Intraoperative pathologically-calibrated diagnosis of lymph nodes involved by breast cancer cells based on electrical impedance spectroscopy; a prospective diagnostic human model study

Abstract

Background Nodal status evaluation is a crucial step in determining prognostic factors and managing treatment strategies for breast cancer patients. Preoperative (CNB), intraoperative (SLNB), and even postoperative techniques (Formalin-Fixed Paraffin-Embedded sectioning, FFPE) have definite limitations of precision or sometimes are time-consuming for the result declaration. The primary purpose of this prospective study is to provide a precise complementary system for distinguishing lymph nodes (LNs) involved by cancerous cells in breast cancer patients intraoperatively. Methods The proposed system, Electrical Lymph Scoring(ELS), is designed based on the dielectric properties of the under-test LNs. The system has a needle-shaped 2-electrode probe entered into SLNs or ALNs dissected from patients through standard surgical guidelines. Impedance magnitude in f = 1 kH (Z1kHz) and Impedance Phase Slope in frequency ranges of 100 kHz–500 kHz (IPS) were then extracted from the impedance spectroscopy data in a cohort study of 77 breast cancer patients(totally 282 dissected LNs) who had been undergone surgery before (n = 55) or after (n = 22) chemical therapies (non-neoadjuvant or neoadjuvant chemotherapy). A new admittance parameterSymbol also proposed for LN detection in neoadjuvant chemotherapy patients. Results Considering the permanent pathology result as the gold standard checked by two independent expert pathologists, a significant correlation was observed between the presence of cancerous cells in LNs and individual ranges of the ELS electrical responses. Compared with normal LNs containing fatty ambient and immune cells, LNs involved by cancerous clusters would reduce the Z1kHz and increase the IPS. These changes correlate with fat metabolism by cancer cells due to their Fatty Acid Oxidation (FAO) in LN, which results in different dielectric properties between high and low-fat content of normal and cancerous LNs, respectively. Conclusions By finding the best correlation between our defined impedimetric parameters and pathological states of tested LNs, a real-time intraoperative detection approach was developed for highly-sensitive (92%, P<0.001) diagnosis of involved sentinel or axillary LNs. The impact of real-time intraoperative scoring of SLNs would make a pre-estimation about the necessity of excising further LNs to help the surgeon for less invasive surgery, especially in the absence of frozen-section equipment. Graphical abstract Highlights

High-Frequency (30 MHz–6 GHz) Breast Tissue Characterization Stabilized by Suction Force for Intraoperative Tumor Margin Assessment

“…Receiver Operating Characteristic curve (ROC) analysis was used to calculate the Area Under the Curve (AUC). These two kinds of statistical analysis were widely used by our and other groups to achieve meaningful correlated results between an electrical sensing approach and gold-standard biological results such as histopathology [29][30][31]. However, other statistical methods, such as ANOVA [32,33], could be applied as an accurate method to improve the results of statistical analyses, which will be used in the next trials of this research in future.…”

Intraoperative use of electrical impedance spectroscopy for adenoid cystic carcinoma of the lacrimal gland: A case report

“…Impedimetric detection is performed using a handheld intraoperative ITDS, which extracts two classification parameters: Z1kHz (impedance magnitude at f = 1 kHz) and IPS (Impedance phase slope in the frequency range of 100 kHz–500 kHz) (Figure 3). These two parameters were previously introduced and evaluated in several projects to diagnose breast tumor margins, intraradiological breast tumor detection, and the diagnosis of involved lymph nodes in breast cancer patients 13,14 …”

“…Many previously released reports reveal that EIS can alter clinical management and improve accuracy. [12][13][14] In this regard, Svoboda et al assessed the impact of EIS results on clinicians' diagnostic accuracy and biopsy decisions. The results showed that the EIS score could lead to a change in the decision to biopsy in 25% of cases, improving diagnostic accuracy and resulting in fewer biopsies of benign lesions and more biopsies of melanomas.…”

Factors Predicting Positive Sentinel Lymph Node Biopsy in Clinically Node-Negative Breast Cancer

“… 7 Other intraoperative methods of SLN detection have been proposed such as intraoperative electrical lymph scoring (ELS) and has shown high sensitivity. 8 A number of studies have shown that SLNB is an accurate reflector of the cancer status of axillary LNs. 2 , 4 , 7 Furthermore, SLNB plays an essential role in the control and local spread of cancer in the axilla.…”