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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Total intravenous anesthesia group | The anesthesia of patients in the total intravenous anesthesia group will be maintained with propofol and remifentanil. |
| |
| Inhalational anesthesia group | The anesthesia of patients in the inhalational anesthesia group will be maintained with sevoflurane and remifentanil. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propofol | Drug | Propofol will be used for anesthesia maintenance in the total intravenous anesthesia group. |
|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Days of hospitalization |
Inclusion Criteria:
Exclusion Criteria:
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Patients with colonal or rectal cancer undergoing cancer resection with general anesthesia
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Guizhi Du, MD, PhD | Contact | +8618980602213 | du_guizhi@yahoo.com | |
| Jin Liu, MD, PhD | Contact | +86 18980601549 | scujinliu@foxmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Jin Liu, MD, PhD | Department of Anesthesiology, West China Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| West China Hospital of Sichuan University, Department of Anesthesiology | Recruiting | Chengdu | Sichuan | 610041 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23374147 | Background | 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(1):6. doi: 10.1186/1756-9966-32-6. | |
| 26497059 |
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All the study outcomes
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Blood of the enrolled patients will be sampled at different time-points for examination of lymphocytes.
| Sevoflurane | Drug | Sevoflurane will be used for anesthesia maintenance in the inhalation anesthesia group. |
|
|
| Remifentanil | Drug | Remifentanil will be used for analgesia in both groups. |
|
|
| 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 |
The duration of patients stay in hospital
| From end of colorectal cancer resection surgery to discharge, up to one month |
| 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. |
| 23166149 | Background | Moller 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. |
| 25009197 | Background | 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. |
| 25009196 | Background | 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. |
| 26556730 | Background | 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. |
| 26425050 | Background | 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. |
| 18823665 | Background | Bayliss DA, Barrett PQ. Emerging roles for two-pore-domain potassium channels and their potential therapeutic impact. Trends Pharmacol Sci. 2008 Nov;29(11):566-75. doi: 10.1016/j.tips.2008.07.013. Epub 2008 Sep 25. |
| 25548913 | Background | 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. |
| 27374629 | Background | 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. |
| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D009369 | Neoplasms |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D015742 | Propofol |
| D000077149 | Sevoflurane |
| D000077208 | Remifentanil |
| ID | Term |
|---|---|
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D008738 | Methyl Ethers |
| D004987 | Ethers |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D011422 | Propionates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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