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1 Department of Radiology, Rm. B1D502G, University of Michigan Medical Center,
1500 E Medical Center Dr., Ann Arbor, MI 48109-0030.
2 Department of Biostatistics, University of Michigan Medical Center, Ann Arbor,
MI 48109-0030.
Received August 12, 2004;
accepted after revision September 27, 2004.
Address correspondence to R. H. Cohan.
Abstract
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MATERIALS AND METHODS. Of 1,344 patients referred for CT with suspected appendicitis between January 1998 and December 2002, 172 patients were identified in whom the radiographic findings were equivocal. Two radiologists reviewed the equivocal CT cases, reassessing appendiceal size and the presence of right lower quadrant stranding, fluid, or an appendicolith. The reviewers' findings were correlated with surgical pathology reports and clinical follow-up.
RESULTS. Fifty-three (31%) of 172 patients with indeterminate findings on CT scans were subsequently diagnosed with appendicitis. For reviewers 1 and 2, respectively, appendicitis was present in five (14%) of 36 and six (13%) of 47 patients who had isolated appendiceal diameter less than 9 mm, and in 11 (52%) of 21 and in 10 (50%) of 20 patients who had isolated appendiceal dilatation equal to or greater than 9 mm. If a normal diameter appendix (< 6 mm) was visualized in a patient who had right lower quadrant stranding or fluid, appendicitis was present in only one (17%) of six and in four (27%) of 15 patients for reviewers 1 and 2, respectively. If the appendix could not be identified but there was right lower quadrant stranding or fluid, appendicitis was present in seven (37%) of 19 and in eight (53%) of 15 patients.
CONCLUSION. Appendicitis is encountered in about 30% of patients with equivocal findings on CT, and the diagnosis should be considered in most of these patients if they are appropriately symptomatic. However, when the appendix measures less than 9 mm alone, the likelihood of appendicitis is much smaller.
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Specific CT findings and criteria for diagnosing appendicitis have been published in the literature [2, 6-8, 19-21]. Different investigators have suggested that varying combinations of signs are needed to diagnose appendicitis. For example, Raptopoulos et al. [16], Funaki et al. [7], and Peck et al. [13] diagnosed appendicitis solely on the basis of the presence of an abnormal appearance of the appendix (> 6 mm, wall thickening, distension, or no filling with enteric contrast). In comparison, Lane et al. [12] diagnosed appendicitis when "right lower quadrant inflammatory change" was present in addition to an abnormal appendix (defined as measuring > 6 mm in diameter), whereas Wijetunga et al. [14] required at least three CT signs. Rather than relying absolutely on the presence of individual signs, Jacobs et al. [4] and Wise et al. [10] used a 5-point Likert scale and a 0-10 confidence scale, respectively, to grade the likelihood of appendicitis. Other studies have not defined specific requirements for diagnosis but instead have relied on the final subjective impression of the interpreting radiologist [3, 5, 6, 11, 13, 22].
Occasionally, some symptomatic patients with right lower quadrant pain are encountered in whom CT images show only one finding of appendicitis (e.g., only appendiceal enlargement or only right lower quadrant stranding or fluid). When faced with this situation, the radiologist may find it difficult to determine whether appendicitis is present.
In 1997, Rao et al. [19] performed a case control study of 100 CT examinations in patients with pathologically proven appendicitis and calculated individual sensitivities, specificities, and predictive values for most of the individually described CT signs of appendicitis; however, in that series, each patient was noted to have at least three CT signs of appendicitis. It is not clear that the predictive values of individual signs of appendicitis in that series would be similar to those in patients in whom only a solitary finding is present.
We reviewed 4 years of our experience with appendiceal CT to assess the value of isolated signs of appendicitis in equivocal CT scans of symptomatic adult patients and to review the overall sensitivity and specificity at our institution in diagnosing appendicitis with CT, particularly in the equivocal cases.
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The remaining 1,344 examinations were then categorized on the basis of the final radiology report as positive, negative, or equivocal. Positive cases were those in which appendicitis was stated by the interpreting radiologist as the final diagnosis. Cases were categorized as negative if a normal appendix was seen or there were no CT signs of appendicitis. Equivocal cases were those in which a definitive CT diagnosis was not made. Instead, a differential diagnosis was provided with appendicitis included as one of several diagnostic considerations or, alternatively, the reviewer stated that the diagnosis of appendicitis was equivocal.
The 302 positive and 176 equivocal cases were then further evaluated. The
CT signs of appendicitis described in each report were recorded, including
presence of an abnormal appendix (abnormal because the appendix was enlarged
at 
6 mm in diameter, abnormally dilated, or thick-walled), right lower
quadrant stranding, free or loculated fluid in the right lower quadrant or
pelvis, or an appendicolith. The total number of CT signs of appendicitis for
each of these patients was counted. A subgroup of 148 CT examinations with
only one reported CT sign of appendicitis was then selected for further
review. Those with CT scans initially interpreted as positive or equivocal who
did not undergo surgery were evaluated for short-term follow-up, including
hospital admission or return clinic visit (within 1 week from initial
presentation) and long-term clinic follow-up. Nine patients were excluded
because of lack of clinical follow-up. This left a study group of 139 patients
for whom only one CT finding of appendicitis was identified.
The 866 examinations categorized as negative for appendicitis were also cross-referenced with operative and surgical pathology notes. In 17 patients, the CT report, although concluded to be negative for appendicitis, noted that the appendix was abnormal according to previously published criteria. Specific terms used in the CT reports included those referring to "diffuse distention" (nine patients, with specific diameter measurements provided in two) and "thickening" or "thickened" (five patients). In three patients, questionable abnormalities were noted only at the appendiceal tip, described with the following comments: "tip at upper limits of normal," "bulbous enlargement of tip," and "slightly prominent tip."
Sixteen additional patients from the negative group underwent operative evaluation specifically for appendicitis despite a negative CT report (in which no CT signs of appendicitis were identified). These 33 cases were added to the study group of 139 patients, for a total of 172 patients. Operative notes, clinic notes, discharge summaries, and surgical pathology reports were reviewed for each of these patients. The CT examinations were retrospectively and blindly interpreted by two reviewers for CT signs of appendicitis.
CT Technique
In our routine protocol to evaluate for appendicitis, 750 mL of oral
contrast material (Scan-C [2.1% barium sulfate suspension], Lafayette
Pharmaceuticals) is administered approximately 90 min before scanning. The
abdomen and pelvis are imaged during the portal venous phase after a dynamic
bolus of 150 mL of nonionic contrast material ([iohexol] Omnipaque 300,
Amersham Health) administered IV by mechanical injector at a rate of 3 mL/sec.
The 172 patients selected for rereview in this study received varying
combinations of oral and IV contrast material, with most being evaluated with
our routine appendiceal CT protocol. One hundred thirty-seven patients (80%)
received both oral and IV contrast material. One patient received only IV
contrast material. Fifteen patients received only oral contrast material
because of a history of prior contrast reaction or compromised renal function.
Rectal contrast material was not administered to any patient. Images for all
contrast-enhanced scans were acquired helically after a 60-sec delay from the
top of the diaphragm through the lesser trochanters using contiguously
reconstructed images at a variety of image thicknesses: 2.5 mm (one patient),
3 mm (one patient), 5 mm (110 patients), 7.0 mm (24 patients), 7.5 mm (24
patients), or 10 mm (12 patients). Thirty-five examinations contained
additional thinner-section images of the pelvis reconstructed from the
original data set. Delayed images, usually through the pelvis, were obtained
in 11 patients at the discretion of the interpreting radiologist, from 18 min
to 3 hr after the initial scanning. Nineteen patients underwent CT using
neither oral nor IV contrast material. In those studies, images were obtained
using 5-mm slice thickness; reformations of the original data were created
with 2.5-mm-thick sections.
Examinations in 125 patients were performed on a 4-MDCT unit (LightSpeed QXi, GE Healthcare). All but five of the remaining patients were scanned on helical single-detector (39 patients) or 8-MDCT (three patients) units (GE Healthcare). The other five patients were studied on a nonhelical conventional axial scanner (GE Healthcare).
CT Image Review
The 172 studies selected for retrospective review were reinterpreted using
a PACS system (MV1000 workstations running VE42 software, Siemens Medical
Solutions). One study was unavailable on the PACS system, so hard-copy images
were reviewed.
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A dramatic increase was seen in the number of appendiceal CT examinations performed over the 5-year study period, from 73 in 1998 to 556 in 2002 (Fig. 1). The increase was so pronounced that approximately 40% of all of the appendiceal CT examinations were performed in the final year (2002). The relative proportion of scans performed in men (approximately one third) and women (approximately two thirds) remained stable throughout the 5-year study period. Despite the marked increase in the number of patients scanned for suspected appendicitis, cases interpreted as positive remained relatively constant at approximately 20% per year. In contrast, cases interpreted as equivocal decreased from 23% in 1998 to 9.5% in 2002, whereas negative cases increased slightly, from 58% to 68% (Fig. 2).
Because of the dramatic increase in the number of patients who underwent CT for suspected appendicitis, a subanalysis was performed whereby interpretations of scans obtained during the first 4 years combined were compared with interpretations of scans obtained during the fifth year. From 1998 to 2001, 788 appendiceal CT examinations were performed, with 178 (23%) interpreted as positive, 123 (16%) as equivocal, and 487 (62%) as negative. In 2002, proportionately fewer scans were considered equivocal and more scans were interpreted as negative: 556 appendiceal CT examinations were performed, with 124 (22%) interpreted as positive, 53 (9%) as equivocal, and 379 (69%) as negative.
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Predictive Value of Isolated CT Findings in the 172 Reviewed Scans
Abnormal appendix alone.—Fifty-seven and 67 cases (for
reviewers 1 and 2, respectively) were identified in which the appendix was
visualized and there were no other CT findings of acute appendicitis. The
presence of appendicitis was then correlated with appendiceal diameter. Not
surprisingly, the prevalence of appendicitis increased with increasing size of
the appendix, as measured by reviewers 1 and 2, respectively. Appendicitis was
present in zero (0%) of four and zero (0%) of 16 patients for appendiceal
diameters of less than 6 mm, zero (0%) of eight and one (8%) of 13 for
appendiceal diameters between 6 and 6.9 mm, zero (0%) of 11 and two (25%) of
eight for appendiceal diameters between 7 and 7.9 mm, and five (39%) of 13 and
three (30%) of 10 for appendiceal diameters between 8 and 8.9 mm. Overall, the
appendicitis rate was only five (14%) of 36 and six (13%) of 47 patients when
the appendiceal diameter was measured as less than 9 mm by reviewers 1 and 2,
respectively. In comparison, appendicitis was much more common when the
appendix was measured as 9 mm or more in diameter, occurring in 11 (52%,
reviewer 1) of 21 and 10 (50%, reviewer 2) of 20 patients (Figs.
3A, and
3B).
A substantial discrepancy occurred in the frequency with which appendiceal wall thickening was thought to be present. Reviewers 1 and 2 stated that this finding was present in 72 and 40 patients, respectively, with appendicitis subsequently diagnosed in 33 (46%) and 24 (60%) of these patients.
Moderate or severe stranding or fluid and a normal visualized appendix.—Only a few cases occurred in which a reviewer identified moderate or severe periappendiceal stranding or fluid accompanying a normal, nondistended (< 6 mm diameter) appendix. In this setting, isolated moderate or severe right lower quadrant fluid or stranding had a relatively low positive predictive value for appendicitis. This situation was encountered on six CT scans as determined by reviewer 1 and on 15 scans as determined by reviewer 2. Acute appendicitis was subsequently diagnosed in only one (17%) and four (27%) of these patients, respectively (Figs. 4A, 4B, 4C, and 4D).
Moderate or severe stranding or fluid and a nonvisualized appendix.—Moderate or severe right lower quadrant stranding or fluid in the absence of appendiceal visualization was a stronger predictor of appendicitis than when a normal appendix was seen. When moderate or severe stranding or fluid was identified in the right lower quadrant, but the appendix could not be visualized, appendicitis was present in seven (37%) of 19 instances for reviewer 1 and eight (53%) of 15 instances for reviewer 2 (Fig. 5).
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Abnormal appendix but reviewer did not think prospectively that appendicitis was present.—Seventeen patients had CT scans in which the original reviewer commented on the fact that the appendix did not appear completely normal but still concluded that the examination was negative for acute appendicitis. None of these 17 patients was subsequently determined to have appendicitis, thus verifying the impression of the initial interpreter. In comparison, the retrospective reviewers predicted that appendicitis was present in five (reviewer 1) and none (reviewer 2) of these 17 patients. The final diagnoses in these patients were Crohn's disease (n = 3), ovarian cysts (n = 1), sickle cell disease (n = 1), pancreatitis (n = 1), gastroenteritis (n = 1), possible nephrolithiasis (n = 1), musculoskeletal strain (n = 1), colitis (n = 1), benzodiazepine withdrawal (n = 1), and nonspecific abdominal pain (n = 6).
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Nonvisualization of the appendix and no right lower quadrant stranding or fluid.—Appendicitis was occasionally present in CT scans of patients in whom the retrospective reviewers failed to identify the appendix and in whom they also failed to detect any right lower quadrant stranding or fluid. This situation occurred in three (17%) of 18 patients for reviewer 1 and three (14%) of 21 patients for reviewer 2. All of these cases but one were originally interpreted as positive or equivocal for appendicitis, with the one case initially interpreted as negative later confirmed to be a false-negative study.
Interobserver Agreement for the 172 Retrospectively Reviewed Cases
Reviewer 1 diagnosed 67 (39%) of the 172 retrospectively reviewed CT scans
as positive for appendicitis, 91 (53%) as negative, and 14 (8%) as equivocal.
Reviewer 2 diagnosed 45 (26%) CT scans as positive, 118 (69%) as negative, and
nine (5%) as equivocal.
Interobserver agreement was calculated for the two experienced abdominal radiologists. Kappa values, which are provided in detail in Table 1, indicated that agreement was only fair to moderate for all assessed criteria; however, several notable discrepancies are summarized here.
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The reviewers disagreed as to whether the appendix could be identified 20% of the time. Reviewer 1 identified the appendix on 16 scans when reviewer 2 was unable to visualize the appendix. Conversely, reviewer 2 identified the appendix on 19 scans in which reviewer 1 was unable to visualize the appendix. The reviewers also disagreed frequently as to the presence of periappendiceal inflammatory stranding (30%), periappendiceal fluid (31%), and an appendicolith (13%). Not surprisingly, these disagreements led to differences in opinion as to whether the patients had acute appendicitis (in more than one third of the cases). A great discrepancy was seen between the two reviewers in the distribution of positive diagnoses. Appendicitis was diagnosed by at least one of the reviewers in 80 (47%) of the 172 patients; however, both reviewers agreed that appendicitis was present in fewer than half this number of patients (32, or 19%).
Reviewer disagreements did not appear to reflect a consistently increased accuracy of one reviewer in diagnosing appendicitis in comparison with the other reviewer (72% for reviewer 1 and 83% for reviewer 2); however, reviewer 1 interpreted scans with a higher sensitivity but lower specificity than did reviewer 2. Counting equivocal cases as positive, sensitivities of reviewers 1 and 2 were 84% and 76%, specificities were 68% and 86%, positive predictive values were 51% and 69%, and negative predictive values were 91% and 90%.
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Many previously published series [1, 3, 6, 11, 12, 19, 24] have not addressed equivocal cases but have categorized appendiceal CT findings only as positive or negative; however, a few studies have acknowledged the presence of an equivocal group. In their analysis of appendiceal CT examinations performed with rectal contrast material only, Funaki et al. [7] planned to classify cases as equivocal if ancillary signs were present but the appendix was not visualized; however, no equivocal cases were prospectively identified in that series. The authors did note retrospectively that two false-positive cases of cecitis and cecal neoplasm probably should have been interpreted as equivocal. In an additional case interpreted as positive (the appendix measured 9 mm in diameter but no adjacent inflammatory change was evident), no appendicitis was found at surgery. Balthazar et al. [2] in 1991 noted equivocal findings, including nonspecific right lower quadrant inflammatory changes suggestive, but not diagnostic, of appendicitis in five (5%) of 100 patients undergoing abdominal and pelvic CT with both oral and IV contrast material. In a follow-up study, Balthazar et al. [22] encountered five additional patients with equivocal CT scans. Peck et al. [13] retrospectively reviewed 401 cases and noted 37 (9.2%) equivocal cases with a border-line single finding. Weyant et al. [17] reviewed 261 scans obtained in patients with suspected appendicitis, of which 19 (7%) had equivocal findings for which the radiologist was unable to state conclusively whether the patient had appendicitis. Stroman et al. [5] reported that eight of 107 patients evaluated for appendicitis had nondiagnostic appendicitis on CT. In our series, of 1,344 CT scans obtained for suspected appendicitis, 176 or 13.1% were prospectively considered to be equivocal.
Some limited data exists regarding the prevalence of appendicitis in patients with CT scans interpreted as equivocal for appendicitis, with a published range of 13-73%. Of the 10 equivocal CT scans reported by Balthazar et al. [2, 22], five (50%) had appendicitis. In the series by Weyant et al. [17], 14 (73%) of 19 patients with equivocal CT scans were subsequently confirmed to have appendicitis. In two other series [13, 17], one (13%) of eight and 15 (41%) of 37 equivocal CT cases were subsequently proven to have appendicitis. In our study, 53 (30%) of 176 equivocal cases were diagnosed as appendicitis.
When we evaluated our equivocal appendiceal CT studies in more detail, we found that the prevalence of appendicitis varied with the nature of the equivocal scan. For example, although a 6-mm threshold for diagnosing abnormal appendiceal diameter has been used, appendicitis was usually not present in our study in patients whose appendix measured less than 9 mm if no other suspicious findings were present. When the appendix measured 9 mm or more in diameter as an isolated finding, appendicitis was present in about half the patients. If moderate or severe right lower quadrant stranding or fluid was present but a normal-diameter appendix was visualized, appendicitis was usually not present; however, if moderate or severe right lower quadrant stranding or fluid was present and the appendix could not be identified, appendicitis was present in about half of the patients.
Several studies have shown that the range of normal and abnormal appendiceal diameters overlaps. For example, Benjaminov et al. [25] found that the mean diameter of a presumed normal appendix was 6.6 ± 1 mm (for patients undergoing CT evaluation for purposes other than suspected appendicitis). Those authors suggested a threshold of 10 mm as the upper limit of normal when luminal contents are not visualized and in the absence of periappendiceal inflammatory changes.
When calculating the sensitivity, specificity, and predictive values of appendiceal CT, some researchers have chosen to include equivocal cases as positive results [17, 22], whereas others have included them as negative results [4, 5, 17, 26]. As a third option, in one report equivocal cases were excluded from one of the analyses [17]. Not surprisingly, decisions concerning how to classify these scans have some bearing on study outcome. Considering equivocal scans as positive will lower study specificity and positive predictive value, whereas considering them as negative will reduce sensitivity and negative predictive value. The effect of assignment of equivocal scans can be seen in our study. Shifting the equivocal studies from the positive to the negative group would reduce CT sensitivity in detecting appendicitis from 99% to 83% and increase specificity from 85% to 97%. Positive predictive value would increase from 67% to 88% and negative predictive value would decrease from nearly 100% to 95%. Obviously, results are best when the equivocal scans are excluded from consideration.
Our recommendation is that equivocal CT studies should be considered separately, as a third group of patients, and that the best the radiologist can do in these instances is to inform the referring physician that symptomatic patients with such CT scans will have an approximately 30% chance of having appendicitis. This likelihood is large enough to justify surgery in most patients; however, the surgeon can be forewarned that appendicitis will be absent in some of these patients. Those unlikely to have appendicitis include patients with mild isolated appendiceal dilatation (< 9 mm), of whom fewer than 20% will have appendicitis. In addition, fewer than one third of patients who have an identifiable normal appendix surrounded by inflammatory stranding or fluid will have appendicitis.
Our prospective assumption was that the great increase in the number of CT examinations performed for suspected appendicitis over the past 5 years would have led to a decline in the percentage of positive studies and increases in the percentages of negative and equivocal studies. This might be expected, assuming that many more patients without classic findings on physical examination are being referred for appendiceal CT. Interestingly, that has not been the case. In our series, the percentage of positive cases remained relatively stable throughout the study period, whereas the percentage of equivocal studies declined. In the final year of our study, only 9.5% of examinations were interpreted as equivocal, compared with 23.3% in the first year. This decrease in the observed number of equivocal cases is likely attributable to a combination of increasing experience on the part of reviewers and technologic improvements, such as improvements in MDCT with thinner slice reconstruction.
Although our study showed interpretations becoming more definitive over the course of the study (with fewer initial interpretations of equivocal), cases that remained problematic appear to be truly equivocal. Two experienced abdominal CT reviewers disagreed often about the presence, absence, and degree of isolated findings and the overall impression of appendicitis.
Limitations of our study include its retrospective design. Our CT technique was not uniform over the 5 years. We lacked definitive follow-up for some patients whose scans were interpreted as negative, and we assumed that they did not have appendicitis. Another limitation is relying on original CT reports to determine the final study population because all CT signs may not have been described in the original report. Indeed, it is quite likely that some patients with CT examinations that may have been considered equivocal by our retrospective reviewers were excluded from the study group because on initial radiologic interpretation those patients were diagnosed as definitely having or not having appendicitis. We included only cases that could be identified retrospectively as equivocal (based on the initial CT interpretation), because a thorough review of all 1,344 CT scans performed in patients with clinically suspected appendicitis was not feasible.
In summary, in this study approximately 10% of patients undergoing CT for appendicitis had equivocal scans on which only one finding suspicious for appendicitis was present. Equivocal scans should be considered as a separate group of scans apart from frankly positive or frankly negative studies. Patients with equivocal scans may need to undergo surgery if clinical and laboratory data make the suspicion of appendicitis strong; however, the surgeon should realize that many of these patients will not have appendicitis. We found the prevalence of appendicitis in specific subgroups of patients with equivocal scans in our highly selected patient population to be as follows: when the appendix was visualized and no other CT findings of acute appendicitis were identified, appendicitis was present in fewer than 15% of cases when the appendix measured less than 9 mm in maximal diameter. However, appendicitis was present in about 50% of patients whose appendices were 9 mm or more in diameter. If stranding or fluid was present with a normal-diameter (< 6 mm) appendix, appendicitis was present in fewer than one third of the cases. If appendiceal distention measured 9 mm or more or if right lower quadrant stranding or fluid was present but the appendix was not detected, appendicitis was present in about 40-50% of patients.
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