Sentinel node identification using microbubbles and contrast-enhanced ultrasonography

Sentinel lymph node (SLN) biopsy has become the recommended method for surgical staging of the axilla in patients with breast cancer. Grey-scale axillary ultrasonography (US) combined with US-guided biopsy is a widely used preoperative staging procedure but has limited sensitivity. US contrast agent “microbubbles”, when injected intradermally, have been shown to have the potential to enter the breast lymphatics, travel rapidly to the axilla, and visualize the putative SLNs. This review illustrates the SLN identification technique using intradermal injection of microbubbles and contrast-enhanced US. The injection method, lymphatic visualization techniques, grey-scale and contrast-enhanced US images of the putative SLNs are reviewed and exemplified.

Introduction

Axillary lymph node status remains the most important prognostic factor in patients with breast cancer and aids therapeutic decisions regarding adjuvant treatment.¹ Axillary staging was traditionally performed by a formal, full axillary lymph node dissection (ALND). However, this operation has a significant associated morbidity, including persistent axillary seroma formation, lymphoedema of the ipsilateral arm, loss of sensation in the upper arm, neuropathy, and shoulder stiffness. Sentinel lymph node (SLN) biopsy has emerged as an alternative approach for staging the axilla. Those patients with uninvolved SLNs can be spared unnecessary axillary clearance, while patients with histopathologically proven metastatic SLNs require surgery to complete a full clearance, i.e., completion ALND.

The role of preoperative ultrasonography (US) of the axilla has proven to be effective in predicting axillary status and US-guided biopsy of suspicious nodes has been shown to be highly specific for the evaluation of the axillary nodes.² Several papers also reported the limitations of grey-scale US that a normal axillary US would miss involved axillae in approximately one in four cases.3, 4

Contrast-enhanced US with intravenous administration of contrast agents has the capacity to show the microvasculature and perfusion of various parenchyma and tumours.⁵ Microbubble contrast agents are composed of tiny bubbles of an injectable gas in a supporting membrane. In an experimental study, Goldberg et al.⁶ showed that microbubbles administered peritumourally in a swine melanoma model were seen to enter lymphatic channels and SLNs were identified accurately by sonography in 90% of cases.

In 2008, in Maidstone Hospital (Kent, UK), a prospective study was approved by the local ethics committee and the Medicine and Healthcare Products Regulatory Agency. Consecutive consenting patients undergoing SLN biopsy received an intradermal injection of microbubbles prior to surgery. The validation results have shown that, with the use of contrast-enhanced US and microbubbles, SLNs were correctly identified in 89% of breast cancer patients.⁷ After the validation period, all microbubble identified presumed SLNs were subjected to a needle biopsy and a recent audit has shown the completion ALND rate fell to 8%, having been 21% prior to the use of microbubbles.⁸ To date more than 450 microbubble procedures have been performed. The purpose of this review is to explain the microbubble technique in the identification of SLN and to share our initial experience with this procedure.