Accuracy of EUS in Differentiating Mucosal versus Submucosal Superficial Esophageal Lesions: A Systematic Review and Meta-analysis

Abstract

Purpose: Background: Endoscopic techniques including photodynamic therapy, laser photoablation, contact thermal coagulation, and endoscopic mucosal resection (EMR) offer minimally invasive treatment options for esophageal lesions limited to the mucosa but not with submucosal invasion. The discrimination of truly superficial from more advanced lesions is thus critical to the selection of patients for endoscopic therapy. EUS provides the most accurate method to stage esophageal carcinoma (EC). Aim: To perform a systematic review and meta-analysis for assessing the sensitivity, specificity, and likelihood ratios (LR) of EUS in differentiating mucosal (T1a) from submucosal (T1b) EC. Methods: MEDLINE, SCOPUS, Cochrane, and CINAHL Plus databases were used to identify studies in which results of EUS based staging of EC were compared with the results of an acceptable standard, including histopathology of EMR or surgically resected lesions. Two independent reviewers extracted standardized data. DerSimonian-Liard random effects model was used to estimate the pooled sensitivity, specificity, and LR. A summary receiver operating characteristic (ROC) curve was constructed. All potential sources of heterogeneity amongst the studies were explored by subgroup and meta-regression analyses. Results: 702 patients with EUS-based staging of EC were examined from 10 prospective studies that satisfied our inclusion criteria. The pooled sensitivity and specificity of EUS in staging mucosal lesions were 0.88 (95% CI, 0.84-0.92) and 0.83 (95% CI, 0.78-0.88). In contrast, for submucosal lesions the pooled sensitivity and specificity were 0.83 (95% CI, 0.77-0.87) and 0.88 (95% CI, 0.84-0.91). The positive and negative LR for mucosal staging were 5.20 (95% CI, 2.43-11.15) and 0.18 (95% CI, 0.10-0.31) and for submucosal staging were 5.60 (95% CI, 3.18-9.87) and 0.19 (95% CI, 0.09-0.40), respectively. The area under the curve (AUC) was 0.93 for both mucosal and submucosal lesions. The P value of X2 heterogeneity for all the pooled estimates was >0.05 suggesting significant heterogeneity amongst the studies. Heterogeneity is probably caused by factors that were inadequately reported in primary studies and, therefore, could not be explored in this meta-analysis. Conclusion: Overall EUS has good accuracy (AUC 0.93) in staging superficial esophageal cancers. However, despite the advances in endoscopic ultrasound techniques preoperative staging between mucosal and submucosal invasion remains challenging. Significant heterogeneity among the included studies suggests that multiple factors including location and type of lesion, method and frequency of EUS probe and experience of endosonographer can affect diagnostic accuracy of EUS.