Jenny Weeks

Preoperative localization of sentinel lymph nodes using intradermal microbubbles and contrast-enhanced ultrasonography in patients with breast cancer

Sentinel lymph node (SLN) biopsy is the standard procedure for axillary staging in early breast cancer. Lymphatic imaging after intraparenchymal microbubble injection has been reported in animal models. The aim of this study was to identify and localize SLNs before surgery by contrast‐enhanced ultrasonography after intradermal injection of microbubbles in patients with breast cancer.

Axillary ultrasound assessment in primary breast cancer: an audit of 653 cases.

Abstract:  Axillary lymph node status is an important factor in determining the prognosis and treatment in patients with invasive breast cancer. The introduction of the sentinel lymph node biopsy technique in the axilla has significantly reduced the number of patients requiring an axillary clearance procedure. However, a proportion of patients will be found to have axillary metastases after a sentinel node biopsy and will then require a second axillary surgical procedure. A retrospective audit of 653 consecutive patients presenting with invasive breast cancer showed a preoperative diagnosis rate of axillary disease of 23% using axillary ultrasound and fine‐needle aspiration (FNA) together. We performed 232 axillary FNAs to diagnose 150 positive axillae. This avoided the need for a second operation in 150 women. The negative predictive value for axillary metastases using this technique was 79%. Overall accuracy was 84%.

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

BACKGROUND 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). METHODS 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. RESULTS 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. CONCLUSION 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.

Dynamic Visualization of Lymphatic Channels and Sentinel Lymph Nodes Using Intradermal Microbubbles and Contrast-Enhanced Ultrasound in a Swine Model and Patients With Breast Cancer

Objective. Sentinel lymph node (SLN) identification using intradermal micro‐bubbles and contrast‐enhanced ultrasound (CEUS) has been recently reported in swine models and patients with breast cancer. The objective of this study was to investigate the dynamics of intradermally administered microbubbles as they travel to draining SLNs in pigs. We also performed a detailed study of the passage of microbubbles through breast lymphatic channels in a small group of patients with breast cancer. Methods. Nine anesthetized healthy pigs were used for the study, and 5 female patients with primary breast cancer were recruited. Pigs received intradermal injections of a microbubble contrast agent in several territories to access lymphatic drainage to regional lymph nodes. Patients had periareolar intradermal injection of the microbubble contrast agent. Ultrasound examination was performed in the real‐time contrast pulse sequencing mode with a commercial scanner. Results. Sentinel lymph nodes were identified rapidly (<1 minute) and consistently in pigs. Intradermal microbubble injection and CEUS were found to have perfect concordance with the Evans blue dye method in locating swine SLNs. In all 5 patients with breast cancer, the microbubble contrast agent entered breast lymphatic channels and traveled to draining ipsilateral axillary SLNs within 3 minutes. Conclusions. Intradermally injected microbubbles traverse readily though lymphatic channels in pigs and human breast tissue. The ability to rapidly identify SLNs in the diagnostic period would enable targeted biopsy and may facilitate preoperative axillary staging in patients with early breast cancer.