The Effects of General Anesthetics on Lymphocytes in Patients Undergoing Colorectal Cancer Resection and Mechanism Involved

Study Overview
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Brief Summary
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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
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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.

Official Title
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Comparison of the Effects of Total Intravenous Anesthesia and Inhalation Anesthesia on Lymphocytes in Patients Undergoing Colorectal Cancer Resection and the Mechanism Involved: a Single-center, Randomized, Prospective Study

Conditions
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Survival Rate, Colorectal Cancer Metastatic, General Anesthetics Toxicity, Lymphocyte Destruction, Molecular Mechanism of Pharmacological Action

Intervention / Treatment
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* Drug: Propofol
* Drug: Sevoflurane
* Drug: Remifentanil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Total intravenous anesthesia group<br>The anesthesia of patients in the total intravenous anesthesia group will be maintained with propofol and remifentanil. | Drug: Propofol<br>* Propofol will be used for anesthesia maintenance in the total intravenous anesthesia group.<br>* Other names: Diprivan;Drug: Remifentanil<br>* Remifentanil will be used for analgesia in both groups.<br>* Other names: YiChang HumanWell Pharmaceutical Co.，LTD. China;|
| Inhalational anesthesia group<br>The anesthesia of patients in the inhalational anesthesia group will be maintained with sevoflurane and remifentanil. | Drug: Sevoflurane<br>* Sevoflurane will be used for anesthesia maintenance in the inhalation anesthesia group.<br>* Other names: Abbvie;Drug: Remifentanil<br>* Remifentanil will be used for analgesia in both groups.<br>* Other names: YiChang HumanWell Pharmaceutical Co.，LTD. China;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline lymphocytes within postoperative 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 | up to 5 years | 
| Cancer free survival | Patients who remain alive without known colonal or rectal tumor recurrence | 5 years or as available | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cancer recurrence rate | Patients who remain alive with known colonal or rectal tumor recurrence | up to 5 years | 
| Cancer metastasis rate | Patients who remain alive with known colonal or rectal tumor metastasis | up to 5 years | 
| Re-operation | Patients who have a surgery under general anesthesia | up to 5 years | 
| Anesthesia scheme for re-operation | Total intravenous anesthesia, inhalational anesthesia or combined anesthesia | up to 5 years | 
| Radiotherapy rate for any cancer | Patients have radiotherapy for any cancer | up to 5 years | 
| Chemotherapy rate for any cancer | Patients have chemotherapy for any cancer | up to 5 years | 
| Circulating tumor cells | 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 | up to 5 years | 
| Concentration of cytokines | 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 | up to 5 years | 
| Colorectal cancer antibodies | 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. | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphocytes, Intravenous anesthesia, Inhalational anesthesia, Colorectal cancer resection, Metastasis, Survival, Molecular mechanism