title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Surgery, Maidstone and Tunbridge Wells NHS Trust, Hermitage Lane, Maidstone, Kent ME16 9QQ, United Kingdom. karina.cox@nhs.net
authors: K
authors: K
authors: Cox
authors: A
authors: A
authors: Sever
authors: S
authors: S
authors: Jones
authors: J
authors: J
authors: Weeks
authors: P
authors: P
authors: Mills
authors: H
authors: H
authors: Devalia
authors: D
authors: D
authors: Fish
authors: P
authors: P
authors: Jones
mesh_terms: D000328:Adult; D000368:Aged; D001365:Axilla / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000601:surgery; D015331:Cohort Studies; D003287:Contrast Media; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis; D008408:Mastectomy / Q000379:methods; D045423:Microbubbles; D008875:Middle Aged; D061206:Neoplasm Micrometastasis / Q000000981:diagnostic imaging / Q000473:pathology; D011300:Preoperative Care / Q000379:methods; D012016:Reference Values; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D021701:Sentinel Lymph Node Biopsy / Q000379:methods*; D018608:Ultrasonography, Doppler / Q000379:methods*
chemical_list: D003287:Contrast Media