Nano Bioelectronics Devices Lab, Cancer Electronics Research Group, School of Electrical and Computer Engineering, Faculty of Engineering, University of Tehran, Tehran, P.O. Box 14395/515, Iran Nano Electronic Center of Excellence, Nano Bio Electronics Devices Lab, School of Electrical and Computer Engineering, University of Tehran, Tehran, P.O. Box 14395/515, Iran ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, P.O. BOX 15179/64311, Tehran, Iran School of Electrical and Computer Engineering, Faculty of Engineering, Amirkabir University of Technology, Tehran, P.O. BOX 1591634311, Iran SEPAS Pathology Laboratory, P.O.Box: 1991945391, Tehran, Iran Cancer Research Center, Shahid Beheshti University of Medical Sciences, P.O. BOX 15179/64311, Tehran, Iran Pathology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, P.O. BOX 15179/64311, Tehran, Iran Cancer Institute, Imam-Khomeini Hospital, Tehran University of Medical Sciences, P.O. BOX 13145-158, Tehran, Iran.
Int J Surg. 2021 Dec;96:106166. doi: 10.1016/j.ijsu.2021.106166. Epub 2021 Nov 9.
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.
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 (Z) 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 parameter(Y) also proposed for LN detection in neoadjuvant chemotherapy patients.
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 Z 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.
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.
淋巴结状态评估是确定乳腺癌患者预后因素和管理治疗策略的关键步骤。术前（CNB）、术中（SLNB）甚至术后技术（福尔马林固定石蜡包埋切片，FFPE）在精确性方面都有一定的局限性，或者有时结果宣布需要花费很长时间。这项前瞻性研究的主要目的是为乳腺癌患者术中区分癌性细胞浸润的淋巴结（LNs）提供一种精确的补充系统。
所提出的系统，即电淋巴评分（ELS），是基于待测试 LNs 的介电特性设计的。该系统具有针状的 2 电极探头，通过标准手术指南插入从患者中解剖出来的 SLNs 或 ALNs。在 77 名接受过手术的乳腺癌患者（共 282 个解剖 LNs）的队列研究中，从阻抗谱数据中提取了频率范围为 100 kHz-500 kHz 时的阻抗幅度（Z）和阻抗相位斜率（IPS）（n=55 例在化疗前，n=22 例在化疗后）。还为新辅助化疗患者的 LN 检测提出了一个新的导纳参数（Y）。
以两位独立的病理专家检查的永久病理结果为金标准，观察到 LNs 中存在癌性细胞与 ELS 电响应的个体范围之间存在显著相关性。与含有脂肪环境和免疫细胞的正常 LNs 相比，癌性簇浸润的 LNs 会降低 Z 值并增加 IPS。这些变化与癌细胞的脂肪代谢有关，因为癌细胞在 LN 中进行脂肪酸氧化（FAO），导致正常和癌性 LNs 的高、低脂肪含量之间具有不同的介电特性。
通过找到我们定义的阻抗参数与测试 LNs 的病理状态之间的最佳相关性，开发了一种用于高灵敏度（92%，P<0.001）检测术中前哨或腋窝 LNs 的实时术中检测方法。实时术中 SLN 评分的影响将有助于外科医生进行更少侵入性的手术，特别是在没有冷冻切片设备的情况下，对进一步切除 LNs 的必要性进行预评估。
