Daily Anesthesiology Research Analysis
A randomized clinical trial showed spinal anesthesia reduced 2-year recurrence after transurethral resection for non–muscle-invasive bladder cancer versus general anesthesia. A mechanistic study in British Journal of Anaesthesia identified kappa opioid receptor internalization driving p38 nuclear translocation to suppress glioma growth, suggesting potential adjuvant use of KOR agonists. A double-blind RCT found intrathecal chloroprocaine shortened time to discharge compared with bupivacaine in a
Summary
A randomized clinical trial showed spinal anesthesia reduced 2-year recurrence after transurethral resection for non–muscle-invasive bladder cancer versus general anesthesia. A mechanistic study in British Journal of Anaesthesia identified kappa opioid receptor internalization driving p38 nuclear translocation to suppress glioma growth, suggesting potential adjuvant use of KOR agonists. A double-blind RCT found intrathecal chloroprocaine shortened time to discharge compared with bupivacaine in ambulatory anorectal surgery.
Research Themes
- Anesthetic technique and oncologic outcomes
- Opioid receptor signaling in tumor biology
- Optimization of ambulatory spinal anesthesia
Selected Articles
1. Anesthetic approaches and 2-year recurrence rates in non-muscle invasive bladder cancer: a randomized clinical trial.
In a single-center RCT (n=287), spinal anesthesia significantly reduced 2-year recurrence after TURBT for NMIBC compared with general anesthesia (ITT 27.4% vs 39.8%). Disease progression trended lower with spinal anesthesia. Findings support considering spinal anesthesia as the preferred approach when feasible.
Impact: This RCT provides high-level evidence that anesthetic technique can influence oncologic outcomes, addressing a long-standing, clinically consequential question.
Clinical Implications: For TURBT in NMIBC, spinal anesthesia may be favored to reduce recurrence, balancing patient-specific contraindications and surgical needs.
Key Findings
- Spinal anesthesia reduced 2-year recurrence compared with general anesthesia (ITT: 27.4% vs 39.8%).
- Modified ITT analysis confirmed lower recurrence with spinal anesthesia (26.8% vs 39.6%).
- Disease progression occurred less often with spinal than general anesthesia (7.8% vs 15.2%), though not statistically significant.
Methodological Strengths
- Prospective randomized controlled design with time-to-event analysis
- Registered trial with clear primary endpoint and modified ITT analysis
Limitations
- Single-center study limits generalizability
- Blinding to anesthetic technique is inherently challenging and may introduce performance bias
Future Directions: Multicenter RCTs across diverse tumor types and mechanistic studies linking immune modulation to anesthesia technique are warranted.
BACKGROUND: The effect of anesthesia methods on non-muscle invasive bladder cancer (NMIBC) recurrence post-resection remains uncertain. We aimed to compare the oncological outcomes of spinal anesthesia (SA) and general anesthesia (GA) in patients with NMIBC. METHODS: This prospective randomized controlled trial recruited 287 patients with clinical NMIBC at Seoul National University Hospital from 2018 to 2020. The patients underwent transurethral resection of the bladder tumor within 4 weeks of randomization. Intrathecal hyperbaric bupivacaine (0.5%) and a mixture of propofol (1-2 mg/kg) and fentanyl (50-100 μg/kg) were used as induction agents in the SA and GA groups, respectively, with desflurane or sevoflurane used for maintaining anesthesia. The primary and secondary outcome measures were disease recurrence and disease progression, respectively, at 2 years after resection. Cumulative incidence of outcomes was compared between the two groups using time-to-event analyses. RESULTS: 15 patients required alternative anesthesia owing to clinical needs such as SA failure or significant obturator reflex, resulting in a modified intention-to-treat (ITT) population of 272 patients. Time-to-event analysis showed a significantly lower recurrence of NMIBC in the SA group than in the GA group, in both ITT (27.4% vs 39.8%) and modified ITT populations (26.8% vs 39.6%). Disease progression occurred more frequently in the GA than in the SA group (15.2% vs 7.8%), although the difference was not statistically significant. CONCLUSIONS: A notable reduction in the 2-year recurrence rate was observed in patients who underwent SA than in those who underwent GA. Thus, SA may be considered the preferred anesthetic approach. TRIAL REGISTRATION NUMBER: NCT03597087.
2. Kappa opioid receptor internalisation-induced p38 nuclear translocation suppresses glioma progression.
Across molecular to in vivo models, higher KOR expression correlated with better glioma prognosis; KOR overexpression suppressed GBM growth and prolonged survival via binding cytoplasmic p38 and promoting its nuclear translocation. The KOR agonist TRK-820 triggered receptor internalization, activated p38 signaling, and reduced glioma cell viability, supporting KOR agonists as potential adjuvants.
Impact: Reveals a novel KOR–p38 nuclear signaling mechanism suppressing glioma and identifies a clinically available KOR agonist (TRK-820) as a testable adjuvant strategy.
Clinical Implications: Perioperative selection of opioidergic agents may influence glioma biology. KOR agonists (e.g., nalfurafine/TRK-820) merit translational trials as adjuncts to standard care.
Key Findings
- Higher tumor KOR expression correlated with better glioma patient prognosis.
- KOR overexpression induced GBM cell cycle arrest and apoptosis; knockdown accelerated growth.
- Internalized KOR bound cytoplasmic p38, promoting its nuclear translocation and phosphorylation.
- TRK-820 (selective KOR agonist) induced KOR internalization, activated p38 signaling, and reduced glioma cell viability in vitro.
- KOR overexpression inhibited tumor growth and prolonged survival in orthotopic mouse models.
Methodological Strengths
- Multi-level validation (bioinformatics, in vitro GBM models, and in vivo orthotopic transplantation)
- Mechanistic dissection linking receptor trafficking to p38 nuclear signaling
Limitations
- Preclinical study; human clinical efficacy and safety are untested
- Potential off-target and systemic effects of KOR agonism require careful evaluation
Future Directions: Translational trials assessing KOR agonists as adjuvants in glioma and biomarker-driven studies stratifying by tumor KOR expression.
BACKGROUND: Recent studies have implicated a role for perioperative medications in determining patient outcomes after surgery for malignant tumours, including relapse and metastasis. METHODS: A combined approach spanned molecular, cellular, and organismal levels, including bioinformatics, immunohistochemical staining of clinical and animal samples, RNA sequencing of glioblastoma multiforme (GBM) cells with Ingenuity Pathway Analysis, lentiviral-mediated gene expression modulation, in vitro cell experiments, and in vivo orthotopic tumour transplantation. RESULTS: We observed a significant correlation between increased kappa opioid receptor (KOP receptor) expression and better prognosis in patients with glioma. Exogenous KOP receptor overexpression in GBM cells in vitro induced cell cycle arrest, suppressed cell growth, and promoted apoptosis. Conversely, reducing KOP receptor expression in GBM cells reduced the proportion of cells in S and G2/M phases, accelerating cell growth. KOP receptor overexpression inhibited glioma cell growth and prolonged survival in mice in vivo, while KOP receptor knockdown had the opposite effect. Mechanistically, internalised KOP receptors were found to bind cytoplasmic p38, facilitating its nuclear translocation and phosphorylation, which influences downstream gene expression. The selective KOP receptor agonist TRK-820 triggered KOP receptor internalisation, activated the p38 pathway, and diminished glioma cell viability in vitro. CONCLUSIONS: This combined molecular, cellular, and in vivo approach supports use of KOP receptor agonists as potential adjuvant therapeutics for glioma.
3. Comparison of 1% chloroprocaine hydrochloride versus hyperbaric bupivacaine spinal in patients undergoing anorectal surgery in an ambulatory surgery center: a double-blind randomized clinical trial.
In a double-blind RCT (n=110), intrathecal 1% chloroprocaine shortened time to meet discharge criteria versus hyperbaric bupivacaine in ambulatory anorectal surgery, without differences in recovery time or increased transient neurologic symptoms within 24 hours.
Impact: Demonstrates a practical anesthetic choice that can improve ambulatory throughput and patient flow without compromising safety.
Clinical Implications: Consider chloroprocaine for ambulatory neuraxial anesthesia when rapid discharge is desired and prolonged block is undesirable.
Key Findings
- Chloroprocaine reduced time to meet discharge criteria compared to bupivacaine (191.4±6.6 vs 230.9±9.4 minutes; p<0.001).
- No significant difference in recovery time (motor and sensory) between groups.
- No transient neurological symptoms were reported within 24 hours in either group.
Methodological Strengths
- Double-blind randomized controlled design
- Clear, clinically meaningful co-primary endpoints with registered trial
Limitations
- Single ambulatory center limits generalizability
- Short follow-up (24 hours) may miss rare delayed neurologic events
Future Directions: Evaluate chloroprocaine across broader ambulatory procedures and assess patient-reported outcomes and cost-effectiveness.
BACKGROUND: Preservative-free chloroprocaine is a promising spinal anesthetic for ambulatory surgeries, offering a short duration of action and minimal side effects, which promote faster recovery and discharge. Thus, this study aimed to compare chloroprocaine hydrochloride to the widely used bupivacaine as a spinal anesthetic in ambulatory anorectal surgeries. We hypothesized that chloroprocaine will lead to quicker recovery and discharge, supporting its use in the ambulatory surgical setting. METHODS: In this double-blind randomized controlled trial, 110 patients were randomized to 1% chloroprocaine or 0.75% bupivacaine treatment groups. Due to the inability to place a spinal anesthetic, five patients were excluded (one in chloroprocaine and four in bupivacaine groups). The co-primary endpoints were recovery time (defined as the time of motor and sensory function return), and time discharge criteria were met. The secondary endpoint was the onset of transient neurological symptoms (TNS). RESULTS: The chloroprocaine group had a significantly shorter time to meet discharge criteria (191.4±6.6 min) than the bupivacaine group (230.9±9.4 min; p=<0.001). There were no significant differences between interventions for recovery time. No TNS were recorded within 24 hours after the procedure for both groups. CONCLUSION: Our study demonstrated a significantly reduced time to meeting discharge criteria with chloroprocaine compared with bupivacaine without an increased risk of TNS. Our results support the use of chloroprocaine for spinal anesthesia in ambulatory anorectal surgeries. TRIAL REGISTRATION NUMBER: NCT03324984.