Objectives: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) utilizes the second-harmonic signals from contrast microbubbles located in the vessels to improve the detectability of microcirculation. Many studies have used CH-EUS to stratify the malignancy risk of submucosal tumors (SMTs), discriminate gastrointestinal stromal tumors (GISTs) from benign SMTs, and predict the malignancy of GISTs based on the regularity of vessels or enhancing patterns. The aim of this study was to conduct a meta-analysis to evaluate the diagnostic performance of CH-EUS in the differential diagnosis of SMTs.
Methods: After searching the Medline, Embase, and Cochrane databases systematically, studies that evaluated the diagnostic accuracy of CH-EUS for the prediction of the malignancy potential of SMTs were pooled. The diagnostic accuracy was computed using a stochastic effect model. The overall test performance was summarized with the summary receiver operating characteristic curve.
Results: Six studies discriminated GISTs from benign lesions, and three studies discriminated low-risk from high-risk GISTs, covering a total of 354 cases of SMT. The overall accuracy of CH-EUS in predicting malignancy risk can be assessed as follows: sensitivity 0.87 (95% CI 0.82-0.91), specificity 0.82 (95% CI 0.74-0.89), positive likelihood ratio of 3.55 (95% CI 2.39-5.27), negative likelihood ratio of 0.21 (95% CI 0.13-0.33), and diagnostic odds ratio of 22.17 (95% CI 10.43-47.10). The overall area under the curve was 0.89. Subgroup analysis of the sensitivity and specificity for studies discriminating low-risk from high-risk GISTs were 0.93 (95% CI 0.77-0.99) and 0.81 (95% CI 0.63-0.93), respectively. There was evidence of significant heterogeneity, but no proof of publication bias.
Conclusions: CH-EUS is an effective tool for improving the diagnostic accuracy of conventional EUS for discriminating SMTs and is superior to other imaging techniques. However, due to the limited number of well-designed control studies, we should take into consideration the uncertainty of this method when altering a treatment plan.
Keywords: Contrast agents; Contrast-enhanced harmonic endoscopic ultrasound; Gastrointestinal stromal tumor; Submucosal tumor.