TO THE EDITOR
Gastric cancer ranks among the world’s most prevalent malignancies. Although annual incidence and mortality rates have steadily declined, it remains a major global health challenge[1]. Recent research advancements have introduced multiple treatment approaches, with gastrectomy remaining the most effective surgical intervention. However, despite significant progress in surgical techniques, the prognosis for patients with gastric cancer remains suboptimal[2]. Anesthetic drug selection and maintenance methods may influence immediate postoperative complications, tumor biology characteristics, and long-term survival rates. Radical gastrectomy requires anesthetic strategies that balance immediate physiological stability with long-term tumor control. A comparative study on sevoflurane inhalational anesthesia vs propofol-based total intravenous anesthesia (TIVA) group by Wang et al[3] published in World Journal of Gastrointestinal Oncology demonstrated comparable overall safety and long-term efficacy in modern perioperative care. However, it revealed two clinical differences: The propofol-based TIVA group exhibited a higher incidence of postoperative nausea and vomiting (PONV) and more pronounced transient elevations in blood pressure and heart rate than the sevoflurane group.
This study challenges the notion that a specific anesthetic better predicts tumor prognosis, providing evidence for individualized anesthesia selection. For example, for patients at high risk of postoperative nausea (e.g., women or those with a history of motion sickness), sevoflurane anesthesia should be prioritized to reduce nausea incidence. For patients requiring strict blood pressure control during surgery (e.g., those with hypertensive heart disease), clinicians should be vigilant about transient blood pressure elevation during propofol-based TIVA group administration and prepare advanced circulatory management plans. The study findings further emphasize the importance of standardized perioperative management. The rigorous standardization of anesthetic procedures, monitoring protocols, and pain management protocols diminishes the clinical differences between the two anesthetic agents, suggesting that clinicians should prioritize consistent management protocols over single-drug superiority. Furthermore, the slightly higher 24-hour Visual Analogue Scale scores observed in the propofol-based TIVA (24.61 vs 22.93), though statistically significant, may be clinically modest. This nonetheless underscores the need for enhanced postoperative pain monitoring within 24 hours for patients who received propofol anesthesia, enabling timely adjustments to analgesic regimens.
Wang et al[3] compared two commonly used anesthesia protocols in a homogeneous surgical population, which is commendable. However, the study’s limitations and connections to existing research, as well as directions for future investigation, require structured discussion.
Study limitations
The retrospective design of this study inherently limits causal inference. Although baseline characteristics were similar between groups, unmeasured confounders, such as surgical stress responses, intraoperative opioid dosage variations, or tumor microenvironment differences, may have influenced the conclusions. For instance, the authors reported a higher incidence of postoperative nausea in the propofol-based TIVA, contradicting meta-analyses reporting the antiemetic properties of propofol[4,5]. This discrepancy warrants further discussion of potential confounders: First, intraoperative opioid consumption is a well-documented risk factor for PONV, and variations in opioid type or dosage between groups (if unaccounted for) could explain the higher incidence in the propofol-based TIVA group[6]. Second, the use or absence of prophylactic antiemetics (e.g., 5-hydroxytryptamine3 antagonists, dexamethasone) was not reported, and inconsistent administration could mask propofol’s intrinsic antiemetic effects. Third, duration of surgery and intraoperative hemodynamic fluctuations may also modulate PONV risk, as prolonged surgical stimulation or unstable perfusion can trigger emetic pathways independent of anesthetic agent[7]. Importantly, this finding of higher PONV in the propofol-based TIVA group should be interpreted as hypothesis-generating rather than confirmatory, given the retrospective design’s inability to establish definitive causal relationships.
Additionally, bispectral index (BIS) assessment revealed significantly higher BIS values in the sevoflurane group, which the authors attributed to the effects of volatile anesthetics on electrical activity in the brain, as evidenced by distinct electroencephalogram changes. While this explanation is plausible, BIS does not equate to the depth of anesthesia. BIS primarily reflects hypnotic components (consciousness level), whereas anesthesia depth is a complex, multidimensional concept encompassing three aspects: Hypnotic, analgesic, and motor responses. Moreover, BIS is influenced by various physiological and pharmacological factors[8,9]. Thus, in the absence of simultaneous measurement of hypnotic state or nociceptive perception, these findings should be interpreted with caution.
Comparison with other studies
The results of this study align with the most recent clinical research, which found no significant differences in major perioperative outcomes and long-term survival between sevoflurane and propofol. For instance, Cao et al[10] found that these two anesthetics did not impact survival in elderly patients undergoing large-scale cancer surgeries. Similarly, a meta-analysis of patients with colorectal cancer showed no effect on recurrence or survival[11]. However, some studies support potential antitumor advantages of propofol. Du et al[12] reported that propofol inhibits the proliferation and colony formation of cervical cancer cells and reduces their invasive potential in vitro. In contrast, sevoflurane was demonstrated to promote the migration, invasion, and colony formation of human glioblastoma cells in vitro, as well as increase tumor volume and enhance invasiveness in vivo[13]. A meta-analysis by Yap et al[14] suggested that the propofol TIVA group could improve recurrence-free and overall survival after cancer surgery. These conflicting results suggest that the effects of anesthetics on tumor biology differ according to tumor type, surgical approach, and individual patient variations. Regarding short-term outcomes, this study is consistent with most literature, reporting no significant differences in complication rates and hospitalization duration between the two anesthetics[15,16]. However, the observed difference in PONV rates, which should still be regarded as hypothesis-generating, warrants further investigation, particularly focusing on the confounders outlined above.
Mechanistic insights
Different anesthetic agents may affect tumor progression through multiple biological pathways. Accumulating evidence has confirmed that propofol can further inhibit the proliferation and invasion of cervical cancer cells by suppressing MIR155HG[12] and exert anti-tumor effects by reducing oxidative stress and regulating immune responses. In contrast, sevoflurane may promote tumor invasiveness by upregulating cell surface proteins (e.g., CD44), thereby enhancing the migration and invasion abilities of glioblastoma cells[13]. Additionally, anesthetics can modulate the functions of immune cells and the expression of inflammatory cytokines in the tumor microenvironment. For example, propofol exerts a weaker inhibitory effect on CD4+ T cells, CD8+ T cells, natural killer cells, immunoglobulin M, and immunoglobulin G in patients undergoing radical resection of colorectal cancer compared with sevoflurane, and exerts a more moderate impact on perioperative immunity and coagulation[17]. Furthermore, RNA sequencing (RNA-seq) analysis has demonstrated significant differences between the two anesthetics in interleukin-1 response, chemokine signaling pathway, and tumor necrosis factor pathway, with sevoflurane showing a more prominent regulatory effect on C-X-C motif chemokine ligand 8 and other inflammation-related genes[18]. These mechanistic differences may underlie the divergent effects of anesthetics on different tumor types, and also highlight the necessity of further investigating the molecular interactions between anesthetics and cancer biology.
Future directions
Future research should prioritize several key directions to strengthen the evidence in this field. First, prospective multicenter randomized controlled trials with random allocation to anesthesia protocols (sevoflurane vs propofol-based TIVA) are warranted. Such trials should include larger sample sizes, encompassing different regions and hospital tiers, and rigorously document potential confounders (e.g., opioid use, prophylactic antiemetic administration, surgical duration, hemodynamics) to clarify the PONV discrepancy observed in retrospective studies. This will further validate the long-term efficacy of the two anesthesia methods while reducing selection bias and geographical limitations, thereby enhancing the generalizability of conclusions. Second, subgroup analyses focusing on special populations, such as older adults, patients with advanced gastric cancer, and patients with multiple organ dysfunction, are recommended to clarify efficacy differences. For example, older adults have a slower rate of anesthetic metabolism and may be more susceptible to postoperative cognitive impairment, necessitating clarification of safety differences between the two anesthetics in this population. Finally, extending the follow-up duration to more than 5 years in future studies is essential to comprehensively evaluate the long-term impact of anesthesia on tumor recurrence.
