Identification of sentinel lymph nodes by contrast-enhanced ultrasonography with Sonazoid in patients with breast cancer: a feasibility study in three hospitals.

The aim of this prospective study was to evaluate the feasibility of periareolar injection of the contrast agent Sonazoid (SNZ) followed by ultrasonography (US) for the identification of sentinel lymph node (SLN) in breast cancer patients with clinically negative node. Patients (n = 100) with T1-2N0M0 breast cancer received a periareolar injection of SNZ followed by US to identify contrast-enhanced SLN. Each contrast-enhanced SLN underwent fine needle aspiration cytology (FNAC) followed by SLN biopsy with a conventional method using blue dye and/or radiocolloid (B/R). In almost all cases, contrast-enhanced lymphatic vessels were clearly visualized by US soon after the periareolar injection of SNZ and the SLNs were easily identified with an identification rate of 98% (98/100) for SNZ and 100% (100/100) for B/R. The number of SLNs identified by SNZ (SNZ-SLN) (mean per patient, 1.52) was significantly lower than that identified by B/R (B/R-SLN) (2.19) (P < 0.0001). Twenty-five patients with positive SLNs had at least one positive SNZ-SLN. On a node-by-node basis, sensitivity, specificity, and accuracy of FNAC for SNZ-SLNs (n = 149) were 33.3%, 99.2%, and 85.9%, respectively. Identification of SLN by periareolar injection of SNZ is a technically simple method with an identification rate as high as 98%. SNZ-SLN thus seems to be a good target for FNAC, but sensitivity of FNAC for SNZ-SLNs needs to be improved.

Shimazu K ，Ito T ，Uji K ，Miyake T ，Aono T ，Motomura K ，Naoi Y ，Shimomura A ，Shimoda M ，Kagara N ，Kim SJ ，Noguchi S ... -  《Cancer Medicine》

Real-Time Visualization of Lymphatic Flow to Sentinel Lymph Nodes by Contrast-Enhanced Ultrasonography with Sonazoid in Patients with Breast Cancer.

Contrast-enhanced ultrasonography with Sonazoid (SNZ) enables real-time visualization, resulting in more precise identification of lymphatic flow to sentinel lymph nodes (SLNs). This study aimed to classify lymphatic drainage patterns to SLNs. Patients (n = 75) with T1-2 N0 M0 breast cancer received a periareolar injection of SNZ to identify SNZ-enhanced SLNs (SNZ-SLNs), followed by SLN biopsy with blue dye. The lymphatic drainage patterns were classified into four types: type A, single lymphatic route/single SLN; type B, multiple lymphatic routes/single SLN; type C, single lymphatic route/multiple SLNs; and type D, multiple lymphatic routes/multiple SLNs. SLNs were successfully identified in all patients using both blue dye and SNZ. The drainage lymphatic pathways identified were as follows: type A in 53 cases (70.7%), type B in seven (9.3%), type C in eight cases (10.7%) and type D in seven (9.3%). SNZ-SLN biopsy is a technically simple method with a 100% identification rate, enabling the real-time visualization of lymphatic flow to SNZ-SLNs.

Shimazu K ，Miyake T ，Tanei T ，Naoi Y ，Shimoda M ，Kagara N ，Kim SJ ，Noguchi S ... -  《-》

Comparative study of two contrast agents for intraoperative identification of sentinel lymph nodes in patients with early breast cancer.

The use of contrast-enhanced ultrasound (CEUS) to locate sentinel lymph nodes (SLNs) in breast cancer has been studied more and more in recent years. This prospective study aimed to compare periareolar injection of two different contrast agents, SonoVue® (SNV) and Sonazoid® (SNZ), followed by CEUS to identify SLNs in breast cancer patients with clinically negative nodes. A total of 205 patients with T1-2N0M0 breast cancer were divided into the SNV group and SNZ group. All were administered a periareolar injection of SNV or SNZ and underwent US to identify contrast-enhanced SLNs. Each contrast-enhanced SLN underwent a biopsy with blue dye and examined again by CEUS in vitro. In all cases, contrast-enhanced lymphatic vessels were clearly visualized using US soon after the periareolar injection of SNZ, and the SLNs were easily identified. The SLN identification rates were 75.27% (210/279) for SNV and 93.58% (102/109) for SNZ. Although the accuracy of detecting SLN metastasis was slightly different between the two groups, there was no statistically significant difference between those groups (P=0.615). Moreover, it was possible to identify SLNs in vitro in the SNZ group, and these could be compared with the lymph nodes (LNs) located using SNZ during the preoperative stage and with blue dye during the procedure. This helped in determining the resection requirements. When comparing the subdermal use of SNV and SNZ, no significant differences in the number of detected SLNs and the diagnosis of metastatic LNs were observed. Because SLNs can be detected for a longer time in living tissues with SNZ, this contrast agent may provide more intraoperative information for complete resection of all preoperative localization of SLN.

Sun Y ，Cui L ，Wang S ，Shi T ，Hao Y ，Lei Y ... -  《-》

Percutaneous Sonazoid-enhanced ultrasonography combined with in vitro verification for detection and characterization of sentinel lymph nodes in early breast cancer.

To assess the efficacy of percutaneous Sonazoid-enhanced ultrasound and in vitro verification for identification sentinel lymph nodes (SLNs) and diagnosis of metastatic SLNs in patients with early breast cancer (BC). Sixty-eight patients with early BC were enrolled finally. After the induction of general anesthesia, 0.4 ml of Sonazoid (SNZ), a new second-generation tissue-specific ultrasound contrast agent (UCA), mixed with 0.6 ml of methylene blue, was injected intradermally. The lymphatic vessels and connected SLNs were immediately observed and marked. After being resected, these SLNs were soaked in saline water and examined still in the mode of contrast-enhanced ultrasound (CEUS) in vitro. This procedure could ensure that all the enhanced nodes had been removed as much as possible. The numbers of SLNs detected by UCA and blue dye were recorded. The enhancement patterns of SLNs were compared with the final pathological results. SLNs detection rate by SNZ-CEUS was 100%, which was higher than that by blue dye (95.59%). CEUS identified a median of 1.5 nodes, while blue dye identified a median of 1.9 nodes per case (p = 0.0012). When homogeneous high perfusion and complete annular high perfusion were regarded as negative nodes, the sensitivity and negative predictive value were 92.31% and 96.79% respectively, while the specificity was 84.21%. Percutaneous SNZ-enhanced ultrasonography combined with in vitro verification is a feasible and reliable method for SLNs identification intraoperatively. Enhancement patterns can be helpful in determining the status of SLNs. • CEUS with percutaneous injection of Sonazoid can successfully identify SLNs with the rate of 100% in early breast cancer patients, higher than 95.59% of blue dye. • Sonazoid, with high affinity with reticuloendothelial cells, increases the imaging time of SLNs and facilitates biopsy intraoperatively better than Sonovue as a lymphatic tracer. • Homogenous high and complete annular high perfusions have a sensitivity of 92.31% and a negative predictive value of 96.79% in the prediction of uninvolved SLNs.

Hao Y ，Sun Y ，Lei Y ，Zhao H ，Cui L ... -  《-》

Sentinel node detection method using contrast-enhanced ultrasonography with sonazoid in breast cancer: preliminary clinical study.

Omoto K ，Matsunaga H ，Take N ，Hozumi Y ，Takehara M ，Omoto Y ，Shiozawa M ，Mizunuma H ，Harashima H ，Taniguchi N ，Kawano M ... -  《-》