From feasibility to biological recovery: Reframing enhanced recovery pathways for elderly gastric cancer patients

Abstract

Enhanced recovery after surgery (ERAS) has reshaped perioperative care in gastrointestinal oncology, but its application in elderly gastric cancer patients requires a shift from feasibility toward a biologically grounded understanding of recovery. Aging is characterized by frailty, sarcopenia, multimorbidity, chronic inflammation, and circadian vulnerability, which collectively influence postoperative resilience. Contemporary evidence shows that ERAS pathways remain feasible and safe in older adults, yet responsiveness varies widely due to physiological heterogeneity rather than chronological age alone. This Editorial reframes recovery as a multidomain process encompassing nutritional-inflammatory balance, sleep-circadian regulation, psychological resilience, and functional mobility. Targeted perioperative nutrition may support metabolic competence; structured sleep-protection strategies can stabilize endocrine-immune rhythms; psychological interventions may mitigate stress-related inflammatory activation; and digital monitoring using step-count trajectories or heart-rate variability provides early indicators of recovery deviation. Implementation challenges-including clinical workload, variable frailty, cognitive impairments, digital acceptance, and uneven access to multidisciplinary expertise-highlight the need for adaptive and pragmatic pathways. As global aging accelerates, ERAS must evolve from standardized protocols to biologically informed, patient-centered systems that align interventions with host physiology and real-time recovery signals. Such an approach may better capture recovery depth, enhance functional outcomes, and promote equitable care for elderly surgical populations.

Key Words: Enhanced recovery after surgery; Gastric cancer; Elderly patients; Functional recovery; Biological resilience; Nutritional support

Core Tip: Enhanced recovery after surgery (ERAS) has demonstrated safety and feasibility for elderly patients with gastric cancer, but feasibility alone does not define success. This editorial reframes ERAS as a pathway toward functional recovery-restoring biological resilience, metabolic homeostasis, and circadian stability while preserving independence. By integrating psychophysiological support, nutritional-inflammatory modulation, and digital monitoring, ERAS can evolve into an adaptive, precision rehabilitation model that bridges chronological age and biological potential.

INTRODUCTION

Enhanced recovery after surgery (ERAS) has redefined perioperative management across gastrointestinal oncology by integrating multimodal, evidence-based elements into a coherent, team-delivered pathway[1-3]. Beyond accelerating postoperative milestones, ERAS attenuates neuroendocrine-inflammatory stress, facilitates early mobilization and nutritional repletion, and yields reproducible gains in safety, efficiency, and value across diverse settings[4,5]. Yet demographic aging reshapes surgical practice worldwide, and a persistent uncertainty remains: Can these standardized pathways maintain their benefit in older adults whose physiological reserve is constrained by frailty, sarcopenia, and multimorbidity[6-8]?

The retrospective analysis by Li et al[9] directly addresses this question in the context of gastrectomy for gastric cancer. In a cohort of 161 patients-82 aged ≥ 65 years-the authors report comparable ERAS adherence, inflammatory biomarker trajectories, and short-term outcomes between older and younger groups, without excess complications or mortality under standardized care[9]. Taken together with prior geriatric-focused series, these results counter the assumption that chronological age per se attenuates the gains of ERAS, and instead suggest that protocolized, physiology-sparing care can be delivered safely and effectively in older patients when implemented with rigor[7-9].

At the same time, not all reports are uniformly optimistic. Studies in colorectal, hepatopancreatobiliary, and mixed gastrointestinal surgery have shown that frailty, cognitive impairment, chronic inflammation, and multimorbidity may attenuate the expected gains of ERAS, leading to higher rates of postoperative complications, delayed mobilization, or failure to meet pathway milestones-even under standardized protocols[10-13]. These findings emphasize that physiologic heterogeneity-not chronological age-is the key determinant of pathway responsiveness, and that certain high-risk subgroups may require tailored modifications or enhanced support within ERAS pathways.

Taken together, current evidence portrays a balanced landscape: ERAS can be delivered safely and effectively in older adults, but its impact is modulated by frailty status, baseline functional reserve, sarcopenia burden, and inflammatory load. This underscores the need to move beyond feasibility and toward a more biologically informed understanding of recovery in an aging surgical population.

Nevertheless, feasibility should be regarded as the floor, not the ceiling, of progress. As perioperative science pivots from logistics toward biology, the central question becomes: What constitutes meaningful recovery for the aging surgical body? Answering this requires a shift from measuring speed to quantifying restoration-of immune-metabolic balance, functional independence, sleep-circadian stability, and psychosocial well-being-domains that together determine long-term resilience[1-3,6].

REINTERPRETING RECOVERY: FROM EARLY DISCHARGE TO BIOLOGICAL RESILIENCE

Conventional metrics-length of stay, time to ambulation, and crude complication counts-are pragmatic but reductionist; they capture throughput, not depth of recovery[1,6]. In older adults, homeostasis is a multi-system equilibrium spanning physiology (inflammation, metabolism), function (mobility, nutrition), and mind-brain health (sleep, mood, cognition). Recovery in geriatric oncology should therefore be conceptualized as resilience reconstruction: The capacity to regain immune-metabolic equilibrium, restore circadian synchrony, and sustain autonomy in daily living after major surgical stress[14-16].

Biologically, aging is accompanied by a chronic, low-grade inflammatory tone-inflammaging-that lowers anabolic efficiency and impairs tissue repair[17]. Superimposed surgical stress can amplify catabolism, reflected by elevations in interleukin (IL)-6 and C-reactive protein (CRP) that correlate with infectious and non-infectious morbidity[14-16]. Under standardized ERAS care, Li et al[9] observed that older patients achieved inflammatory trajectories comparable to those of younger counterparts, reinforcing the principle that biologic adaptability, rather than chronological age, governs postoperative recovery potential. This insight reframes the target from “fast-track surgery” to precision rehabilitation-context-aware care that synchronizes biological, psychological, and social recovery processes and is audited not only by time-based milestones but also by host-response signals and patient-centered outcomes[1,2,6,18].

Operationalizing this reinterpretation entails two practical moves. First, upgrade outcome hierarchies: Retain efficiency metrics but co-primary endpoints should index host biology (e.g., resolution of inflammatory perturbation), functional reserve (nutrition, mobility), and lived experience (sleep quality, mental health)[14-16,18]. Second, align pathway levers with these endpoints: Prioritize early, targeted nutrition and anti-catabolic strategies; protect sleep-circadian integrity in the ward environment; and embed scalable psychobehavioral support-each a modulator of the same immune-metabolic network that determines recovery depth in the elderly[1,2,6,18].

Integrating the psychophysiological, nutritional, and metabolic axes

Elderly surgical patients embody a complex interface of biological frailty and psychosocial vulnerability[19-21]. Surgical recovery in this population is shaped by intersecting biological, behavioral, and environmental determinants rather than physiological stabilization alone. To evolve ERAS from feasible to transformative, perioperative pathways should address these axes simultaneously, harmonizing cellular, systemic, and psychological recovery processes. An integrative conceptual framework of these multidimensional axes and their hypothesized relationships is illustrated in Figure 1.

Figure 1 Integrative framework of psychophysiological, nutritional, and metabolic axes within enhanced recovery after surgery pathways in elderly gastric cancer surgery. The schematic illustrates how multidomain perioperative interventions-nutritional-inflammatory modulation, circadian and sleep regulation, psychological resilience, and digital monitoring-interact through mechanistic axes involving inflammation control, metabolic competence, and autonomic-endocrine-immune balance. These pathways converge toward hypothesis-driven clinical outcomes including reduced short-term complications, improved functional independence, and potential long-term survival benefits. Implementation is governed by biomarker-guided (“if-then”) triggers, multidisciplinary oversight, and prospective validation to ensure safety and causal inference.

Nutritional-inflammatory modulation: Rebuilding metabolic competence

Malnutrition, sarcopenia, and chronic inflammation may form a reinforcing triad that undermines resilience in older adults[21,22]. Catabolism, immune suppression, and impaired wound repair share a common metabolic substrate-inefficient protein synthesis and energy imbalance. Recent prospective studies in elderly gastrointestinal surgery populations have shown that perioperative immunonutrition can modestly reduce infectious complications and support early functional recovery, particularly in patients with sarcopenia or elevated inflammatory tone[23]. Additional meta-analytic evidence from 2023 suggests that immunonutrition may shorten length of stay and improve short-term nutritional status in high-risk oncology patients, although heterogeneity remains and causal inference is limited[24]. Emerging evidence suggests that targeted perioperative nutrition-early enteral feeding, carbohydrate loading, and immunonutrition enriched with arginine, ω-3 fatty acids, and nucleotides-can attenuate these cascades and shorten recovery time[19,20]. The study by Li et al[9] reported ERAS compliance exceeding 85% among elderly patients, underscoring that nutritional optimization is both achievable and central to systemic equilibrium. Future ERAS models could move beyond uniform feeding protocols toward biomarker-guided algorithms [e.g., Prognostic Nutritional Index or Prognostic Inflammatory and Nutritional Index (PINI) trajectories] to tailor intensity and composition according to inflammatory and nutritional dynamics[20,21,25]. This reframes nutrition from supportive care to an active biological modulator, while acknowledging that causal effects require prospective validation.

Circadian and sleep regulation: Synchronizing recovery biology

Sleep architecture is a sentinel of systemic homeostasis. Circadian disruption is associated with amplified surgical inflammation, reduced insulin sensitivity, and delayed anabolism[18]. Hospital lighting/noise and nocturnal care interruptions routinely fragment sleep and may exacerbate cytokine activation. Recent clinical trials in older inpatients have demonstrated that structured sleep-protection bundles-controlling nocturnal noise/Light and optimizing timing of care-can reduce delirium incidence and improve glucose stability, supporting the mechanistic plausibility of circadian-informed ERAS components[26]. Similarly, melatonin supplementation has been associated with improved postoperative sleep efficiency and reduced early delirium risk in older surgical patients[27]. Incorporating structured sleep strategies-melatonin, timed light exposure, and CBT-I elements-within ERAS can help recalibrate endocrine-immune rhythms and potentially accelerate wound healing[18]. In older adults, restoring circadian synchrony is not ancillary but foundational, with signals suggesting reductions in delirium and glucose instability when sleep is protected[18,28]. This embeds chronobiology into perioperative design while keeping claims explicitly hypothesis-driven.

Psychological resilience and cognitive preservation

Psychological resilience-the adaptive capacity to restore equilibrium under stress-correlates with perioperative outcomes[28]. Anxiety, depression, and helplessness can heighten sympathetic tone and IL-6-mediated inflammation, reinforcing catabolism. Prospective studies in geriatric oncology have shown that brief perioperative psychological interventions-including structured education, coping-skills training, and narrative-based approaches-may reduce postoperative anxiety and support earlier functional mobilization[29]. Early evidence also suggests that resilience training may modulate inflammatory markers modestly in older adults undergoing major cancer surgery, though confirmatory data are required[30]. Prehabilitation strategies-narrative therapy, cognitive-behavioral interventions, and structured education-are plausible routes to down-modulate hypothalamic-pituitary-adrenal-axis reactivity and support immune competence[19,20]. Integrating these modalities positions recovery as a biopsychosocial phenomenon, in which immune restoration and psychological adaptation may mutually reinforce a positive loop; causality remains to be tested.

These concepts are supported by our recent randomized trial in gastric cancer, in which combined psychological and sleep-focused interventions were associated with improved inflammatory profiles, enhanced sleep quality, and favorable oncologic outcomes[31].

Digital monitoring and predictive analytics: From observation to anticipation

Wearables quantifying sleep efficiency, mobility, and heart-rate variability (HRV) provide continuous proxies of autonomic and metabolic recovery[6]. Analytics can flag deviations from expected recovery curves ahead of overt clinical deterioration, aligning ERAS with predictive, preventive, and personalized principles[1,2,6]. Recent feasibility studies in elderly abdominal surgery patients demonstrate that step-count trajectories and HRV indices derived from consumer-grade wearables correlate with complication risk and delayed mobilization, supporting their potential role as low-burden adjuncts in perioperative monitoring[32]. To make this tractable without overstating causality, we propose if-then operational triggers governed by multidisciplinary team (MDT) review (Table 1).

Table 1 Operational framework for integrating psychophysiological, nutritional, and metabolic axes within enhanced recovery after surgery pathways in elderly surgical patients.

Trigger	Definition/threshold	Rationale/mechanistic link	Prompted action (MDT-governed)	Governance/notes
Autonomic-sleep dysregulation (≤ 72 hours post-op)	HRV ↓ ≥ 20% from baseline and sleep efficiency < 80%	Autonomic imbalance → sympathetic predominance → catabolic & inflammatory surge	Review analgesia/sedation timing. Activate sleep-protection bundle (timed light, noise reduction, melatonin). Screen for early delirium/uncontrolled pain (geriatric input as needed)	Process prompt; not therapeutic. Requires prospective validation
Reduced mobility trajectory (POD 2-5)	Step-count ↓ ≥ 30% from prior day or below ward target ≥ 48 hours	Impaired recovery reserve → pulmonary and thrombotic risk	Escalate physiotherapy/mobilization. Reassess nutrition (protein ≥ 1.2 g/kg). Check orthostatic vitals	Needs wearable or nurse-logged data; align with ERAS mobility KPIs
Metabolic stress signature (any time)	Resting nocturnal HR ↑ ≥ 10 bpm for ≥ 2 nights plus appetite decline	Hypermetabolic state; low-grade inflammation; energy deficit	Rule out infection/pain. Review fluid/glucose management. Consider early immunonutrition based on PINI trend	MDT review trigger; actions supervised jointly by surgical, geriatric, and nutrition teams
Inflammatory-nutritional deviation (POD 3-7)	PINI > 1 or PNI < 40 or CRP > 50 mg/L persistent ≥ 48 hours	Sustained inflammation & malnutrition predict delayed recovery	Initiate targeted nutrition (ω-3, arginine, nucleotides). Evaluate infection source. Recheck markers in 48 hours	Exploratory markers; standardization needed for multicenter use
Behavioral-psychological distress (pre- or early post-op)	HADS-A ≥ 8 or PHQ-9 ≥ 10	Psychological stress → HPA activation → IL-6 ↑ → impaired healing	Initiate CBT/narrative-based support. Arrange mental-health professional review. Consider IL-6 monitoring if available	Optional; integrate with perioperative mental-health resources under psychology/geriatric oversight

These thresholds and responses are hypothesis-driven process prompts, not validated outcome predictors. All interventions should operate within institutional audit and feedback frameworks until prospective validation is achieved. Multidisciplinary governance involves surgeons, geriatricians, anesthesiologists, dietitians, psychologists, and physiotherapists, each contributing to domain-specific assessment and intervention. ERAS: Enhanced recovery after surgery; HR: Heart rate; HRV: Heart-rate variability; POD: Postoperative day; PINI: Prognostic Inflammatory and Nutritional Index; PNI: Prognostic Nutritional Index; HADS: Hospital Anxiety and Depression Scale; PHQ-9: Patient Health Questionnaire-9; MDT: Multidisciplinary team; HPA: Hypothalamic-pituitary-adrenal; CRP: C-reactive protein; IL-6: Interleukin-6; KPIs: Key performance indicators.

Trigger A (within 72 hours post-op): HRV (time-domain metric) decreases ≥ 20% from individual baseline and nocturnal sleep efficiency < 80% → Action: Review analgesia/sedation timing; initiate or upgrade the sleep-protection bundle (timed light, noise control, melatonin); assess for uncontrolled pain or early delirium risk (screen only).

Trigger B (post-op days 2-5): Step-count trajectory falls ≥ 30% from the prior day or fails to reach ward target for 48 hours → Action: Escalate physiotherapy and mobilization goals; reassess nutrition (protein/energy adequacy); check orthostatic vitals.

Trigger C (any time): Resting nocturnal heart rate ≥ 10 bpm above baseline for two consecutive nights with appetite score decline → Action: Rule-out infection/pain, review fluid balance, and consider early immunonutrition supplement pending PINI/CRP trends.

These triggers are process prompts, not outcome guarantees; they should operate within a continuous quality-improvement loop (audit & feedback) and be evaluated prospectively for safety and efficacy in elderly subgroups.

From protocol compliance to adaptive, precision rehabilitation

The success of ERAS has long been gauged by compliance rates-how closely clinicians adhere to standardized elements[9]. While essential for quality assurance, compliance is a surrogate, not a destination. The true benchmark should be biological responsiveness: The degree to which interventions restore physiologic stability, function, and quality of life[1,3].

A next-generation model of precision rehabilitation envisions a continuous feedback loop linking host biology, patient behavior, and system adaptation. Serial monitoring of inflammatory markers (IL-6, CRP, albumin), behavioral metrics (sleep efficiency, mobility), and psychometric scores (resilience, fatigue) can generate individualized recovery trajectories[14-16,18]. Predictive algorithms can then flag stagnation or regression, prompting targeted adjustments-more intensive nutritional support, revised mobilization pacing, or psychological reinforcement[19-21].

In this vision, MDT-surgeons, anesthesiologists, geriatricians, nutritionists, psychologists, and data scientists-operate not in silos but as an ecosystem of recovery engineering[1,2,6]. ERAS thus evolves from a protocol to an adaptive system, guided by continuous physiologic intelligence.

Despite its conceptual appeal, operationalizing an adaptive and biologically informed ERAS pathway in an aging society presents several practical challenges. First, implementation requires substantial clinical bandwidth: Nursing workload, geriatric assessment, structured sleep protection, and nutritional optimization all demand time and coordination that may be difficult to sustain in resource-constrained hospitals. Second, heterogeneity among older adults-frailty, cognitive vulnerability, multimorbidity, sensory impairment-means that standardized pathways may not capture the full spectrum of recovery needs, necessitating individualized adjustments that are not yet routinely built into ERAS workflows. Third, although digital monitoring offers promising insights, real-world limitations remain, including device acceptance among older patients, data quality variability, and the absence of validated perioperative thresholds for clinical decision-making. Finally, the successful delivery of multidomain interventions depends on workforce training; geriatricians, psychologists, physiotherapists, dietitians, and data specialists are not uniformly available across institutions, and multidisciplinary integration remains an aspirational goal in many centers.

Addressing these barriers will require incremental innovation rather than wholesale redesign. Scalable approaches-such as simplified frailty screening, targeted sleep-protection bundles, basic wearable metrics (step count, nocturnal heart rate), and brief psychological support-may offer high-yield entry points that align with existing ERAS elements. As population aging accelerates globally, the evolution of ERAS will hinge on its ability to accommodate physiologic diversity, leverage low-burden monitoring tools, and embed multidisciplinary thinking into everyday perioperative practice. These adaptations will help ensure that the pathway remains equitable, feasible, and clinically meaningful for an increasingly elderly surgical population.

Global context: The convergence of ERAS and aging science

Global research trends, highlighted through Reference Citation Analysis, reveal four converging trajectories redefining perioperative science[1,4,6,9]: (1) Inflammation-based prognostic modeling, quantifying the host response as a therapeutic target; (2) Nutritional and sarcopenic optimization, reframing recovery through metabolic competence; (3) Psychophysiological and circadian interventions, uniting mental health with immunologic recalibration; and (4) Digital precision monitoring, operationalizing recovery through continuous data analytics.

Li et al’s findings[9] reinforce the first pillar-validating the physiologic tolerance of ERAS in the elderly-and indirectly affirm the others, demonstrating that aging biology can accommodate complex, multimodal recovery frameworks without excess risk. The next step is translational: To integrate these dimensions into composite recovery indices that capture depth rather than speed of convalescence. Prospective multicenter studies should test hybrid endpoints-integrating inflammatory resolution, muscle preservation, cognitive integrity, and patient-reported outcomes-to establish a biologically grounded hierarchy of recovery metrics[10,17,18]. This convergence signals the emergence of recovery medicine as an autonomous scientific discipline, bridging gerontology, immunometabolism, and behavioral science.

ETHICAL AND CONCEPTUAL IMPLICATIONS: AGE AS A SPECTRUM, NOT A BARRIER

Persisting exclusion of older adults from intensive perioperative programs reflects a vestige of ageism rooted in outdated assumptions of fragility[7-9]. The evidence by Li et al[9] dismantles this bias: Age alone is a poor surrogate for recovery potential. Physiologic age-quantified through frailty indices, sarcopenia scores, and inflammatory load-offers a more rational basis for personalization[21,22].

From an ethical standpoint, the future of ERAS must prioritize inclusivity-designing adaptive frameworks that accommodate physiologic heterogeneity rather than restricting participation because of it[6,9,25,28]. The elderly, heterogeneous yet resilient, should be reimagined not as the limits of surgical possibility but as the testing ground for perioperative innovation. Their outcomes will ultimately define whether modern surgery can deliver humane precision medicine.

CONCLUSION

The study by Li et al[9] represents a pivotal inflection point in ERAS evolution. By proving that standardized, evidence-based recovery pathways are safe and feasible for elderly gastric cancer patients, it dissolves the conceptual ceiling that age equates to vulnerability. The future imperative is clear: Elevate ERAS from procedural compliance to a biologically intelligent, patient-centered paradigm that restores not merely function but wholeness.

In this reframed paradigm, recovery transcends the linear journey from operation to discharge. It becomes a dynamic continuum of reintegration-encompassing immune equilibrium, metabolic vitality, cognitive clarity, and emotional steadiness. The elderly surgical patient, once perceived as a marginal beneficiary, emerges as the benchmark for surgical excellence-the definitive test of whether medicine can heal completely rather than merely quickly.

ERAS began as a revolution in perioperative logistics; its next revolution must be in meaning. The true measure of success will no longer be hours saved but lives restored to harmony and dignity.

ACKNOWLEDGEMENTS

The author extends sincere appreciation to Li JY, Ge MM, Pan HF, and Jiang ZW for their valuable contributions to the evidence base of ERAS in elderly gastric cancer patients.