Ultrasonographic Axillary Localization

Study Overview
=================
Brief Summary
-----------------
Breast cancer is the most common cancer of women. Surgery for early breast cancer includes axillary lymph nodes staging. Axillary surgery may lead to intractable complications like permanent arm swelling. Axillary sentinel lymph node biopsy (SLNB) has been introduced to minimize the incidence of these complications. Several methods are routinely used for identification of the sentinel node during operation. Some of these methods necessitate facilities that are not universally available; specially in countries with limited resources. In its simplest form, SLNB using the methylene blue dye technique has an identification rate of 88-94%. If the sentinel node can not be identified, full axillary dissection may be required and the risk of arm swelling is increased. The objective of this study is to maximize the identification rate of the sentinel node thus avoiding the need for extensive axillary surgery. The investigators assumed that preoperative tattooing of the suspicious lymph node during ultrasonographical imaging may help the surgeon in localizing the sentinel lymph node. In this study, the sonographer will perform preoperative tattooing of the suspicious node. The surgeon will perform SLNB by the methylene blue dye. The sensitivity of ultrasonographical tattooing relative to SLNB will be calculated. The study will determine if the tattooing technique may localize additional nodes that are missed by the methylene blue.

Detailed Description
-----------------
Introduction Axillary nodal staging is an integral part of breast cancer management. Sentinel lymph node biopsy (SLNB) has become a standard of care in patients with clinically negative axillae. Various methods have been investigated to decrease the false negative rate of SLNB. Ultrasonography is an established tool for preoperative axillary staging. The diagnostic accuracy of B-mode ultrasonographic criteria and of US-guided FNAC (Fine Needle Aspiration Cytology) has been described in the literature and its role in preoperative axillary staging has been emphasized. Ultrasonographic aspiration of suspicious axillary nodes are widely used to identify axillary metastases and obviate the need for SLNB. Previous studies retrospectively examined the concordance of ultrasonographic identification of suspicious lymph nodes with subsequent SLNB results. However, ultrasonographic axillary staging have not been prospectively compared to SLNB. In addition, concomitant ultrasonographic and SLNB are thought to increase the overall accuracy of axillary staging. In this study, the investigators will perform preoperative ultrasonographic axillary evaluation and tattooing of suspicious lymph nodes followed by SLNB with methylene blue technique. Head-to-head and node-to-node comparison of ultrasonographic and surgical staging will be conducted. Specific aims Determination of the diagnostic accuracy of preoperative ultrasonic guided tattooing of suspicious axillary lymph nodes. Determination of node-to-node concordance of ultrasonographic tattooing relative to blue dye SLNB.

Official Title
-----------------
Diagnostic Accuracy of Preoperative Ultrasonographic Tattooing of Suspicious Axillary Lymph Nodes in Breast Cancer Patients With Clinically Negative Axilla. A Prospective Cohort Study.

Conditions
-----------------
Breast Neoplasm

Intervention / Treatment
-----------------
* Diagnostic Test: Ultrasonographical tattooing of suspicious axillary lymph nodes.
* Procedure: Sentinel lymph node biopsy
* Diagnostic Test: Histopathological examination of the axillary nodes
* Procedure: Further axillary management


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Biopsy-proven invasive breast adenocarcinoma. Clinically non palpable axillary lymph nodes. T0-3, N0, M0 Scheduled for definitive surgery. Exclusion Criteria: Patient unwilling to participate. Contraindication to methylene blue technique: hypersensitivity, pregnancy. T4 primary tumor. Previous axillary surgery.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-sentinel node biopsy ultrasonographical tattooing<br>Preoperative ultrasonographical tattooing of the suspicious lymph nodes. Sentinel Lymph Node Biopsy (SLNB), | Diagnostic Test: Ultrasonographical tattooing of suspicious axillary lymph nodes.<br>* Patients with clinically negative axillae scheduled for sentinel lymph node biopsy (SLNB) will have axillary ultrasonographical imaging of the ipsilateral axilla with a high-frequency linear probe. Suspicious lymph nodes are identified according to any of the following criteria: Round shape. Cortical thickness > 3 mm Eccentric cortical thickness. Loss of hilum. For each patient, node dimensions and the presence of each of the above-mentioned criteria are recorded. Tattooing of all suspicious nodes is done using I ml of sterile liquid charcoal.<br>Procedure: Sentinel lymph node biopsy<br>* Sentinel node biopsy is performed with peri-areolar subdermal injection of 3 ml methylene blue 5%. The lymphatics are tracked to the first blue lymph node. All blue, enlarged and /or tattooed nodes are separately biopsied and labelled as SLN and/or tattooed node.<br>Diagnostic Test: Histopathological examination of the axillary nodes<br>* All tattooed nodes are excised and sent to frozen section examination; labelled tattoo node. All enlarged or blue stained nodes are excised and sent to frozen section examination; labelled sentinel node. All nodes are bisected and a single 5 um section examined. All frozen section examinations are followed by routine paraffin section examination.<br>Procedure: Further axillary management<br>* Further axillary management is performed as per institutional guidelines. If SLNB is negative, no further surgery is required. Axillary lymph node dissection is performed if sentinel lymph node is positive or not identified. Management of positive SLNB as per the American College Of Surgeons' Oncology Group (ACOSOG) Z0011 protocol is not currently adopted on routine basis at the investigators' institution. In this study, patients with tattooed nodes with positive histopathological findings are offered full axillary dissection even if their sentinel nodes are negative.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of ultrasonographical tattooing | The ratio of the tattooed lymph nodes (that are positive by histopathological examination) to the sentinel lymph nodes (that are positive by histopathological examination). | at the date of surgery. | 
| Identification benefit of the ultrasonographical tattooing. | The ratio of the cases with successfully tattooed nodes and non identified sentinel node to the total number of analyzed cases. | at the date of surgery. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
sentinel lymph node biopsy, Axillary ultrasonography