Effect of anterior quadratus lumborum block with ropivacaine on the immune response after laparoscopic surgery in colon cancer: a substudy of a randomized clinical trial.

BACKGROUND: Surgery induces a temporal change in the immune system, which might be modified by regional anesthesia. Applying a bilateral preoperative anterior quadratus lumborum block has proven to be a safe and effective technique in pain management after abdominal and retroperitoneal surgery, but the effect on the immune response is not thoroughly investigated. METHODS: This study is a substudy of a randomized, controlled, double-blinded trial of patients undergoing laparoscopic hemicolectomy due to colon cancer. Twenty-two patients were randomized to undergo either a bilateral anterior quadratus lumborum nerve block with a total of 60 mL ropivacaine 0.375% or placebo with corresponding isotonic saline injections. The main objective of this exploratory substudy was to investigate the systemic immune response in the first postoperative day by examining changes in blood transcript levels (n=750) and stimulated secretion of cytokines (n=17) on ex vivo activation with microbial ligands and anti-CD3/CD28. RESULTS: Using unsupervised data analysis tools, we observed no effect of the bilateral anterior quadratus lumborum nerve block on gene expression in immune cells (permutational multivariate analysis of variance using distance matrices: F=0.52, p=0.96), abundances of major immune cell populations (Wilcoxon rank-sum test: p>0.05), and stimulated cytokine secretion (Wilcoxon rank-sum test: p>0.05). CONCLUSIONS: Our study provides evidence that administration of bilateral anterior quadratus lumborum nerve block as a part of a multimodal analgesic regimen in an enhanced recovery after surgery for laparoscopic hemicolectomy in this cohort does not alter the systemic immune response.Trial registration number NCT03570541.

Anterior quadratus lumborum block does not reduce postoperative opioid consumption following laparoscopic hemicolectomy: a randomized, double-blind, controlled trial in an ERAS setting.

BACKGROUND AND AIMS: An opioid-sparing postoperative analgesic regimen following laparoscopic hemicolectomy is optimal to promote minimal postoperative pain, early mobilization, and improved quality of recovery. Various regional anesthesia techniques have been tested to improve postoperative pain management after laparoscopic hemicolectomy. In this study, we aimed to assess the effect of administering a preoperative bilateral ultrasound-guided anterior quadratus lumborum nerve block on postoperative opioid consumption after laparoscopic colon cancer surgery. METHODS: In this randomized, controlled, double-blinded trial, 69 patients undergoing laparoscopic hemicolectomy due to colon cancer were randomized to receive an anterior quadratus lumborum block with ropivacaine 0.375% 30 mL on each side or isotonic saline (placebo). The primary outcome measure was total opioid consumption during the first 24 hours postsurgery. The secondary outcome measures were pain scores, accumulated opioid consumption in 6-hour intervals, nausea and vomiting, ability of postoperative ambulation, time to first opioid, orthostatic hypotension or intolerance, postoperative Quality of Recovery-15 scores, surgical complications, length of hospital stay, and adverse events. RESULTS: The total opioid consumption in the first 24 hours postsurgery was not significantly reduced in the ropivacaine group compared with the saline group (mean 129 mg (SD 88.4) vs mean 127.2 mg (SD 89.9), p=0.93). In addition, no secondary outcome measures showed any statistically significant intergroup differences. CONCLUSION: The administration of a preoperative bilateral anterior quadratus lumborum nerve block as part of a multimodal analgesic regimen for laparoscopic hemicolectomy did not significantly reduce opioid consumption 24 hours postsurgery. Trial registration number NCT03570541.

An exploration of immunohistochemistry-based prognostic markers in patients undergoing curative resections for colon cancer.

BACKGROUND: The immune system recognizes and destroys cancer cells. However, cancer cells develop mechanisms to avoid detection by expressing cell surface proteins. Specific tumour cell surface proteins (e.g. HLA-G, PD-L1, CDX2) either alone or in combination with the relative presence of immune cells (CD3 and CD8 positive T-cells) in the tumour tissue may describe the cancer cells' ability to escape eradication by the immune system. The aim was to investigate the prognostic value of immunohistochemical markers in patients with colon cancer. METHODS: We conducted a retrospective study including patients diagnosed with pT3 and pT4 colon cancers. Immunohistochemical staining with HLA-G, PD-L1, CDX2, CD3, and CD8 was performed on tissue samples with representation of the invasive margin. PD-L1 expression in tumour cells and immune cells was reported conjointly. The expression of CD3 and CD8 was reported as a merged score based on the expression of both markers in the invasive margin and the tumour centre. Subsequently, a combined marker score was established based on all of the markers. Each marker added one point to the score when unfavourable immunohistochemical features was present, and the score was categorized as low, intermediate or high depending on the number of unfavourable stains. Hazard ratios for recurrence, disease-free survival and mortality were calculated. RESULTS: We included 188 patients undergoing colon cancer resections in 2011-2012. The median follow-up was 41.7 months, during which 41 (21.8%) patients had recurrence and 74 (39.4%) died. In multivariable regression analysis positive HLA-G expression (HR = 3.37, 95%CI [1.64-6.93]) was associated with higher recurrence rates, while a preserved CDX2 expression (HR = 0.23, 95%CI [0.06-0.85]) was associated with a lower risk of recurrence. An intermediate or high combined marker score was associated with increased recurrence rates (HR = 20.53, 95%CI [2.68-157.32] and HR = 7.56, 95%CI [1.06-54.16], respectively). Neither high expression of PD-L1 nor high CD3-CD8 score was significantly associated with recurrence rates. Patients with a high CD3-CD8 score had a significantly longer DFS and OS. CONCLUSIONS: In tumour cells, expression of HLA-G and loss of CDX2 expression were associated with cancer recurrence. In addition, a combination of certain tumour tissue biomarkers was associated with colorectal cancer recurrence.

Effect of sevoflurane versus propofol on neutrophil-to-lymphocyte ratio in healthy individuals: a sub-study of a randomised crossover trial.

Background: Sevoflurane and propofol are commonly used drugs in general anaesthesia. However, their effects on perioperative immune function are incompletely understood. We hypothesised that sevoflurane and propofol differentially affect immune function in healthy individuals. Therefore, we investigated the effect of sevoflurane and propofol on neutrophil-to-lymphocyte ratio before, during, and after general anaesthesia. Methods: In this randomised crossover study, 19 healthy individuals underwent 2 h of general anaesthesia with either propofol or sevoflurane. After 4 weeks, anaesthesia was repeated using the other drug. Blood samples were obtained before, during, 1 h after, and 1 day after anaesthesia. The primary outcome was whole-blood neutrophil-to-lymphocyte ratio, and secondary outcomes were specific white blood cell differential counts. A linear mixed-effects model was used to estimate effect sizes. Results: The neutrophil-to-lymphocyte ratio was higher in the propofol compared with the sevoflurane group during anaesthesia, 2.8 (confidence interval [CI]: 2.3-3.3) vs 1.6 (CI: 1.1-2.1), and 1 day after anaesthesia, 2.6 (CI: 2.1-3.1) vs 1.9 (CI: 1.4-2.4). In all patients, we observed transient lymphopaenia during propofol anaesthesia, 1.1 × 109 cells × L-1 (CI: 0.9-1.4), compared with sevoflurane anaesthesia, 1.9 × 109 cells × L-1 (CI: 1.7-2.1). In addition, neutrophil counts were higher 1 day after propofol anaesthesia, 4.4 × 109 cells × L-1 (CI: 4.0-4.9), compared with sevoflurane anaesthesia, 3.5 × 109 cells × L-1 (CI: 3.1-4.0). We observed no differences in the remaining white blood cell subgroups. Conclusions: In healthy individuals undergoing general anaesthesia without surgery, the neutrophil-to-lymphocyte ratio was affected by the type of hypnotic used. Transient lymphopaenia was observed in all participants during propofol anaesthesia.

Anaesthetic technique and outcomes after colorectal cancer surgery.

INTRODUCTION: Previous studies have suggested that choice of anaesthesia can affect long-term outcome. In this study, the association between type of anaesthesia and outcomes in terms of survival, recurrence, post-operative complications and recovery after surgery for colorectal cancer was investigated in an Enhanced Recovery after Surgery (ERAS) setting. METHODS: This was a retrospective study including patients undergoing elective curative-intended surgery for colorectal cancer between April 2013 and May 2015 at Zealand University Hospital, Denmark. Patients were stratified by anaesthetic technique. The primary outcome was cancer recurrence. Cox regression analyses were used for time-to-event variables; recurrence, disease-free survival, mortality, length of hospitalisation and time to bowel movement. Odds ratios for post-operative complications and time to discharge were estimated using logistic regression. RESULTS: A total of 534 patients were included, 51 were exposed to inhalational anaesthesia and 483 had total intravenous anaesthesia. We found no statistically significant difference in recurrence (hazard ratio (HR) = 0.70; 95% confidence interval (CI): 0.21-1.68; p = 0.421). Patients in the inhalational aneasthesia group had a significantly lower chance of discharge per post-operative day (HR = 0.66; 95% CI: 0.48-0.91; p = 0.012). The same was seen for time to bowel movement (HR = 0.65; 95% CI: 0.46-0.90; p = 0.011). No statistically significant differences were seen for the other outcomes. CONCLUSION: Anaesthetic technique might influence time to discharge and bowel function in an ERAS setting. FUNDING: none TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (record number 2008-58-0020). Under Danish law, consent from participants is not required in observational studies.