Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Intraoperative Cryosurgical Freezing Assists with Local Drug Delivery and Targeting of Tumor Fluids in VX2 Model, which Translates in Locoregional Drug Targeting of Tumor Fluids during Cryoprobe-Assisted Surgical Resection of Breast Cancer

Version 1 : Received: 23 May 2019 / Approved: 30 May 2019 / Online: 30 May 2019 (13:44:41 CEST)

How to cite: Le Pivert, P.; Xiao, Y.; He, X.; Dronov, O.; Korpan, N. Intraoperative Cryosurgical Freezing Assists with Local Drug Delivery and Targeting of Tumor Fluids in VX2 Model, which Translates in Locoregional Drug Targeting of Tumor Fluids during Cryoprobe-Assisted Surgical Resection of Breast Cancer. Preprints 2019, 2019050370. https://doi.org/10.20944/preprints201905.0370.v1 Le Pivert, P.; Xiao, Y.; He, X.; Dronov, O.; Korpan, N. Intraoperative Cryosurgical Freezing Assists with Local Drug Delivery and Targeting of Tumor Fluids in VX2 Model, which Translates in Locoregional Drug Targeting of Tumor Fluids during Cryoprobe-Assisted Surgical Resection of Breast Cancer. Preprints 2019, 2019050370. https://doi.org/10.20944/preprints201905.0370.v1

Abstract

Background: We assess locoregional drug targeting effectiveness of intraoperative (IO) cryoprobe-assisted injection of blue dye (BD) and cytotoxic-tracer mixture (TTM), in VX2 tumor model, and its translational value to cryo-assisted breast tumor surgery with BD alone. Methods: Under computed tomography (CT) guidance, we injected two ml TTM in five aliquots in the margin of 16 frozen or normothermic VX2 tumors. We evaluated the IO and post-operative drug targeting and therapeutic efficacy in tumor-host interface (T-HI) by CT, gross examination, and histopathology. In twenty-six T1 to T4 primary breast cancer (BRCA) we performed ultrasound-guided (US) cryoprobe-assisted tumor freezing, BD guided lymphatic mapping, and surgery. We evaluated, IO and in freshly resected specimen, BD distribution pattern in T-HI, lymph node(s), breast parenchyma, and resection cavity. Results: Fluids-impervious frozen VX2 or breast tumor transported drug(s) an arc-like pattern at T-HI regardless of freeze dose, number of freeze-thaw cycles, drug dose fractionation, tumor characteristics or dimensions. During melting, TTM spread within fifty percent VX2 tumor mirrored that of T-HI; it was massive in normothermia. In VX2 twenty percent focal margin necrosis at pathology coincided with CT gap; in both studies, BD dose-staining spread in T-HI and tumor was linear. Eighty-four patients had one to twelve stained axillary lymph nodes; sixty-nine percent and all respectively, had another quadrant and resection cavity stained. Conclusion: Intraoperative freezing-assisted drug delivery and targeting techniques during cryoablation of VX2 tumor translate successfully to locoregional BD targeting, lymphatic mapping during cryo-assisted surgery of breast cancer.

Keywords

Targeted drug delivery, VX2 tumor, breast cancer, cryoablation, cryo-assisted injection, cryo-assisted resection, blue dye, epirubicin.

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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