Epidural Anesthesia-analgesia and Long-term Outcome
Condition: Elderly; Malignant Tumor; Surgical Resection; Epidural Anesthesia; Long-term Outcome
MeSH terms: Neoplasms
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Combined epidural-general anesthesia; General anesthesia
Intervention type(s): Drug; Drug
Intervention description(s): 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.
Other intervention name(s): Combined epidural-general anesthesia and postoperative epidural analgesia; General anesthesia and postoperative intravenous analgesia
Intervention MeSH terms: Anesthetics
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention
Keywords: Elderly; Cancer surgery; Epidural anesthesia and analgesia; Long-term survival