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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Anesthesia and Surgical Stress on the Expression of Programmed Death-1 and Programmed Death-1 Ligand on T Lymphocyte After Breast Cancer Surgeries

Conditions
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Programmed Cell Death 1

Intervention / Treatment
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* Procedure: Thoracic Paravertebral block


Participation Criteria
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Eligibility Criteria
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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 .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: control group<br>all patients will receive general anesthesia and will receive intravenous paracetamol (1 g) before skin closure and then given every 6 hrs in the 1st postoperative day | |
| Active Comparator: TPVB group<br>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. | Procedure: Thoracic Paravertebral block<br>* TPVB will be given using high frequency linear U/S transducer, place the U/S ultrasound probe was placed parallel to the vertebral spine at T4, and, T6 level and shifted 2-3 cm laterally to obtain the appropriate visualization. Following the identification of pleura, transverse process and paravertebral space, the needle was inserted in caudocranial direction using in-plane approach. Confirm negative vessel or pleural breach via aspiration then proceed with local anaesthetic 0.25% bupivacaine (20 ml) delivery slowly divided equally at T4and T6; the pleura will be seen to be pushed downward<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in level of PD1 and PD1 ligand postoperatively | 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. | preoerative (day-0),1st day, and 3 rd day after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total request of analgesia | the total amount of analgesia (paracetamol) will be recorded and calculated | 24 hours postoperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brest cancer, programmed cell death1, programmed cell death ligand 1