Clinical trial NCT03193710: The Effects of General Anesthetics on Lymphocytes in Patients Undergoing Colorectal Cancer Resection and Mechanism Involved
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Colorectal Cancer Metastatic
Survival Rate
General Anesthetics Toxicity
Lymphocyte Destruction
Molecular Mechanism of Pharmacological Action
Keywords: Intravenous anesthesia
Inhalational anesthesia
Colorectal cancer resection
Lymphocytes
Metastasis
Survival
Molecular mechanism
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2017-06-21
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with colonal or rectal cancer undergoing cancer resection with general anesthesia

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline lymphocytes within postoperative 5 years
timeFrame: up to 5 years
measure: Cancer free survival
timeFrame: 5 years or as available
Secondary outcomes:
measure: Cancer recurrence rate
timeFrame: up to 5 years
measure: Cancer metastasis rate
timeFrame: up to 5 years
measure: Re-operation
timeFrame: up to 5 years
measure: Anesthesia scheme for re-operation
timeFrame: up to 5 years
measure: Radiotherapy rate for any cancer
timeFrame: up to 5 years
measure: Chemotherapy rate for any cancer
timeFrame: up to 5 years
measure: Circulating tumor cells
timeFrame: up to 5 years
measure: Concentration of cytokines
timeFrame: up to 5 years
measure: Colorectal cancer antibodies
timeFrame: up to 5 years
Other outcomes:
measure: Re-operation during hospitalization
timeFrame: From end of colorectal cancer resection surgery to discharge, up to one month
measure: Days of hospitalization
timeFrame: From end of colorectal cancer resection surgery to discharge, up to one month
Locations:
city: Chengdu
country: China
facility: West China Hospital of Sichuan University, Department of Anesthesiology
state: Sichuan
Study officials:
affiliation: Department of Anesthesiology, West China Hospital
name: Jin Liu, MD, PhD
role: STUDY_CHAIR
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