Reihane Mahdavi

Immune checkpoint inhibitors (ICIs) have revolutionized cancer immunotherapy by enhancing T-cell-mediated anti-tumor responses in solid malignancies. However, their efficacy is often limited by tumor-specific factors, T-cell dysfunction in cold tumors, or in the presence of lymph node metastasis (LNM). Moreover, clinical trials indicate no significant survival advantage of sentinel lymph node biopsy (SLNB) over no lymph node surgery in early-stage cancers, highlighting the need for novel combinatorial approaches to improve treatment outcomes. Tumor electrochemotherapy (ECT) can overcome immunosuppressive barriers in the tumor microenvironment by applying high electric fields that create transient micropores in cell membranes. This allows the enhanced uptake of chemotherapeutic drugs, resulting in increased cytotoxicity and the release of damage-associated molecular patterns (DAMPs). This triggers immunogenic cell death (ICD), a process that signals immune cells to attack cancer and promotes tumor regression. Considering advancements in lymphatic-targeted therapies and the immunostimulatory potential of uninvolved tumor-draining lymph nodes (TDLNs), TDLN-targeted ECT may act as an in situ cancer vaccination, activating immune cells within TDLNs through the release of DAMPs and serving as a hub to orchestrate systemic anti-tumor immunity. In patients with negative preoperative lymph node assessments, this approach may preserve lymph node integrity and lymphatic drainage while eradicating tumor cell colonies. When applied as neoadjuvant therapy before any TDLN treatment, TDLN-targeted ECT may leverage higher tumor-associated antigen loads, foster persistent immune memory, and reduce the risk of post-operative immune evasion.

Background: The primary objective of this research is to propose an intra-operative tumor detection probe calibrated on human models of gastrointestinal (G.I.) cancers, enabling real-time scanning of dissected masses. Methods: Electrical Gastrointestinal Cancer Detection (EGCD) measures impedimetric characteristics of G.I. masses using a handpiece probe and a needle-based head probe. Impedance Phase Slope (IPS) and impedance magnitude (Z1kHz) are extracted as the classification parameters. EGCD was tested on palpable G.I. masses and compared to histopathology results. Results: Calibration was carried out on 120 GI mass samples. Considering pathological results as the gold standard, most cancer masses showed Z1kHz between 100 Ω and 2500 Ω while their IPS was between −15 and −1. The EGCD total sensitivity and specificity of this categorization in G.I. cancer patients with palpable tumors were 86.4% and 74.4%, respectively (p-value < 0.01). Conclusion: EGCD scoring can be used for 3D scanning of palpable tumors in G.I. tumors during surgery, which can help clarify the tumors’ pathological response to neoadjuvant chemotherapy or the nature of intra-operative newly found G.I. tumors for the surgeon to manage their surgical procedure better.

A gigahertz (GHz) range antenna formed by a coaxial probe has been applied for sensing cancerous breast lesions in the scanning platform with the assistance of a suction tube. The sensor structure was a planar central layer and a metallic sheath of size of 3 cm² connected to a network analyzer (keySight FieldFox N9918A) with operational bandwidth up to 26.5 GHz. Cancer tumor cells have significantly higher water content (as a dipolar molecule) than normal breast cells, changing their polarization responses and dielectric losses to incoming GHz-based stimulation. Principal component analysis named S₁₁, related to the dispersion ratio of the input signal, is used as a parameter to identify malignant tumor cells in a mouse model (in vivo) and tumor specimens of breast cancer patients (in vitro) (both central and marginal parts). The results showed that S₁₁ values in the frequency range from 5 to 6 GHz were significantly higher in cancer-involved breast lesions. Histopathological analysis was the gold standard for achieving the S₁₁ calibration to distinguish normal from cancerous lesions. Our calibration on tumor specimens presented 82% positive predictive value (PPV), 100% negative predictive value (NPV), and 86% accuracy. Our goal is to apply this system as an in vivo non-invasive tumor margin scanner after further investigations in the future.

Precise diagnosis of thyroid nodules is challenging due to non-diagnostic/inconclusive results and uncertainties about the malignancy of follicular neoplasms (FNs), even in frozen-section pathology. Therefore, surgical management, especially in Bethesda III and IV categories, may be complicated, and sometimes a second surgery may be required. The Thyroid Nodule Impedance Measurement System (TN-IMS) consists of a metallic patch attached to submental skin and a G20 I.V. cannula inserted into the targeted nodules. Two impedance-based parameters named Z_1kHz and impedance phase slope (IPS) in 100 kHz to 500 kHz of the thyroid nodules are recorded and compared with their histopathological results as the gold standard. TN-IMS was intra-surgically applied to 103 human thyroid nodules and normal thyroid tissues. A remarkable consistency between defined co-ranges of Z_1kHz/IPS and the histopathological status of specimens was achieved (p < 0.001). Based on these measurements, it was concluded that intraoperative bioelectrical impedance scanning of thyroid nodules would be a helpful complementary approach to detecting high-risk excision-required thyroid nodules.