Diagnostic value of different contrast-enhanced ultrasound (CEUS) methods for sentinel lymph node metastasis in patients with breast neoplasms: a meta-analysis and indirect comparison.

Background: Breast cancer is the most common malignant tumor in female patients. It is important to evaluate axillary lymph node metastasis before surgery to select the most appropriate treatment and evaluate the prognosis of breast cancer patients. In breast cancer, the sentinel lymph node (SLN) is the first lymph node to which tumor cells metastasize, and thus can indicate the status of the axillary lymph nodes. This meta-analysis sought to quantify the performance of contrast medium via intravenous injection or via four-point subcutaneous injection (i.e., into the skin around the areola at 3, 6, 9 and 12 o'clock) to evaluate which method had the best diagnostic performance in the diagnosis of SLN metastasis of breast cancer, provide a more accurate non-invasive assessment of axillary staging in clinical breast cancer patients, and improve patient outcomes.

Methods: The PubMed, Web of Science, Embase, OVID, and Cochrane Library databases were used to evaluate the value of the two injection methods in diagnosing SLN metastasis in breast cancer patients. In total, 17 articles (with 19 datasets) met the inclusion criteria of the study and were included in the meta‑analysis. All the analyses were conducted using Stata 14.0 software. The summary statistics, including the sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic score, diagnostic odds ratio (DOR), and area under the receiver operating characteristic (ROC) curve, were calculated to assess the diagnostic value of the two methods. This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (No. CRD42023475494).

Results: The four-point subcutaneous injection method around the areola had a relative SEN of 1.26 [95% confidence interval (CI): 0.88-1.81], a relative SPE of 0.95 (95% CI: 0.88-1.00), a relative PLR of 0.76 (95% CI: 0.34-1.71), a relative NLR of 0.44 (95% CI: 0.17-1.16), a relative diagnostic score of 1.15 (95% CI: 0.84-1.58), and a relative DOR of 1.61 (95% CI: 0.44-5.90). The missed diagnosis rate of the four-point subcutaneous injection was 12%, and the area under the ROC curve was 0.94 (95% CI: 0.91-0.96); while the missed diagnosis rate of the intravenous injection was 42%, and the area under the ROC curve was 0.94 (95% CI: 0.92-0.96).

Conclusions: Compared to the intravenous injection, the four-point subcutaneous injection around the areola improved the SEN of contrast-enhanced ultrasound in the diagnosis of breast cancer SLN metastasis and reduced the rate of missed diagnosis, was better able to diagnose SLN status, and provided more accurate axillary lymph node staging for breast cancer patients, and thus could help to improve patient prognosis.