Contrast-enhanced endoscopic ultrasound for the differential diagnosis between benign and malignant lymph nodes: a meta-analysis

Abstract

Background The differential diagnosis between benign and malignant lymph nodes (LNs) is crucial for patient management and clinical outcome. The use of contrast-enhanced endoscopic ultrasound (EUS) has been evaluated in several studies with diverse results. The aim of this meta-analysis was to evaluate the pooled diagnostic accuracy of contrast-enhanced EUS (CE-EUS) and contrast-enhanced harmonic EUS (CH-EUS) in this setting. Methods A systematic electronic search was performed, including all original papers dealing with assessment of the nature of the LNs using CE-EUS or CH-EUS. A meta-analysis was performed to obtain pooled sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio. The Summary Receiver Operating Characteristic (ROC) Curve method was used to calculate the area under the curve. Statistical analysis was carried out using Meta-Disc V.1.4, Stata V.12.0 and Review Manager V.5.2. Results Among 210 pertinent studies, four (336 patients) were included in the analysis. The pooled sensitivity was 82.1 % (75.1 – 87.7 %) and pooled specificity was 90.7 % (85.9 – 94.3 %) with significant heterogeneity found in sensitivity; the positive-likelihood ratio (LR) was 7.77 (5.09 – 11.85) and the negative-LR was 0.15 (0.05 – 0.46); the pooled diagnostic odds ratio (DOR) was 54 (15 – 190). Subgroup analysis including studies performed using CH-EUS (two studies, 177 LNs) showed a pooled sensitivity of 87.7 % (77.0 – 93.9 %) and a pooled specificity of 91.8 % (84.5 % – 96.4 %) with no significant heterogeneity; the pooled positive-LR was 9.51 (4.95 – 18.28) and the pooled negative-LR was 0.14 (0.06 – 0.35); pooled DOR was 68.42 (15.5 – 301.4). Conclusions From these data, CE-EUS is not recommended due to inadequate sensitivity. On the other hand, CH-EUS studies showed optimal accuracy (pooled sensitivity 87.7 % and specificity 91.8 %), comparable to elastography and even EUS-guided fine needle aspiration (EUS-FNA), suggesting a role in the diagnostic algorithm.

Endoscopic Ultrasound Fine-Needle Aspiration versus Fine-Needle Biopsy for Lymph Node Diagnosis: A Large Multicenter Comparative Analysis

“…3,13,14 These results may be related to the limitations of this method, such as damage of the LN architecture limiting histological evaluation. 1,4 To overcome these limitations, FNB has more recently been used in several centers. Yet, to date, no studies have compared these techniques for LN sampling.…”

“…Endoscopic ultrasound (EUS) is well-suited to assess lymphadenopathy in the posterior mediastinum, celiac axis, and peri-intestinal area in patients with benign or malignant gastrointestinal or thoracic diseases, allowing real-time, high-resolution imaging with relatively low cost. [1][2][3] In the past, EUS was used only to provide morphological characteristics such as size, echogenicity, architecture, shape, borders, and vascular pattern; however, EUS diagnosis of LN based on morphological characteristics alone has limited accuracy. 4 While different size cutoffs have been proposed for each anatomical district, diagnosis based on size is associated with reduced accuracy.…”

“…Previous literature has shown that up to 30% of LNs <5 mm may be malignant, while LNs >20 mm may be benign in the setting of inflammation. 1,5 Modalities to improve the diagnosis of LN such as contrast enhancement and elastography have been utilized, albeit with widely variable results. Although these innovations have demonstrated higher sensitivity rates than standard EUS imaging, these techniques do not include tissue sampling and yield unsatisfactory specificity rates.…”

“…In general, this procedure can be safely performed in an outpatient setting without general anesthesia. 1,4 Compared to alternative techniques available for sampling mediastinal LNs, EUS-guided tissue sampling is safer and less invasive. 7 Additionally, for abdominal LNs, a prospective study including 142 patients with non-diagnostic or non-feasible percutaneous image-guided sampling demonstrated that EUS-guided sampling was successful in 92% of patients and produced a diagnosis in 91%.…”

“…4 These marginal results may, in part, be due to damage of the LN architecture, thereby limiting histological evaluation. 1,4 To overcome the limitations of EUS-FNA, novel fine-needle biopsy (FNB) systems have been designed to provide a larger sample and preserve the tissue architecture of the tissue, potentially leading to better results. For the evaluation of LNs of an unknown origin, such as lymphoma, metastasis, mycobacterial infection, and sarcoidosis, core biopsy with preservation of the LN architecture is particularly important.…”