Bonilla Castillo Luis*, Pérez Herrero, María A and Abad Anna
Received: January 27, 2020; Published: February 03, 2020
Corresponding author: Bonilla Castillo Luis, The Department of General Surgery and the digestive system. University Hospital of Fuenlabrada offers comprehensive surgical assistance, Spain
Surgery has a very important role in solid tumors multimodal treatment. The primary excision can be curative itself or can be combined with neoadjuvant or adjuvant chemotherapy and / or radiotherapy. Despite therapy advances, recurrence and metastases appear as an important source of morbidity and mortality in cancer patients. There is a huge growing interest in events related to surgery and the perioperative period that not only help to release cancer cells into general circulation, but also facilitate its growing, leading to regional recurrences and metastases. Data obtained from laboratory and animal experimentation suggest that anesthetics drugs may affect long-term results after cancer surgery. In this review, we summarize the experimental and clinical data that we have nowadays, and we present the potential role of anesthetic techniques (inhalation and intravenous) in cancer recurrence and survival.
A bibliographic search has been done out using Medline / PubMed database and Embase, using as key words “anesthesia and metastasis”, “anesthetic drugs and cancer”, “halogenated and cancer”, “volatile anesthetic agents and cancer”, “propofol and cancer”, anesthetic technique and cancer”. They have been included the most relevant English or Spanish papers (Table 1).
a. Surgery itself and the neuroendocrine response related
to stress have a negative effect on immune system due to cellmediated
immunity depression they cause. Even after the
complete tumor excision, circulating tumor cells released during
the surgical procedure may lead to recurrence or metastasis
thanks to their ability to avoid immunological process .
Thereby, they can decrease antiangiogenic protective factors
concentration (e.g. angiostatin and endostatin) while increase
angiogenic factors such as vascular endothelial growth factor
(VEGF). Surgery is also associated with transforming growth
factor-beta (TGF-B) which plays a significant role in tumor
blood supply and cell proliferation .
b. Anesthesia process also interacts with several immune functions, including those related to neutrophils, macrophages, dendritic cells, T cells and natural killer cells (NK). In vitro studies about the possible metastasis induction of inhalation anesthetics role are based on their time-and-dose-dependent inhibitory effects. Thus, they modify neutrophil function, suppress mononuclear cells cytokines release, decrease lymphocyte proliferation and promote lymphocyte apoptosis. Moreover, inhalation anesthetics also promote the growth and proliferation of endothelial stem cells (proangiogenic effect) which would improve tumor growth and / or teratogenicity . Nevertheless, propofol does not seem to depress immune system, according to evidence available. It seems to improve NK cells cytotoxicity, to reduce motility and tumor cells invasion, to inhibit cyclooxygenase and to not promote HIF (antiangiogenic effect) synthesis .
c. Opioid drugs inhibit both cellular and humoral human immune function, increase angiogenesis and promote the growth of breast tumoral cellular in rodents. In this way, they also interfere with immune functions by depressing NK cells activity  However, these drugs can reduce stress response caused by pain and offer some benefit. Clinical evidence.
d. Most of the available evidence nowadays is based on intermediate results (substituted variables: cell reduction, inhibitory activity…) such as the previous ones mentioned and the only studies with patient-centered results (final variables: survival, mortality, recurrence) are the ones that we are going to review. A recent retrospective analysis composed by more than 7,000 patients from an oncology hospital in United Kingdom was carried out to determine long-term survival of patients who were receiving inhalation anesthesia (isofluoran or sevofluorane) versus intravenous anesthesia (propofol and remifentanil) in cancer surgery. After several analysis, including multivariate analysis, it was found that those who received inhalation anesthetics were those who had a lower survival (HR [hazard ratio] 1.46; 95% CI 1.29-1.66 if we compared with the group who received intravenous anesthesia .
e. Lee JH, the author of another retrospective analysis composed by more than 300 patients taken from an oncology hospital South Korea, determined the association between the type of anesthesia (inhalation or intravenous) and recurrence or survival in patients that have undergone radical mastectomy. Large significant differences were not found between the two groups about survival (HR of 0.550; 95% CI 0.311- 0.973) but they found a lower recurrence in the intravenous anesthesia group Enlund M  found greater survival in patients undergoing cancer surgery with propofol compared to sevofluoran, but when multivariate analysis is used with variables such as type of tumor (breast, colon and rectum), this association disappears  (Table 2).
Unfortunately, there is a drawback to available evidence; in vitro conditions used in many studies do not accurately replicate cancer cells biological condition. Therefore, the speculative extrapolation of these results to clinical scenario is not ideal. However, retrospective clinical studies about the type of anesthesia (inhalation versus intravenous) and cancer recurrence or survival after tumor excision are beginning to be published. The main disadvantages of these retrospective studies are selection, information and confusion biases. Wigmore , incorporated the propensity analysis, which is the best method to control known confounding variables in observational studies. However important variables such as type (including more than 20 cancer types with different prognoses), cancer stage or mortality attributable to cancer (despite it had been considered total mortality) was not considered. Notwithstanding that, the strength of this study falls on the large number of patients included. However, Lee JH  included in his study a single type and stage of cancer at the beginning of the study, but it still seemed that there were biases not included in the analysis, such as the use of nitrous oxide or morphics and the anesthetic technique preference of anesthesiologists. Moreover, they could also exist several hidden confounding factors which were not taken into account in a multivariate analysis of retrospective, observational, nonrandomized data. About these words, it is also important to consider the regional anesthetic techniques (RA), which are almost always a complement to general anesthesia. Studies have demonstrated lots of advantages of RA in cancer patients by reducing recurrences. The role of intrathecal and epidural opioids commonly used in regional analgesia and pain management has not been explored .
As mentioned previously, immune function combined with surgical stress and the direct effects of anesthetic drugs, create a favorable environment for tumor growth and dissemination, which finally affect patient survival. Reducing the response to surgical stress, minimizing inflammation and using optimal anesthetic and analgesic techniques are the main key to reduce long-term negative effects of cancer surgery. However, overall progress in this area, the actual lack of evidence leads to the impossibility of change our daily clinical practice. More and better randomized clinical trials, prospective cohorts are needed to prove that there is causality between the type of anesthesia and cancer recurrence.
Bio chemistryUniversity of Texas Medical Branch, USA
Department of Criminal JusticeLiberty University, USA
Department of PsychiatryUniversity of Kentucky, USA
Department of MedicineGally International Biomedical Research & Consulting LLC, USA
Department of Urbanisation and AgriculturalMontreal university, USA
Oral & Maxillofacial PathologyNew York University, USA
Gastroenterology and HepatologyUniversity of Alabama, UK
Department of MedicineUniversities of Bradford, UK
OncologyCirculogene Theranostics, England
Radiation ChemistryNational University of Mexico, USA
Analytical ChemistryWentworth Institute of Technology, USA
Minimally Invasive SurgeryMercer University school of Medicine, USA
Pediatric DentistryUniversity of Athens , Greece
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