Colorectal Cancer Metastatic, General Anesthetics Toxicity, Lymphocyte Destruction, Molecular Mechanism of Pharmacological Action, Survival Rate
Conditions
Keywords
Intravenous anesthesia, Inhalational anesthesia, Colorectal cancer resection, Lymphocytes, Metastasis, Survival, Molecular mechanism
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.
Interventions
DRUGPropofol
Propofol will be used for anesthesia maintenance in the total intravenous anesthesia group.
DRUGSevoflurane
Sevoflurane will be used for anesthesia maintenance in the inhalation anesthesia group.
DRUGRemifentanil
Remifentanil will be used for analgesia in both groups.
Sponsors
Guizhi Du
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cancer free survival | 5 years or as available | Patients who remain alive without known colonal or rectal tumor recurrence |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiotherapy rate for any cancer | up to 5 years | Patients have radiotherapy for any cancer |
| Chemotherapy rate for any cancer | up to 5 years | Patients have chemotherapy for any cancer |
| 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 |
| Cancer metastasis rate | up to 5 years | Patients who remain alive with known colonal or rectal tumor metastasis |
| Re-operation | up to 5 years | Patients who have a surgery under general anesthesia |
| 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 |
| 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. |
| Cancer recurrence rate | up to 5 years | Patients who remain alive with known colonal or rectal tumor recurrence |
| Anesthesia scheme for re-operation | up to 5 years | Total intravenous anesthesia, inhalational anesthesia or combined anesthesia |
Other
| Measure | Time frame | Description |
|---|---|---|
| Re-operation during hospitalization | From end of colorectal cancer resection surgery to discharge, up to one month | Patients receive a reoperation for any reason during hospitalization |
| Days of hospitalization | From end of colorectal cancer resection surgery to discharge, up to one month | The duration of patients stay in hospital |
Countries
China
Contacts
Primary ContactGuizhi Du, MD, PhD
Backup ContactJin Liu, MD, PhD
Outcome results
None listed