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

Colorectal Cancer Metastatic Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03193710
• Other study ID #: WestChinaHospital
• Status: Recruiting
• Phase: N/A
• First received: June 12, 2017
• Last updated: November 1, 2017
• Start date: September 1, 2017
• Est. completion date: October 2023

Study information

• Verified date: June 2017
• Source: West China Hospital
• Contact: Guizhi Du, MD, PhD
• Phone: +8618980602213
• Email: du_guizhi[@]yahoo.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: October 2023
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer Metastatic
• Colorectal Neoplasms
• General Anesthetics Toxicity
• Lymphocyte Destruction
• Molecular Mechanism of Pharmacological Action
• Survival Rate

Intervention

Drug:
• Propofol
Propofol will be used for anesthesia maintenance in the total intravenous anesthesia group.
• Sevoflurane
Sevoflurane will be used for anesthesia maintenance in the inhalation anesthesia group.
• Remifentanil
Remifentanil will be used for analgesia in both groups.

Locations

Country	Name	City	State
China	West China Hospital of Sichuan University, Department of Anesthesiology	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
Guizhi Du

Country where clinical trial is conducted

China, 

References & Publications (10)

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Buckley A, McQuaid S, Johnson P, Buggy DJ. Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: a pilot study. Br J Anaesth. 2014 Jul;113 Suppl 1:i56-62. doi: 10.1093/bja/aeu200. Epub 2014 Jul 9. — View Citation

Jaura AI, Flood G, Gallagher HC, Buggy DJ. Differential effects of serum from patients administered distinct anaesthetic techniques on apoptosis in breast cancer cells in vitro: a pilot study. Br J Anaesth. 2014 Jul;113 Suppl 1:i63-7. doi: 10.1093/bja/aet581. Epub 2014 Jul 9. — View Citation

Möller Petrun A, Kamenik M. Bispectral index-guided induction of general anaesthesia in patients undergoing major abdominal surgery using propofol or etomidate: a double-blind, randomized, clinical trial. Br J Anaesth. 2013 Mar;110(3):388-96. doi: 10.1093/bja/aes416. Epub 2012 Nov 19. — View Citation

Pei L, Tan G, Wang L, Guo W, Xiao B, Gao X, Wang L, Li H, Xu Z, Zhang X, Zhao J, Yi J, Huang Y. Comparison of combined general-epidural anesthesia with general anesthesia effects on survival and cancer recurrence: a meta-analysis of retrospective and prospective studies. PLoS One. 2014 Dec 30;9(12):e114667. doi: 10.1371/journal.pone.0114667. eCollection 2014. — View Citation

Qiao Y, Feng H, Zhao T, Yan H, Zhang H, Zhao X. Postoperative cognitive dysfunction after inhalational anesthesia in elderly patients undergoing major surgery: the influence of anesthetic technique, cerebral injury and systemic inflammation. BMC Anesthesiol. 2015 Oct 23;15:154. doi: 10.1186/s12871-015-0130-9. — View Citation

Shi C, Thum C, Zhang Q, Tu W, Pelaz B, Parak WJ, Zhang Y, Schneider M. Inhibition of the cancer-associated TASK 3 channels by magnetically induced thermal release of Tetrandrine from a polymeric drug carrier. J Control Release. 2016 Sep 10;237:50-60. doi: 10.1016/j.jconrel.2016.06.044. Epub 2016 Jul 1. — View Citation

Sofra M, Fei PC, Fabrizi L, Marcelli ME, Claroni C, Gallucci M, Ensoli F, Forastiere E. Immunomodulatory effects of total intravenous and balanced inhalation anesthesia in patients with bladder cancer undergoing elective radical cystectomy: preliminary results. J Exp Clin Cancer Res. 2013 Feb 3;32:6. doi: 10.1186/1756-9966-32-6. — View Citation

Wigmore TJ, Mohammed K, Jhanji S. Long-term Survival for Patients Undergoing Volatile versus IV Anesthesia for Cancer Surgery: A Retrospective Analysis. Anesthesiology. 2016 Jan;124(1):69-79. doi: 10.1097/ALN.0000000000000936. — View Citation

Woo JH, Baik HJ, Kim CH, Chung RK, Kim DY, Lee GY, Chun EH. Effect of Propofol and Desflurane on Immune Cell Populations in Breast Cancer Patients: A Randomized Trial. J Korean Med Sci. 2015 Oct;30(10):1503-8. doi: 10.3346/jkms.2015.30.10.1503. Epub 2015 Sep 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Re-operation during hospitalization	Patients receive a reoperation for any reason during hospitalization	From end of colorectal cancer resection surgery to discharge, up to one month
Other	Days of hospitalization	The duration of patients stay in hospital	From end of colorectal cancer resection surgery to discharge, up to one month
Primary	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
Primary	Cancer free survival	Patients who remain alive without known colonal or rectal tumor recurrence	5 years or as available
Secondary	Cancer recurrence rate	Patients who remain alive with known colonal or rectal tumor recurrence	up to 5 years
Secondary	Cancer metastasis rate	Patients who remain alive with known colonal or rectal tumor metastasis	up to 5 years
Secondary	Re-operation	Patients who have a surgery under general anesthesia	up to 5 years
Secondary	Anesthesia scheme for re-operation	Total intravenous anesthesia, inhalational anesthesia or combined anesthesia	up to 5 years
Secondary	Radiotherapy rate for any cancer	Patients have radiotherapy for any cancer	up to 5 years
Secondary	Chemotherapy rate for any cancer	Patients have chemotherapy for any cancer	up to 5 years
Secondary	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
Secondary	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-a, IFN-? and GCSF	up to 5 years
Secondary	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