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

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

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.

Study Overview

• Status: Unknown
• Conditions: Programmed Cell Death 1
• Intervention / Treatment: Procedure: Thoracic Paravertebral block

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 Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: shereen M kamal, assocate professor; Phone Number: 01006279209; Email: sheridouh79@yahoo.com
• Study Contact Backup: Name: Hassan I Kotb, professor; Phone Number: 01287332042; Email: kotbhi@yahoo.com

Study Locations

• Egypt
  • Assiut, Egypt, 11715
    • Recruiting
    • South Egypt Cancer Institute
    • Contact: Hassan M Kotb, Professor; Email: kotbhi@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: control group; 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; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): November 1, 2021

Study Registration Dates

• First Submitted: November 17, 2020
• First Submitted That Met QC Criteria: December 5, 2020
• First Posted (Actual): December 8, 2020

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 5, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: brest cancer; programmed cell death1; programmed cell death ligand 1
• Additional Relevant MeSH Terms: Pathologic Processes; Death
• Other Study ID Numbers: 359

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No