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Systematic Review: Computed Tomography and Ultrasonography To Detect Acute Appendicitis in Adults and Adolescents

Teruhiko Terasawa, MD; C. Craig Blackmore, MD, MPH; Stephen Bent, MD; and R. Jeffrey Kohlwes, MD, MPH
[+] Article and Author Information

From the San Francisco Veterans Affairs Medical Center and University of California, San Francisco, San Francisco, California; and Harborview Medical Center, University of Washington, Seattle, Washington.


Acknowledgments: The authors thank Shyr-Chyr Chen, MD; Marc Horton, MD; Herman Kan, MD; Susan Walker, MD; Terry Gilliland, MD; Bernard Vermeulen, MD; and Scott Wise, MD, for providing the data on their original work. They also thank Bernard Birnbaum, MD, for reviewing the English-language literature retrieval results and Hubert J. Vesselle, MD, PhD, and Ken F. Linnau, MD, for assistance in translating French- and German-language publications.

Grant Support: Drs. Terasawa and Kohlwes were supported in part by the PRIME residency program, University of California, San Francisco, San Francisco, California. Dr. Terasawa was supported in part by a Grant-in-Aid for Postgraduate Medical Education and Training in Primary Care from the Ministry of Health, Labour, and Welfare, Japan. Dr. Blackmore was supported in part by the Agency for Healthcare Research and Quality (grant K08-HS11291). Dr. Bent was supported in part by the National Center for Complementary and Alternative Medicine (grant 1 K08-AT001338-01).

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Teruhiko Terasawa, MD, Department of Clinical Research and Hematology, Nagoya National Hospital, 4-1-1 Sannomaru, Naka-ku, Nagoya, Japan 460-0001; e-mail, terasawa@nnh.hosp.go.jp.

Current Author Addresses: Dr. Terasawa: Nagoya National Hospital, 4-1-1 Sannomaru, Naka-ku, Nagoya, Japan 460-0001.

Drs. Bent and Kohlwes: San Francisco Veterans Affairs Medical Center, 4150 Clement Street, Box 111, San Francisco, CA 94121.

Dr. Blackmore: Harborview Medical Center, 325 Ninth Avenue, Box 359728, Seattle, WA 98104.


Ann Intern Med. 2004;141(7):537-546. doi:10.7326/0003-4819-141-7-200410050-00011
Text Size: A A A

Background: Although clinicians commonly use computed tomography or ultrasonography to diagnose acute appendicitis, the accuracy of these imaging tests remains unclear.

Purpose: To review the diagnostic accuracy of computed tomography and ultrasonography in adults and adolescents with suspected acute appendicitis.

Data Sources: The authors used MEDLINE, EMBASE, bibliographies, review articles, textbooks, and expert opinion to retrieve English- and non–English-language articles published from 1966 to December 2003.

Study Selection: The authors included prospective studies evaluating computed tomography or ultrasonography followed by surgical confirmation or clinical follow-up in patients at least 14 years of age with suspected appendicitis.

Data Extraction: One assessor (for non–English-language studies) or 2 assessors (for English-language studies) independently reviewed each article to abstract relevant study characteristics and results.

Data Synthesis: Twelve computed tomography studies and 14 ultrasonography studies met inclusion criteria. Computed tomography had an overall sensitivity of 0.94 (95% CI, 0.91 to 0.95), a specificity of 0.95 (CI, 0.93 to 0.96), a positive likelihood ratio of 13.3 (CI, 9.9 to 17.9), and a negative likelihood ratio of 0.09 (CI, 0.07 to 0.12). Ultrasonography had an overall sensitivity of 0.86 (CI, 0.83 to 0.88), a specificity of 0.81 (CI, 0.78 to 0.84), a positive likelihood ratio of 5.8 (CI, 3.5 to 9.5), and a negative likelihood ratio of 0.19 (CI, 0.13 to 0.27). Verification bias and inappropriate blinding of reference standards were noted in all of the included studies.

Limitations: The summary assessment of the diagnostic accuracy for both tests was limited by the small number of studies, heterogeneity among study samples, and poor methodologic quality in the original studies.

Conclusions: Computed tomography is probably more accurate than ultrasonography for diagnosing appendicitis in adults and adolescents. Prospective studies that apply gold standard diagnostic testing to all study participants would more reliably estimate the true diagnostic accuracy of these tests.

Figures

Grahic Jump Location
Figure 2.
Sensitivity and specificity of appendiceal computed tomography (top) and appendiceal ultrasonography (bottom).

The vertical line represents the summary estimate. The size of each square is proportional to the sample size for each study (the number of patients with appendicitis for sensitivity and the number of patients without appendicitis for specificity). Horizontal lines are 95% CIs.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Positive likelihood ratio and negative likelihood ratio of appendiceal computed tomography (top) and appendiceal ultrasonography (bottom).

The vertical line represents the summary estimate. The size of each square is proportional to the sample size for each study (all study participants). Horizontal lines are 95% CIs.

Grahic Jump Location
Grahic Jump Location
Figure 4.
Receiver-operating characteristic plotting of appendiceal computed tomography and ultrasonography.

Individual study estimates of sensitivity and 1 − specificity are shown for computed tomography (circles) and ultrasonography (squares). The size of each square or circle is proportional to the sample size for each study (all study participants).

Grahic Jump Location
Grahic Jump Location
Figure 5.
Post-test probability of acute appendicitis after computed tomography (CT) or ultrasonography (US).

Post-test probabilities are shown as a function of pretest probability for patients with positive results on CT, positive results on US, negative results on CT, and negative results on US.

Grahic Jump Location

Tables

References

Letters

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Comments

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Is CT the right answer for Atypical Appendicitis
Posted on October 25, 2004
Junaid A Razzak
The Aga Khan university, Karachi, Pakistan
Conflict of Interest: None Declared

I would like to thank Terasawa et. al. for the systematic review comparing CT scan to Ultrasound (US) in the diagnosis of appendicitis in patients with atypical presentations.

The article suggested that overall, CT is a better then US.[1] For many of us it clarifies the clinical decision making, for others practicing in low resource setting this may actually complicate the decision making. CT, in many low income countries, often costs many times the monthly salary of the family. It is important to carefully answer the following questions before we recommend CT as a standard of care:

1- What about the cost and cost-effectiveness? A focal appendiceal CT in our practice setting costs about 6 times more than an US. This focal CT would likely tell the clinician if patient does or does not have appendicitis. When confronted with the broader question: What is the cause of this abdominal pain if it is not appendicitis? the cost differences are even greater. A complete abdominal/pelvic CT with PO/IV contrasts costs about 18 times more than the US. It may thus be less expensive to admit/observe a patient than ordering a CT. The only group that will benefit is a relatively small group who would get operated earlier in CT group versus US group. Those with negative tests would still need admission or a close follow-up since none of the tests have 100% specificity.

2- Is CT a better diagnostic test than US for all patients or is CT better than US in some patients while US is better than CT in others? Current literature needs to better define sensitivities and specificities for sub-group of patients. Thus it would help to know if CT is as good for a 30 years old thin male as it is for 30 years old female or a 60 years old diabetic with non-specific abdominal pain. Another issue is being more specific in describing the degree of "a-typicality" or the level of pretest probability. Literature does not answer the question on how to make a decision if a clinician thinks that a patient may have appendicitis but is not sure; versus when the clinician does not think that the patients has appendicitis and is not sure. Thirdly, as most of the literature originated in high income countries, would the conclusions of this study hold true for relatively leaner population in low and middle income countries.

[1]Terasawa T, Blackmore CC, Bent S, Kohlwes RJ. Systematic Review: Computed Tomography and Ultrasonography To Detect Acute Appendicitis in Adults and Adolescents Ann Intern Med 2004; 141: 537-546

Conflict of Interest:

None declared

Summary ROC is useful
Posted on October 30, 2004
Toshiya Shiga
Department of Anesthesia, Nippon Medical School Chiba Hokusoh Hospital, Chiba, JAPAN
Conflict of Interest: None Declared

Dear Editor:

We congratulate Terasawa et al. for demonstrating the advantage of computed tomography over ultrasonography in the diagnosis of acute appendicitis in adults and adolescents (1). We note that although they plotted the false-positive rate against the true- positive rate on their graph, they did not construct a summary receiver- operating characteristic curve (ROC). The summary ROC curve as described by Moses et al (2), is a powerful tool for depicting diagnostic performance and showing how the diagnostic performance is affected by the test threshold. Briefly, the regression model is expressed as D = a + b*S, where D is the diagnostic log odds ratio and S is the measure of how the test characteristics vary with the test threshold. We could not resist plotting summary ROC curves (Figure not shown here) from the 2x2 contingency tables in the article by Terasawa et al. Comparing their original figure with ours, it is apparent that the diagnostic performance of computed tomography is superior to that of ultrasonography in cases of appendicitis. The authors state that in most of studies reviewed, appendiceal diameter greater than 6 mm was used as the positive diagnostic criterion for appendicitis. But, judging from the table, most of the studies seem to have the plural criteria. However, both regression coefficients b are between "“1.0 and 1.0 (P > 0.05), suggesting that there is not significant variation in diagnostic performance with threshold. Diagnostic log odds ratio (logit transformation of the ratio of positive to negative likelihood obtained by the Mantel-Haenszel method) of computed tomography is estimated to be 5.0 (95% confidence interval (CI), 1.3-8.7), and that of ultrasonography is 3.4 (95% CI, 0.9-5.9), indicating again that computed tomography is superior to ultrasonography.

In addition, we created a funnel plot to explore the publication bias. The funnel plot is asymmetric, indicating that publication bias is likely. It is possible that some studies of small sample populations that indicate low diagnostic accuracy for these tests have not been published.

Our additional analysis does not mean the conclusion offered by Terasawa et al. needs alteration; rather, it strengthens their conclusion. We believe that they provided an elegant systematic review.

(1) Terasawa T, Blackmore CC, Bent S, Kohlwes RJ. Systematic review: computed tomography and ultrasonography to detect acute appendicitis in adults and adolescents. Ann Intern Med. 2004;141:537-46. (2) Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med. 1993;12:1293-316.

Conflict of Interest:

None declared

Summary ROC is useful
Posted on October 30, 2004
Toshiya Shiga
Department of Anesthesia, Nippon Medical School Chiba Hokusoh Hospital, Chiba, JAPAN
Conflict of Interest: None Declared

Dear Editor:

We congratulate Terasawa et al. for demonstrating the advantage of computed tomography over ultrasonography in the diagnosis of acute appendicitis in adults and adolescents (1). We note that although they plotted the false-positive rate against the true- positive rate on their graph, they did not construct a summary receiver- operating characteristic curve (ROC). The summary ROC curve as described by Moses et al (2), is a powerful tool for depicting diagnostic performance and showing how the diagnostic performance is affected by the test threshold. Briefly, the regression model is expressed as D = a + b*S, where D is the diagnostic log odds ratio and S is the measure of how the test characteristics vary with the test threshold. We could not resist plotting summary ROC curves (Figure not shown here) from the 2x2 contingency tables in the article by Terasawa et al. The results is that D = 5.2 - 0.49*S for computed tomography and D = 3.8 - 0.005*S for ultrasonography. Comparing their original figure with ours, it is apparent that the diagnostic performance of computed tomography is superior to that of ultrasonography in cases of appendicitis. The authors state that in most of studies reviewed, appendiceal diameter greater than 6 mm was used as the positive diagnostic criterion for appendicitis. But, judging from the table, most of the studies seem to have the plural criteria. However, both regression coefficients b are between "“1.0 and 1.0 (P > 0.05), suggesting that there is not significant variation in diagnostic performance with threshold. Diagnostic log odds ratio (logit transformation of the ratio of positive to negative likelihood obtained by the Mantel-Haenszel method) of computed tomography is estimated to be 5.0 (95% confidence interval (CI), 1.3-8.7), and that of ultrasonography is 3.4 (95% CI, 0.9-5.9), indicating again that computed tomography is superior to ultrasonography.

In addition, we created a funnel plot to explore the publication bias. The funnel plot is asymmetric, indicating that publication bias is likely. It is possible that some studies of small sample populations that indicate low diagnostic accuracy for these tests have not been published.

Our additional analysis does not mean the conclusion offered by Terasawa et al. needs alteration; rather, it strengthens their conclusion. We believe that they provided an elegant systematic review.

(1) Terasawa T, Blackmore CC, Bent S, Kohlwes RJ. Systematic review: computed tomography and ultrasonography to detect acute appendicitis in adults and adolescents. Ann Intern Med. 2004;141:537-46. (2) Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med. 1993;12:1293-316.

Conflict of Interest:

None declared

Computed Tomography versus Ultrasonography for Suspected Acute Appendicitis
Posted on December 16, 2004
Teruhiko Terasawa
National Hospital Organization, Nagoya Medical Center
Conflict of Interest: None Declared

We thank Drs. Razzak, Shiga, and Goto for their interest in our paper on imaging for adults and adolescents with suspected appendicitis.

We agree with Dr. Razzak that cost-effectiveness is critical to selection of appropriate imaging, as is local availability of imaging technologies. Further, different imaging strategies may be appropriate in different subsets of patients. These areas would benefit from further investigation.

We agree with Dr. Shiga that summary receiver operating characteristics (ROC) curves (1) and funnel plots may be useful in meta- analysis. We had performed similar analyses but did not include the results because of several concerns. Summary ROC curves may be affected by the assumptions used in curve calculation and are less useful at bedside than likelihood ratios, which enable understanding of disease probabilities. Asymmetrical funnel plots are affected by both publication bias and other factors that cause heterogeneity, including small study effects (2).

In response to Dr. Goto's comments, the global sensitivity analysis (GSA) that he used (3) can apply to studies with partial verification bias, where not all participants receive diagnosis confirmation by the single reference standard, but not to differential verification bias, as in the case of appendicitis. Under the GSA approach, the range of disease prevalence in the unverified patients is applied to define the possible range of sensitivity and specificity for the test under consideration. This is appropriate if nothing is known about the subjects who did not receive the reference standard (surgery). However, in the studies included in our review, most of the negative imaging results were verified by a secondary clinical reference standard (4). This differential verification bias will lead to some overestimation of overall accuracy as we discuss in the paper. However, most subjects with appendicitis should have progressed with symptoms and therefore would have been identified through clinical follow-up. It seems certain that Goto's assumptions of a prevalence of undiagnosed appendicitis of 0.10 to 0.50 in subjects without operation but with no appendicitis identified on clinical follow-up is not clinically sensible. The use of clinical follow-up is a valuable if imperfect reference standard, and is clearly superior to the GSA assumption that nothing is known about these patients.

In summary, based on the data, although some differential verification bias is present leading to overestimation of diagnostic accuracy for both tests, CT scanning is a more sensitive and specific imaging modality to detect appendicitis in patients of indeterminate clinical suspicion.

Teruhiko Terasawa, MD National Hospital Organization, Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya, Japan 460-0001

C. Craig Blackmore, MD, MPH Harborview Medical Center, 325 Ninth Avenue, Box 359728, Seattle, WA 98104.

References 1. Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med. 1993;12:1293-316. PMID: 8210827 2. Sterne JA, Egger M, Smith GD. Systematic reviews in health care: Investigating and dealing with publication and other biases in meta- analysis. BMJ. 2001;323:101-5. Review. PMID: 11451790 3. Kosinski AS, Barnhart HX. A global sensitivity analysis of performance of a medical diagnostic test when verification bias is present. Stat Med. 2003;22:2711-21. PMID: 12939781 4. Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003;3:25. PMID: 14606960

Conflict of Interest:

None declared

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