Effect of Propofol and Desflurane on Nucleic Acid of Liver Circulating Tumor
Condition: Hepatocellular Carcinoma; Desflurane Adverse Reaction; Propofol Adverse Reaction; Circulating Tumor Cells
MeSH terms: Neoplastic Cells, Circulating
Study type: Interventional
Phase: Phase 2

Summary: 
      To investigate the effects of perioperative anesthetic drugs propofol and desflurane on
      circulating tumor nucleic acids (CK7, ELF3, EGFR and EphB4 mRNA) in the blood of patients
      with liver cancer, so as to provide scientific reference for clinical anesthesia in the
      perioperative treatment of tumor
    

Detailed description: 
      Hepatocellular carcinoma (HCC) is one of the most malignant tumors in oncology. Its incidence
      is increasing, and there is a lack of reliable biomarkers for early diagnosis, prognosis
      evaluation and efficacy evaluation. There is a pool of tumor molecules derived from primary
      tumors in the blood circulation, including Circulating tumor proteins, Circulating tumor
      cells (CTCs), Extracellular vesicles, Evs, Tumor "educated" platelets (TEPs), and Circulating
      Tumor nucleic acids, known as Circulating Tumor DNA, CtDNA is a Circulating cell-free DNA
      (ccfDNA). Liquid biopsy is performed to detect tumor molecules from blood circulation. Small
      RNA (miRNA) and long noncoding RNA (miRNA) in liquid biopsy are detected. Circulating tumor
      RNA (ctRNA), such as lncRNA, can be used as epigenetic biomarkers to improve the early
      diagnosis of HCC and to treat patients with early and advanced HCC. Propofol and desflurane,
      as important anesthesia drugs in perioperative period, have been shown to affect the
      concentration of circulating nucleic acid in patients. Furong Song found that propofol could
      inhibit the overexpression of HOXA11-AS, which reversed the inhibitory effect of propofol
      treatment on HCC cell progression, by promoting the expression of Mir-4458, and had an impact
      on HCC cell progression . However, Dongmei Wang and their colleagues found that circulating
      H19 inhibited the effect of propofol in promoting HCC cell apoptosis by upregulating LIMK1
      (LIM domain kinase 1) through spongy Mir-520a-3p . Meanwhile, Buschmann and his team found
      that propofol and desflurane inhibited key cancer-related pathways such as proliferation and
      migration in colorectal cancer, and found that propofol did not affect the size distribution
      and protein labeling of circulating vesicles, but could reduce their concentration . Compared
      with inhaled anesthetics, Bon-Wook Koo found that HCC patients treated with propofol had a
      lower recurrence rate and a longer average recurrence time than those treated with inhaled
      anesthetics . Hou-chuan Lai found that compared with desflurane anesthesia regimen, propofol
      anesthesia regimen significantly improved the survival rate of patients with liver cancer
      without distant metastasis or local recurrence . Meanwhile, Frederique Hovaguimian found that
      in nonmetastatic and metastatic breast cancer, the maximum number of circulating tumor cells
      increased by 36% after sevoflurane inhalation anesthesia and was independently associated
      with a higher risk of disease recurrence and reduced survival . At this time, the monitoring
      of circulating tumor cells can represent promising methods, such as the detection of suitable
      markers of circulating tumor cells, such as Cytokeratin 7 (CK7), E74-like factor 3 (ELF3),
      Epidermal growth factor receptor (EGFR) and Peripheral blood mononuclear cells, The
      expression of erythropoietin-producing hepatocellular carcinoma receptor B4 (EphB4) mRNA in
      PMBCs, In order to better understand the effect of anesthesia on perioperative tumor
      treatment, this evidence has been supported by domestic and foreign studies . Soo-ho Lee and
      his colleagues found that CK7-negative liver cancer patients had a higher survival rate than
      all positive patients [9], which was supported by Xialing Huang and his team . Longbo Zheng
      found that ELF3 inhibits ZE1 by inhibiting Mir-141-3p, thereby inhibiting E-cadherin in HCC
      cells and promoting EMT, which is a potential prognostic biomarker and/or therapeutic target
      for HCC . Zhe Wu found that lncrNA-UBE2R2-AS1 in HCC shows carcinogenic effect through the
      up-regulation of EGFR by Mir-302b, and can be used as a potential therapeutic target and
      prognostic biomarker for HCC patients , and this mechanism of action was confirmed by
      Zhen-Jiang Ma and his research . At the same time, it was found that the expression level of
      EphB4 was increased in HCC tumor tissues, and the levels of EphB4 and P-JAK2 were positively
      correlated in samples of HCC patients , while the expression of CIRC-EPHB4 was
      down-regulated. Circ-ephb4 overexpression inhibited the viability of HCC cells, induced
      apoptosis, and inhibited cell migration and invasion by inhibiting the expression of
      hypoxia-inducible factor-1α (HIF-1α) . However, the perioperative effects and molecular
      mechanisms of propofol and desflurane on circulating tumor nucleic acids in liver cancer are
      not very clear at present, and further relevant studies are needed to clarify, so as to
      provide support and guidance for the development of perioperative anesthesia plan and
      clinical diagnosis of liver cancer.
    

Intervention name(s): Desﬂurane; Propofol
Intervention type(s): Drug; Drug
Intervention description(s): Propofol general anesthesia group (P group) : intravenous propofol infusion was slowly pushed until consciousness disappeared, and then anesthesia was maintained at 4-8 mg/kg/h. In the general anesthesia group with desflurane (group D), intravenous propofol infusion was slowly pushed until consciousness disappeared, and then anesthesia was maintained with 4-6% desflurane. The analgesic and muscle relaxant regimens were the same in both groups except for sedative drugs. All patients were treated with no medication before operation, and the operation was completed under endotracheal intubation and general anesthesia. The amount of propofol or desflurane was adjusted according to BIS or MAC values and hemodynamic changes during operation. Add 10mg of rocuronium every half hour. Vasoactive drugs can be used to maintain hemodynamic stability during the operation, and corresponding records should be made; Propofol general anesthesia group (P group) : intravenous propofol infusion was slowly pushed until consciousness disappeared, and then anesthesia was maintained at 4-8 mg/kg/h.
Other intervention name(s): group D; group P
Intervention MeSH terms: Propofol; Desflurane
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Propofol general anesthesia group (P group) : intravenous propofol infusion was slowly pushed until consciousness disappeared, and then anesthesia was maintained at 4-8 mg/kg/h.
In the general anesthesia group with desflurane (group D), intravenous propofol infusion was slowly pushed until consciousness disappeared, and then anesthesia was maintained with 4-6% desflurane
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Desflurane; HCC; propofol; CTC