Does anesthesia choice shape oncologic destiny in gastric cancer surgery?

Abstract

Anesthetic management in gastric cancer surgery has progressed from a technical necessity to a potential influencer of perioperative immune function and long-term oncologic outcomes. The perioperative period-marked by inflammation, stress responses, and immunosuppression-is increasingly seen as critical to cancer recurrence risk. This has prompted investigations into whether anesthetic agents could shape oncologic trajectories. The recent study by Wang et al contributes valuable data by comparing sevoflurane inhalation anesthesia and propofol-based total intravenous anesthesia in patients undergoing radical gastrectomy. While no significant differences were observed in survival outcomes, subtle variations in post-operative nausea and intraoperative hemodynamics raise important considerations about anesthetic-specific physiologic effects. This editorial reflects on these findings in the broader context of ongoing efforts to individualize perioperative care in oncology. It also underscores the need for future prospective studies integrating immune, molecular, and clinical endpoints to determine whether anesthetic techniques can play a meaningful role in long-term cancer control. As the field advances, anesthesia should no longer be viewed as a neutral backdrop but as a modifiable component of comprehensive cancer care. Determining when, how, and for whom an anesthetic technique matters remains an open but essential question.

Key Words: Anesthesia; Gastric cancer; Propofol; Sevoflurane; Total intravenous anesthesia

Core Tip: Anesthetic choice in gastric cancer surgery extends beyond technical preference, potentially influencing immune function, stress response, and oncologic outcomes. Propofol-based total intravenous anesthesia demonstrates promising molecular and clinical anti-tumor properties-modulating microRNAs, enhancing natural killer cell activity, and improving post-operative recovery-while sevoflurane, though traditionally considered neutral, shows emerging immunoregulatory and gene-expression effects. Current evidence, including the recent Wang et al’s study, suggests both agents yield comparable perioperative safety and survival outcomes; however, their distinct molecular profiles highlight anesthesia as a modifiable element in personalized cancer care. Future biomarker-driven research is essential to clarify when and how anesthetic selection might influence long-term oncologic prognosis.

INTRODUCTION

Gastric cancer constitutes a major global health challenge, ranking fifth in both incidence and cancer-related mortality worldwide, thereby underscoring its substantial impact on public health[1]. Although gastric cancer incidence varies geographically, its prevalence is particularly high in East Asia, especially in China[2]. The disease is frequently diagnosed at an advanced stage, and surgical resection remains the cornerstone of curative treatment. In recent years, increasing attention has been directed toward the potential influence of perioperative and intraoperative factors, particularly anesthetic techniques, on oncologic and post-operative outcomes. Emerging evidence suggests that different anesthetic agents may modulate immune and inflammatory responses, oxidative stress, hemodynamic stability, and even tumor cell biology, thereby potentially influencing the risk of recurrence and overall survival following cancer surgery[3]. Among commonly used anesthetic methods, propofol-based total intravenous anesthesia (TIVA) and inhalational anesthesia have demonstrated varying effects on intraoperative hemodynamics, oxygen delivery, stress response, and post-operative recovery. Consequently, elucidating how anesthetic choice affects both intraoperative physiological parameters and long-term outcomes in gastric cancer surgery has become a growing area of clinical and research interest.

PROPOFOL

Propofol, first synthesized in 1973, entered clinical use in the United Kingdom and New Zealand in 1986 and received United States Food and Drug Administration approval in 1989[4]. It is one of the most widely used intravenous anesthetic agents for both induction and maintenance of general anesthesia. Beyond the operating room, propofol serves as a procedural sedative in diagnostic and therapeutic interventions such as interventional radiology, percutaneous or needle-guided biopsies, and local oncologic treatments including radiofrequency ablation and trans-arterial chemoembolization[5]. It is also commonly administered for the sedation of intubated and mechanically ventilated patients in intensive care settings and has off-label uses in refractory status epilepticus and post-operative nausea and vomiting[6]. Owing to its broad clinical applications and well-established safety profile, propofol is included in the World Health Organization’s List of Essential Medicines[7].

SEVOFLURANE

Sevoflurane is a commonly used volatile anesthetic agent characterized by its rapid onset, low blood-gas solubility, and favorable recovery profile. Since its introduction into clinical practice in the 1990s, it has become a preferred agent for both induction and maintenance of general anesthesia in a wide range of surgical procedures. Owing to its low airway irritability, predictable and titratable hemodynamic profile, and overall safety, sevoflurane is commonly selected for major abdominal and oncologic procedures, including gastric cancer resections, particularly in patients with comorbidities or in prolonged surgeries requiring stable anesthetic depth; however, like other volatile agents, it may cause dose-dependent reductions in systemic vascular resistance and arterial pressure[8,9]. Owing to these properties, sevoflurane remains a mainstay of modern anesthesia practice worldwide.

MAIN CONTENT

In their study, Wang et al[10] compared the short- and long-term effects of sevoflurane inhalation anesthesia and propofol-TIVA in patients undergoing radical gastrectomy for gastric cancer. The authors retrospectively analyzed 204 patients and reported no significant differences between the two anesthetic modalities in intraoperative indicators, post-operative complications, or long-term survival outcomes. Although both techniques provided comparable perioperative safety profiles, the propofol group exhibited slightly higher post-operative nausea incidence and transient elevations in blood pressure and heart rate at incision. These findings suggest that anesthetic selection-when applied within a standardized perioperative protocol-may be tailored to patient-specific conditions without substantially influencing oncologic prognosis. Given the increasing clinical focus on how intraoperative and perioperative factors affect cancer biology, immune modulation, and hemodynamic stability, a concise review of the existing evidence becomes essential to contextualize the potential implications of anesthetic choice in gastric cancer surgery.

Propofol has gained increasing attention as an anesthetic with potential anti-tumor properties in various malignancies, including gastric cancer, through diverse molecular pathways. In vitro experiments have consistently demonstrated that propofol suppresses the proliferation and migration of gastric cancer cells while inducing apoptosis[11-13]. Beyond these mechanisms, Cao et al[14] further revealed that propofol suppresses gastric cancer cell proliferation by inhibiting the NRF2-mediated polyol metabolic pathway, suggesting a link between anesthetic exposure and redox regulation in tumor biology. These effects are frequently mediated by the modulation of non-coding RNAs, including microRNAs (miRNAs) and circular RNAs, which are critical regulators of gene expression in tumor development and progression. For example, propofol was shown to upregulate miR-29, leading to downregulation of MMP-2 and thereby inhibiting cell invasiveness[11]. Similarly, regulation of the circPDSS1/miR-1324/SOX4 axis has been identified as a mechanism through which propofol suppresses gastric cancer cell growth[12]. Additional work indicates that propofol increases miR-205, which inhibits YAP1, a key oncogenic effector in the Hippo pathway, thereby reducing both proliferation and invasion[15]. Moreover, inhibition of Wnt/β-catenin signaling via the miR-493-3p/DKK1 pathway provides another mechanism by which propofol impairs tumor progression[16]. Beyond its direct tumor-suppressive effects, propofol has been implicated in sensitizing gastric cancer cells to chemotherapy. In particular, it has been shown to downregulate the lncRNA MALAT1/miR-30e/ATG5 axis, thereby inhibiting autophagy and enhancing cisplatin sensitivity[17]. These findings suggest a potential role for propofol as an adjuvant in overcoming chemoresistance, one of the significant challenges in gastric cancer therapy. Complementing the molecular data, clinical evidence supports the beneficial role of propofol in surgical oncology. A retrospective study reported that patients undergoing gastric cancer surgery under propofol-based TIVA had better post-operative outcomes compared to those receiving inhalational anesthesia[18]. Additionally, propofol has been shown to enhance the cytotoxicity of natural killer (NK) cells, potentially improving perioperative immune surveillance[19].

In contrast to the accumulating evidence supporting propofol's anticancer properties, findings regarding sevoflurane remain more nuanced and context-dependent. While traditionally considered immunosuppressive or neutral in the oncological setting, emerging studies suggest that sevoflurane may also exert tumor-inhibitory effects in gastric cancer through several molecular and immunological mechanisms. Recent preclinical investigations have demonstrated that sevoflurane can modulate non-coding RNA networks and transcription factors involved in tumor progression. Notably, Chen et al[20] reported that sevoflurane exposure led to upregulation of miR-34a, which subsequently suppressed TGIF2 expression, a known promoter of epithelial-mesenchymal transition and tumor invasiveness. Similarly, Liu and Chen[21] found that sevoflurane’s anti-tumor effect is enhanced when ZC3H13, a regulator of N6-methyladenosine (m6A) RNA modification, is silenced. This regulation affected the oncogenic activity of lncRNA DLX6-AS1, further suppressing gastric cancer cell malignancy.

Sevoflurane also appears to influence immune dynamics during the perioperative period. In a clinical study involving gastric cancer patients undergoing radical surgery, Yong et al[22] observed a post-operative increase in CD4+CD25+FOXP3+ regulatory T cells (Tregs) in those anesthetized with sevoflurane, indicating an immunomodulatory effect whose functional relevance in tumor control remains under debate. Interestingly, the same research group previously demonstrated that sevoflurane could inhibit cancer cell migration and invasion by downregulating FOXP3 expression within tumor cells, suggesting distinct effects depending on cell type and context[23].

Although much of the earlier literature on sevoflurane focused on systemic outcomes-such as its renal safety profile during low-flow anesthesia[24]-recent data call for a reevaluation of its role in oncologic anesthesia. The ability of sevoflurane to regulate miRNA activity, RNA methylation, and transcriptional networks opens new possibilities for its integration into perioperative cancer care strategies, particularly when considering tumor-type specificity.

Several retrospective and mechanistic studies have compared propofol and sevoflurane in the context of gastric cancer, offering valuable insights into their differential impact on tumor progression, immune response, and clinical outcomes. Clinical data suggest that propofol-based TIVA may be associated with improved perioperative immune modulation and survival benefits. For example, Zheng et al[18] reported better post-operative recovery and fewer inflammatory complications with propofol. Similarly, both Wu et al[25] and Oh et al[26] found that patients receiving propofol had significantly better long-term survival and lower 1-year mortality than those receiving sevoflurane.

Comparative immunologic data also favor propofol. In a prospective analysis, Ai and Wang[19] demonstrated that NK cell activity was higher in patients anesthetized with propofol, suggesting a more robust anti-tumor immune response. Li et al[27] extended this finding to post-operative cognitive and emotional recovery, showing that propofol preserved neurocognitive function better than sevoflurane. On the other hand, Song et al[28] found no significant difference in acute kidney injury incidence between the two agents, indicating comparable organ protection. Additionally, Liu and Yang[29] observed that propofol produced more stable glucose and cytokine profiles during surgery in diabetic patients with gastric cancer, reinforcing its systemic homeostatic advantages (Tables 1, 2, and 3).

Table 1 Summary of preclinical and clinical studies investigating the antitumor and immunomodulatory effects of propofol in gastric cancer.

Ref.	Key findings	Method
Ni et al[11]	Suppresses cell invasion via MMP-2 inhibition through miR-29	In vitro
Liu et al[12]	Inhibits tumor growth via the circPDSS1/miR-1324/SOX4 axis	In vitro
Xian et al[15]	Reduces proliferation through YAP1 inhibition mediated by miR-205	In vitro
Zhan et al[16]	Inhibits tumor progression through the miR-493-3p/DKK1/Wnt-β-catenin axis	In vitro
Zhang et al[17]	Increases cisplatin sensitivity via lncRNA MALAT1/miR-30e/ATG5 pathway	In vitro + chemotherapy sensitivity
Ai et al[19]	Enhances antitumor immunity by increasing NK cell activity	Clinical study
Zheng et al[18]	Propofol-TIVA associated with better postoperative outcomes	Retrospective clinical
Liu and Yang[29]	Provides more stable glucose and cytokine profiles (in diabetic patients)	Clinical study
Li et al[27]	Observed improved neurocognitive recovery	Clinical study
Cao et al[14]	Suppresses tumor proliferation via NRF2	In vitro

NK: Natural killer; TIVA: Total intravenous anesthesia.

Table 2 Overview of experimental and clinical studies assessing the effects of sevoflurane on gastric cancer biology and immune responses.

Ref.	Key findings	Method
Chen et al[20]	Increased miR-34a → Suppression of TGIF2 → Reduced EMT and invasion	In vitro
Liu and Chen[21]	Tumor suppression via DLX6-AS1/epigenetic modulation through ZC3H13 knockdown	In vitro
Yong et al[23]	Decreased FOXP3 expression in tumor cells leads to reduced invasion	In vitro
Yong et al[22]	Increased CD4+CD25+FOXP3+ Treg cells; indicates immune modulation	Clinical study

Table 3 Comparative clinical studies evaluating perioperative and oncologic outcomes of propofol vs sevoflurane in gastric cancer surgery.

Ref.	Key findings	Method
Wang et al[10]	No difference in long-term survival; propofol group had more PONV	Retrospective clinical
Zheng et al[18]	Fewer inflammatory complications and better postoperative recovery with propofol	Retrospective clinical
Wu et al[25]	Propofol group showed better long-term survival	Retrospective clinical
Oh et al[26]	One-year mortality lower with propofol	Retrospective analysis
Ai and Wang[19]	Propofol → Higher NK cell activity (immune advantage)	Prospective clinical
Song et al[28]	No significant difference in AKI incidence	Retrospective matched analysis
Li et al[27]	Propofol → Better cognitive and emotional postoperative recovery	Clinical study

PONV: Postoperative nausea-vomiting; AKI: Acute kidney injury; NK: Natural killer.

CONCLUSION

The perioperative period represents a critical interface between surgical intervention and oncologic fate. While existing evidence, including the study by Wang et al[10], suggests that both sevoflurane and propofol anesthesia offer comparable short- and long-term outcomes in gastric cancer surgery, emerging molecular data reveal nuanced immunological and tumor-biological effects that warrant further exploration. Given the complexity of cancer pathophysiology, anesthetic choice alone may not dictate oncologic prognosis, yet it remains a potentially modifiable factor within a broader perioperative strategy. Future prospective, biomarker-integrated, and immunologically informed trials are essential to delineate the contextual significance of anesthetic agents. Until such clarity is achieved, anesthetic selection should be guided by patient-specific physiological profiles, institutional expertise, and multidisciplinary consensus-acknowledging that in the landscape of oncologic surgery, even subtle perioperative variables may echo beyond the operating room.