Effect of Thoracic Epidural Anesthesia on Perioperative Neutrophil Extracellular Trapping Markers in Patients Undergoing Anesthesia and Surgery for Colorectal Cancer: A Randomized, Controlled Trial.

BACKGROUND: Neutrophil extracellular trapping (NETosis) is an immunologic mechanism strongly linked with increased metastatic risk in colorectal cancer. The authors hypothesized that patients who received propofol-epidural anesthesia (PEA) would exhibit decreases in the expression of serum neutrophil myeloperoxidase (MPO) and citrullinated histone H3 (H3Cit) levels compared with patients who received general anesthesia (GA). METHODS: Colorectal cancer surgery patients were randomly assigned to the PEA (n = 30) or GA (n = 30) group. Serum MPO, H3Cit, and metalloproteinase-9 (MMP-9) levels before surgery and 24 h after surgery were measured, and visual analogue scale (VAS) scores were recorded. RESULTS: The patients who received PEA showed decreases in MPO (28.06 ± 11.23 vs 20.54 ± 7.29 ng/ ml; P = 0.004) and H3Cit [3.22 ± 0.86 vs 2.73 ± 0.94 ng/ ml; P = 0.042) 24 h after surgery compared with the patients subjected to GA. In addition, there was no difference in MMP-9 levels (75.98 ± 26.9 vs 73.45 ± 28.4 ng/ ml; P = 0.726). The visual analogue scale scores 2 h and 24 h after operation were significantly lower in PEA group (P < 0.05). The number of postoperative analgesia pump pressings and sufentanil consumptions within 48 h after surgery were significantly lower in the PEA group (P < 0.001). CONCLUSIONS: Propofol-epidural anesthesia reduces the expression of NETosis (MPO and H3Cit) in serum during colorectal cancer surgery. CLINICAL TRIAL REGISTRATION: ChiCTR2200066708 ( www.chictr.org.cn ).

Surgical trauma contributes to progression of colon cancer by downregulating CXCL4 and recruiting MDSCs.

Surgical stress has been shown to facilitate the tumor growth and metastasis of colon cancer. To unravel the mechanisms underlying surgery induced-colon cancer progression, a syngeneic transplantation tumor model was established with murine colon cancer CT26 cells and the effect of laparotomy on tumor progression was investigated. Especially the expression of several CXC chemokines was assayed, and its roles in regulating myeloid-derived suppressor cells (MDSCs) recruitment were analyzed. We found that laparotomy promoted in vivo tumor growth and angiogenesis. CXCL4 expression was significantly downregulated by laparotomy in the tumor tissue and the peritoneal cavity. Functionally, CXCL4 overexpression significantly reduces tumor volume compared to control. Through analysis of CD11b+/Gr1+ MDSCs cell, we found an upregulated proportion of MDSCs in the tumor tissues and peritoneal cavity following laparotomy, and this enhancement was blocked after CXCL4 overexpression. Further, a negative correlation was found between CXCL4 expression and MDSC amounts in clinical samples. Higher CXCL4 expression and lower MDSCs proportion is positively related to overall survival. CONCLUSION: Surgical trauma contributes to colon cancer progression by downregulating CXCL4 and hence promoting MDSC recruitment, which leads to an immunosuppressive environment.

Ultrasound-Guided Intercostal Nerve Block Following Esophagectomy for Acute Postoperative Pain Relief in the Postanesthesia Care Unit.

OBJECTIVE: To explore the feasibility, effectiveness, and safety of ultrasound-guided intercostal nerve block (ICNB) for immediate relief of moderate and severe pain following esophagectomy in a postanesthesia care unit (PACU). METHODS: Eighty-one patients who complained of moderate to severe pain on arrival to the PACU after an Ivor Lewis esophagectomy were randomly assigned to 2 groups: a sufentanil treatment group (Group A, n = 41) and an intercostal nerve block treatment group (Group B, n = 40). The visual analog scale (VAS) pain scores at rest and on cough at 1, 2, 4, 12, 24, and 48 hours after treatment were monitored. The heart rate, blood pressure, and pulse oxygen saturation (SpO2 ) 2 hours after treatment and the patients' length of stay in the PACU after treatment were recorded. Patient-controlled intravenous analgesia consumption and the incidence of nausea, vomiting, and other adverse reactions were also recorded. RESULTS: Ultrasound-guided ICNB was performed successfully in all patients in Group B without puncture-related complications. The VAS pain scores at rest and on cough at 1, 2, and 4 hours after treatment in Group B were significantly lower than those in Group A (P < 0.05). The consumption of sufentanil and the incidence of nausea and vomiting were significantly decreased in Group B compared with those in Group A. CONCLUSION: Ultrasound-guided ICNB could provide effective and safe pain relief for patients who suffer from moderate to severe pain (VAS score ≥ 5) after esophagectomy in the PACU.

Altered metabolomic profiles may be associated with sevoflurane-induced neurotoxicity in neonatal rats.

Experimental studies demonstrate that inhaled anesthetics can cause neurodegeneration and neurobehavioral dysfunctions. Evidence suggests changes in cerebral metabolism following inhaled anesthetics treatment can perturb cerebral homeostasis, which may be associated with their induced neurotoxicity. Seven-day-old rat pups were divided into two groups: control group (Group C) and sevoflurane group (Group S, 3 % sevoflurane exposure for 6 h). Gas chromatography-mass spectrometry (GC-MS) was used for analyzed differential metabolites of cerebral cortex in both groups, Also western blot, flow cytometry, enzymatic methods and electron microscopy were performed in various biochemical and anatomical assays. Sevoflurane exposure significantly elevated caspase-3 activation and ROS levels, decreased mitochondrial cardiolipin contents, and changed cellular ultrastructure in the cerebral cortex. Correspondingly, these results corroborated the GC-MS findings which showed altered metabolic pathways of glucose, amino acids, and lipids, as well as intracellular antioxidants and osmolyte systems in neonatal brain following prolonged exposure to high sevoflurane concentration. Our data indicate that sevoflurane anesthesia causes significant oxidative stress, neuroapoptosis, and cellular ultrastructure damage which is associated with altered brain metabotype in the neonatal rat. Our study also confirmed that GC-MS is a strategic and complementary platform for the metabolomic characterization of sevoflurane-induced neurotoxicity in the developing brain.

Propofol protects against hydrogen peroxide-induced oxidative stress and cell dysfunction in human umbilical vein endothelial cells.

Propofol has been reported to protect vascular endothelial cells against oxidative stress and dysfunction, but the underlying mechanisms are not clear. In this study, we studied hydrogen peroxide (H(2)O(2))-induced oxidative stress and cell dysfunction in human umbilical vein endothelial cells (HUVECs) and especially, their modulation by propofol. HUVECs were treated with different concentrations (0.1 and 0.5 mM) of H(2)O(2) for different times (1, 3, and 6 h). Then HUVECs were pretreated with different concentrations of propofol (10, 25, and 50 microM), followed by H(2)O(2) treatment (0.5 mM, 3 h). In another set of experiments, we pretreated cells with p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, followed by H(2)O(2) treatment (0.5 mM, 3 h). After treatment, oxidative stress, p38 MAPK phosphorylation, transcription factor NF-kappaB activation, nitric oxide synthase (NOS) expression, nitric oxide (NO) production, and monocyte adhesion were measured. We observed H(2)O(2) treatment significantly induced oxidative stress, which could be attenuated by 25 microM propofol pretreatment. In addition, H(2)O(2) treatment significantly induced p38 MAPK phosphorylation, NF-kappaB activation, NOS expression, and NO production. More importantly, our study showed these H(2)O(2)-induced changes were attenuated by propofol or SB203580 pretreatment. Further, we measured monocyte adhesion as a marker of endothelial cell dysfunction. H(2)O(2) increased the adhesion of monocytes to HUVECs, and propofol pretreatment reduced the adhesion in a fashion similar to SB203580. We concluded that propofol, by inhibiting p38 MAPK and NF-kappaB activity, decreasing NOS expression, reducing NO production, could protect HUVECs which are exposed to oxidative stress and becoming dysfunctional.

Intracellular Ca2+ homeostasis and JAK1/STAT3 pathway are involved in the protective effect of propofol on BV2 microglia against hypoxia-induced inflammation and apoptosis.

BACKGROUND: Perioperative hypoxia may induce microglial inflammation and apoptosis, resulting in brain injury. The neuroprotective effect of propofol against hypoxia has been reported, but the underlying mechanisms are far from clear. In this study, we explored whether and how propofol could attenuate microglia BV2 cells from CoCl2-induced hypoxic injury. METHODS: Mouse microglia BV2 cells were pretreated with propofol, and then stimulated with CoCl2. TNF-α level in the culture medium was measured by ELISA kit. Cell apoptosis and intracellular calcium concentration were measured by flow cytometry analysis. The effect of propofol on CoCl2-modulated expression of Ca2+/Calmodulin (CaM)-dependent protein kinase II (CAMKIIα), phosphorylated CAMKIIα (pCAMKIIα), STAT3, pSTAT3Y705, pSTAT3S727, ERK1/2, pERK1/2, pNFκB(p65), pro-caspase3, cleaved caspase 3, JAK1, pJAK1, JAK2, pJAK2 were detected by Western blot. RESULTS: In BV2 cell, CoCl2 treatment time-dependently increased TNF-α release and induced apoptosis, which were alleviated by propofol. CoCl2 (500µmol/L, 8h) treatment increased intracellular Ca2+ level, and caused the phosphorylation of CAMKIIα, ERK1/2 and NFκB (p65), as well as the activation of caspase 3. More importantly, these effects could be modulated by 25µmol/L propofol via maintaining intracellular Ca2+ homeostasis and via up-regulating the phosphorylation of JAK1 and STAT3 at Tyr705. CONCLUSION: Propofol could protect BV2 microglia from hypoxia-induced inflammation and apoptosis. The potential mechanisms may involve the maintaining of intracellular Ca2+ homeostasis and the activation of JAK1/STAT3 pathway.