Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial

Background: Enhanced recovery following surgery can be achieved through the introduction of evidence-based perioperative maneuvers. This review aims to present a consensus for optimal perioperative ...

Consensus Review of Optimal Perioperative Care in Breast Reconstruction: Enhanced Recovery after Surgery (ERAS) Society Recommendations.

Volatile general anesthetics continue to be an important part of clinical anesthesia worldwide The impact of volatile anesthetics on the immune system has been investigated at both mechanistic and clinical levels, but previous studies have returned conflicting findings due to varied protocols, experimental environments, and subject species While many of these studies have focused on the immunosuppressive effects of volatile anesthetics, compelling evidence also exists for immunoactivation Depending on the clinical conditions, immunosuppression and activation due to volatile anesthetics can be either detrimental or beneficial This review provides a balanced perspective on the anesthetic modulation of innate and adaptive immune responses as well as indirect effectors of immunity Potential mechanisms of immunomodulation by volatile anesthetics are also discussed A clearer understanding of these issues will pave the way for clinical guidelines that better account for the impact of volatile anesthetics on the immune system, with the ultimate goal of improving perioperative management

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Immune Modulation by Volatile Anesthetics

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.

Despite progressive improvements in the management of patients with locoregionally confined, advanced-stage solid tumours, distant metastasis remains a very common - and usually fatal - mode of failure after attempted curative treatment. Surgery and radiotherapy are the primary curative modalities for these patients, often combined with each other and/or with chemotherapy. Distant metastasis occurring after treatment can arise from previously undetected micrometastases or, alternatively, from persistent locoregional disease. Another possibility is that treatment itself might sometimes cause or promote metastasis. Surgical interventions in patients with cancer, including biopsies, are commonly associated with increased concentrations of circulating tumour cells (CTCs). High CTC numbers are associated with an unfavourable prognosis in many cancers. Radiotherapy and systemic antitumour therapies might also mobilize CTCs. We review the preclinical and clinical data concerning cancer treatments, CTC mobilization and other factors that might promote metastasis. Contemporary treatment regimens represent the best available curative options for patients who might otherwise die from locally confined, advanced-stage cancers; however, if such treatments can promote metastasis, this process must be understood and addressed therapeutically to improve patient survival.

Does the mobilization of circulating tumour cells during cancer therapy cause metastasis

Background Animal models and retrospective clinical data suggest that certain anaesthetic techniques can attenuate immunosuppression and minimize metastasis after cancer surgery. Natural killer (NK) T cells are a critical component of the anti-tumour immune response. We investigated the effect of serum from women undergoing primary breast cancer surgery, randomized to propofol–paravertebral block (PPA) or sevoflurane–opioid (GA) anaesthetic techniques, on healthy human donor NK cell function and cytotoxicity against oestrogen and progesterone receptor-positive breast cancer cells (HCC1500). Methods Ten subjects who donated serum before operation and 24 h after operation in an ongoing randomized prospective trial (NCT 00418457) were randomly selected. Serum from PPA ( n =5) and GA ( n =5) subjects was co-cultured with HCC1500 and healthy primary NK cells. NK cell activating receptors (NKp30, NKp44, NKp46, 2b4, CD16, NKG2D), cytokine production, NK CD107a expression, and cytotoxicity towards HCC1500 were examined. Results Serum from PPA subjects did not alter normal NK marker expression or secretion of cytokines. Serum from GA subjects reduced NK cell activating receptor CD16 [from mean (sem), 82 (2)% to 50 (4)%, P =0.001], IL-10 [from 1700 (80) to 1200 (92) pg ml −1 , P =0.001], and IL-1β [from 68 (12) to 19 (4) pg ml −1 , P =0.01]. An increase in NK cell CD107a [23 (2)% to 37(3)%, P =0.007] and apoptosis of HCC1500 [11 (1)% to 21 (2)%, P =0.0001] was observed with PPA serum, but not GA serum, treated NK cells. Conclusion Serum from women with breast cancer undergoing surgical excision who were randomized to receive a PPA anaesthetic technique led to greater human donor NK cell cytotoxicity in vitro compared with serum from women who received GA. Clinical trial registration NCT 041857.

Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: a pilot study.

http://bja.oxfordjournals.org/content/111/5/855P.full.pdf

The ‘College of Anaesthetists of Ireland’—Delaney Medal Competition Held at College of Anaesthetists of Ireland, Thursday, 14 March 2013, 22 Merrion Square North, Dublin, Ireland

Clinicians may wish to assess differences in diaphragmatic excursion between the right and left lung at the point of care, in order to exclude diaphragmatic pathology (e.g. phrenic nerve palsy), particularly if a chest X-ray is not available. We conducted an exploratory study comparing the accuracy of lung auscultation against lung ultrasound for point-of-care assessment of the extent of basal lung excursion during maximal inspiration (Austin Human Research Ethics Committee approval LNR/21/Austin/19). A height difference of more than one intercostal space (ICS) between diaphragmatic domes during maximal inspiration on chest X-ray is a commonly used ‘rule of thumb’ suggesting reduced basal lung ventilation on the affected side. 1 We compared the most caudad point of audible breath sounds by stethoscope auscultation to the most caudad point of visible ‘sliding lung’ sign using B-mode ultrasound (US) at the bases of both lungs on 25 healthy consenting volunteers at maximal inspiration, along bilateral parallel lines drawn on the skin at 5 cm from the line of the spinous processes (Figure 1). This most caudad point of visible ‘sliding lung’ sign is known as the ‘lung point’ when used to diagnose pneumothorax, defining an interface at which mobile apposition of the parietal and visceral pleura is lost. US was considered the reference standard for data analysis. Anecdotally, we had previously observed that US detected reduced basal lung expansion by loss of lung point descent and a more cranial lung point at maximal inspiration in two patients scanned pre and post interscalene block. To identify a reference height difference comparable to measurements using a chest X-ray, we measured the perpendicular

A. Buckley

Papers

Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: a pilot study.

The ‘College of Anaesthetists of Ireland’—Delaney Medal Competition Held at College of Anaesthetists of Ireland, Thursday, 14 March 2013, 22 Merrion Square North, Dublin, Ireland

Lung auscultation versus point-of-care ultrasound for assessment of basal lung excursion at maximal inspiration: An exploratory study

The College of Anaesthetists of Ireland: Delaney Medal Competition 2014 College of Anaesthetists of Ireland, Dublin, Ireland, March 6, 2014