We identified 42 primary studies with 4220 participants. Twenty studies provided accuracy data based on the number of individual participants (seven of which provided data with and without the use of contrast). Sixteen of these studies evaluated the accuracy of CDUS. These studies were generally of moderate to low quality: only three studies fulfilled all the QUADAS items; in six (40%) of the studies, the delay between the tests was unclear or longer than four weeks; in eight (50%), the blinding of either the index test or the reference standard was not clearly reported or was not performed; and in two studies (12%), the interpretation of the reference standard was not clearly reported. Eleven studies evaluated the accuracy of CE-CDUS. These studies were of better quality than the CDUS studies: five (45%) studies fulfilled all the QUADAS items; four (36%) did not report clearly the blinding interpretation of the reference standard; and two (18%) did not clearly report the delay between the two tests.
Based on the bivariate model, the summary estimates for CDUS were 0.82 (95% confidence interval (CI) 0.66 to 0.91) for sensitivity and 0.93 (95% CI 0.87 to 0.96) for specificity whereas for CE-CDUS the estimates were 0.94 (95% CI 0.85 to 0.98) for sensitivity and 0.95 (95% CI 0.90 to 0.98) for specificity. Regression analysis showed that CE-CDUS was superior to CDUS in terms of sensitivity (LR Chi2 = 5.08, 1 degree of freedom (df); P = 0.0242 for model improvement).
Seven studies provided estimates before and after administration of contrast. Sensitivity before contrast was 0.67 (95% CI 0.47 to 0.83) and after contrast was 0.97 (95% CI 0.92 to 0.99). The improvement in sensitivity with of contrast use was statistically significant (LR Chi2 = 13.47, 1 df; P = 0.0002 for model improvement).
Regression testing showed evidence of statistically significant effect bias related to year of publication and study quality within individual participants based CDUS studies. Sensitivity estimates were higher in the studies published before 2006 than the estimates obtained from studies published in 2006 or later (P < 0.001); and studies judged as low/unclear quality provided higher estimates in sensitivity. When regression testing was applied to the individual based CE-CDUS studies, none of the items, namely direction of the study design, quality, and age, were identified as a source of heterogeneity.
Twenty-two studies provided accuracy data based on number of scans performed (of which four provided data with and without the use of contrast). Analysis of the studies that provided scan based data showed similar results. Summary estimates for CDUS (18 studies) showed 0.72 (95% CI 0.55 to 0.85) for sensitivity and 0.95 (95% CI 0.90 to 0.96) for specificity whereas summary estimates for CE-CDUS (eight studies) were 0.91 (95% CI 0.68 to 0.98) for sensitivity and 0.89 (95% CI 0.71 to 0.96) for specificity.