The Effects of General Anesthetics on Lymphocytes in Patients Undergoing Colorectal Cancer Resection and Mechanism Involved
- Conditions
- Survival RateLymphocyte DestructionColorectal Cancer MetastaticGeneral Anesthetics ToxicityMolecular Mechanism of Pharmacological Action
- Interventions
- Registration Number
- NCT03193710
- Lead Sponsor
- Guizhi Du
- Brief Summary
The body immunity is important to the development of tumor. The immune system is in charge of monitoring and cleaning tumor cells in circulation. Anesthesia may alter the immune response and affect the elimination of tumor cells. The purpose of the trial is to test whether inhalational anesthetic is relevant to tumor metastasis and recurrence of patients undergoing colorectal cancer resection through depression of lymphocytes-mediated immunity.
- Detailed Description
With the increasing number of patients diagnosed with colorectal cancer, the proportion of patients undergoing surgical resection with general anesthesia increased. However, the operation can lead tumor cells releasing into the blood or peritoneal implantation, and the impaired immune response can make patients susceptible to the development of tumor metastasis and recurrence which is the the main reason of death. It is well known that B lymphocytes and T lymphocytes are the main immune cells, and B lymphocytes by secreting antibodies are related to humoral immunity and T lymphocytes which play the most important role in antitumor are related to cell-mediated immunity. Surgery stress leads to metabolic and neuroendocrine changes causing significant depression of immunity. Although general anesthesia could reduce surgical stress, studies indicated general anesthetics including intravenous and inhalational agents both have variable effects on tumor cells growth by immuno-modulation and some cytokines. A number of studies have demonstrated deleterious effects on the function of lymphocytes associated with the administration of volatile inhalational anesthetic agents. It was suggested that the use of volatile inhalational agent may augment tumor cells growth by inhibiting the activity of lymphocytes, NK cells and dendritic cells which are important for recognizing, capturing and killing tumor cells, however, the alternative propofol has a converse (beneficial) effect by decreasing the plasma level of cytokines secreted by activated lymphocytes, macrophages and NK cells. The detailed mechanism of how volatile anesthetics affect the activity of antitumor cells remains unknown. Thus the investigators will conduct the clinical investigation to study the effect of volatile anesthetics on the immune response and metastasis in patients undergoing colorectal cancer resection, exploring molecular mechanism involved if inhalational anesthetics show an effect. The findings of this study would be valuable for anesthetic regimen guidance of colorectal cancer patients undergoing surgical resection in terms of long-term survival.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 260
- All the patients diagnosed with colonal or rectal cancer
- Aged 18-65
- ASA I-III
- Assigned to receive resection surgery under general anesthesia, with an expected duration of 2 hours or more
- Agree to participate and give signed written informed consent.
- Severe organic heart, liver and kidney diseases
- Diabetes or hemopoietic disorders
- Allergy to general anesthetics
- Family historical malignant hyperthermia
- Cognition dysfunction
- End-stage cancer or with over 2 cancer metastasis, pathological results were benign tumor or TNM stage was over T1- 3N0 - 2M0
- Other primary malignant tumor
- Immune deficiency or dysfunction or autoimmune disease or long-term usage of corticoids or immunosuppressants
- Receiving general anesthesia within the last 3 months before the resection surgery
- Perioperative transfusion
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Total intravenous anesthesia group Remifentanil The anesthesia of patients in the total intravenous anesthesia group will be maintained with propofol and remifentanil. Total intravenous anesthesia group Propofol The anesthesia of patients in the total intravenous anesthesia group will be maintained with propofol and remifentanil. Inhalational anesthesia group Sevoflurane The anesthesia of patients in the inhalational anesthesia group will be maintained with sevoflurane and remifentanil. Inhalational anesthesia group Remifentanil The anesthesia of patients in the inhalational anesthesia group will be maintained with sevoflurane and remifentanil.
- Primary Outcome Measures
Name Time Method Change from baseline lymphocytes within postoperative 5 years up to 5 years Blood will be drawn preoperatively ( at least 24 hours before surgery), prior to anesthesia induction, immediately postoperatively, 24 hours postoperatively, and at postoperative appointments for testing CD4+/CD8+, B lymphocytes, dendritic cells, natural killer cells
Cancer free survival 5 years or as available Patients who remain alive without known colonal or rectal tumor recurrence
- Secondary Outcome Measures
Name Time Method Radiotherapy rate for any cancer up to 5 years Patients have radiotherapy for any cancer
Cancer metastasis rate up to 5 years Patients who remain alive with known colonal or rectal tumor metastasis
Anesthesia scheme for re-operation up to 5 years Total intravenous anesthesia, inhalational anesthesia or combined anesthesia
Cancer recurrence rate up to 5 years Patients who remain alive with known colonal or rectal tumor recurrence
Chemotherapy rate for any cancer up to 5 years Patients have chemotherapy for any cancer
Colorectal cancer antibodies up to 5 years Blood will be drawn preoperatively (at least 24 hours before surgery), prior to anesthesia induction, immediately postoperatively, 24 hours postoperatively, and at postoperative appointments for testing CEA, CA199, GP87 and TPA.
Re-operation up to 5 years Patients who have a surgery under general anesthesia
Circulating tumor cells up to 5 years Blood will be drawn preoperatively (at least 24 hours before surgery), prior to anesthesia induction, immediately postoperatively, 24 hours postoperatively, and at postoperative appointments for testing circulating tumor cells
Concentration of cytokines up to 5 years Blood will be drawn preoperatively (at least 24 hours before surgery), prior to anesthesia induction, immediately postoperatively, 24 hours postoperatively, and at postoperative appointments for testing IL, TNF-α, IFN-γ and GCSF
Trial Locations
- Locations (1)
West China Hospital of Sichuan University, Department of Anesthesiology
🇨🇳Chengdu, Sichuan, China