Validation of a technique using microbubbles and contrast enhanced ultrasound (CEUS) to biopsy sentinel lymph nodes (SLN) in pre-operative breast cancer patients with a normal grey-scale axillary ultrasound.

In patients with breast cancer, grey-scale ultrasound often fails to identify lymph node (LN) metastases. We aimed to validate the technique of contrast-enhanced ultrasound (CEUS) as a test to identify sentinel lymph node (SLN) metastases and reduce the numbers of patients requiring a completion axillary node clearance (ANC). 371 patients with breast cancer and a normal axillary ultrasound were recruited. Patients received periareolar intra-dermal injection of microbubble contrast agent. Breast lymphatics were visualised by CEUS and followed to identify and biopsy axillary SLN. Patients then underwent standard tumour excision and either SLN excision (benign biopsy) or axillary clearance (malignant biopsy) with subsequent histopathological analysis. The technique failed in 46 patients, 6 patients had indeterminate biopsy results and 24 patients were excluded. In 295 patients with a conclusive SLN biopsy, the sensitivity of the technique was 61% and specificity 100%. Given a benign SLN biopsy result, the post-test probability that a patient had SLN metastases was 8%. 35 patients were found to have SLN metastases and had a primary ANC (29 macrometastases and 6 micrometastases/ITC). There were 22 false negative results (10 macrometastases and 12 micrometastases). Macrometastases in core biopsy specimens correlated with LN macrometastases on surgical excision. Pre-operative biopsy of SLN reduced the numbers of patients requiring completion ANC. Despite the low sensitivity, only 22 patients (8%) with a benign SLN biopsy were subsequently found to have LN metastases. Without the confirmation of macrometastases on core biopsy specimens, patients with micrometastases/ITC may be inadvertently selected for primary ANC.

Cox K ，Sever A ，Jones S ，Weeks J ，Mills P ，Devalia H ，Fish D ，Jones P ... -  《-》

Contrast-Enhanced Ultrasound Biopsy of Sentinel Lymph Nodes in Patients with Breast Cancer: Implications for Axillary Metastases and Conservation.

Cox K ，Weeks J ，Mills P ，Chalmers R ，Devalia H ，Fish D ，Sever A ... -  《-》

Enhanced pre-operative axillary staging using intradermal microbubbles and contrast-enhanced ultrasound to detect and biopsy sentinel lymph nodes in breast cancer: a potential replacement for axillary surgery.

Cox K ，Taylor-Phillips S ，Sharma N ，Weeks J ，Mills P ，Sever A ，Lim A ，Haigh I ，Hashem M ，de Silva T ，Satchithananda K ，Tang M ，Wallis M ... -  《-》

One Step Nucleic Acid Amplification (OSNA) positive micrometastases and additional histopathological NSLN metastases: Results from a single institution over 53 months.

The role of sentinel lymph node micrometastases on histopathological analysis is controversial in axillary staging and management in clinically node negative breast cancer. Long-term studies addressing the clinical relevance of occult breast cancer in sentinel lymph nodes based on molecular analysis are lacking. One Step Nucleic Acid Amplification (OSNA), a highly sensitive assay of cytokeratin 19 mRNA, is used intra-operatively for the detection of lymph node macro- and micrometastases in breast cancer. The aim of this study is to review the rate of micrometastases and further histopathological NSLN metastases, in our unit following the introduction of OSNA in Guildford. Data was collected prospectively from the period of introduction 01/12/2008 to 31/05/2013. All patients eligible for sentinel lymph node biopsy were offered OSNA and operations were performed by the consultant breast surgeons. Presence or absence of micro-metastases depends on the agreed cut-off point on the amplification curve. On detection of micrometastases (+) and positive but inhibited (i+) metastases, a level 1 axillary clearance (ANC) was performed and for a macrometastasis (++), a level 3 ANC was carried out. 66% of the patients had negative SLN (n = 672) and 34% (n = 336) had positive sentinel lymph nodes who had further axillary surgery. Of these, 45% (n = 152/336) had macrometastases, 40% (n = 136/336) had micrometastases and 15% (48/336) had positive but inhibited results. There was no difference in the patient demographics and tumour characteristics in the various positive SLN groups. In patients with micrometastases, 15% (20/136) had further positive NLSNs and a further 6% (8/136) had >4 overall positive nodes (SLN + NSLN) thus requiring adjuvant supraclavicular/chest wall radiotherapy (p < 0.05). 25% of node positive patients had further NLSN metastases (85/336) and in these patients, the ratio of positive SLN/harvested SLN (+SLN/SLN) is constant at 1:1. This shows the likelihood of further positive NSLNs if all the harvested lymph nodes are positive. This linear trend is present in both micro-and macrometastases, thus correlating with the size and number of NSLN metastases. Our study reflects the tumour burden of NSLNs based on the molecular analysis of the SLN. OSNA has the potential to accurately identify axillary micrometastases. Micro-metastases are important as some of the patients with micrometastases had overall four positive nodes [SLN + NSLN] (criteria for radiotherapy in the absence of other adverse clinicopathological features). Also, our study highlights certain factors that predict the NSLN metastases, pending validation by further prospective long-term data. This will allow accurate calculation of the axillary tumour burden, particularly in patients with micro-metastases.

Babar M ，Madani R ，Jackson P ，Layer GT ，Kissin MW ，Irvine TE ... -  《SURGEON-JOURNAL OF THE ROYAL COLLEGES OF SURGEONS OF EDINBURGH AND IRELAND》

Does Contrast Enhanced Ultrasound (CEUS) of Normal/Benign Axillary Lymph Nodes in Patients with Breast Cancer Identify Significant Axillary Nodal Burden?

Contrast enhanced ultrasound (CEUS) of the axilla allows preoperative identification and biopsy of the sentinel lymph node. Our aims were to evaluate the accuracy of the CEUS procedure for identifying axillary lymph node metastases preoperatively and compare the volume of axillary metastases in patients with malignant versus benign CEUS guided core biopsy at end of primary surgical treatment. Retrospective analysis of prospectively collected data on patients with breast cancer with normal axillary ultrasound or benign axillary FNAC undergoing preoperatively CEUS guided sentinel lymph node biopsy between 2013 and 2018. SLN was successfully identified by CEUS in 186 (90.7%) of patients with definitive diagnosis obtained in 163 (87.6%). Overall sensitivity was 55.77%, but significantly higher for high volume disease (77.78%) than for low volume disease (32.00%, odds ratio = 7.44, 95% CI = 2.16 to 25.62, p = .001) Specificity was 100%. NPV was 82.84% overall, 86.72% for low volume disease and 94.87 % for high volume disease. 72.4% of patients with initial malignant CEUS guided SLN core biopsy had two or more macrometastases at end of surgical treatment compared to 4.47% of patients with initial benign CEUS guided core biopsy. When disease was present, CEUS guided sentinel lymph node core biopsy identify nodal metastases in 55.77% of patients with normal axillary grey scale ultrasound. This study suggests that the likelihood of extensive axillary disease at end of surgical treatment is low with an initial benign CEUS guided SLN core biopsy.

Nielsen Moody A ，Cox K ，Haigh I ，Chen Y ，Sharma N ... -  《-》