Summary Surgery is an important treatment modality for the majority of solid organ cancers. Unfortunately, cancer recurrence following surgery of curative intent is common, and typically results in refractory disease and patient death. Surgery and other perioperative interventions induce a biological state conducive to the survival and growth of residual cancer cells released from the primary tumour intraoperatively, which may influence the risk of a subsequent metastatic disease. Evidence is accumulating that anaesthetic and analgesic interventions could affect many of these pathophysiological processes, influencing risk of cancer recurrence in either a beneficial or detrimental way. Much of this evidence is from experimental in vitro and in vivo models, with clinical evidence largely limited to retrospective observational studies or post hoc analysis of RCTs originally designed to evaluate non-cancer outcomes. This narrative review summarises the current state of evidence regarding the potential effect of perioperative anaesthetic and analgesic interventions on cancer biology and clinical outcomes. Proving a causal link will require data from prospective RCTs with oncological outcomes as primary endpoints, a number of which will report in the coming years. Until then, there is insufficient evidence to recommend any particular anaesthetic or analgesic technique for patients undergoing tumour resection surgery on the basis that it might alter the risk of recurrence or metastasis.

Influence of perioperative anaesthetic and analgesic interventions on oncological outcomes: a narrative review.

Summary Anaesthesiologists and non-anaesthesiologist sedationists have a limited set of available i.v. hypnotics, further reduced by the withdrawal of thiopental in the USA and its near disappearance in Europe. Meanwhile, demand for sedation increases and new clinical groups are using what traditionally are anaesthesiologists' drugs. Improved understanding of the determinants of perioperative morbidity and mortality has spotlighted hypotension as a potent cause of patient harm, and practice must be adjusted to respect this. High-dose propofol sedation may be harmful, and a critical reappraisal of drug choices and doses is needed. The development of remimazolam, initially for procedural sedation, allows reconsideration of benzodiazepines as the hypnotic component of a general anaesthetic even if their characterisation as i.v. anaesthetics is questionable. Early data suggest that a combination of remimazolam and remifentanil can induce and maintain anaesthesia. Further work is needed to define use cases for this technique and to determine the impact on patient outcomes.

Current status of perioperative hypnotics, role of benzodiazepines, and the case for remimazolam: a narrative review

Background There is growing interest in the effect of postoperative analgesics on oncological outcomes after cancer surgery. We investigated the impact of tramadol after breast cancer surgery on recurrence and mortality and explored the mechanism by which tramadol affects cultured breast cancer cells in vitro. Methods Electronic medical records of patients who underwent breast cancer surgery between November 2005 and December 2010 at Severance Hospital in Korea were reviewed. Cox regression analyses were used to identify factors related to postoperative recurrence and mortality. We performed the sensitivity test with propensity score matching to adjust for selection bias. In addition, we investigated the effects of tramadol on human breast adenocarcinoma (Michigan Cancer Foundation-7 [MCF-7]) cells via assessment of cell viability, clonogenic assay, and cell cycle analysis in vitro. Results Of 2588 breast cancer patients, 36.4% had received tramadol. Those who received tramadol had a 0.71-fold decreased risk of recurrence and a 0.56-fold decrease in mortality. The MCF-7 cell viability assays showed that tramadol had an anti-proliferative effect by cell cycle arrest, suppressing colony formation, and regulation of oestrogen and progesterone receptors. Tramadol induced apoptosis of MCF-7 cells via extracellular signal-regulated kinases by decreasing of 5-hydroxytryptamine (HT)2B receptor and transient receptor potential vanilloid-1 expression. Conclusions After breast cancer surgery, patients who received tramadol had a decreased risk of postoperative recurrence and mortality. The anti-tumour effect of tramadol appears to involve inhibition of proliferation, induction of apoptosis, and effects on 5-HT2B receptor and TRPV-1.

Tramadol use is associated with enhanced postoperative outcomes in breast cancer patients: a retrospective clinical study with in vitro confirmation

Dexmedetomidine (DEX) is an anesthetic that is widely used in the clinic, and it has been reported to exhibit paradoxical effects in the progression of multiple solid tumors In this study, we sought to explore the mechanism by which DEX regulates hepatocellular carcinoma (HCC) progression underlying liver fibrosis We determined the effects of DEX on tumor progression in an orthotopic HCC mouse model of fibrotic liver A coculture system and a subcutaneous xenograft model involving coimplantation of mouse hepatoma cells (H22) and primary activated hepatic stellate cells (aHSCs) were used to study the effects of DEX on HCC progression We found that in the preclinical mouse model of liver fibrosis, DEX treatment significantly shortened median survival time and promoted tumor growth, intrahepatic metastasis and pulmonary metastasis The DEX receptor (ADRA2A) was mainly expressed in aHSCs but was barely detected in HCC cells DEX dramatically reinforced HCC malignant behaviors in the presence of aHSCs in both the coculture system and the coimplantation mouse model, but DEX alone exerted no significant effects on the malignancy of HCC Mechanistically, DEX induced IL-6 secretion from aHSCs and promoted HCC progression via STAT3 activation Our findings provide evidence that the clinical application of DEX may cause undesirable side effects in HCC patients with liver fibrosis

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Dexmedetomidine promotes the progression of hepatocellular carcinoma through hepatic stellate cell activation

Cancer is the leading cause of death by disease in developed countries Children and adolescents with cancer need surgical interventions (ie, biopsy or major surgery) to diagnose, treat, or palliate their malignancies Surgery is a period of high vulnerability because it stimulates the release of inflammatory mediators, catecholamines, and angiogenesis activators, which coincides with a period of immunosuppression Thus, during and after surgery, dormant tumors or micrometastasis (ie, minimal residual disease) can grow and become clinically relevant metastasis Anesthetics (ie, volatile agents, dexmedetomidine, and ketamine) and analgesics (ie, opioids) may also contribute to the growth of minimal residual disease or disease progression For instance, volatile anesthetics have been implicated in immunosuppression and direct stimulation of cancer cell survival and proliferation Contrarily, propofol has shown in vitro anticancer effects In addition, perioperative blood transfusions are not uncommon in children undergoing cancer surgery In adults, an association between perioperative blood transfusions and cancer progression has been described for some malignancies Transfusion-related immunomodulation is one of the mechanisms by which blood transfusions can promote cancer progression Other mechanisms include inflammation and the infusion of growth factors In the present review, we discuss different aspects of tumorigenesis, metastasis, angiogenesis, the immune system, and the current studies about the impact of anesthetics, analgesics, and perioperative blood transfusions on pediatric cancer progression

Impact of Anesthetics, Analgesics, and Perioperative Blood Transfusion in Pediatric Cancer Patients: A Comprehensive Review of the Literature.

Editor’s PerspectiveWhat We Already Know about This TopicDexmedetomidine reduces cellular apoptosis, and it has been demonstrated previously that this antiapoptotic effect can not only increase cancer cell proliferation and migration but also reduce survival in experimental models of cancer growth.M

Tanweer Datoo

Papers

Midazolam and Dexmedetomidine Affect Neuroglioma and Lung Carcinoma Cell Biology In Vitro and In Vivo