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1 Harvard Medical School and Department of Radiology, Massachusetts General Hospital, Boston, MA 02114.
Received June 2, 2004;
accepted after revision September 25, 2004.
Address correspondence to J. T. Rhea
(jrhea{at}sfghrad.uscsf.edu).
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MATERIALS AND METHODS. Patient records from 2001 that included clinical or CT preoperative examination were analyzed, with follow-up through 2003. Patient age and sex, clinical presentation, CT techniques, CT interpretations, operative reports, pathology reports, and patient disposition were determined. Final diagnoses were provided by pathologic criteria, patient follow-up, or patient survey. Statistical analysis included Fisher's exact test and receiver operating characteristic (ROC) curves.
RESULTS. Of 753 patients, 663 (88%) were examined on CT for suspected appendicitis and 90 had an appendectomy without undergoing CT. The incidence of appendicitis in the patients who underwent CT was 39.2%. The sensitivity and specificity of CT were 99% and 95%, respectively; the area under the ROC curve was 0.9896; and the percentage of equivocal CT interpretations was 3.3%. The false-negative appendectomy rates were 3.0% and 5.6% for patients with and without CT, respectively (for all patients, p = 0.326; for female pediatric patients, p = 0.030).
CONCLUSION. Five years ago, the negative appendectomy rate dropped from 20% to 7%, and it is now 3.0%. The incidence of appendicitis in patients who are examined on CT is stable compared with similar cohorts from prior investigations. Patients who do not undergo CT also have a low negative appendectomy rate, but this relatively small group is selected on the basis of a convincing clinical presentation. Female pediatric patients likely would have a lower negative appendectomy rate with greater use of CT.
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Conflicting reports concerning the effectiveness of CT in reducing the negative appendectomy rate have appeared in the literature. Some investigations have found beneficial results, whereas others have found little change in the negative appendectomy rate [2-15]. The purpose of this investigation was to determine the status of appendiceal CT 5 years after its introduction including determination of the percentage of patients with suspected appendicitis who underwent CT as a part of their diagnostic evaluation; the incidence of appendicitis in those patients who had CT; the sensitivity, specificity, and receiver operating characteristic (ROC) curve of appendiceal CT in routine practice; the percentage of equivocal CT interpretations; and the negative appendectomy rates for those patients who had CT and those patients who went to surgery without CT.
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The gold standard for the patients who underwent surgery was considered to be the pathology report. The pathologic criteria for diagnosis of acute appendicitis included, at a minimum, the presence of polymorphonuclear cells in the lamina propria. Other criteria for appendicitis included cryptitis, crypt abscess, or transmural necrosis of the appendix. The specific pathologic diagnosis was recorded for all patients. Patients were classified as having acute appendicitis if the pathology report included one of the following terms: acute appendicitis, acute suppurative appendicitis and periappendicitis, acute appendicitis and periappendicitis, acute appendicitis and serositis, or acute and chronic appendicitis. Pathologic findings not consistent with acute appendicitis included lymphoid hyperplasia, periappendicitis, fibrous obliteration, and carcinoid.
We used several criteria for the presence or absence of acute appendicitis for the patients who did not undergo surgery at this hospital. A specific emergency department discharge diagnosis other than appendicitis, such as ruptured ovarian cyst or diverticulitis, was considered indicative of the absence of appendicitis. This emergency department discharge diagnosis was established by the emergency department physicians and was based on any imaging, laboratory tests, and clinical findings. In addition, clinical follow-up was reviewed if the patients returned to this hospital after their initial evaluation for suspected appendicitis. The lack of a subsequent appendicitis in those patients with follow-up was considered indicative of the absence of appendicitis during their initial CT examination. For those patients not having surgery who did not return to this hospital, a questionnaire was sent at the end of 2002 with two yes-no questions: Did symptoms go away? and Was the appendix removed at another hospital? Space for patient comments was included on the questionnaire.
Patients were excluded from this investigation if no follow-up information or pathology results were available, if an incidental appendectomy was performed during other surgery, or if the diagnosis before CT or before surgery did not include suspected appendicitis.
CT images were interpreted by emergency, gastrointestinal, or pediatric radiology staff or fellows from various divisions who worked in the emergency radiology area in conjunction with the radiology residents. CT interpretations were considered positive for appendicitis if acute appendicitis, possible appendicitis, or probable appendicitis was indicated in the report. Findings of acute appendicitis included a distended appendix of greater than 6 mm in diameter; hyperemia of the appendiceal wall if IV contrast material were given; fat stranding; fascial thickening; edema at the origin or the appendix, as indicated by focal cecal apical thickening, the arrowhead sign, or a cecal bar; and phlegmon or abscess around the appendix [16]. Although some of these findings are more specific than others, the CT diagnoses for this investigation were based on the individual radiologist's conclusions at the time of interpretation. CT interpretations were considered negative for appendicitis if the appendix was seen and called normal or if the report concluded that the examination was probably or possibly normal. The findings of a normal appendix included visualization of the appendix to its blind ending tip, diameter of 6 mm or less, and the absence of secondary findings of appendiceal inflammation [16]. CT interpretations were considered equivocal if the study was said to be indeterminate or equivocal or if, as in one patient, there were conflicting statements about the diagnosis of appendicitis in the body and the conclusion of the report. The CT findings that led to a determination that the examination was equivocal were determined. The images were reviewed for all equivocal, false-positive, and false-negative CT examinations.
The incidence of appendicitis for all patients undergoing CT for suspected appendicitis was calculated by dividing the number of true-positive and false-negative CT findings plus the number of equivocal CT findings that had appendicitis by the total number of patients who had CT for suspected appendicitis. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were determined for all patients, for a subset of pediatric patients who were 18 years old or younger, geriatric patients 65 years old or older, and female and male patients. The percentage of equivocal CT interpretations was determined as the number of equivocal interpretations divided by the total number of CT interpretations.
CT scans were obtained on a 4-MDCT scanner (LightSpeed, GE Healthcare). Scans were obtained using a detector configuration of 4 x 2.5 mm with image spacing of 2.5 mm, image thickness of 2.5 mm, and a table speed of 15 mm/rotation. Various combinations of contrast agents or no contrast material was given depending on various factors including the patient's condition, the patient's wishes, and the differential diagnoses being considered in addition to appendicitis.
Colon contrast material consisted of 40 mL of meglumine diatrizoate in 1,000 mL of saline, connected by IV tubing to a small pediatric rectal catheter. The volume of contrast material was determined by patient tolerance and size. Most adult patients were given 1,000 mL. If the CT scout image did not reveal contrast material in the cecum, additional rectal contrast material was given. Some patients who received rectal contrast material also received IV contrast material at the discretion of the radiologist. Thin adults and most children received IV contrast material. IV contrast material consisted of nonionic iopromide (Ultravist, Berlex Laboratories) and was injected at a rate of 2.0 mL per second with a 150-sec delay in adults and was hand-injected in young children. Outpatients not examined in the emergency department and some emergency department patients whose suspected diagnosis before CT diagnosis was not limited to appendicitis were given oral and IV contrast material. Oral contrast material for emergency department patients was diatrozoate meglumine (Gastrograffin, Bracco Diagnostics) and for outpatients was barium sulfate suspension (Readi-Cat 2, E-Z-EM).
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Of the 663 patients who underwent CT for suspected appendicitis, there were 22 equivocal CT diagnoses (3.3%). The CT diagnoses, incidence of acute appendicitis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy are provided for all patients and for adult, pediatric, geriatric, male, and female patients in Tables 1 and 2. The ROC curve for patients who underwent CT for suspected appendicitis is reproduced in Figure 1; the area under that ROC curve is 0.9896.
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Appendectomy was performed on 268 of the 663 patients who were examined with CT. The negative appendectomy rate for these 268 patients was 3.0% (n = 8 patients). The negative appendectomy rates for all patients and subgroups of patients are provided in Table 3. The average age for these 663 patients was 33 years with a range of from less than 1 year to 87 years. The male-female ratio was 260:403. Of the eight patients who had a CT examination and then negative findings at appendectomy, the average age was 26 years and six of the eight patients were female.
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The negative appendectomy rate for the 90 patients taken to surgery without CT was 5.6% (n = 5 patients). The average age for these 90 patients was 38 years with ages ranging from 2 to 85 years. The male-female ratio was 65:25. Of the five patients who had a negative appendectomy, the average age was 13 years old and three of the five patients were female. The difference in the negative appendectomy rate for the patients having CT (3.0%) and those for whom CT was not deemed necessary (5.6%) was not statistically significant (p = 0.326) (Table 3).
Pediatric Patients
Included in the 753-patient cohort were 172 pediatric patients (
18
years). Of these 172 pediatric patients, 138 were examined with CT for
suspected appendicitis and 34 were taken to surgery for suspected appendicitis
without undergoing CT.
Of the 138 pediatric patients who had a CT examination for suspected appendicitis, there were 12 equivocal CT diagnoses (8.7%). The average age for these 138 patients was 11 years with a range of from less than 1 year to 18 years. The male-female ratio was 66:72. The CT diagnoses and accuracy are given in Tables 1 and 2. Of the 138 pediatric patients who underwent CT, 64 were taken to surgery. Two patients did not have a pathologic diagnosis of acute appendicitis, which yields a false-negative appendectomy rate of 3.1%. Of the two pediatric patients who had a CT examination and then negative findings at appendectomy, there was one boy who was 8 years old and one girl who was 14 years old. One of these patients had follicular hyperplasia of the appendix, and the other patient had evidence of chronic appendicitis. The CT interpretations were no acute appendicitis (true-negative) in one patient and acute appendicitis (false-positive) in the other patient.
The negative appendectomy rate for the 34 pediatric patients taken to surgery without undergoing CT was 14.7% (n = 5 patients). The average age for these 34 patients was 12 years with a range of from less than 1 year to 18 years. The male-female ratio was 26:8. Of the five patients who had a negative appendectomy, two were boys who were 14 and 15 years old and three were girls who were 10, 11, and 13 years old. The difference in the negative appendectomy rates for the pediatric patients who underwent CT (3.1%) and those for whom CT was not performed (14.7%) was statistically significant (p = 0.047).
Geriatric Patients
Included in the 753-patient cohort were 47 patients who were 65 years old
or older, 44 of whom had CT before appendectomy and three of whom were taken
to surgery for suspected appendicitis without CT. No equivocal, 27
true-negative, and 17 true-positive CT diagnoses were reported. The
sensitivity and specificity for these 44 patients was 100%. The incidence of
acute appendicitis in the 44 patients having CT was 38.6%. The three patients
who went to surgery without CT all had acute appendicitis.
Female and Male Patients
Of the 663 patients who underwent CT for suspected appendicitis, 403 were
female and 260 were male. Of the 90 patients taken to surgery without CT, 71
were male and 19 were female.
The percentage of equivocal CT diagnoses was 2.7% for males and 3.7% for females. The CT diagnoses and accuracy are given in Tables 1 and 2. The negative appendectomy rates for males having CT and males not having CT before surgery were 1.4% and 2.8%, respectively. This difference is not statistically significant with a p value of 0.602. The negative appendectomy rates for females having CT and females not having CT before surgery were 4.8% and 15.8%, respectively. This difference also is not statistically significant (p = 0.096).
CT Technique
Of the 663 patients who underwent CT, the types of contrast material
administered were as follows: rectal only, 248; rectal and IV, 187; rectal and
oral, seven; oral and IV, 181; oral only, 10; IV only or none followed by IV,
23; none, six; and indeterminate in one patient whose images were unavailable
for review and for whom the type of contrast material was not mentioned in the
radiology report. The CT sensitivity and specificity and the percentage of
equivocal examinations for the most frequent types of contrast material given
did not differ significantly.
Equivocal CT Diagnoses
There were 22 equivocal CT diagnoses (3.3%) among the 663 patients of all
ages who underwent CT for suspected appendicitis. Twelve equivocal CT
diagnoses (8.8%) were reported among the 138 pediatric patients having CT for
suspected appendicitis. Pediatric patients represented 20.5% of the total
patient cohort and had 54.5% of the equivocal CT diagnoses. The mean age for
all patients with an equivocal diagnosis was 25 years (range, 2-62 years), and
most were females (male-female ratio, 7:15).
The causes of the 22 equivocal diagnoses were poor or nonvisualization of the appendix or its tip in 14 patients, borderline size of the appendix or its tip in seven, and no mention of the appendix in either the body or conclusion of the radiology report in one. Contributing factors to the equivocal CT examinations included the following: inability to find the appendix or clearly define its tip even in retrospect, little or no fat in the right lower quadrant, stranding in the fat adjacent to an otherwise normal appendix, no contrast material in the cecum, and patient motion. Stranding adjacent to the appendix was seen in one patient with diverticulitis of the sigmoid colon, which was redundant to the right, and in one patient who had omental torsion. Of the seven patients in whom the appendix was considered borderline in size, the appendix ranged from 7 to 9 mm in five patients, the tip was 12 mm in one patient, and the tip was considered at the top of the normal range in size but had an appendolith in one patient.
Of the 22 equivocal CT diagnoses, eight patients had surgery and five of these patients had acute appendicitis. One patient had fibrous obliteration of the appendix at pathology, one patient had omental torsion found at surgery, and one patient had ovarian torsion. Six of the 22 patients with equivocal CT diagnoses were admitted for 1-3 days, did not have surgery, and the presenting pain resolved or an alternative diagnosis was established. The remaining eight of 22 patients with an equivocal CT diagnosis had a normal appendix as determined by clinical follow-up or patient survey.
Alternative Diagnoses Found in Patients with True-Negative CT Findings
Alternative diagnoses or findings to explain symptoms were found in 145
(39.5%) of the 367 patients with a true-negative CT diagnosis for acute
appendicitis. These alternative diagnoses or findings, seen on CT or
subsequent imaging, included gynecologic conditions in 49 patients,
diverticulitis in 20, mesenteric adenitis in 15, renal conditions in 12,
colitis in 11, ileitis in nine, and other conditions in 29.
False-Negative CT Diagnoses
Of the 663 patients who underwent CT, the three patients with
false-negative CT diagnoses were determined as follows: two patients indicated
on the survey that they had had their appendix removed elsewhere, and one
patient had a laparoscopic appendectomy at our institution 7 weeks after the
CT examination with pathologically proven acute appendicitis. These patients
were an 11-year-old boy, a 13-year-old girl, and a 25-year-old man.
CT findings in these three patients were as follows: one patient had a 7-mm appendix with no secondary signs of appendicitis, one patient had a 7-mm appendix and evidence of cecal inflammation, and there was no mention in the radiology report of the presence or absence of the appendix or signs of appendicitis in one patient.
False-Positive CT Diagnoses
The 19 patients with false-positive CT diagnoses among the 663 patients who
underwent CT were determined as follows: three patients had appendectomy with
no acute appendicitis found at pathology, four had surgery that revealed other
conditions (torsed fibroid, sigmoid diverticular abscess, hydrosalpinx, and
toxic megacolon), eight were discharged from the emergency department and
clinical follow-up showed resolution of symptoms, and four patients were
admitted with resolution of pain in two and establishment of an alternative
diagnosis in two.
The CT findings in these 19 patients included the following: The size of the appendix was said to range from 7 to 15 mm; five patients had no signs of inflammation; and 14 patients had signs of inflammation, seven with one sign and seven with multiple signs. Signs of inflammation included three patients with enhancement of the appendix, five with cecal thickening, three with adenopathy, eight with fat stranding adjacent to the appendix or its tip, three with free fluid near the appendix, one with an appendolith, and one with abscess that proved to be from sigmoid diverticulitis. Review of the images did not reveal errors of observation of these findings.
Patient Management and Incidence of Appendicitis
Of the 663 patients who were examined with CT for suspected appendicitis,
285 were discharged from the emergency department, three of whom had
appendicitis. The remaining 378 patients were admitted. Of those admitted, 286
had surgery for suspected appendicitis or another condition and 92 had medical
therapy for a specific condition or resolution of symptoms without specific
therapy.
The incidence of acute appendicitis in the 663 patients having CT was 39.2%. The incidence for subgroups of patients is provided in Table 2. Of those 285 patients discharged from the emergency department after CT, 1% had appendicitis found subsequently. Of the 378 patients admitted after CT, 68% had acute appendicitis.
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Incidence of Appendicitis in Patients Who Undergo CT
The incidence of acute appendicitis in the patient cohort for this
investigation was 39.2% and does not appear to have changed over time when
compared with other investigations with comparable patient cohorts. In 1997,
two investigations of patients referred from the emergency department for
suspected appendicitis (a similar patient cohort compared with this
investigation) found an incidence of acute appendicitis of 30-37%
[17,
18]. In 1997, we found an
incidence of appendicitis ranging from 53% to 61%. However, the patient
cohorts were patients to be admitted for suspected appendicitis and did not
include patients who were discharged from the emergency department
[16].
False-Negative Appendectomy Rate and the Decision to Perform CT
Patient diagnostic workup before 1996 at this hospital did not include CT
to evaluate specifically for suspected appendicitis. Patient workup during
this investigation included a decision by the referring physician whether to
perform CT. When we introduced CT for suspected appendicitis at this hospital
in 1996, the rate of surgery in patients without acute appendicitis dropped
from 20% to 7% [3]. Now that CT
is selectively used in routine practice and was not in the spotlight of a
known ongoing investigation, this retrospective study shows that the initial
gains in reducing the negative appendectomy rate have continued, with a
current negative appendectomy rate of 3.0% for patients who have a CT
examination. The negative appendectomy rate for those patients who did not
undergo CT before surgery in this investigation was found to be 5.6%. There is
no statistically significant difference currently in the negative appendectomy
rates for patients sent for CT and for patients whose clinical and laboratory
findings were judged sufficient to go to surgery without CT (p =
0.326). We conclude that our clinical colleagues are appropriately selecting a
group of patients for surgery without CT. We also conclude that CT should be
used in most patients with suspected appendicitis.
The appropriateness of the decision whether to perform CT may be refined by considering subgroups of patients based on age and sex (Table 3). Selection of certain males including pediatric males for surgery without CT appears to be in appropriate balance because the p values show no statistical difference in negative appendectomy rates. That is, those males whose clinical diagnosis is uncertain have CT and those males who are likely to have appendicitis do not have CT. However, for pediatric females, there is a statistically significant difference in the negative appendectomy rates, with those having CT before surgery having a lower negative appendectomy rate. Because the sensitivity of CT for acute appendicitis is similar in males and females, the clinical decision threshold to perform CT in pediatric females probably should be lowered. Female pediatric patients would likely have a lower negative appendectomy rate if CT were used more liberally before surgery.
Obtaining more CT images for suspected appendicitis must take into account the theoretic harm of diagnostic radiation. The concern for morbidity and mortality from diagnostic radiation exposure (in females especially) must be considered in light of the morbidity and mortality of appendectomy. In a review of more than 10,000 patients in 1992, Velanovich and Satava [19] documented the morbidity and mortality of appendectomy. Morbidity and mortality from appendectomy for patients having a normal appendix were found to be 4.6% and 0.14%, respectively; 6.1% and 0.24% for those with acute appendicitis; and 19.3% and 1.66% for those with perforated appendicitis [19]. In the future, the use of MRI instead of CT in selected patients, especially pediatric and female patients, may be shown to be effective in reducing the negative appendectomy rate and will have no theoretic detrimental effects. In addition, recent advances in CT technology, including automated tube-current modulation, are able to reduce CT radiation exposure.
Equivocal CT Interpretations
Equivocal CT interpretations have a different effect on patient management
than positive or negative interpretations for appendicitis. The equivocal
interpretation adds nothing to management decisions unless an alternative
diagnosis is found, and even then appendicitis might remain suspect. If the CT
examination is equivocal, management should proceed as if CT had not been
performed—that is, observation, surgery, or discharge based on clinical
judgment.
The percentage of CT images interpreted as equivocal in this investigation was 3.3%, ranging from 1.9% in adults to 8.7% in pediatric patients. Pediatric patients tend to have less intraperitoneal fat than adults, which may explain the higher percentage of equivocal interpretations.
The overall percentage of equivocal interpretations found in this investigation compares favorably with the 3-8% previously reported in the literature [13, 20, 21]. Although direct comparison with other investigations is not possible, the use of thin (2.5 mm) image thickness and spacing, administration of contrast material, and experience of interpreters, because of the large volume of cases, seen may be contributing factors in obtaining a low percentage of equivocal interpretations.
The use of rectal contrast material helps to identify the normal appendix because reflux into the appendix is seen in approximately 70-80% of patients with a normal appendix [18, 22, 23]. Rectal contrast material also helps identify the abnormal appendix because in some patients changes of edema may be seen at the cecal apex where the appendix originates. The use of oral contrast material helps identify the normal or abnormal appendix because of an improved ability to distinguish the small bowel from the appendix. IV contrast material helps identify the abnormal appendix because of enhancement of the hyperemic appendiceal wall. It is clear that despite attempts to optimize CT techniques, a certain low percentage of examinations should be called equivocal so that our clinical colleagues are not misled.
False-Negative and False-Positive CT Findings
Three of the 663 patients had a false-negative CT diagnosis. Two of the
three had a 7-mm appendix, one of whom had inflammation adjacent to the
appendix. There is an overlap of the appearance of the normal and early
abnormal appendix, which is an inherent limitation of the CT examination. In
retrospect, the patient with a 7-mm appendix and periappendiceal inflammation
was probably an error of interpretation. The third false-negative CT
examination, in which the appendix was not mentioned in the CT report despite
a history of suspected appendicitis, reflects an error of interpretation. The
patients with false-negative CT diagnoses were discharged from the emergency
department. We conclude that if there is doubt, the CT examination should be
called equivocal rather than negative for acute appendicitis.
Nineteen of the 663 patients had a false-positive CT diagnosis. All appendixes in the false-positive group were larger than 6 mm, and 14 patients had secondary signs of inflammation. These patients had resolution of symptoms, and some may have represented cases of resolving appendicitis. The five patients with a large appendix and no secondary signs of inflammation may have represented an inherent limitation of the CT technique from the overlap of normal and abnormal findings.
Clinical judgment was key in improving the management of patients with a false-positive CT diagnosis. Eight of the 19 patients with false-positive CT findings were discharged from the emergency department and did not prove subsequently to have appendicitis. Seven of the patients with false-positive CT findings were taken to surgery where surgical conditions were found in four. Four patients were admitted with other diagnoses being attained or with resolution of symptoms. Clinical judgment resulted in the appropriate patient management in 16 of the 19 patients with false-positive CT diagnoses.
In summary, 5 years after its introduction, CT was used in 88% of patients with suspected appendicitis. The negative appendectomy rate for all patients undergoing CT was 3.0%. This false-negative appendectomy rate is similar to that for those selected for surgery without CT (5.6%) on the basis of a strong clinical suspicion of appendicitis. The negative appendectomy rate was markedly better for the female pediatric subgroup who had CT. Clinical judgment is important for selecting patients who need CT for suspected appendicitis, but use of CT in most patients is essential to reduce the negative appendectomy rate.
CT is highly accurate in routine use given its ROC curve and the sensitivity and specificity of 99% and 95%, respectively. Clinical judgment is key in deciding whether to perform CT, in detecting patients with a false-positive CT diagnosis, and in successfully managing the 3.3% of patients with an equivocal or indeterminate CT diagnosis.
The incidence of acute appendicitis, 39.2%, is comparable to prior investigations from 1997 with similar patient cohorts. This similarity suggests that the use of appendiceal CT stabilizes once it is established as a useful diagnostic tool.
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