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Anesthetics

Patients assigned to this group receive combined epidural-general anesthesia and postoperative patient-controlled epidural analgesia.

Patients assigned to this group receive general anesthesia and postoperative patient-controlled intravenous analgesia.

Combined epidural-general anesthesia and postoperative epidural analgesia.

Combined epidural-general anesthesia

General anesthesia and postoperative intravenous analgesia.

General anesthesia

Dong-Xin Wang, MD, PHD

Surgical resection is one of the most important treatments for solid organ cancer. Whereas cancer recurrence and/or metastasis are the major reasons of treatment failure. The outcomes after surgery are mainly dependent on the balance between the immune function of the body and the invasiveness of residual cancer. Preclinical and retrospective studies suggest that anaesthetic techniques and drugs may affect the long-term outcomes in patients undergoing cancer surgery. The investigators hypothesize that epidural anesthesia-analgesia may improve long-term survival in the elderly who undergo major surgery for cancer.

Surgical resection is the main treatment for potentially curable solid organ cancer. However, long-term survival after cancer surgery is far from satisfactory. Quite a number of patients develop tumor metastasis and/or recurrence after surgery, which are associated with poor long-term outcomes. The development of tumor recurrence and/or metastasis after surgery is mostly dependent on the balance between the anti-tumor immune function of the body and the ability of implantation, proliferation and neovascularization of the residual cancer cells.

Studies showed that anaesthetic techniques and drugs may influence the cellular immune function and long-term outcomes. For example, it was found that ketamine and thiopental, but not propofol, suppresses natural killer (NK) cell activity; all three drugs caused a significant reduction in NK cell number; isoflurane and halothane inhibit interferon stimulation of NK cell cytotoxicity; nitrous oxide interferes with deoxyribonucleic acid, purine, and thymidylate synthesis and depresses neutrophil chemotaxis; opioids have been shown to suppress cell-mediated and humoral immunity.

Considering the potential harmful effects of general anesthesia/anesthetics, there is increasing interest on the effect of regional anaesthesia. Retrospective studies investigating the relationship between epidural anesthesia and outcomes after cancer surgery provide different results. In a meta-analysis of retrospective studies, regional anesthesia was associated with improved survival, but had no effect on the occurrence of cancer recurrence/metastasis. The investigators hypothesize that epidural anesthesia may produce favorable effects on long-term survival in the elderly who undergo major surgery for cancer under general anesthesia. However, there are no sufficient evidences in this aspect.

Epidural Anesthesia and Long-term Outcomes in Elderly Patients After Surgery

Impact of Epidural Anesthesia-analgesia on Long-term Outcomes in Elderly Patients After Surgery: 5-year Follow-up of a Multicenter Randomized Controlled Trial

Time from surgery to the date of all-cause death.

Time from surgery to the date of cancer-specific death. Patients who die from other causes being censored at the time of death.

Time from surgery to the date of cancer recurrence/metastasis or all-cause death, whichever comes first.

Time from surgery to the first date of cancer recurrence/metastasis, new onset cancer, new serious non-cancer disease, or death from any cause.

Cognitive function is assessed with the modified Telephone Interview for Cognitive Status (TICS-m; a 12-item questionnaire that assesses global cognitive function by verbal communication via telephone. The score ranges from 0 to 50, with higher score indicating better function).

Quality of life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF; a 24-item questionnaire that assesses the quality of life in physical, psychological, social relationship and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function).

Peking University People's Hospital

Peking University Third Hospital

Beijing Hospital

Beijing Shijitan Hospital, Capital Medical University

Peking University First Hospital

Professor

Adjuvants, Anesthesia

Analgesics

Platelet Aggregation Inhibitors

Sufentanil

Ropivacaine

Morphine

Propofol

Sevoflurane

Dsuvia

Patients assigned to this group (experimental group) receive combined epidural-general anesthesia and postoperative patient-controlled epidural analgesia.

Patients assigned to this group (control group) receive general anesthesia and postoperative patient-controlled intravenous analgesia.

Combined epidural-general anesthesia and postoperative epidural analgesia. General anesthesia is performed as that in the general anesthesia group. Epidural anesthesia is performed with ropivacaine. Epidural analgesia is performed with a mixture of ropivacaine and sufentanil.

General anesthesia and postoperative intravenous analgesia. General anesthesia is performed with propofol induction and propofol and/or sevoflurane maintenance. Intravenous analgesia is performed with morphine.

Dong-Xin Wang, MD

Surgical resection is one of the most important treatments for resectable cancer; on the other hand, cancer recurrence and/or metastasis are the major reasons of treatment failure. The development of recurrence/metastasis after cancer surgery mostly depends on the balance between the immunity of human body and the capability of implantation, proliferation and neovascularization of the residual cancer. Preclinical and retrospective clinical studies suggest that anaesthetic management may affect the long-term outcomes after cancer surgery. The investigators hypothesize that use of epidural anesthesia-analgesia may improve long-term survival in elderly patients after major surgery for cancer.

Surgical resection is the main treatment for potentially curable solid organ cancer. However, it is unavoidable that some cancer cells are disseminated into the circulatory or lymphatic system during surgery. And quite a number of patients develop cancer recurrence and/or metastasis after surgery, which are associated with poor long-term outcomes. The development of cancer recurrence and/or metastasis after surgery is mostly dependent on the balance between the anti-tumor immune function of the human body and the ability of implantation, proliferation and neovascularization of the residual cancer cells.

Multiple surgical factors may influence the balance between the anti-cancer immune function and cancer recurrence. For example, the presence of the primary cancer inhibits angiogenesis, whereas cancer resection eliminates this safeguard against angiogenesis; surgical manipulation releases cancer cells into the circulation; surgery-related stress response inhibits natural killer (NK) cell activity and can promote the development of cancer metastasis; local and systemic release of growth factors during surgery may also promote cancer recurrence both locally and at distant sites.

Available studies showed that general anaesthesia/anesthetics may influence the cellular immune function and long-term outcomes. For example, it was found that ketamine and thiopental, but not propofol, suppressed NK cell activity; all three drugs caused a significant reduction in NK cell number; isoflurane and halothane inhibit interferon (IFN) stimulation of NK cell cytotoxicity; nitrous oxide interferes with DNA, purine, and thymidylate synthesis and depresses neutrophil chemotaxis; opioids have been reported to suppress cell-mediated and humoral immunity.

Considering the potential harmful effects of general anesthesia/anesthetics, there is an increasing interest on the effect of regional anaesthesia. Retrospective studies investigating the relationship between epidural anesthesia and outcome after cancer surgery gave different results. In a meta-analysis, regional anesthesia is associated with improved survival (hazard ratio \[HR\] 0.84, 95% confidence interval \[CI\] 0.74-0.96, P = 0.013), but not cancer recurrence/metastasis (HR 0.88, 95% Cl 0.64-1.22, P = 0.457). The investigators hypothesize that combined use of epidural anesthesia may produce favorable effects on the long-term survival in elderly patients undergoing major cancer surgery.

Epidural Anesthesia-analgesia and Long-term Outcome

Impact of Epidural Anesthesia-analgesia on Long-term Outcome in Elderly Patients After Surgery: 5-year Follow-up of a Multicenter Randomized Controlled Trial

Time from surgery to the date of cancer-specific death. Patients who die from other causes will be censored at the time of death.

Time from surgery to the date of cancer recurrence/metastasis or all-cause death, whichever come first.

Quality of life is assessed with the World Health Organization Quality of Life-brief version (WHOQOL-BREF; a 24-item questionnaire that assesses the quality of life in physical, psychological, social relationship and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Epidural Anesthesia and Long-term Outcomes in Elderly Patients After Surgery	NCT03335826	Elderly Patient... Solid Organ Can... Surgical Resect... Epidural Anesth... Long-term Outco...	Combined epidur... General anesthe...	60 Years - 90 Years	Peking University First Hospital
Epidural Anesthesia and Long-term Outcomes in Elderly Patients After Surgery	NCT03335826	Elderly Patient... Solid Organ Can... Surgical Resect... Epidural Anesth... Long-term Outco...	Combined epidur... General anesthe...	60 Years - 90 Years	Peking University First Hospital
Epidural Anesthesia-analgesia and Long-term Outcome	NCT03012945	Elderly Malignant Tumor Surgical Resect... Epidural Anesth... Long-term Outco...	Combined epidur... General anesthe...	60 Years - 90 Years	Peking University First Hospital

Spots Global Cancer Trial Database for epidural anesthesia and analgesia