Reihane Mahdavi1, Narges Yousefpour1, Fereshteh Abbasvandi2, Hossein Ataee3, Parisa Hoseinpour4, Mohammad Esmaeil Akbari5, Mohammad Parniani6, Belal Delshad5, Maryam Avatefi5, Zeinab Nourinejad6, Saeed Abdolhosseini1, Sajad Mehrvarz1, Farzane Hajighasemi1, Mohammad Abdolahad7. 1. 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. 2. 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. 3. 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; School of Electrical and Computer Engineering, Faculty of Engineering, Amirkabir University of Technology, Tehran, P.O. BOX 1591634311, Iran. 4. 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; SEPAS Pathology Laboratory, P.O.Box: 1991945391, Tehran, Iran. 5. Cancer Research Center, Shahid Beheshti University of Medical Sciences, P.O. BOX 15179/64311, Tehran, Iran. 6. Pathology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, P.O. BOX 15179/64311, Tehran, Iran. 7. 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; Cancer Institute, Imam-Khomeini Hospital, Tehran University of Medical Sciences, P.O. BOX 13145-158, Tehran, Iran. Electronic address: m.abdolahad@ut.ac.ir.
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 parameter(Yn') 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.
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 parameter(Yn') 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.