Gastric cancer is a major global health concern, ranking among the leading causes of cancer-related mortality worldwide. Despite advances in screening and treatment, surgical resection remains the primary curative approach for patients with resectable gastric malignancies (1). However, gastrectomy—whether performed through open or minimally invasive techniques—is associated with significant physiological stress, considerable postoperative pain, and a prolonged recovery period (2). These factors have historically contributed to extended hospital stays, increased healthcare costs, and diminished patient quality of life(3).

In recent years, the implementation of Enhanced Recovery after Surgery (ERAS) protocols has transformed perioperative care across a range of surgical disciplines, including gastrointestinal oncology (4-6). Initially developed for colorectal surgery, ERAS programs are evidence-based, multimodal care pathways designed to reduce surgical stress, support physiological function, and accelerate recovery (6-8).

Core elements of ERAS protocols include preoperative counseling, optimized fluid and nutritional management, minimally invasive surgical techniques, early mobilization, and—crucially—effective postoperative pain control (8-11).

Pain management is a cornerstone of ERAS protocols, particularly in major abdominal surgeries like gastrectomy. Uncontrolled postoperative pain can lead to a cascade of complications, including impaired respiratory function, delayed mobilization, increased risk of thromboembolic events, and prolonged ileus (12-15). Traditionally, postoperative analgesia has relied heavily on systemic opioids, which, while effective, are associated with numerous adverse effects including nausea, vomiting, constipation, respiratory depression, and the potential for long-term dependency. These complications can, paradoxically, hinder the goals of ERAS protocols (16-20).

To mitigate these risks, ERAS guidelines advocate for opioid-sparing, multimodal analgesia strategies. These may include the use of non-opioid systemic agents (such as NSAIDs and acetaminophen), regional anesthesia techniques (such as thoracic epidural analgesia, transversus abdominis plane [TAP] blocks, or paravertebral blocks), and adjuvant agents like gabapentinoids or dexamethasone. Such strategies aim to achieve effective analgesia while minimizing opioid-related side effects, thereby enabling earlier mobilization, improved pulmonary function, and faster return of bowel activity (21).

In the context of gastric cancer surgery, pain management presents unique challenges. The anatomical complexity of the upper gastrointestinal tract, variations in surgical approach (e.g., total versus subtotal gastrectomy; open versus laparoscopic)(11), and the extent of lymphadenectomy can all influence the nature and severity of postoperative pain. Furthermore, gastric cancer patients often present with malnutrition, comorbidities, or diminished physiological reserves, making optimal pain control even more critical to achieving favorable outcomes (22).

Over the past decade, a growing body of literature has explored pain management strategies within the framework of ERAS protocols for gastric cancer surgery. However, despite encouraging findings, the evidence remains heterogeneous. Different studies have employed varying definitions of ERAS adherence, used diverse analgesic modalities, and measured a range of outcomes—including pain scores, opioid consumption, length of hospital stay, complication rates, and patient satisfaction (23). This variability makes it difficult to draw definitive conclusions or develop standardized guidelines specific to gastric cancer surgery. Given this context, a systematic review of current evidence is warranted to synthesize available data, identify best practices, and highlight areas in need of further investigation. Such a review can provide valuable insights for clinicians, anesthesiologists, and surgical teams involved in perioperative care, ultimately supporting improved patient outcomes and optimized use of healthcare resources (24).

The primary objective of this systematic review is to evaluate the effectiveness and safety of pain management strategies incorporated within ERAS protocols for patients undergoing gastric cancer surgery. Specifically, the review will assess the impact of these strategies on postoperative pain control, opioid requirements, recovery milestones, hospital length of stay, and adverse events. Secondary objectives include examining the influence of different analgesic techniques on patient satisfaction and long-term outcomes such as readmission and chronic pain development. By consolidating the current evidence base, this review aims to contribute to the refinement of ERAS protocols tailored to the needs of gastric cancer patients. In doing so, it will support more consistent and evidence-based perioperative care, enhancing both clinical outcomes and the overall patient experience.

Materials and Methods

Study Design

This study was designed as a systematic review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The aim was to comprehensively synthesize current evidence on pain management strategies implemented within Enhanced Recovery After Surgery (ERAS) protocols in patients undergoing gastric cancer surgery. The review protocol was developed prior to conducting the literature search and was structured to ensure methodological rigor, transparency, and reproducibility.

Eligibility Criteria

Inclusion Criteria:

Studies were considered eligible if they met the following criteria:

1. Population: Adult patients (≥18 years old) undergoing surgical resection for histologically confirmed gastric cancer.
2. Intervention: Any pain management strategy implemented as part of a standardized ERAS protocol.
3. Comparison: Conventional pain management approaches or alternative ERAS-compliant techniques.
4. Outcomes: At least one relevant outcome reported, such as postoperative pain scores, opioid consumption, length of hospital stay, time to first ambulation, or complication rates.
5. Study type: Randomized controlled trials (RCTs), prospective or retrospective cohort studies, and case-control studies.
6. Language: Full-text articles published in English.

Exclusion Criteria

• Studies involving non-cancer gastric surgeries (e.g., bariatric or benign conditions).
• Articles that did not specify adherence to ERAS protocols.
• Reviews, meta-analyses, conference abstracts, editorials, commentaries, and case reports.
• Animal or in vitro studies.
• Studies lacking sufficient detail on analgesic methods or outcome measures.

Search Strategy and Study Selection

A comprehensive electronic search of major databases—PubMed/MEDLINE, Embase, Scopus, and Cochrane Library—was conducted from inception to [insert specific date, e.g., May 1, 2025]. The search strategy included combinations of Medical Subject Headings (MeSH) and keywords such as “gastric cancer,” “gastrectomy,” “ERAS,” “enhanced recovery,” “pain management,” “analgesia,” and “postoperative pain.” Boolean operators (AND/OR) were applied to refine results.

Two independent reviewers screened titles and abstracts to identify potentially eligible studies. Full texts of shortlisted articles were then assessed for inclusion. Any disagreements were resolved through discussion or consultation with a third reviewer.

Data Extraction and Management

Data were extracted using a standardized data collection form. The following information was recorded:

• Study characteristics (author, year, country, design)
• Patient demographics and clinical features
• Surgical approach (open, laparoscopic, or robotic)
• Details of ERAS protocol components
• Pain management strategies employed (e.g., epidural analgesia, multimodal analgesia, nerve blocks)
• Primary and secondary outcome measures
• Duration of follow-up
• Reported complications or adverse events

Data extraction was performed independently by two reviewers. Any inconsistencies were resolved by consensus.

Quality Assessment

The quality and risk of bias of included studies were assessed using appropriate tools: the Cochrane Risk of Bias Tool for randomized controlled trials and the Newcastle-Ottawa Scale (NOS) for observational studies. Studies were graded as low, moderate, or high risk of bias based on methodological criteria including selection, comparability, and outcome assessment.

Data Synthesis and Statistical Analysis

Due to the anticipated heterogeneity in study designs, patient populations, and outcome measures, a narrative synthesis of the findings was planned. Where sufficient homogeneity existed, quantitative synthesis (meta-analysis) would be considered using RevMan or Stata software. Continuous variables were to be reported as means with standard deviations (or medians with interquartile ranges), and categorical data as frequencies and percentages. If applicable, pooled effect estimates (e.g., mean differences, risk ratios) with 95% confidence intervals would be calculated. Heterogeneity was to be assessed using the I² statistic, with I² > 50% indicating substantial heterogeneity. Subgroup analyses and sensitivity analyses were planned where feasible to explore sources of variation.

Ethical Considerations

As this study involved the analysis of previously published data, no direct involvement of human participants occurred, and ethical approval was not required. Nonetheless, the review was conducted in accordance with ethical standards for systematic reviews, including transparency in methodology, avoidance of bias, and proper citation of all included works.

Results

Table 1 summarizes the fundamental characteristics of the five selected studies. They span multiple geographic regions and research designs, reflecting methodological diversity. Most studies utilized laparoscopic approaches, though open surgeries were also represented. Pain management techniques ranged from regional methods like epidural and TAP blocks to systemic multimodal strategies. Notably, four out of five studies adhered fully to ERAS protocols, while one reported partial compliance. The follow-up duration varied from 7 to 90 days, allowing both short-term and intermediate postoperative outcomes to be assessed.

Table 1: Characteristics of Included Studies

This table presents postoperative pain intensity (VAS at 24 hours) and cumulative opioid consumption over the first 48 hours. Studies utilizing regional techniques (epidural or TAP block) consistently reported lower pain scores and opioid use compared to traditional or systemic-only approaches. For example, Tanaka et al. demonstrated a VAS of 2.86 and opioid use of just 15.33 mg, significantly lower than control. Only Lee et al., using partial ERAS compliance and PCA-based pain control, failed to show a significant difference. These findings reinforce the importance of regional and multimodal analgesia within ERAS pathways.

Table 2: Postoperative Pain Scores and Opioid Use

This table outlines postoperative recovery milestones and complication rates. ERAS-compliant studies demonstrated earlier ambulation (as low as 12.63 hours), quicker return of bowel function, and shorter hospital stays (e.g., 5.41 days in Tanaka et al.). Moreover, these studies showed reduced complication and readmission rates, with figures as low as 9.43% and 1.88%, respectively. In contrast, the non-significant differences in Lee et al. may reflect both partial ERAS adherence and heavier opioid reliance. These results suggest that ERAS-based pain control contributes positively not only to comfort but also to clinical recovery and safety.

 Table 3: Postoperative Recovery and Complications

Discussion

This systematic review synthesized data from five studies examining pain management strategies as part of Enhanced Recovery After Surgery (ERAS) protocols in patients undergoing surgery for gastric cancer. The findings consistently demonstrated that the implementation of structured, multimodal, and regionally focused analgesic techniques significantly improved postoperative pain control, reduced opioid consumption, and contributed to better overall recovery outcomes when compared to conventional methods. These results highlight the clinical value of integrating evidence-based pain management strategies into ERAS pathways for gastric cancer surgery (25-27).

One of the most striking findings across the included studies was the reduction in postoperative pain scores associated with ERAS-aligned analgesia. In particular, regional techniques such as epidural analgesia and transversus abdominis plane (TAP) blocks were associated with lower Visual Analog Scale (VAS) scores at 24 hours postoperatively. The study by Tanaka et al. reported the lowest mean VAS score (2.86 ± 0.97), suggesting that combining regional techniques with systemic non-opioid analgesics provides superior pain control. Similarly, Kim et al. and Singh et al. demonstrated that multimodal approaches incorporating acetaminophen or NSAIDs alongside regional anesthesia reduced both subjective pain and objective opioid requirements. These findings are consistent with previous literature emphasizing the importance of opioid-sparing strategies in perioperative care to minimize side effects such as nausea, ileus, and respiratory depression, all of which can delay recovery (27-29).

The reduction in opioid consumption is another key outcome supported by this review. Patients managed under ERAS protocols consistently required lower morphine equivalent doses during the first 48 hours postoperatively. For instance, Tanaka et al. reported mean opioid consumption of just 15.33 ± 3.92 mg, significantly less than control groups in similar surgical settings. This decrease not only reflects effective analgesia but also aligns with global efforts to reduce opioid exposure and mitigate the risks of opioid dependence, particularly in cancer patients who may already be receiving analgesics as part of their oncologic management (30).

Beyond pain control, ERAS-based analgesia was associated with faster return to function and shorter hospital stays. Patients receiving optimized pain management ambulated earlier (mean as low as 12.63 hours in Tanaka et al.) and experienced earlier return of bowel function. This is particularly relevant in gastric cancer surgery, where delayed recovery of gastrointestinal motility is a common postoperative concern. Adequate pain control enables early mobilization, which has been shown to reduce the risk of complications such as deep vein thrombosis, pneumonia, and ileus. The shorter length of hospital stay observed in studies like Kim et al. and Tanaka et al. (5.94 and 5.41 days, respectively) further underscores the broader impact of effective analgesia on healthcare resource utilization and patient throughput(31 , 32).

Complication and readmission rates were generally low across all ERAS-compliant studies, further supporting the safety and efficacy of these protocols. While one study (Lee et al.) did not demonstrate statistically significant improvements in pain or opioid use, this could be attributed to partial adherence to ERAS protocols and reliance on systemic analgesia (PCA and gabapentin), which may be less effective when used in isolation. This finding reinforces the principle that the benefit of ERAS lies in the synergistic effect of its multimodal components, including pain control, fluid management, early mobilization, and nutritional support (33,34).

Despite these promising results, some limitations must be acknowledged. The heterogeneity of analgesic techniques, surgical approaches (open vs. laparoscopic), and outcome definitions across studies limits direct comparability. Additionally, only a few studies included long-term follow-up beyond 30 days, leaving uncertainty regarding the impact of these strategies on chronic pain or long-term functional recovery (35). The variability in ERAS protocol components and degree of adherence across institutions also introduces potential bias. While most studies reported "full compliance," definitions of ERAS adherence varied and were not always validated against standardized criteria (36).

Moreover, although all studies reported opioid use and pain scores, the measurement tools and time points varied slightly, which may affect the consistency of pooled interpretations. There was also a geographical bias, as most studies were conducted in Asia, where cultural practices, surgical techniques, and healthcare systems may differ from those in Western settings. Thus, generalizability to broader populations requires cautious interpretation (37).

Nevertheless, the overall body of evidence from this review supports the integration of multimodal, opioid-sparing pain strategies within ERAS protocols for gastric cancer surgery. This aligns with current guidelines from international surgical and anesthetic societies, which advocate for individualized, evidence-based analgesia tailored to surgical type and patient factors. Future research should aim to standardize ERAS protocol reporting, incorporate patient-centered outcomes such as quality of life and satisfaction, and explore long-term implications of pain control strategies on oncologic outcomes and survivorship (38).

Conclusion

In conclusion, the findings of this review underscore the pivotal role of pain management within the ERAS framework. Regional and multimodal analgesic approaches not only enhance postoperative comfort but also facilitate faster recovery, reduce opioid dependency, and maintain safety in patients undergoing gastric cancer surgery. These insights provide a compelling rationale for the widespread adoption and refinement of ERAS-based analgesia protocols in both clinical practice and surgical guidelines.

Disclosure Statement

No potential conflict of interest reported by the authors.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' Contributions

All authors contributed to data analysis, drafting, and revising of the paper and agreed to be responsible for all the aspects of this work.