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Original Research |
1 Department of Radiology, Fujioka General Hospital, 942-1 Fujioka, Fujiokashi,
Gunma 375-8503, Japan.
2 Department of Radiology, Gunma Cancer Tomo Hospital, Gunma, Japan.
Received September 3, 2006;
accepted after revision December 6, 2006.
Address correspondence to T. Moteki
(pwd8ja227h{at}md.point.ne.jp).
Abstract
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MATERIALS AND METHODS. The study included 59 patients showing a normal appendix with diameter greater than 6 mm and having no adjacent lesions (noncomplicated-normal-appendix group), 30 patients showing a normal appendix with diameter greater than 6 mm and having adjacent lesions (complicated-normal-appendix group), and 38 patients showing appendicitis without periappendiceal inflammation (appendicitis group). The following specific CT findings were retrospectively evaluated: maximum appendiceal diameter greater than 6 mm, maximum appendiceal wall thickness greater than 3 mm, appendiceal wall enhancement, focal cecal wall thickening, adjacent adenopathy, appendicolith, and maximum depth of the intraluminal appendiceal fluid.
RESULTS. The mean maximum depth of the intraluminal appendiceal fluid in the appendicitis group was significantly higher than in the two groups with a normal appendix (Mann-Whitney U test: p < 0.001). When using maximum depth of the intraluminal appendiceal fluid greater than 2.6 mm for a criterion of appendicitis, sensitivity and specificity for differentiation between the appendicitis group and the other two groups with a normal appendix were both greater than 80%. In contrast, when using another CT a criterion, either sensitivity or specificity was 50% or less.
CONCLUSION. The new CT criterion based on the maximum depth of the intraluminal appendiceal fluid greater than 2.6 mm is particularly useful for differentiating appendicitis without periappendiceal inflammation from a normal appendix with a diameter greater than 6 mm.
Keywords: abdominal imaging • appendicitis • CT • gastrointestinal imaging
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However, no reports use CT findings to differentiate between a normal appendix with a diameter of more than 6 mm and appendicitis without periappendiceal inflammation. If CT differentiation between such cases is possible, CT may be useful to evaluate patients who present equivocal symptoms of appendicitis, who present clinical signs of appendicitis with little adipose tissue in the abdomen, or who present with vague abdominal pain while showing an appendix with a diameter of more than 6 mm.
Hence, we undertook this study to evaluate whether differences exist in CT findings between appendicitis without periappendiceal inflammation and a normal appendix with a diameter of more than 6 mm. In addition to classic CT findings for the diagnosis of appendicitis, we also evaluated the finding of intraluminal appendiceal fluid because we have the impression that cases of appendicitis tend to show more intraluminal appendiceal fluid than cases with a normal appendix.
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In 98 patients, periappendiceal inflammatory changes (e.g., stranding, thickening of the lateral conal fascia, phlegmon, or abscess) were detected and diagnosed as appendicitis; 82 of these patients underwent surgery, and 16 patients were conservatively treated. In 130 patients, diseases other than appendicitis were detected on CT: 31 (23.8%) cases of diverticulitis; 21 (16.2%) cases of enteritis; seven (5.4%) cases of colon cancer, metastatic tumors, or lymphoma in the right lower abdomen; 28 (21.5%) cases of gynecologic pathology (e.g., ovarian tumors, pelvic inflammatory disease); 13 (10%) cases of urolithiasis; 12 (9.2%) cases of pyelonephritis (complicating urolithiasis in eight cases); and 18 (13.8%) cases of acute cholecystitis. In 46 patients, no obvious lesions were seen on CT, and their symptoms subsequently resolved. Fifteen patients were lost to follow-up after CT examination.
Twelve patients with insufficient clinical presentation for the diagnosis of acute appendicitis were conservatively treated after CT failed to detect periappendiceal inflammation. Sixteen patients without periappendiceal inflammation on CT were proven to have appendicitis at surgery that was performed because of worsening clinical symptoms (operations were performed 10-31 hours [mean, 16.5 hours] after CT) and were included in the appendicitis group. These patients did not have repeated CT examinations before their operations. Twenty-two patients without periappendiceal inflammation on CT were also included in the appendicitis group. In these patients, the clinical symptoms were considered sufficient for a diagnosis of acute appendicitis (i.e., abdominal pain of recent onset that was initially periumbilical and then localized to a point in the right iliac fossa [such as the McBurney point] and abdominal pain associated with vomiting, fever, and an elevated WBC) [6, 10]; these symptoms resolved after the administration of antibiotics.
Excluding cases of appendicitis and clinically suspected appendicitis, we identified cases in which a whole-length normal appendix was delineated and the appendix showed a diameter of more than 6 mm on initial CT interpretation over a 14-month period (October 2003 to November 2004). A normal appendix was identified in 68.3% (1,038/1,520) of the cases studied, and 132 cases satisfying these all conditions were assigned to a temporary-normal-appendix group. From this group, we excluded cases in which any patients had leukocytosis or showed pain, tumors, or inflammatory lesions in the right lower abdomen. We also excluded repetitively performed CT examinations in a patient except the representative examination.
We assigned these remaining 59 cases to the noncomplicated-normal-appendix group. From the temporary-normal-appendix group, we also picked up CT examinations in which patients had lesions at or along the ileocecal region (except for appendicitis). We assigned these cases (n= 30) to the complicated-normal-appendix group. These patients consisted of 11 (36.7%) cases of diverticulitis, two (6.7%) cases of pelvic inflammatory disease, six (20%) cases of enteritis, two (6.7%) cases of abscess, one (3.3%) case of pancreatitis, three (10%) cases of peritonitis, two (6.7%) cases of ileus, and three (10%) cases of cecal tumors (cancer, lymphoma, and metastasis from sigmoid colon cancer).
CT images were obtained using a 4-MDCT scanner (LightSpeed Plus, GE Healthcare). For patients who were suspected of having appendicitis, diverticulitis, and pelvic inflammatory disease, scanning was performed from the top of the liver to the symphysis pubis with 120 or 140 kVp using Auto mA (a function that automatically controls tube current so as to stabilize image quality). Table feed was 3.75 mm/0.5 s of scanner rotation (a pitch of 0.75:1.0). From the raw data of each acquisition, 7-mm-thick transverse sections were reconstructed from the diaphragmatic dome to the iliac crest, and 3.5- or 2.5-mm-thick transverse sections of the pelvis were reconstructed.
For these patients, 2 mg/kg (when the patients were < 50 kg in body weight) or 100 mL of IV contrast material (Iopamiron 300 Syringe [iopamidol], Nippon Schering) was administered at a rate of 0.04 mL/s/kg of body weight (in patients < 50 kg) or 2 mL/s with a scanning delay of 65 seconds. This CT protocol (the CT protocol for appendicitis) was performed in all 38 (100%) patients in the appendicitis group, eight (26.7%) patients in the complicated-normal-appendix group, and two (3.4%) patients in the noncomplicated-normal-appendix group. For other patients, fine 3.5- or 2.5-mm-thick transverse sections at the appendiceal level were also obtained in 18 (60%) patients in the complicated-normal-appendix group and 22 (37.3%) patients in the noncomplicated-normal-appendix group. For the remaining patients, 5- or 7-mm-thick transverse sections at the appendiceal level were obtained. Except for patients who were scanned with the CT protocol for appendicitis, injection speed and scanning delay of IV contrast medium varied depending on the clinical history provided. No patient received oral or rectal contrast material.
Interpretation of CT images was mainly based on the positive and negative criteria described by Rao et al. [11] and Rao and Mueller [12]. The following conventional specific CT findings were evaluated: maximum appendiceal diameter, maximum appendiceal wall thickness, presence or absence of appendiceal wall enhancement, presence or absence of focal cecal wall thickening, presence or absence of adjacent adenopathy, and presence or absence of appendicolith. In addition, we also evaluated the maximum depth of the intraluminal appendiceal fluid. We judged appendiceal wall enhancement as positive when the appendiceal wall showed focally or diffusely higher density than the surrounding small intestinal or colon walls on enhanced CT. We did not necessarily use the same appendiceal CT image for measurement of maximum appendiceal wall thickness as the image for measurement of maximum appendiceal diameter because optimal appendiceal CT images for these criteria were not typically identical, especially when an appendix was focally expanded with intraluminal contents (such as intraluminal fluid, gas, appendicolith, or barium).
When the appendiceal lumen was collapsed at the image for measurement of maximum appendiceal wall thickness, we adopted half of diameter of the appendix for this criterion. To evaluate the intraluminal appendiceal fluid, we did not use maximum width of the intraluminal appendiceal fluid but instead used maximum depth (anteroposterior diameter) of the intraluminal appendiceal fluid because maximum depth more closely approximates the amount of the intraluminal appendiceal fluid than does maximum width when an air-fluid level is seen in the appendiceal lumen to be measured. We obtained the maximum depth of the intraluminal appendiceal fluid by measuring the maximum anteroposterior diameter of the intraluminal content that showed lower density than the appendiceal wall on enhanced CT images, excluding appendicolith, barium, and intraluminal gas.
Evaluation of CT images and measurements of the appendix were performed on a workstation (Centricity RA 1000, GE Healthcare) using an electronic ruler. With no knowledge of the clinical course of the patients, a single, board-certified radiologist with 15 years of experience in radiology performed all the measurements for these CT criteria for appendicitis and interpreted whether an appendix satisfied each CT criteria, except for the equivocal cases. In equivocal cases, a decision was made on the basis of the consensus of the same radiologist and another radiologist with 15 years of experience in radiology.
For each CT criterion, a comparison between groups (appendicitis group vs noncomplicated- and complicated-normal-appendix groups) was performed using the Mann-Whitney U test. A p value less than 0.05 was considered statistically significant. For maximum appendiceal wall thickness and maximum depth of the intraluminal appendiceal fluid, receiver operating characteristic (ROC) curves were constructed to depict the curves of those features and to obtain cutoff values for the maximum depth of the intraluminal appendiceal fluid that best differentiated the appendicitis group from the two normal-appendix groups.
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The noncomplicated-normal-appendix group (Fig. 2) consisted of 59 patients, ranging in age from 26 to 89 years (59 ± 16 years). There were 35 men and 24 women in this group. The complicated-normal-appendix group (Figs. 3 and 4) consisted of 30 patients ranging in age from 18 to 86 years (51 ± 19 years). There were 18 men and 12 women in this group.
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In comparison with the noncomplicated- and complicated-normal-appendix groups, the appendicitis group was not significantly different with respect to the mean maximum appendiceal diameter, mean maximum appendiceal wall thickness, number having appendiceal wall enhancement, and number of appendicoliths (p > 0.05, Mann-Whitney U test). The number of cases of focal cecal wall thickening in the appendicitis group was less than in the complicated-normal-appendix group (p < 0.001) and was not significantly different from the noncomplicated-normal-appendix group (p > 0.05). The number of cases of adjacent adenopathy in the appendicitis group was higher than in the noncomplicated-normal-appendix group (p < 0.05) and was not significantly different from the complicated-normal-appendix group (p > 0.05). The mean maximum depth of the intraluminal appendiceal fluid in the appendicitis group was significantly greater than in the noncomplicated- and complicated-normal-appendix groups (p < 0.001).
When ROC analyses were performed on maximum depth of the intraluminal appendiceal fluid and maximum appendiceal wall thickness comparing the appendicitis group with the noncomplicated- and complicated-normal-appendix groups (Fig. 5A, 5B), the areas under the ROC curves for maximum depth of the intraluminal appendiceal fluid (0.949 ± 0.026 [SE] and 0.863 ± 0.050, respectively) were significantly larger than the areas for maximum appendiceal wall thickness (0.603 ± 0.059 and 0.528 ± 0.072, respectively) (p < 0.001). These results indicate that maximum depth of the intraluminal appendiceal fluid is more helpful for the differentiation of appendicitis from normal appendix than maximum appendiceal wall thickness.
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The cutoff value of maximum depth of the intraluminal appendiceal fluid for the best differentiation between the appendicitis group and the other two groups with a normal appendix was 2.6 mm (ROC analysis). Using a cutoff value of 2.6 mm of maximum depth of the intraluminal appendiceal fluid for differentiation between the appendicitis group and the noncomplicated-normal-appendix group, the sensitivity and specificity were 86.8% (33/38) and 94.3% (33/35), respectively. Using this same cutoff value for differentiation between the appendicitis group and the complicated-normal-appendix group, the sensitivity and specificity were 86.8% (33/38) and 84.6% (33/39), respectively.
The sensitivity and specificity for differentiation between the appendicitis group and the two normal-appendix groups, when using other conventional criteria (maximum appendiceal diameter > 6 mm, maximum appendiceal wall thickness > 3 mm, presence of appendiceal wall enhancement, presence of focal cecal wall thickening, presence of adjacent adenopathy, and presence of appendicolith) are shown in Table 2.
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Our results show that the incidence of a normal appendix with maximum appendiceal diameter of more than 6 mm is much higher than the incidence of appendicitis showing no significant periappendiceal inflammation. Furthermore, the incidence of a normal appendix satisfying two major conventional CT criteria for appendicitis (maximum appendiceal diameter of > 6 mm and maximum appendiceal wall thickness of > 3 mm) exceeded the incidence of appendicitis showing no significant periappendiceal inflammation. The incidences of appendiceal wall enhancement, appendicolith, adjacent adenopathy, or focal cecal wall thickening in the appendicitis group were too low for clinical use for differentiation between a normal appendix with maximum diameter of more than 6 mm and appendicitis without periappendiceal inflammation and were not significantly higher than the incidences of these criteria in the complicated-normal-appendix group.
These results suggest that no reliable conventional specific CT criteria exist for the differentiation between appendicitis and a normal appendix when an appendix shows a diameter of more than 6 mm and no significant periappendiceal inflammation. Hence, another specific CT criterion is needed to perform such differentiation.
The pathophysiology of appendicitis is most likely the result of a closed-loop obstruction of its lumen related to a fecalith or resulting from hyperplasia of submucosal lymphoid follicles caused by viral or bacterial infection. In the presence of obstruction, the mucosa continues to secrete, resulting in an accumulation of mucoid material and increasing intraluminal pressure. Bacteria located in the lumen of the appendix proliferate in the presence of stasis and obstruction. Continued mucus production and proliferation of bacteria cause a further rise of intraluminal pressure, resulting in the development of acute appendicitis with edema, lymphatic obstruction, and necrotizing ulceration of the mucosa [15, 16]. In other words, intraluminal accumulation of mucoid material (intraluminal fluid collection) is considered to be closely related to appendiceal obstruction that could cause appendicitis.
However, no reports have evaluated the depth or width of the intraluminal appendiceal fluid for differentiation between appendicitis and a normal appendix, except for a partially relevant report that stated that the graded-compression technique on sonography might be useful to differentiate appendicitis from a normal appendix because the intraluminal obstruction that causes appendicitis also causes the intraluminal content (including the intraluminal appendiceal fluid) to remain despite compression [17].
In our study, the mean maximum depth of the intraluminal appendiceal fluid in the appendicitis group was significantly higher than in the other two groups with a normal appendix. We consider this result to be reasonably explained by the preceding theory; if appendiceal obstruction is absent, a normal appendix might show a lower depth of the intraluminal appendiceal fluid than appendicitis (regardless of whether complicated lesions are present at or along the ileocecal region). Furthermore, when using a cutoff value of 2.6 mm for maximum depth of the intraluminal appendiceal fluid to differentiate between appendicitis without periappendiceal inflammation and a normal appendix with maximum appendiceal diameter of more than 6 mm, the sensitivity and specificity were more than 80%. In contrast, conventional CT criteria had either sensitivity or specificity of 50% or less for differentiating these conditions (Table 2).
From these results, we believe that maximum depth of the intraluminal appendiceal fluid of more than 2.6 mm (Fig. 1) is more useful than conventional CT criteria for differentiating appendicitis without periappendiceal inflammation from a normal appendix with a maximum diameter of more than 6 mm, regardless of whether complicated lesions are present at or along the ileocecal region (Table 1, Figs. 1, 2 and 3). Therefore, maximum depth of the intraluminal appendiceal fluid of more than 2.6 mm should become a useful, specific diagnostic criterion for acute appendicitis, especially when periappendiceal inflammatory changes are absent (Fig. 1) or unclear because of poor periappendiceal fat.
In the complicated-normal-appendix group, six cases satisfied the criterion of maximum depth of the intraluminal appendiceal fluid of more than 2.6 mm. Three of these cases (complicated by enteritis in two cases and cecal diverticulitis in one case) were also associated with large fluid collection in the cecum (> 20 mm in depth) (Fig. 4). In these cases, we believe that a larger hydrostatic pressure that is generated from the larger cecal fluid collection might cause accumulation of more intraluminal appendiceal fluid. In one of these cases (complicated by cecal cancer), the orifice of the appendix was obstructed by the tumor. Hence, the depth of the intraluminal appendiceal fluid may not be helpful to differentiate between appendicitis and a normal appendix when the cecum contains a larger amount of intraluminal fluid or when a closed-loop obstruction of the appendix is caused by a cecal tumor.
A limitation of our results is that the appendicitis group included many cases that were not surgically proven, although these cases showed a certified clinical course. Thus, the presence of a few cases of normal appendix in the appendicitis group would reduce the diagnostic sensitivity of both conventional CT criteria and our new criterion based on maximum depth of the intraluminal appendiceal fluid. However, we consider that this limitation does not negate the usefulness of the new criterion because the subgroup of the appendicitis group consisting of the surgically proven cases satisfied this criterion with a higher incidence (93.8%) than the appendicitis group (86.8%), as shown in Table 1.
Another limitation of our data is that our evaluation between the appendicitis group and the two groups with a normal appendix was performed under the condition that two major criteria (the presence of periappendiceal inflammation and maximum appendiceal diameter of > 6 mm) were inefficient. Hence, we cannot determine whether maximum depth of the intraluminal appendiceal fluid of more than 2.6 mm is useful to differentiate between appendicitis and a normal appendix in comparison with these two major criteria. However, our results show that the maximum depth of the intraluminal appendiceal fluid of more than 2.6 mm is more useful than the other conventional CT criteria, including the criterion of maximum appendiceal wall thickness of more than 3 mm.
The last limitation of our study is that an optimal CT protocol for the diagnosis of appendicitis was principally performed in clinically suspected cases of appendicitis. Thus, all cases in the appendicitis group were scanned with optimal enhancement and optimal fine sections for evaluation of the appendix, which differed from the other two groups with a normal appendix, in which many cases were not scanned with optimal enhancement or optimal fine sections for evaluating an appendix. Although such optimal imaging for evaluation of an appendix might be advantageous to detect appendiceal wall enhancement in the appendicitis group, the incidence of cases satisfying this CT criterion in the appendicitis group was still low and showed no significant difference compared with the incidence in the other two groups with a normal appendix. With other CT criteria, errors of measurements and assessment of specific CT findings in the groups with a normal appendix might be somewhat larger than in the appendicitis group. However, we consider these errors to be small because only cases in which the whole-length appendix was clearly delineated were assigned to the groups having a normal appendix, and the complicated-normal-appendix group contains cases with fine 3.5- or 2.5-mm-thick appendiceal sections at the high rate of 86.7% (26/30). Furthermore, in general, such errors in the groups with a normal appendix would tend to obscure differences between these patients and those in the appendicitis group. Hence, the differences in mean maximum depth of the intraluminal appendiceal fluid between the appendicitis group and the groups with a normal appendix are considered to be still robust. However, this limitation may be completely resolved if a 64-MDCT scanner were used and fine sections were routinely obtained.
In conclusion, when an appendix with a diameter of more than 6 mm has no periappendiceal inflammation, conventional CT criteria have limited efficacy in differentiating appendicitis from a normal appendix. However, the new CT criterion based on a maximum depth of the intraluminal appendiceal fluid of more than 2.6 mm is helpful in this differentiation.
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