No abstract

Background Regional anesthesia and analgesia reduce the stress response to surgery and decrease the need for volatile anesthesia and opioids, thereby preserving cancer-specific immune defenses. This study therefore tested the primary hypothesis that combining epidural anesthesia–analgesia with general anesthesia improves recurrence-free survival after lung cancer surgery. Methods Adults scheduled for video-assisted thoracoscopic lung cancer resections were randomized 1:1 to general anesthesia and intravenous opioid analgesia or combined epidural–general anesthesia and epidural analgesia. The primary outcome was recurrence-free survival (time from surgery to the earliest date of recurrence/metastasis or all-cause death). Secondary outcomes included overall survival (time from surgery to all-cause death) and cancer-specific survival (time from surgery to cancer-specific death). Long-term outcome assessors were blinded to treatment. Results Between May 2015 and November 2017, 400 patients were enrolled and randomized to general anesthesia alone (n = 200) or combined epidural–general anesthesia (n = 200). All were included in the analysis. The median follow-up duration was 32 months (interquartile range, 24 to 48). Recurrence-free survival was similar in each group, with 54 events (27%) with general anesthesia alone versus 48 events (24%) with combined epidural–general anesthesia (adjusted hazard ratio, 0.90; 95% CI, 0.60 to 1.35; P = 0.608). Overall survival was also similar with 25 events (13%) versus 31 (16%; adjusted hazard ratio, 1.12; 95% CI, 0.64 to 1.96; P = 0.697). There was also no significant difference in cancer-specific survival with 24 events (12%) versus 29 (15%; adjusted hazard ratio, 1.08; 95% CI, 0.61 to 1.91; P = 0.802). Patients assigned to combined epidural–general had more intraoperative hypotension: 94 patients (47%) versus 121 (61%; relative risk, 1.29; 95% CI, 1.07 to 1.55; P = 0.007). Conclusions Epidural anesthesia–analgesia for major lung cancer surgery did not improve recurrence-free, overall, or cancer-specific survival compared with general anesthesia alone, although the CI included both substantial benefit and harm. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Oxaliplatin is a widely used chemotherapeutic agent that induces both acute and chronic peripheral neuropathy. Based on previous research indicating that estrogen replacement may attenuate some forms of pain in ovariectomized animals, we examined the effects of 17β-estradiol in OXAIPN. We discovered that local cold exposure induces an abnormal vascular response in both acute and chronic models of OXAIPN (oxaliplatin-induced peripheral neuropathy) that may be used as an easy and non-invasive method to predict which patients may be susceptible to the development of severe, chronic OXAIPN. Neuropathy was induced by injection of oxaliplatin on the first two days for the short-term OXAIPN group and twice a week for 3 weeks for the long-term OXAIPN group. Local cold-induced vascular responses were recorded in the presence or absence of subcutaneously injected transient receptor potential ankyrin 1 (TRPA1) antagonist HC033031 or transient receptor potential melastatin 8 (TRPM8) antagonist AMTB using laser Doppler flowmetry. Both short-term and long-term OXAIPN groups exhibited abnormal local cold-induced vascular responses, characterized by initial vasodilation followed by vasoconstriction. Local blockade of TRPA1 or TRPM8 receptors attenuated the initial vasodilation. Changes in release of calcitonin gene related peptide (CGRP) and nitric oxide (NO) metabolites due to local cold exposure at the hind paw were also involved. Administration of 17β-estradiol resulted in an anti-nociceptive effect and attenuating abnormal vasodilation.

For patients undergoing surgery for lung adenocarcinoma under general anesthesia, use of epidural anaesthesia increased CD8 T cells infiltration but decreased FOXP3 T cells accumulation in tumor tissues. Epidural anaesthesia may affect TILs in a manner that preserves immune function.

Background Elucidation of mechanisms underlying continuous training-related atrial fibrillation (AF) may inform formulation of novel therapeutic approaches and training method selection. This study was aimed at assessing mechanisms underlying continuous training-induced AF in an animal model. Methods Healthy New Zealand rabbits were divided into three groups (n=8 each), namely, control (C), and moderate intensity (M), and high intensity (H) continuous training according to treadmill speed. Atrial size andintrinsic and resting heart rates were measured by transthoracic echocardiography before, and 8 and 12 weeks after training. Using a Langendorff perfusion system, AF was induced by S1S2 stimulation and the induction rate was recorded. Atrial IK1 and IKAch ion current densities were recorded using whole-cell patch-clamp technique in isolated atrial myocytes. Changes in atrial Kir2.1, Kir2.2, Kir3.1, and Kir3.4 mRNA expression were assessed by reverse transcriptase-coupled polymerase chain reaction. Results After 8 and 12 weeks, Groups M and H vs. Group C had greater (all P < 0.05) atrial anteroposterior diameter; greater incidence of AF (60% and 90% vs. 45%, respectively; P < 0.05, also between Groups H and M); and greater atrial IKAch current density. In Group H, Kir2.1 and Kir2.2 mRNA expression in the left and right atria was increased (P < 0.05, vs. Groups C and M) as was left atrial Kir3.1 and Kir3.4 mRNA expression (P < 0.05, vs. Group C). Conclusion In a rabbit model, continuous training enlarges atrial diameter leading to atrial structural and electrical remodeling and increased AF incidence.