Effect of Anesthesia on Expression of Programmed Death-1 and Programmed Death-1 Ligand in Breast Cancer

Not Applicable

• Conditions: Programmed Cell Death 1
• Interventions: Procedure: Thoracic Paravertebral block

• Registration Number: NCT04657237
• Lead Sponsor: Assiut University

Brief Summary

Surgery is first-line treatment for solid tumors. However, surgical trauma-induced physiologic stress has been demonstrated to facilitate metastasis and recurrence in different types of cancer. It has been reported that the PD-1/PD-L1 pathway could be activated by surgical stress. Hence, we instigate the effect of anesthetic technique on expression of PD1 and PD1 ligand.

Detailed Description

The cellular immune response plays a central part in postoperative clearance of tumor cells. T lymphocytes and natural killer (NK) cells are two predominant cytotoxic effector cells that are the major components of antitumor immunity. In mouse models, proliferation of T lymphocytes in response to surgical trauma is defective . Programmed death-1 (PD-1) belongs to the CD28 receptor superfamily. It is an inhibitory receptor, and its expression is upregulated on activated leukocytes, resulting in an inhibited immune response. PD-1 interacts with two ligands: programmed death ligand-1 (PD-L1, also referred to as B7-H1) and programmed death ligand-2 (PD-L2, also known as B7-DC). PD-L2 is expressed mainly on activated dendritic cells (DCs) and macrophages, whereas PD-L1 is distributed widely. In addition to immune cells, some subsets of tumor cells also express PD-L1 to escape from immunosurveillance. It has been reported that the PD-1/PD-L1 pathway could be activated by surgical stress. Hence, we instigate the effect of anesthetic technique on expression of PD1 and PD1 ligand.

Study Timeline

• Study Start: 2017-01
• Study First Submitted: 2020-11-17
• Status Verified: 2020-12
• Study First Submitted QC: 2020-12-05
• Last Update Submitted: 2020-12-05
• Study First Posted: 2020-12-08
• Last Update Posted: 2020-12-08
• Primary Completion: 2021-09
• Study Completion: 2021-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 20

Inclusion Criteria

• patients scheduled for breast cancer surgery

Exclusion Criteria

• compromised immune function (such as infection with the human immunodeficiency virus, immunodeficiency, or treatment with corticosteroids, immunosuppressive drugs, or chemotherapy)
• ASA > III
• age> 70 years old.
• patients refusal to the procedure.
• Infection of the skin at or near site of needle puncture.
• Coagulopathy .
• Drug hypersensitivity or allergy to the studied drugs.
• Central or peripheral neuropthy .
• Pre-operative opoid consumption ( within 24 hours preoperative )
• Anomalies of the vertebral column .

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TPVB group	Thoracic Paravertebral block	Patients will receive total volume (20 ml) 0.25% bubivicaine divided equally at each level of T4 and T6 at thoracic paravertebral space then they will recive general anesthesia.

Primary Outcome Measures

Name	Time	Method
change in level of PD1 and PD1 ligand postoperatively	preoerative (day-0),1st day, and 3 rd day after surgery	blood sample will be withdrawn and human peripheral blood monocyte cells (PBMCs) will be separated with a Ficoll-Isopaque density gradient. Flow cytometric analyses will be carried out immediately. For ex vivo experiments, PBMCs will be cultured with Iscove's modified Dulbecco's medium (IMDM) containing 10 % human serum albumin.

Secondary Outcome Measures

Name	Time	Method
total request of analgesia	24 hours postoperative	the total amount of analgesia (paracetamol) will be recorded and calculated

Trial Locations

Locations (1)

South Egypt Cancer Institute; 🇪🇬 Assiut, Egypt