Modulation of the circulation of tumor cells and cytokines after neuroaxis anesthesia in an experimental model of prostate cancer

Author(s)

Gustavo Noboru Cavallari Inoue

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2023-03-07

Examining board members

Sabrina Thalita dos Reis Faria; Mauricio Dener Cordeiro; Katia Ramos Moreira Leite; Daniel Perin

• Advisor: Sabrina Thalita dos Reis Faria

Abstract

Introduction: Despite being one of the treatment options for localized prostate cancer (PC), radical prostatectomy can cause damage and homeostatic changes in patients. The surgical insult causes neurohumoral alterations in the body that change the production of cytokines responsible for activating innate immunity cells that are important in the defense against potential metastatic cells. In this context, the anesthetic technique may play an important role in oncologic surgeries. The relationship between different types of anesthesia and oncological outcomes has been studied in different cancers, and regional anesthesia seems to be advantageous in oncological surgeries as it has a protective effect on the perioperative systemic inflammatory response. Objectives: To compare the spread of cancer cells in the bloodstream in different groups submitted to combined anesthesia (spinal anesthesia and general anesthesia) or general anesthesia using an in vivo model of PC after surgery for subcutaneous tumor removal, as well as to analyze the pattern of expression of pro and anti-inflammatory cytokines and the amount of Natural Killer (NK) cells cells between groups. Methods: We used a subcutaneous tumor model, in male NOD/SCID mice, aged 11 weeks, with the PC-3M cell line transfected with a luciferase producing gene (PC-3M-luc-C6). Tumor growth was assessed with an in vivo bioluminescence system and with digital caliper measurements. After proper tumor establishment and before tumors become metastatic, interventions were performed. Animals were submitted to tumor excision surgeries receiving general anesthesia only or combined anesthesia. The control group was only anesthetized. Twenty-four hours after the procedures, blood samples were collected for analysis and the animals were killed. Tissues were later removed for histological analysis. Results: Our subcutaneous tumor model with PC-3M-luc-C6 cells lineage was effective in causing distant metastases after 35 days. The number of circulating tumor cells in the blood of animals undergoing combined anesthesia were lower than the amounts found in the general anesthesia group (p=0.015). We also observed that interleukin 6 levels were different in all groups, with a considerable increase in the group undergoing general anesthesia. Conclusions: Our results suggest that the combination of spinal and general anesthesia can reduce the amount of tumor cells circulating in the blood in the postoperative period. Furthermore, the change in serum levels of interleukin 6 suggests that combined anesthesia alters the neuroendocrine response to surgical trauma (AU)

• FAPESP's process: 19/16459-9 - Analysis of neuraxial anesthesia and the prognosis of Prostate Cancer
• Grantee: Gustavo Noboru Cavallari Inoue
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)