noninflamed appendix of one patient without appendicitis was not included in the data acquisition because it was superiorly located in the right upper quadrant. An inflamed retrocecal appendix of a third patient with acute appendicitis was incompletely scanned with this technique. Scans in two cases involving an inflamed appendix were misinterpreted at focused nonenhanced CT by all three readers and were ultimately encoded as false-negative diagnoses in this study.
Analysis of the 51 cases of proved appendicitis revealed that all three readers identified a significantly greater number of inflamed appendices at nonfocused intravenous contrast material–enhanced CT (range of detection, 90%–94%) than they identified at focused nonenhanced CT (range of detection, 71%–78%) (Table 2). No statistically significant difference was noted between the CT techniques for normal appendiceal identification in patients without acute appendicitis. The normal appendix in patients without appendicitis was identified in 36.4%–77.3% with nonfocused enhanced CT and in 35.8%–67.9% with focused nonenhanced CT.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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We found no marked difference between the two CT techniques evaluated in this study in their ability to help identify the normal appendix. Marked differences between the protocols were observed, however, in their ability to depict the abnormal appendix. All three readers demonstrated significantly improved ability in identifying the inflamed appendix in patients with acute appendicitis with nonfocused enhanced CT. In previous articles (7,8,12–14), intravenous contrast material was used to aid appendiceal recognition by demonstrating a thickened, enhanced appendiceal wall with either a homogeneous mural enhancement pattern or a heterogeneous mural stratification (target sign) pattern (Fig 5). We believe that this improved ability to help identify the inflamed appendix was the primary contributing factor to the improved diagnostic accuracy seen when nonfocused enhanced CT was compared with focused nonenhanced CT (statistically significant improvement in two of the three readers with a trend toward significance in the third reader).
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Periappendiceal inflammation is considered to be a necessary criterion for diagnosing acute appendicitis by many investigators (1,2,4,5,10) who use CT protocols without administration of intravenous contrast material. Previous studies (8,9,12) have shown, however, that these periappendiceal inflammatory changes may be absent in acute appendicitis. This is thought to be more common in patients with mild incipient forms of appendicitis (14). Our results confirm that reliance on identification of periappendiceal inflammation may lead to false-negative CT diagnoses. We believe that appendicitis can be confidently diagnosed with CT if the inflamed appendix is definitively seen, with or without associated periappendiceal inflammatory changes. In fact, the inappropriate dependence on visualizing periappendiceal inflammation has resulted in the reporting of false-negative cases in prior studies (5,8,10) of appendicitis.
Although some investigators continue to advocate performance of limited CT data acquisitions through the lower abdomen and upper pelvis to evaluate right lower quadrant pain, we found that use of a focused technique resulted in incomplete or totally absent visualization of the appendix in three (1.4%) of 210 patients (two patients with and one patient without appendicitis). This limitation of the focused CT technique has been reported in at least one prior study (5) of appendicitis in the literature. Because appendiceal length and position can vary, appendiceal identification and CT interpretation may be more difficult if the appendix is in an atypical location when helical CT scanning is limited to the right lower quadrant.
In addition, limiting the scanning field of view may adversely affect one’s ability to diagnose alternative conditions, especially those originating in the upper abdomen, that may account for the patient’s pain. In the study by Rao et al (4), this appears to have been the case in one of eight patients in whom findings at focused right lower quadrant CT were negative. Subsequent findings proved that this patient had chronic cholecystitis.
In our study, use of nonfocused enhanced CT compared with focused nonenhanced CT significantly improved all three readers’ confidence in making an alternative diagnosis. However, accuracy could not be assessed due to the lack of a consistent reference standard and the large number of alternative diagnoses. Review of published studies of appendicitis shows varying results for the ability of these techniques to help establish an alternative diagnosis. Reported results (1,2,5) with these techniques for helping to establish alternative diagnoses in these study populations have ranged from 22% to 62%. Findings in the study by Rao et al (4) showed that an alternative diagnosis could be established in 80% of patients with a focused right lower quadrant data acquisition following oral and intravenous administration of contrast material. It should be noted, however, that this was a highly selected patient population from which patients who had acute gynecologic conditions that were previously diagnosed with ultrasonography or patients who had commonly confusing alternative diagnoses of pancreatitis, peptic ulcer disease, and acute cholecystitis were excluded.
We believe that our study cohort was representative of a typical metropolitan population of patients who may present with acute right lower quadrant pain to emergency centers and physicians’ offices. This belief is supported by the fact that the final clinical diagnoses established at surgery and clinical follow-up in our study were quite similar to those reported in a large study (15) of 10,682 patients who presented with acute abdominal pain. Our study population also included a high percentage of women with an acute gynecologic abnormality, an alternative diagnosis that may be especially difficult to clinically differentiate from acute appendicitis. A potential limitation of our study was that the clinical decision to perform surgery was made with the knowledge of the CT examination results. This potentially could have led to work-up bias or verification bias.
In this study, we did not attempt to assess the potential benefits of bowel opacification. Proponents (1,4,5,10) of CT protocols that are performed without bowel opacification or with rectally administered colonic contrast agents have stressed the advantages of reduced patient waiting time and patient discomfort. We believe that our patients tolerated the ingestion of oral contrast material with minimal or no discomfort.
In conclusion, our study findings demonstrated that use of intravenous contrast material significantly improved the readers’ ability to identify the inflamed appendix, to diagnose acute appendicitis, and to establish alternative diagnoses. The study results also demonstrated that periappendiceal inflammatory changes may be absent in a substantial number of patients with acute appendicitis. Physicians should not rely on this finding as a necessary criterion for diagnosing appendicitis. Finally, diagnosis of appendicitis may be missed with a focused helical CT technique if the inflamed appendix lies outside the limited scanning field of view.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 Current address: Department of Radiology, Baptist Hospital, Miami, Fla.
Abbreviation: ROC = receiver operating characteristic
Author contributions: Guarantors of integrity of entire study, J.E.J., B.A.B.; study concepts, J.E.J., B.A.B.; study design, J.E.J., B.A.B., C.P.L.; literature research, J.E.J.; clinical studies, J.E.J., B.A.B.; data acquisition, J.E.J., B.A.B., D.D.M., A.M.A.; data analysis/interpretation, M.M., A.J.M., G.I.; statistical analysis, C.P.L.; manuscript preparation and definition of intellectual content, J.E.J., B.A.B.; manuscript editing, B.A.B.; manuscript revision/review, J.E.J., B.A.B., M.M., A.J.M., D.D.M., C.P.L.; manuscript final version approval, all authors.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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) was 0.951 ± 0.025, that for reader 2 (
) was 0.902 ± 0.029, and that for reader 3 (
) was 0.901 ± 0.035. FPF = false-positive fraction, TPF = true-positive fraction.
