Latest Advances in Regional Anaesthesia.

Training and expertise in regional anaesthesia have increased significantly in tandem with increased interest over the past two decades. This review outlines the most recent advances in regional anaesthesia and focuses on novel areas of interest including fascial plane blocks. Pharmacological advances in the form of the prolongation of drug duration with liposomal bupivacaine are considered. Neuromodulation in the context of regional anaesthesia is outlined as a potential future direction. The growing use of regional anaesthesia outside of the theatre environment and current thinking on managing the rebound plane after regional block regression are also discussed. Recent relevant evidence is summarised, unanswered questions are outlined, and priorities for ongoing investigation are suggested.

Local anaesthetics and chemotherapeutic agents: a systematic review of preclinical evidence of interactions and cancer biology.

Background: Local anaesthetics are widely used for their analgesic and anaesthetic properties in the perioperative setting, including surgical procedures to excise malignant tumours. Simultaneously, chemotherapeutic agents remain a cornerstone of cancer treatment, targeting rapidly dividing cancer cells to inhibit tumour growth. The potential interactions between these two drug classes have drawn increasing attention and there are oncological surgical contexts where their combined use could be considered. This review examines existing evidence regarding the interactions between local anaesthetics and chemotherapeutic agents, including biological mechanisms and clinical implications. Methods: A systematic search of electronic databases was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Selection criteria were designed to capture in vitro, in vivo, and clinical studies assessing interactions between local anaesthetics and a wide variety of chemotherapeutic agents. Screening and data extraction were performed independently by two reviewers. The data were synthesised using a narrative approach because of the anticipated heterogeneity of included studies. Results: Initial searches yielded 1225 relevant articles for screening, of which 43 met the inclusion criteria. The interactions between local anaesthetics and chemotherapeutic agents were diverse and multifaceted. In vitro studies frequently demonstrated altered cytotoxicity profiles when these agents were combined, with variations depending on the specific drug combination and cancer cell type. Mechanistically, some interactions were attributed to modifications in efflux pump activity, tumour suppressor gene expression, or alterations in cellular signalling pathways associated with tumour promotion. A large majority of in vitro studies report potentially beneficial effects of local anaesthetics in terms of enhancing the antineoplastic activity of chemotherapeutic agents. In animal models, the combined administration of local anaesthetics and chemotherapeutic agents showed largely beneficial effects on tumour growth, metastasis, and overall survival. Notably, no clinical study examining the possible interactions of local anaesthetics and chemotherapy on cancer outcomes has been reported. Conclusions: Reported preclinical interactions between local anaesthetics and chemotherapeutic agents are complex and encompass a spectrum of effects which are largely, although not uniformly, additive or synergistic. The clinical implications of these interactions remain unclear because of the lack of prospective trials. Nonetheless, the modulation of chemotherapy effects by local anaesthetics warrants further clinical investigation in the context of cancer surgery where they could be used together. Clinical trial registration: Open Science Framework (OSF, project link: https://osf.io/r2u4z).

Pathological findings associated with the updated European Society of Cardiology 2022 guidelines for preoperative cardiac testing: an observational cohort modelling study.

BACKGROUND: In 2022, the European Society of Cardiology updated guidelines for preoperative evaluation. The aims of this study were to quantify: (1) the impact of the updated recommendations on the yield of pathological findings compared with the previous guidelines published in 2014; (2) the impact of preoperative B-type natriuretic peptide (NT-proBNP) use for risk estimation on the yield of pathological findings; and (3) the association between 2022 guideline adherence and outcomes. METHODS: This was a secondary analysis of MET-REPAIR, an international, prospective observational cohort study (NCT03016936). Primary endpoints were reduced ejection fraction (EF<40%), stress-induced ischaemia, and major adverse cardiovascular events (MACE). The explanatory variables were class of recommendations for transthoracic echocardiography (TTE), stress imaging, and guideline adherence. We conducted second-order Monte Carlo simulations and multivariable regression. RESULTS: In total, 15,529 patients (39% female, median age 72 [inter-quartile range: 67-78] yr) were included. The 2022 update changed the recommendation for preoperative TTE in 39.7% patients, and for preoperative stress imaging in 12.9% patients. The update resulted in missing 1 EF <40% every 3 fewer conducted TTE, and in 4 additional stress imaging per 1 additionally detected ischaemia events. For cardiac stress testing, four more investigations were performed for every 1 additionally detected ischaemia episodes. Use of NT-proBNP did not improve the yield of pathological findings. Multivariable regression analysis failed to find an association between adherence to the updated guidelines and MACE. CONCLUSIONS: The 2022 update for preoperative cardiac testing resulted in a relevant increase in tests receiving a stronger recommendation. The updated recommendations for TTE did not improve the yield of pathological cardiac testing.

Regional anaesthesia truncal blocks for acute postoperative pain and recovery: a narrative review.

Significant acute postoperative pain remains prevalent among patients who undergo truncal surgery and is associated with increased morbidity, prolonged patient recovery, and increased healthcare costs. The provision of high-quality postoperative analgesia is an important component of postoperative care, particularly within enhanced recovery programmes. Regional anaesthetic techniques have become increasingly prevalent within multimodal analgesic regimens and the widespread adoption of ultrasonography has facilitated the development of novel fascial plane blocks. The number of described fascial plane blocks has increased significantly over the past decade, leading to a burgeoning area of clinical investigation. Their applications are increasing, and truncal fascial plane blocks are increasingly recommended as part of procedure-specific guidelines. Some fascial plane blocks have been shown to be more efficacious than others, with favourable side-effect profiles compared with neuraxial analgesia, and are increasingly utilised in breast, thoracic, and other truncal surgery. However, use of these blocks is debated in regional anaesthesia circles because of limitations in our understanding of their mechanisms of action. This narrative review evaluates available evidence for the analgesic efficacy of the most commonly practised fascial plane blocks in breast, thoracic, and abdominal truncal surgery, in particular their efficacy compared with systemic analgesia, alternative blocks, and neuraxial techniques. We also highlight areas where investigations are ongoing and suggest priorities for original investigations.

Tumour excisional surgery, anaesthetic-analgesic techniques, and oncologic outcomes: a narrative review.

Cancer is a growing global burden; there were an estimated 18 million new cancer diagnoses worldwide in 2020. Excisional surgery remains one of the main treatments for solid organ tumours in cancer patients and is potentially curative. Cancer- and surgery-induced inflammatory processes can facilitate residual tumour cell survival, growth, and subsequent recurrence. However, it has been hypothesised that anaesthetic and analgesic techniques during surgery might influence the risk of cancer recurrence. This narrative review aims to provide an updated summary of recent observational studies and new randomised controlled clinical trials on whether certain specific anaesthetic and analgesic techniques or perioperative interventions during tumour resection surgery of curative intent materially affect long-term oncologic outcomes.

Anaesthetic Techniques and Strategies: Do They Influence Oncological Outcomes?

BACKGROUND: With the global disease burden of cancer increasing, and with at least 60% of cancer patients requiring surgery and, hence, anaesthesia over their disease course, the question of whether anaesthetic and analgesia techniques during primary cancer resection surgery might influence long term oncological outcomes assumes high priority. METHODS: We searched the available literature linking anaesthetic-analgesic techniques and strategies during tumour resection surgery to oncological outcomes and synthesised this narrative review, predominantly using studies published since 2019. Current evidence is presented around opioids, regional anaesthesia, propofol total intravenous anaesthesia (TIVA) and volatile anaesthesia, dexamethasone, dexmedetomidine, non-steroidal anti-inflammatory medications and beta-blockers. CONCLUSIONS: The research base in onco-anaesthesia is expanding. There continue to be few sufficiently powered RCTs, which are necessary to confirm a causal link between any perioperative intervention and long-term oncologic outcome. In the absence of any convincing Level 1 recommending a change in practice, long-term oncologic benefit should not be part of the decision on choice of anaesthetic technique for tumour resection surgery.

Current practice in the perioperative management of patients with diabetes mellitus: a narrative review.

The prevalence of diabetes is increasing, and patients with diabetes mellitus have both an increased likelihood of requiring surgery and of developing postoperative complications when they do. We summarise available evidence underpinning current guidelines on preoperative assessment and optimisation, perioperative management of prescribed insulin and oral hypoglycaemic medication, intraoperative glycaemic control, and postoperative patient care.

Anaesthesia, analgesia, and cancer outcomes: time to think like oncologists?

Cao and colleagues present a follow-up analysis of a previous RCT among >1200 older adults (mean age 72 yr) undergoing cancer surgery, originally designed to evaluate the effect of propofol or sevoflurane general anaesthesia on delirium, here to evaluate the effect of anaesthetic technique on overall survival and recurrence-free survival. Neither anaesthetic technique conferred an advantage on oncological outcomes. We suggest that although it is entirely plausible that the observed results are truly robust neutral findings, the present study could be limited, like most published studies in the field, by its heterogeneity and understandable absence of underlying individual patient-specific tumour genomic data. We argue for a precision oncology approach to onco-anaesthesiology research that recognises that cancer is not one but rather many diseases and that tumour genomics (and multi-omics) is a fundamental determinant relating drugs to longer-term outcomes.

Anaesthesia and cancer recurrence: the influence of perioperative anaesthetic technique on cancer recurrence after surgery.

PURPOSE OF REVIEW: Cancer is a leading cause of death worldwide, and incidence is increasing. Excisional surgery is essential in approximately 70% of solid organ tumours. Emerging research in onco-anaesthesiology suggests that perioperative anaesthetic and analgesic techniques might influence long-term oncologic outcomes. RECENT FINDINGS: Prospective, randomized control trials (RCTs) demonstrate that perioperative regional and neuraxial anaesthetic techniques do not affect cancer recurrence. Ongoing trials are investigating the potential outcome benefits of systemic lidocaine. Retrospective studies indicate improved postoperative oncologic outcomes for certain types of breast cancer with higher intraoperative opioid dosage, nuancing available evidence on the effect of opioids. RCT evidence suggests that propofol has no beneficial effect compared with volatiles on breast cancer recurrence, although it remains unclear whether this applies to other cancer types. SUMMARY: Although regional anaesthesia definitively does not affect cancer recurrence, ongoing prospective RCTs with oncological outcomes as primary endpoints are awaited to establish if other anaesthetic or analgesic techniques influence cancer recurrence. Until such trials conclusively identify a causal relationship, insufficient evidence exists to recommend specific anaesthetic or analgesic techniques for tumour resection surgery based on altering the patient's risk of recurrence.

Postoperative recovery with continuous erector spinae plane block or video-assisted paravertebral block after minimally invasive thoracic surgery: a prospective, randomised controlled trial.

BACKGROUND: PROcedure SPECific Postoperative Pain ManagemenT (PROSPECT) guidelines recommend erector spinae plane (ESP) block or paravertebral block (PVB) for postoperative analgesia after video-assisted thoracoscopic surgery (VATS). However, there are few trials comparing the effectiveness of these techniques on patient-centric outcomes, and none evaluating chronic postsurgical pain (CPSP). Furthermore, there are no available trials comparing ultrasound-guided ESP with surgically placed PVB in this patient cohort. METHODS: We conducted a two-centre, prospective, randomised, double-blind, controlled trial, comparing anaesthesiologist-administered, ultrasound-guided ESP catheter with surgeon-administered, video-assisted PVB catheter analgesia among 80 adult patients undergoing VATS. Participants received a 20 ml bolus of levobupivacaine 0.375% followed by infusion of levobupivacaine 0.15% (10-15 ml h-1) for 48 h. Primary outcome was Quality of Recovery-15 score (QoR-15) at 24 h. Secondary outcomes included QoR-15 at 48 h, peak inspiratory flow (ml s-1) at 24 h and 48 h, area under the pain verbal response score vs time curve (AUC), opioid consumption, Comprehensive Complication Index, length of stay, and CPSP at 3 months after surgery. RESULTS: Median (25-75%) QoR-15 at 24 h was higher in ESP (n=37) compared with PVB (n=37): 118 (106-134) vs 110 (89-121) (P=0.03) and at 48 h: 131 (121-139) vs 120 (111-133) (P=0.03). There were no differences in peak inspiratory flow, AUC, Comprehensive Complication Index, length of hospital stay, and opioid consumption. Incidence of CPSP at 3 months was 12 (34%) for ESP and 11 (31%) for PVB (P=0.7). CONCLUSIONS: Compared with video-assisted, surgeon-placed paravertebral catheter, erector spinae catheter improved overall QoR-15 scores at 24 h and 48 h but without differences in pain or opioid consumption after minimally invasive thoracic surgery. CLINICAL TRIAL REGISTRATION: NCT04729712.

Investigating the Influence of Anaesthesiology for Cancer Resection Surgery on Oncologic Outcomes: The Role of Experimental In Vivo Models.

The incidence and societal burden of cancer is increasing globally. Surgery is indicated in the majority of solid tumours, and recent research in the emerging field of onco-anaesthesiology suggests that anaesthetic-analgesic interventions in the perioperative period could potentially influence long-term oncologic outcomes. While prospective, randomised controlled clinical trials are the only research method that can conclusively prove a causal relationship between anaesthetic technique and cancer recurrence, live animal (in vivo) experimental models may more realistically test the biological plausibility of these hypotheses and the mechanisms underpinning them, than limited in vitro modelling. This review outlines the advantages and limitations of available animal models of cancer and how they might be used in perioperative cancer metastasis modelling, including spontaneous or induced tumours, allograft, xenograft, and transgenic tumour models.

Ultrasound-guided, continuous erector spinae plane (ESP) block in minimally invasive thoracic surgery-comparing programmed intermittent bolus (PIB) vs continuous infusion on quality of recovery and postoperative respiratory function: a double-blinded randomised controlled trial.

BACKGROUND: Minimally invasive thoracic surgery (MITS) has been shown to reduce postoperative pain and contribute to better postoperative quality of life as compared to open thoracic surgery (Bendixen et al., Lancet Oncol 17:836-44, 2016). However, it still causes significant post-operative pain. Regional anaesthesia techniques including fascial plane blocks such as the erector spinae plane block (ESP) have been shown to contribute to post-operative pain control after MITS (Finnerty et al., Br J Anaesth 125:802-10, 2020). Case reports relating to ESP catheters have described improved quality of pain relief using programmed intermittent boluses (PIB) instead of continuous infusion (Bendixen et al., Lancet Oncol 17:836-44, 2016). It is suggested that larger, repeated bolus dose may provide superior pain relief, possibly because of improved spread of the local anaesthetic medications (Ilfeld and Gabriel, Reg Anesth Pain Med 44:285-86, 2019). Evidence for improved spread of local anaesthetic may be found in one study which demonstrated that PIB increased the spread of local anaesthetic medication compared to continuous infusions for continuous paravertebral blocks, which are another type of regional anaesthesia technique for the chest wall (Hida et al., Reg Anesth Pain Med 44:326-32, 2019). Similarly, regarding labour epidural analgesia, the weight of evidence is in favour of PIB providing better pain relief compared with continuous infusion (Onuoha, Anesthesiol Clin 35:1-14, 2017). Since fascial plane blocks, such as ESP, rely on the spread of local anaesthetic medication between muscle layers of the chest wall, intermittent boluses may be particularly useful for this group of blocks. However, until recently, pumps capable of providing automated boluses in addition to patient-controlled boluses were not widely available. To best of our knowledge, there are no randomised controlled trials comparing continuous infusion versus intermittent bolus strategies for erector spinae plane block for MITS in terms of patient centred outcomes such as quality of recovery. METHODS: This trial will be a prospective, double-blinded, randomised controlled superiority trial. A total of 60 eligible patients will be randomly assigned to receive an intermittent bolus regime of local anaesthetic vs a continuous infusion of local anaesthetic. The medication will be delivered via an ultrasound-guided erector spinae plane block catheter which will be inserted by an anaesthesiologist while the patient is under general anaesthetic before their MITS surgery begins. The primary outcome being measured is the Quality of Recovery (QoR-15) score between the two groups 24 h after surgery. Secondary outcomes include respiratory testing of maximal inspiratory volume measured with a calibrated incentive spirometer, area under the curve for Verbal Rating Score for pain at rest and on deep inspiration versus time over 48 h, total opioid consumption over 48 h, QoR-15 score at 48 h and time to first mobilisation. DISCUSSION: Despite surgical advancements in thoracic surgery, severe acute post-operative pain following MITS is still prevalent. This study will provide new knowledge and possible recommendations about the efficacy of programmed intermittent bolus regimen of local anaesthetic vs a continuous infusion of local anaesthetic via an ultrasound-guided erector spinae plane catheter for patients undergoing MITS. TRIAL REGISTRATION: This trial was pre-registered on ClinicalTrials.gov Identifier: NCT05181371 . Registered on 6 January 2022. All item from the World Health Organization Trial Registration Data set have been included.

Regional and neuraxial anaesthesia techniques for spinal surgery: a scoping review.

BACKGROUND: Whilst general anaesthesia is commonly used to undertake spine surgery, the use of neuraxial and peripheral regional anaesthesia techniques for intraoperative and postoperative analgesia is an evolving practice. Variations in practice have meant that it is difficult to know which modalities achieve optimal outcomes for patients undergoing spinal surgery. Our objective was to identify available evidence on the use of regional and neuraxial anaesthesia techniques for adult patients undergoing spinal surgery. METHODS: This study was conducted using a framework for scoping reviews. This included a search of six databases searching for articles published since January 1980. We included studies that involved adult patients undergoing spinal surgery with regional or neuraxial techniques used as the primary anaesthesia method or as part of an analgesic strategy. RESULTS: Seventy-eight articles were selected for final review. All original papers were included, including case reports, case series, clinical trials, or conference publications. We found that general anaesthesia remains the most common anaesthesia technique for this patient cohort. However, regional anaesthesia, especially non-neuraxial techniques such as fascial plane blocks, is an emerging practice and may have a role in terms of improving postoperative pain relief, quality of recovery, and patient satisfaction. In comparison with neuraxial techniques, the popularity of fascial plane blocks for spinal surgery has significantly increased since 2017. CONCLUSIONS: Regional and neuraxial anaesthesia techniques have been used both to provide analgesia and anaesthesia for patients undergoing spinal surgery. Outcome metrics for the success of these techniques vary widely and more frequently use physiological outcome metrics more than patient-centred ones.

Solid Tumor Opioid Receptor Expression and Oncologic Outcomes: Analysis of the Cancer Genome Atlas and Genotype Tissue Expression Project.

Background: Opioid receptors are expressed not only by neural cells in the central nervous system, but also by many solid tumor cancer cells. Whether perioperative opioids given for analgesia after tumor resection surgery might inadvertently activate tumor cells, promoting recurrence or metastasis, remains controversial. We analysed large public gene repositories of solid tumors to investigate differences in opioid receptor expression between normal and tumor tissues and their association with long-term oncologic outcomes. Methods: We investigated the normalized gene expression of µ, κ, δ opioid receptors (MOR, KOR, DOR), Opioid Growth Factor (OGFR), and Toll-Like 4 (TLR4) receptors in normal and tumor samples from twelve solid tumor types. We carried out mixed multivariable logistic and Cox regression analysis on whether there was an association between these receptors' gene expression and the tissue where found, i.e., tumor or normal tissue. We also evaluated the association between tumor opioid receptor gene expression and patient disease-free interval (DFI) and overall survival (OS). Results: We retrieved 8,780 tissue samples, 5,852 from tumor and 2,928 from normal tissue, of which 2,252 were from the Genotype Tissue Expression Project (GTEx) and 672 from the Cancer Genome Atlas (TCGA) repository. The Odds Ratio (OR) [95%CI] for gene expression of the specific opioid receptors in the examined tumors varied: MOR: 0.74 [0.63-0.87], KOR: 1.27 [1.17-1.37], DOR: 1.66 [1.48-1.87], TLR4: 0.29 [0.26-0.32], OGFR: 2.39 [2.05-2.78]. After controlling all confounding variables, including age and cancer stage, there was no association between tumor opioid receptor expression and long-term oncologic outcomes. Conclusion: Opioid receptor gene expression varies between different solid tumor types. There was no association between tumor opioid receptor expression and recurrence. Understanding the significance of opioid receptor expression on tumor cells remains elusive.

Multimodal opioid sparing onco-anesthesia: A consensus practice guideline from Society of Onco-Anesthesia and Perioperative Care (SOAPC).

Opioids are an indispensable part of perioperative pain management of cancer surgeries. Opioids do have some side effects and abuse potential, and some laboratory data suggest a possible association of cancer recurrence with perioperative opioid use. Opioid-free anesthesia and opioid-sparing anesthesia are emerging new concepts worldwide to safeguard patients from adverse effects of opioids and potential abuse. Opioid-free anesthesia could lead to ineffective pain management, leaving the perioperative physician with limited options, while opioid-sparing anesthesia may be a rational approach. This consensus guideline includes general considerations of the safe use of perioperative opioids along with concomitant use of central neuraxial or regional blockade and systematic nonopioid analgesics. Region-specific onco-surgeries with their specific recommendations and consensus statements for judicious use of opioids are suggested. Use of epidural analgesia or regional catheter during thoracic, abdominal, pelvic, and lower limb surgeries and use of regional nerve blocks/catheter in head neck, neuro, and upper limb onco-surgeries, wherever possible along with nonopioids analgesics, are suggested. Short-acting opioids in small aliquots may be allowed to control breakthrough pain for expedient control of pain. The purpose of this consensus practice guideline is to provide the practicing anesthesiologists with best practice evidence and consensus recommendations by the expert committee of the Society of Onco-Anesthesia and Perioperative Care for safe opioid use in onco-surgeries.

Protocol for a prospective, international cohort study on the Management and Outcomes of Perioperative Care among European Diabetic Patients (MOPED).

INTRODUCTION: Diabetes is common (about 20 million patients in Europe) and patients with diabetes have more surgical interventions than the general population. There are plausible pathophysiological and clinical mechanisms suggesting that patients with diabetes are at an increased risk of postoperative complications. When postoperative complications occur in the general population, they increase major adverse events and subsequently increase 1-year mortality. This is likely to be worse in patients with diabetes. There is variation in practice guidelines in different countries in the perioperative management of patients with diabetes undergoing major surgery and whether this may affect postoperative outcome has not been investigated on a large scale. Neither is it known whether different strata of preoperative glycaemic control affects outcome. METHODS AND ANALYSIS: A prospective, observational, international, multicentre cohort study, recruiting 5000 patients with diabetes undergoing elective or emergency surgery in at least n=50 centres. Inclusion criteria are any patient with diabetes undergoing surgery under any substantive anaesthetic technique. Exclusion criteria are not being a confirmed diabetic patient and patients with diabetes undergoing procedures under monitored sedation or local anaesthetic infiltration only. Follow-up duration is 30 days after surgery. Primary outcome is days at home at 30 days. Secondary outcomes are Comprehensive Complications Index, Quality of Recovery (QoR-15) score on Day 1 postoperatively, 30-day mortality, length of hospital stay and incidence of specific major adverse events (Myocardial Infarction (MI), Myocardial Injury after Non-cardiac Surgery (MINS), Acute Kidney Injury (AKI), Postoperative Pulmonary Complications (PPC), Cerebrovascular Accident (CVA), Pulmonary Embolism (PE), DVT, surgical site infection, postoperative pulmonary infection). Tertiary outcomes include time to resumption of normal diabetes therapy, incidence of diabetic ketoacidosis or hypoglycaemia, incidence and duration of use of intravenous insulin infusion therapy and change in diabetic management at 30 days. ETHICS AND DISSEMINATION: This study will adhere to the principles of the Declaration of Helsinki (amendment 2013) by the World Medical Association and the ICH-Good Clinical Practice (GCP) Guidelines E6(R2). Specific national and local regulatory authority requirements will be followed as applicable. Ethical approval has been granted by the Institutional Review Board of the Mater Misericordiae University Hospital, Dublin, Ireland (Reference: 1/378/2167). As enrolment for this study is ongoing, ethical approval from additional centres is being added continuously. The main results of Management and Outcomes of Perioperative Care among European Diabetic Patients and its substudies will be published in peer-reviewed international medical journals and presented at Euroanaesthesia congress and other international and national meetings. TRIAL REGISTRATION NUMBER: NCT04511312.

Neutrophil Extracellular Trapping Role in Cancer, Metastases, and Cancer-Related Thrombosis: a Narrative Review of the Current Evidence Base.

PURPOSE OF REVIEW: Neutrophil extracellular trap (NET) formation is a newly discovered, reactive oxygen species-dependent regulated process, whereby neutrophils degranulate and extrude genetic material, after engulfing various infectious or neoplastic antigens, culminating in a measurable serologic footprint. Recent research has highlighted the involvement of NETs in cancer and cancer-related pathologies. We review the role of NET formation in cancer biology, prognosis and potential therapeutic modulators. RECENT FINDINGS: Elevated NET levels are associated with cancer metastasis and may be modified by some anaesthetic-analgesic techniques during tumour resection surgery. It promotes tumour cell migration, angiogenesis and hypercoagulability. Although there are potential anti-NET formation therapeutics available, their role has not been formally assessed in cancer patients. Limited available evidence suggests an association between elevated NET expression and cancer metastasis, but its validity as a prognostic indicator for cancer-related outcomes is inconclusive. Further observational and interventional studies are warranted to comprehend the potential prognostic and therapeutic role of NETs in cancer.

Perioperative Intravenous Lidocaine and Metastatic Cancer Recurrence - A Narrative Review.

Cancer is a major global health problem and the second leading cause of death worldwide. When detected early, surgery provides a potentially curative intervention for many solid organ tumours. Unfortunately, cancer frequently recurs postoperatively. Evidence from laboratory and retrospective clinical studies suggests that the choice of anaesthetic and analgesic agents used perioperatively may influence the activity of residual cancer cells and thus affect subsequent recurrence risk. The amide local anaesthetic lidocaine has a well-established role in perioperative therapeutics, whether used systemically as an analgesic agent or in the provision of regional anaesthesia. Under laboratory conditions, lidocaine has been shown to inhibit cancer cell behaviour and exerts beneficial effects on components of the inflammatory and immune responses which are known to affect cancer biology. These findings raise the possibility that lidocaine administered perioperatively as a safe and inexpensive intravenous infusion may provide significant benefits in terms of long term cancer outcomes. However, despite the volume of promising laboratory data, robust prospective clinical evidence supporting beneficial anti-cancer effects of perioperative lidocaine treatment is lacking, although trials are planned to address this. This review provides a state of the art summary of the current knowledge base and recent advances regarding perioperative lidocaine therapy, its biological effects and influence on postoperative cancer outcomes.