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