Concentrated enteral nutrition in colorectal cancer surgery: Recovery K5 signal and research priorities

Abstract

In this editorial, we comment on the article by Shinji et al published in the recent issue of the World Journal of Gastrointestinal Surgery. Colorectal cancer ranks as the second leading cause of cancer-related mortality globally, with postoperative surgical site infections (SSIs) occurring in up to 22.5% of cases, significantly contributing to morbidity and costs. Malnutrition is a well-known contributor to postoperative morbidity and mortality, and preoperative nutrition is a significant modifiable risk factor associated with SSIs. Recovery K5 (RK5) is a concentrated liquid formulation that combines balanced soy and milk proteins with collagen peptides for peristress and recovery support. The RK5 trial provides an early signal in this domain and highlights the need for larger multicenter validation, as reported by Shinji et al. It integrates soy and milk proteins in balanced ratios, accompanied by collagen peptides, rendering it appropriate for nutritional support throughout both stress and recovery stages. The RK5 study showed a decrease in the frequency of SSIs from 33.3% to 5.9% (P = 0.0695). The proportion of patients who were able to achieve target energy intake was higher in the RK5 group, which highlighted challenges in meeting perioperative nutritional goals. Immunonutrition improves immune function and affects the tumor environment, which may help people live longer after planned colorectal cancer surgery. Evidence of moderate certainty indicates that perioperative nutritional supplements reduce SSI risk (odds ratio = 0.54, 95% confidence interval: 0.40-0.72). Economic assessments report that immunonutrition may save money by decreasing complications, length of stay, and readmissions; these estimates depend on confirmed clinical benefit and local cost structures. Accordingly, reported savings should be seen as scenario estimates rather than actual outcomes until effectiveness is confirmed in randomized trials and validated locally. This editorial reviews the RK5 findings and supports evaluation within research or step-by-step implementation frameworks rather than routine implementation at this stage.

Key Words: Colorectal cancer surgery; Surgical site infections; Concentrated enteral nutrition; Immunonutrition; Recovery K5; Perioperative nutrition; Enhanced recovery after surgery; Cost-effectiveness

Core Tip: Recovery K5 is a concentrated liquid formulation with a balanced blend of soy and milk proteins, together with collagen peptides. The recovery K5 study demonstrated a non-significant trend in the reduction of surgical site infections, decreasing from 33.3% to 5.9%, P = 0.0695. Economic consequences must be regarded as modeled and dependent on verified therapeutic benefits and local expenses; hence, no actual savings are asserted.

This editorial refers to “Clinical utility of a novel concentrated enteral formula in patients undergoing colorectal cancer surgery: A randomized controlled trial” by Shinji et al, 2025; https://dx.doi.org/10.4240/wjgs.v17.i11.112557.

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INTRODUCTION

Colorectal cancer is the second leading cause of cancer-related mortality globally[1]. Postoperative infections remain a significant concern in colon cancer surgery, resulting in prolonged recovery times and elevated healthcare costs. Surgical site infections (SSIs) are among the most prevalent complications associated with surgical treatments. The incidence of postoperative SSIs may reach 22.5%, a notably concerning statistic that highlights the prevalence of colorectal cancer[2]. Malnutrition contributes to heightened postoperative mortality and morbidity[3], and the patient’s preoperative diet is a significant modifiable risk factor that contributes to SSIs. Enhanced perioperative nutritional assistance was acknowledged as a fundamental subject and research inquiry in the World Health Organization Global Guidelines for the Prevention of SSIs in 2018[4]. Inadequate preoperative nutritional status has consistently been associated with a heightened incidence of postoperative complications and worse surgical outcomes[5]. Severe malnutrition frequently occurs in patients after surgery for gastrointestinal cancers, elevating the risk of mortality within 30 days post-surgery for colorectal or gastric cancer[6]. Two-hour indirect calorimetry is a predictor of 24-hour energy consumption in critically sick patients[7]. Nonetheless, the majority of current systematic reviews and meta-analyses concerning the efficacy of perioperative nutritional supplements in reducing SSIs encompass parenteral nutritional supplements, prebiotics, probiotics, synbiotics, or direct comparisons of enteral formulae[4].

Immunonutrition (IMN) products composed of arginine, omega-3 fatty acids, glutamine, and/or nucleotides are frequently promoted as effective means to mitigate adverse clinical outcomes such as infection and inflammation in colorectal cancer patients. Despite research investigating the function of IMN in preoperative treatment to emphasize safety and efficacy, it has yet to be established as the standard of care for elective colorectal cancer surgery[2]. Moreover, the majority of published studies investigating the impact of IMN on gastrointestinal surgery are heterogeneous in design, encompassing a diverse array of study populations that include both upper and lower gastrointestinal surgeries, the incorporation of parenteral nutrition, varied diseases, and differences in nutritional status[8]. The recovery K5 (RK5) trial provides an early signal in this domain and highlights the need for larger multicenter validation, as reported by Shinji et al[9] published in the World Journal of Gastrointestinal Surgery. RK5 is a concentrated liquid formulation produced by Nutri Co., Ltd., Tokyo, Japan. It has a balanced blend of soy and milk proteins, together with collagen peptides, rendering it appropriate for nutritional support throughout stress and recuperation stages. Moreover, RK5 has a different nutritional profile compared to regular hospital meals, which can help reduce postoperative infections; however, evidence is still preliminary, and very few studies have focused on colorectal cancer. RK5 comprises heat-killed lactic acid bacteria that exhibit gastric protective properties in acute gastric injury models by diminishing pro-inflammatory mediators and cytokines.

Current research demonstrates the efficacy of concentrated enteral feeding programs. Pre-operative IMN may decrease the incidence of wound infections and reduce the duration of hospitalization in patients undergoing elective colorectal surgery[8]. Furthermore, moderate assurance data indicate that nutritional supplements diminish the probability of SSIs (Odds ratio = 0.54, 95% confidence interval: 0.40-0.72)[4]. There is an urgent need to evaluate whether perioperative dietary interventions can enhance early outcomes following gastrointestinal cancer surgery globally[6]. The efficacy of regular IMN in this context remains uncertain due to the lack of substantial evidence from adequately powered trials[3]. This exploratory trial involving 35 patients (17 in the intervention group and 18 in the control group) needs to be followed up with multicenter randomized controlled studies with adequate power estimates to ascertain the validity of these preliminary findings. This editorial evaluates the growing evidence from the RK5 trial in relation to concentrated enteral feeding as a specific strategy to mitigate SSIs in colorectal cancer surgery. This indicates an essential requirement for evidence-based dietary solutions to be integrated into conventional perioperative treatment.

CLINICAL IMPLICATIONS

SSIs in patients can result in symptoms including fever and pain, extend hospitalization, delay recovery, and escalate healthcare expenses. The RK5 study suggested a trend toward reduced incidence of SSI from 33.3% to 5.9% (P = 0.0695); however, this difference is not statistically significant. Still, the 27.4 percentage reduction shows a clinically significant effect, but does not achieve P = 0.05, and shows considerable potential clinical benefits. At present, evaluation should start within research or step-by-step implementation frameworks rather than immediately adapting the routine. The proportion of patients attaining their target energy intake was significantly greater in the RK5 supplementation group, highlighting the critical difficulty of adequate perioperative nutritional supply. Furthermore, IMN modulates the tumor microenvironment by enhancing immune activity and can prolong survival in individuals undergoing elective surgery for colorectal cancer. This mechanistic comprehension offers a biological justification for adoption, as patients treated with IMN exhibited reduced length of stay (LOS), diminished readmission rates, and lower 180-day mortality, consistent with prior research. The findings consistently indicate that IMN as an intervention is correlated with reduced wound infection rates and a LOS[10].

The clinical significance of concentrated enteral feeding is evident when considering the difficulties associated with colorectal surgery. In colorectal cancer surgeries, the incidence of SSIs ranges from 5% to 30%, contingent upon the study, and SSIs represent a significant factor in both morbidity and mortality for patients undergoing colorectal procedures[11]. Modern surgical practice encounters a significant push to enhance outcomes while minimizing expenses. Complications that arise after elective surgery for colorectal cancer put a burden on healthcare systems due to longer hospital stays and increased medical expenses, supporting evaluation within research frameworks and step-by-step implementation dependent on confirmatory data. Evidence indicates that preoperative oral administration of rifaximin and metronidazole, in conjunction with mechanical bowel preparation, significantly reduces postoperative SSI rates; however, nutritional interventions provide a more holistic approach by targeting the underlying immunocompromise[1]. Moreover, malnutrition exacerbates inflammatory responses, hinders wound healing, and compromises immunological function, indicating that concentrated enteral nutrition is an essential element of comprehensive perioperative care rather than just a complement.

Socioeconomic indicators present a compelling argument for the implementation of healthcare systems. Healthcare expenditures are escalating swiftly, and the widening disparity between costs and available resources has become a significant concern, particularly exacerbated during the severe acute respiratory syndrome coronavirus 2 pandemic amid the financial crisis. In this environment, concentrated enteral nutrition may be considered a good strategy with sufficient resources if the benefit is confirmed in randomized trials and validated locally. Economic assessments report that IMN may save money by decreasing complications, LOS, and readmissions; these estimates depend on confirmed clinical benefit and local cost structures. Specifically, the study indicates that the treatment of IMN generated savings across all analyzed patient cohorts. Within enhanced recovery after surgery pathways, IMN may have sufficient resources, but any net savings are estimates and depend on confirmed clinical benefit, local pricing, and implementation; specific currency figures have been removed to avoid suggesting actual financial savings[11]. From a broader perspective, the economic benefit includes more than just immediate hospital savings. The expenses associated with prolonged hospitalization resulting from problems following colorectal cancer surgery can impose a significant financial strain on both the healthcare system and patients. Economic projections should be seen as scenario estimates rather than actual savings until effectiveness is confirmed in randomized trials and validated locally[8].

POLICY RECOMMENDATIONS AND FUTURE DIRECTIONS

The integration of clinical efficacy, logical comprehension, and economic advantage establishes a robust basis for policy recommendations. Healthcare institutions should focus on integrating concentrated enteral feeding programs into standard colorectal surgery practices. Strengthening the patient’s immune system before surgery may enable IMN to diminish the incidence of postoperative problems, potentially reducing both the duration of hospital stays and associated expenditures[8]. The previously identified cost-saving patient group indicates that the healthcare system might possibly save millions annually if widely utilized in colon cancer surgery. Healthcare organizations must judiciously integrate these approaches into regular care to enhance surgical outcomes via evidence-based nutritional optimization. This signifies a transition from reactive complication management to proactive prevention by nutritional optimization, aligning with contemporary value-based healthcare delivery models that emphasize outcomes and cost reduction.

CONCLUSION

The evidence positions concentrated enteral nutrition as an intervention capable of bridging the important gap between the increasing burden of colorectal cancer and inadequate perioperative nutritional interventions. SSIs in patients may manifest as fever and pain, potentially prolonging hospitalization, delaying recovery, and escalating healthcare expenses. The RK5 trial showed a trend towards decreased occurrence of SSI (P = 0.0695) and provides promising evidence that needs validation through more extensive trials. Pre-operative IMN may diminish the incidence of wound infection and lessen the duration of hospitalization in patients undergoing elective colorectal surgery. The escalation of healthcare expenditures and the widening disparity between expenses and available resources have become a significant concern, particularly exacerbated by the economic downturn during the severe acute respiratory syndrome coronavirus 2 pandemic. Any economic impact should be seen as a projected estimate dependent on confirmed clinical benefit and local costs; routine use is premature until it is validated by randomized trials. Implementing preoperative IMN guidelines may result in significant cost savings for healthcare systems, enhance patient recovery rates, and increase the overall efficacy of colorectal cancer surgeries. Clinicians can consider using concentrated enteral nutrition in selected patients within enhanced recovery after surgery as a part of ongoing studies or step-by-step protocols until the benefit is confirmed. Policymakers should consider making conditional recommendations that encourage participation in multicenter trials and local cost assessments before announcing guidelines. Researchers must undertake multicenter trials to establish optimal formulations and timing. Enhancing the patient’s immune system before surgery may diminish the incidence of postoperative problems, decreasing hospital stays and reducing healthcare expenses. The future necessitates collaborative innovation to establish standardized, globally accessible nutritional techniques that shift colorectal cancer surgery from reactive complication treatment to proactive nutritional optimization for prevention.