• epidural anaesthesia
• general anaesthesia
• patient-reported outcome measures
• perioperative care
• spinal anaesthesia

• Humans
• Anesthesia, Epidural/methods
• Anesthesia, Spinal/methods
• Postoperative Complications/prevention & control
• Adult
• Surgical Procedures, Operative/methods
• Surgical Procedures, Operative/adverse effects
• Perioperative Care/methods
• Treatment Outcome

• Cancer
• Lidocaine
• Local anesthesia
• Surgery
• Survival
• Tumor microenvironment

• Humans
• Lidocaine/therapeutic use
• Lidocaine/pharmacology
• Neoplasms/drug therapy
• Neoplasms/pathology
• Anesthetics, Local/therapeutic use
• Anesthetics, Local/pharmacology
• Anesthetics, Local/administration & dosage
• Animals
• Disease Progression
• Tumor Microenvironment/drug effects
• Antineoplastic Agents/therapeutic use
• Antineoplastic Agents/pharmacology

• R01 CA250412 NCI NIH HHS
• R01 CA251545 NCI NIH HHS
• R01 EB029596 NIBIB NIH HHS
• R37 CA248018 NCI NIH HHS

• Cancer
• immunity
• local anesthetics
• stress

• Humans
• Anesthetics, Local/therapeutic use
• Prospective Studies
• Retrospective Studies
• Antineoplastic Agents/therapeutic use
• Neoplasms/drug therapy

• Inflammatory markers
• Microwave ablation
• Paravertebral block
• Sufentanil
• Transarterial chemoembolization
• Visual analog scale

• Cancer recurrence
• General anesthesia
• Meta-analysis
• Metastasis
• Regional anesthesia

• Adult
• Male
• Humans
• Prospective Studies
• Anesthesia, Conduction
• Prostatic Neoplasms
• Anesthesia, Epidural
• Anesthesia, General

• 202134071 to FM Jinan Science and Technology Plan
• TP2022002 to WH the Second Affiliated Hospital of Hainan Medical University

• Abdominal cancer
• Cancer recurrence
• Overall survival
• regional anesthesia and analgesia

• analgesia
• anesthesia
• anesthetics
• cancer recurrence
• metastasis
• opioids
• prostate cancer
• statins
• surgery and inflammatory response

The conventional treatment of cancer has been based on the delivery of non-selective toxins and/or ionizing energy that affect both the cancer and normal tissues in the hope of destroying the offending disease before killing the patient. Unfortunately, resistance often develops to these treatments and patients experience severe, dose-limiting adverse effects that reduce treatment efficacy and compromise quality of life. Recent advances in our knowledge of the biology of tumor cells and their microenvironment, the recognition of surface proteins that are unique to specific cancers and essential to cell growth and survival and signaling pathways associate with invasion and metastasis have led to the development of targeted therapies that are able to identify specific cellular markers and more selectively deliver lethal treatment to the invading cancer thus improving efficacy and limiting adverse effects. In the context of targeted approaches to cancer therapy, we present targeted osmotic lysis as a novel and fundamentally different approach for treating advanced-stage carcinoma that exploits the conserved relationship between voltage-gated sodium channels and Na⁺, K⁺-ATPase and has the potential to increase survival without compromising quality of life in a broad spectrum of highly malignant forms of cancer.

• cancer
• cell death
• immunity
• local anesthetics
• surgery

Surgical resection is the main curative avenue for various cancers. Unfortunately, cancer recurrence following surgery is commonly seen, and typically results in refractory disease and death. Currently, there is no consensus whether perioperative epidural analgesia (EA), including intraoperative and postoperative epidural analgesia, is beneficial or harmful on cancer recurrence and survival. Although controversial, mounting evidence from both clinical and animal studies have reported perioperative EA can improve cancer recurrence and survival via many aspects, including modulating the immune/inflammation response and reducing the use of anesthetic agents like inhalation anesthetics and opioids, which are independent risk factors for cancer recurrence. However, these results depend on the cancer types, cancer staging, patients age, opioids use, and the duration of follow-up. This review will summarize the effects of perioperative EA on the oncological outcomes of patients after cancer surgery.

• cancer recurrence
• cancer surgeries
• cancer survival
• epidural analgesia
• oncological outcomes

Despite advances in cancer treatments, surgery remains one of the most important therapies for solid tumors. Unfortunately, surgery promotes angiogenesis, shedding of cancer cells into the circulation and suppresses anti-tumor immunity. Together this increases the risk of tumor metastasis, accelerated growth of pre-existing micro-metastasis and cancer recurrence. It was theorized that regional anesthesia could influence long-term outcomes after cancer surgery, however new clinical evidence demonstrates that the anesthesia technique has little influence in oncologic outcomes. Several randomized controlled trials are in progress and may provide a better understanding on how volatile and intravenous hypnotics impact cancer progression. The purpose of this review is to summarize the effect of the anesthesia techniques on the immune system and tumor microenvironment (TME) as well as to summarize the clinical evidence of anesthesia techniques on cancer outcomes.

• analgesia
• anesthesia
• cancer recurrence
• general anesthesia (GA)
• metastasis
• opioids
• regional anesthesia - palliative care - cancer pain
• total intravenous anaesthesia (TIVA)

• anesthesia
• neoplasm
• progression
• survival

• Cancer
• Disease-free survival
• Long-term outcomes
• NSAIDs
• Perioperative
• Surgery

• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Disease-Free Survival
• Humans
• Neoplasms/diet therapy
• Neoplasms/surgery
• Pain, Postoperative/drug therapy
• Postoperative Complications/prevention & control
• Time Factors

Voltage-gated sodium channels are membrane proteins that change conformation in response to depolarization of the membrane potential, allowing sodium ions to flow into cells. While voltage-gated sodium channels are normally studied in terms of neuron impulses and skeletal or cardiac muscle contraction, abnormal ion channel expression is a feature of many cancer cells. The aim of our study was to assess the expression of voltage-gated sodium channels in ovarian cancer cells. We found that ovarian cancer cells generally express lower levels of voltage-gated sodium channels than normal cells and that two voltage-gated sodium channels, SCN8A and SCN1B, were prognostic biomarkers for ovarian cancer overall survival. In vitro studies suggested that drugs that block voltage-gated sodium channels, such as certain anti-epileptic drugs and local anesthetics, might sensitize ovarian cancer cells to chemotherapy. These findings suggest that voltage-gated sodium channels may be interesting targets for ovarian cancer therapy.

Abnormal ion channel expression distinguishes several types of carcinoma. Here, we explore the relationship between voltage-gated sodium channels (VGSC) and epithelial ovarian cancer (EOC). We find that EOC cell lines express most VGSC, but at lower levels than fallopian tube secretory epithelial cells (the cells of origin for most EOC) or control fibroblasts. Among patient tumor samples, lower SCN8A expression was associated with improved overall survival (OS) (median 111 vs. 52 months; HR 2.04 95% CI: 1.21–3.44; p = 0.007), while lower SCN1B expression was associated with poorer OS (median 45 vs. 56 months; HR 0.69 95% CI 0.54–0.87; p = 0.002). VGSC blockade using either anti-epileptic drugs or local anesthetics (LA) decreased the proliferation of cancer cells. LA increased cell line sensitivity to platinum and taxane chemotherapies. While lidocaine had similar additive effects with chemotherapy among EOC cells and fibroblasts, bupivacaine showed a more pronounced impact on EOC than fibroblasts when combined with either carboplatin (ΔAUC −37% vs. −16%, p = 0.003) or paclitaxel (ΔAUC −37% vs. −22%, p = 0.02). Together, these data suggest VGSC are prognostic biomarkers in EOC and may inform new targets for therapy.

• high-grade serous ovarian cancer
• local anesthetics
• sodium channels

Background: In patients with prostatic and breast cancer the application of peridural anesthesia (PDA) showed a beneficial effect on prognosis. This was explained by reduced requirements for general anesthetics and perioperative opioids as well as a lower perioperative stress level. The impact of PDA in patients with more aggressive types of cancer has not been completely elucidated. Here, we analyzed the prognostic influence of PDA on overall survival after surgery as primary in patients that underwent radical resection of pancreatic adenocarcinoma. Methods: Records of 98 consecutive patients were reviewed. In 70 of these cases PDA was applied. Patient characteristics such as demographics, TNM stage, and operative data were retrospectively collected from medical records and analyzed. Survival data were analyzed by Cox’s proportional hazard regression model. Results: Overall, no significant prognostic influence of PDA on recurrence or overall survival (p = 0.762, Hazard Ratio [HR] 0.884, 95% confidence interval [CI] 0.398–1.961) was found. However, there was a trend towards a longer overall survival (p = 0.069, HR 0.394, 95% CI 0.144–1.078) associated with PDA in a subgroup of patients with better differentiation of pancreatic adenocarcinoma. Conclusion: The observation of longer survival associated with PDA in our subgroup of patients with better-differentiated pancreatic carcinomas is in line with previous reports on various other less aggressive tumor entities. Our results indicate that PDA might improve the oncological outcome of patients with pancreatic adenocarcinoma.

• oncological outcome
• pancreatic adenocarcinoma
• recurrence
• staging

• Chemotherapy
• neoplasm recurrence
• postoperative care
• radiation oncology
• regional anesthesia
• surgical oncology

• advanced-stage cervical cancer
• sodium channels
• sodium pumps
• targeted osmotic lysis

• Carcinoma, Squamous Cell
• Female
• Humans
• Sodium/metabolism
• Uterine Cervical Neoplasms/drug therapy
• Voltage-Gated Sodium Channels

• biochemical recurrence
• cancer recurrence
• multimodal analgesia
• opioid
• opioid-free anaesthesia
• prostate cancer
• prostatectomy

The perioperative use of regional anesthesia and local anesthetics is part of almost every anesthesiologist’s daily clinical practice. Retrospective analyses and results from experimental studies pointed towards a potential beneficial effect of the local anesthetics regarding outcome—i.e., overall and/or recurrence-free survival—in patients undergoing cancer surgery. The perioperative period, where the anesthesiologist is responsible for the patients, might be crucial for the further course of the disease, as circulating tumor cells (shed from the primary tumor into the patient’s bloodstream) might form new micro-metastases independent of complete tumor removal. Due to their strong anti-inflammatory properties, local anesthetics might have a certain impact on these circulating tumor cells, either via direct or indirect measures, for example via blunting the inflammatory stress response as induced by the surgical stimulus. This narrative review highlights the foundation of these principles, features recent experimental and clinical data and provides an outlook regarding current and potential future research activities.

• cancer
• inflammation
• local anesthetics
• metastasis
• recurrence

• cancer recurrence
• onco-anaesthesia
• peri-operative medicine
• regional anaesthesia

• Epidural anesthesia
• gastric cancer
• general anesthesia
• metastasis
• recurrence

• Cdc42
• Rac1
• ketorolac
• metastasis
• non-steroidal anti-inflammatory drug (NSAID)
• ovarian cancer
• peri-operative period
• therapeutic targets

Post-operative recurrence and metastasis of malignant tumors are difficult to control, which probably results from multiple factors that affect the prognosis and the undefined mechanism. Anesthesia may be an influential factor. Researchers have performed many meaningful studies on the relationship between anesthetic drugs/methods and tumor growth/immune function, which provide important references for the anesthetic selection and peri-operative management of tumor patients. Anesthetics, analgesics, and sedatives should be used with caution because their effects in post-operative patients remain controversial. This review summarizes the emerging progress on the effect of anesthesia on post-operative tumor recurrence and metastasis, particularly focusing on the effects of anesthetic drugs, anesthetic methods, and post-operative analgesia on tumor growth and metastasis. Future studies should provide strict criteria for the proper use of anesthetics in patients with malignant tumors and provide experimental evidence for the improvement and development of novel anesthetics and anesthetic methods that have the important clinical significance.

• Anesthesia
• NK cells
• analgesia
• anesthetic
• immune function
• immunosuppression
• malignant
• post-operative
• tumor metastasis
• tumor recurrence

• anaesthesia, general
• anaesthesia, inhalational
• anaesthesia, intravenous
• analgesia
• cancer, recurrence
• inflammation
• opioid
• stress response
• surgery

• Anesthesia, Epidural/mortality
• Anesthesia, General/mortality
• Carcinoma/mortality
• Carcinoma/secondary
• Carcinoma/surgery
• China/epidemiology
• Cohort Studies
• Colorectal Neoplasms/pathology
• Female
• Humans
• Liver/pathology
• Liver/surgery
• Liver Neoplasms/mortality
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Male
• Middle Aged

Anti-cancer effects of local anesthetics have been reported but the mode of action remains elusive. Here, we examined the bioenergetic and REDOX impact of levobupivacaine on human prostate cancer cells (DU145) and corresponding non-cancer primary human prostate cells (BHP). Levobupivacaine induced a combined inhibition of glycolysis and oxidative phosphorylation in cancer cells, resulting in a reduced cellular ATP production and consecutive bioenergetic crisis, along with reactive oxygen species generation. The dose-dependent inhibition of respiratory chain complex I activity by levobupivacaine explained the alteration of mitochondrial energy fluxes. Furthermore, the potency of levobupivacaine varied with glucose and oxygen availability as well as the cellular energy demand, in accordance with a bioenergetic anti-cancer mechanism. The levobupivacaine-induced bioenergetic crisis triggered cytostasis in prostate cancer cells as evidenced by a S-phase cell cycle arrest, without apoptosis induction. In DU145 cells, levobupivacaine also triggered the induction of autophagy and blockade of this process potentialized the anti-cancer effect of the local anesthetic. Therefore, our findings provide a better characterization of the REDOX mechanisms underpinning the anti-effect of levobupivacaine against human prostate cancer cells.

•

Local anesthetics reduce cancer recurrence in prostate cancer.

• Glycolysis
• Levobupivacaine
• Oxidative phosphorylation
• Prostate cancer
• Wortmannin

• cancer
• epithelial carcinoma
• sodium channels
• sodium pumps
• targeted osmotic lysis

Several animal and observational studies have evaluated the effects of neuraxial anesthesia on the recurrence and survival of cancer surgery; studies reported benefit, whereas others did not. To provide further evidence that neuraxial anesthesia(combined with or without general anesthesia (GA))may be associated with reduced cancer recurrence and long-term survival after cancer surgery, we conducted this meta-analysis. A total of 21 studies were identified and analyzed, based on searches conducted using PubMed, Web of Science, EMBASE database and the Cochrane Database of Systematic Reviews. After data abstraction, adjusted hazard ratios (HR) with 95% confidence intervals (CIs) were used to assess the impact of neuraxial anesthesia (combined with or without GA) and GA on oncological outcomes after cancer surgery. For overall survival (OS), a potential association between neuraxial anesthesia and improved OS (HR 0.853, CI 0.741-0.981, P = 0.026, the random-effects model) was observed compared with GA. Specifically, we found a positive association between neuraxial anesthesia and improved OS in colorectal cancer (HR 0.653, CI 0.430-0.991, P = 0.045, the random-effects model). For recurrence-free survival (RFS), a significant association between neuraxial anesthesia and improved RFS (HR 0.846, CI 0.718-0.998, P = 0.047, the random-effects model) was detected compared with GA. Our meta-analysis suggests that neuraxial anesthesia may be associated with improved OS in patients with cancer surgery, especially for those patients with colorectal cancer. It also supports a potential association between neuraxial anesthesia and a reduced risk of cancer recurrence. More prospective studies are needed to elucidate whether the association between neuraxial use and survival is causative.

• cancer outcome
• cancer recurrence
• general anesthesia
• neuraxial anesthesia
• survival

Whether regional analgesia techniques have favorable impact on prognosis after cancer surgery is unclear, and existing reports show controversial results. The aim of the present study was to evaluate and compare recurrence and mortality between patients that received either intravenous (IV) or epidural patient controlled analgesia (PCA) for pain control after curative surgery for gastric cancer.

Medical records of patients that underwent curative gastrectomy for gastric cancer between November 2005 and December 2010 were reviewed. Identified patients were categorized according to the use of IV or epidural PCA for postoperative analgesia. Demographic and perioperative variables including type of PCA were analyzed by univariate and multiple regression analysis to investigate any association with recurrence and mortality after surgery. Propensity score matching was done to adjust for selection bias.

Of the 3,799 patients included in this analysis, 374 and 3, 425 patients received IV and epidural PCAs, respectively. No difference in recurrence (HR, 1.092; 95% CI 0.859 to 1.388; P = 0.471) or mortality (HR, 0.695; 95% CI 0.429 to 1.125; P = 0.138) was identified between the use of IV and epidural PCA. Propensity score matching also showed no difference in recurrence (HR, 1.098; 95% CI 0.756 to 1.596; P = 0.623) or mortality (HR, 0.855; 95% CI 0.391 to 1.869; P = 0.695) between the two groups.

Postoperative use of epidural analgesia was not found to be associated with reduced recurrence or mortality after curative surgery in gastric cancer patients. This finding needs to be confirmed with prospective studies in the future.

• analgesia
• epidural
• gastric cancer
• patient controlled

• Anesthetic technique
• Angiogenesis
• Cancer recurrence
• Immunosuppression
• Oncologic surgery

• Analgesics–opioid
• angiogenesis inducing agents
• morphine
• neoplasm metastasis

• Analgesic techniques
• Anesthesia
• Cancer
• Metastases
• Recurrence

• Aged
• Analgesia, Epidural
• Anastomotic Leak/etiology
• Anastomotic Leak/pathology
• Anastomotic Leak/prevention & control
• Anesthesia, Intravenous
• C-Reactive Protein/metabolism
• Esophagectomy/rehabilitation
• Female
• Humans
• Hypotension/etiology
• Hypotension/physiopathology
• Hypotension/prevention & control
• Length of Stay/statistics & numerical data
• Male
• Middle Aged
• Pain/physiopathology
• Pain/prevention & control
• Pain Management/methods
• Pneumonia/etiology
• Pneumonia/physiopathology
• Pneumonia/prevention & control
• Postoperative Complications
• Retrospective Studies
• Treatment Outcome
• Urinary Catheters

• Guangdong Science and Technology Program

To investigate the effects and underlying mechanism of dexmedetomidine on the cultured human dendritic cells (DCs).

Human DCs and cytotoxic T lymphocytes (CTLs) were obtained from human cord blood mononuclear cells by density gradient centrifugation. Cultured DCs were divided into three groups: dexmedetomidine group, dexmedetomidine plus yohimbine (dexmedetomidine inhibitor) group and control group. DCs in the three groups were treated with dexmedetomidine, dexmedetomidine plus yohimbine and culture medium, respectively. After washing, the DCs were co-incubated with cultured CTLs. The maturation degree of DCs was evaluated by detecting (1) the ratios of HLA-DR-, CD86-, and CD80-positive cells (flow cytometry), and (2) expression of IL-12 and IL-23 (PCR and Elisa). The function of DCs was evaluated by detecting the proliferation (MTS assay) and cytotoxicity activity (the Elisa of IFN-γ) of CTLs. In addition, in order to explore the mechanisms of dexmedetomidine modulating DCs, α2-adrenergic receptor and its downstream signals in DCs were also detected.

The ratios of HLA-DR-, CD86-, and CD80-positive cells to total cells were similar among the three groups (P>0.05). Compared to the control group, the protein levels of IL-12 and IL-23 in the culture medium and the mRNA levels of IL-12 p35, IL-12 p40 and IL-23 p19 in the DCs all decreased in dexmedetomidine group (P<0.05). In addition, the proliferation of CTLs and the secretion of IFN-γ also decreased in the dexmedetomidine group, compared with the control group (P<0.05). Moreover, these changes induced by dexmedetomidine in the dexmedetomidine group were reversed by α2-adrenergic receptor inhibitor yohimbine in the dexmedetomidine plus yohimbine group. It was also found the decrease of mRNA levels of IL-12 p35, IL-12 p40 and IL-23 p19 in the dexmedetomidine group could be reversed by ERK1/2 or AKT inhibitors.

Dexmedetomidine could negatively modulate human immunity by inhibiting the maturation of DCs and then decreasing the proliferation and cytotoxicity activity of CTLs. The α2-adrenergic receptors and its downstream molecules ERK1/2 and AKT are closely involved in the modulation of dexmedetomidine on DCs.

• Adrenergic alpha-2 Receptor Agonists/pharmacology
• Blotting, Western
• Cells, Cultured
• Dendritic Cells/cytology
• Dendritic Cells/drug effects
• Dendritic Cells/immunology
• Dendritic Cells/metabolism
• Dexmedetomidine/pharmacology
• Fetal Blood/cytology
• Fetal Blood/drug effects
• Fetal Blood/immunology
• Fetal Blood/metabolism
• Humans
• Immunophenotyping
• Interleukin-12/genetics
• Interleukin-12/metabolism
• Interleukin-23/genetics
• Interleukin-23/metabolism
• RNA, Messenger/genetics
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• T-Lymphocytes, Cytotoxic/immunology

• Anestesia geral
• Anestesia regional
• Apoptose
• Apoptosis
• Artroplastia total do joelho
• General anesthesia
• Linfócitos
• Lymphocytes
• Regional anesthesia
• Total knee replacement

• Adult
• Aged
• Aged, 80 and over
• Analgesia, Epidural/statistics & numerical data
• Colorectal Neoplasms/complications
• Colorectal Neoplasms/pathology
• Colorectal Neoplasms/surgery
• Female
• Follow-Up Studies
• Humans
• Liver Neoplasms/complications
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Neoplasm Recurrence, Local/etiology
• Neoplasm Recurrence, Local/prevention & control
• Neoplasm Staging
• Pain/etiology
• Pain/prevention & control
• Prognosis
• Retrospective Studies
• Survival Rate
• Young Adult

• CA016672 NCI NIH HHS

• Anesthesia
• Animal Studies
• Cancer
• Cancer Recurrence
• Human Studies
• Local Anesthetics
• Opioids
• Regional Anesthesia
• Stress Response

• anaesthesia, conduction
• anaesthetics, inhalation
• anaesthetics, local
• cancer
• opioid

• Analgesics, Opioid/adverse effects
• Anesthesia, Conduction/methods
• Anesthetics, General/adverse effects
• Anesthetics, Local
• Animals
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Colorectal Neoplasms/surgery
• Disease Progression
• Humans
• Male
• Neoplasm Metastasis
• Neoplasms/immunology
• Neoplasms/prevention & control
• Neoplasms/surgery
• Prognosis
• Prostatic Neoplasms/surgery
• Recurrence
• Stress, Physiological
• Survival Analysis

• Analgesics, Opioid/adverse effects
• Humans
• Neoplasm Recurrence, Local/epidemiology
• Neoplasms/surgery
• Pain, Postoperative/drug therapy

• T32 GM075774 NIGMS NIH HHS

• biochemical recurrence-free survival
• overall survival
• prostate cancer
• regional anesthesia