Parenteral nutrition versus enteral nutrition after gastric cancer surgery: a systematic review and meta-analysis of randomized controlled trials

Introduction

Gastric cancer remains the fifth most frequently diagnosed malignancy and the third leading cause of cancer-related mortality worldwide (1,2), with the highest incidence in Eastern Asia, Eastern Europe, and South America (1). The incidence is higher in men than in women (1,2). Despite advances in multidisciplinary management, including surgery, chemotherapy, and radiotherapy (3,4), prognosis remains poor, with a reported 5-year survival rate of patients with gastric cancer is 37% or, more specifically, 67% in localized disease, 31% in advanced stage, and 5% in metastatic disease (2).

Nutritional support is a cornerstone of perioperative care for gastric cancer patients, particularly following gastrectomy and D2 lymphadenectomy (5), procedures that often compromise oral intake and predispose patients to malnutrition and related complications (6-8). Two major approaches are commonly employed: parenteral nutrition (PN) and enteral nutrition (EN). However, the optimal strategy remains controversial. Several studies suggest that PN may prolong hospital stay, increase the risk of infections and metabolic complications, and offer little advantage in nutritional recovery compared to EN (9,10). Conversely, other reports indicate that PN is equally effective and safe, especially in patients unable to tolerate EN, and may even improve immune function and clinical outcomes in certain settings (9,11-13). Similarly, while EN has been associated with fewer complications and shorter hospital stays in some trials (13), these findings are not universal, with other studies reporting no significant differences or even favoring PN under specific circumstances.

These conflicting results may stem from differences in study design, patient populations, timing and composition of nutritional interventions, and definitions of clinical endpoints. Such heterogeneity complicates the interpretation of individual studies and highlights the need for a rigorous synthesis of the available evidence.

Therefore, it remains essential to investigate the impact of PN versus EN in patients with gastric cancer, with the goal of clarifying their impact on perioperative outcomes and informing clinical practice. This study sought to evaluate the effects of PN versus EN in such patients. We present this article in accordance with the PRISMA reporting checklist (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-242/rc) (14).

Methods

Literature search

The search strategy was elaborated following the PICOS principle (15).

Inclusion and exclusion criteria

The inclusion criteria were: (I) included patients with gastric cancer; (II) the intervention group received PN; (III) the control group received EN; (IV) the outcomes were the length of hospital stay, nutritional variables (albumin, prealbumin, and CD4 cells/CD8 cells ratio), and adverse events; and (V) randomized controlled trial (RCTs).

The exclusion criteria were: (I) studies presented as abstracts, case reports, meta-analyses, reviews, animal studies, or protocols; (II) publications not in English; (III) inability to retrieve the full text; or (IV) absence of available data.

Search strategy

PubMed, Web of Science, Embase, and the Cochrane Library databases were searched for papers published from inception up to August 2025, using “Stomach Neoplasms”, “Parenteral Nutrition, Total”, as well as other relevant keywords (Table S1). The search and study selection process was done independently by two authors (Y.L.P. and Y.L.H.). Discrepancies were examined by a third reviewer (Y.L.).

Data extraction and quality assessment

The data retrieved included the names of the authors, year, country, patient characteristics (male percentage, age, and cancer types), study characteristics (sample size and interventions), and outcomes.

The quality assessment of included RCTs were evaluated according to the Cochrane risk of bias tool (RoB 2.0 Tool) (16), by two independent investigators (** and **). Uncertainties were discussed in the reviewer team in order to achieve consensus. The RoB 2.0 tool evaluates five domains: randomization process, deviations from intended interventions, missing outcome data, measurement of outcomes, and selection of reported results. Each domain was rated as “low risk”, “some concerns”, or “high risk”. Studies were judged as low risk if all domains were low risk, high risk if any domain was high risk or multiple domains raised concerns, and “some concerns” if at least one domain raised concerns but none were high risk.

Statistical analysis

All analyses were conducted using STATA SE 14.0 software. Relative risks (RRs), weighted mean differences (WMDs), and their corresponding 95% confidence intervals (CIs) were utilized as effect sizes. Heterogeneity among the included studies was assessed using Cochran’s Q test and the I² statistic. An I² value >50% indicated significant heterogeneity. When high heterogeneity was present, a random-effects model was utilized; in all other cases, a fixed-effects model was applied (17). A P value <0.05 was considered statistically significant. Subgroup analyses based on surgical methods were performed to explore potential sources of heterogeneity. Publication bias was assessed using Begg’s and Egger’s tests. In addition, sensitivity analyses were performed to identify the individual study effects on pooled results and test the reliability of results.

Results

Identification and selection of the eligible studies

From the databases, a total of 704 records were initially identified, with 233 being excluded prior to screening. Of the remaining 471 records that underwent screening, 170 were further excluded. Subsequently, 301 reports were considered for retrieval, but 287 were discarded due to irrelevant outcomes. Among the 14 reports assessed for eligibility, five lacked available data. Ultimately, nine studies were included in this meta-analysis (Figure 1).

Figure 1 Study selection process.

Study characteristics and quality assessment

The 9 studies included 641 participants in the PN group and 637 in the EN group. Six studies were performed in China (13,18-22), one in South Korea (23), one in Japan (24), and one in the USA (Table 1) (25). With regard to the analysis of the risk of bias for all-cause mortality, five studies were considered to be at low risk and four at unclear risk of bias on the randomization process (Figure 2).

Figure 2 Quality assessment of Cochrane risk of bias tool (RoB 2.0 Tool).

Primary outcome

Length of hospital stay (days)

Eight RCTs presented data about the effect of PN on the length of hospital stay. The results indicate that the length of hospital stay was longer with EN than PN (13,18,20-25) (WMD =3.45 days, 95% CI: 2.29–4.61, P<0.001; I² =80.4%, P_{heterogeneity}<0.001) (Figure 3A). Then, a subgroup analysis of the effect of PN on the length of hospital stay was performed according to surgical method. Six studies reported a surgical method of radical gastrectomy, and two studies reported others. In both cases, there was a benefit of PN on the length of hospital stay (radical gastrectomy: WMD =3.39 days, 95% CI: 1.49–5.29, P<0.001; I² =85.2%, P_{heterogeneity}<0.001; others: WMD =3.47 days, 95% CI: 2.67–4.27, P<0.001; I² =0.00%, P_{heterogeneity}=0.91) (Figure 3B).

Figure 3 Forest plot of the length of hospital stay (days). (A) Overall. (B) Subgroup analysis (radical gastrectomy and other). CI, confidence interval; WMD, weighted mean difference.

Secondary outcomes

Anal exhaust time (days)

Four RCTs presented data about the effect of PN on the anal exhaust time. The results indicate that the anal exhaust time was longer with EN than PN (13,20-22) (WMD =1.04 days, 95% CI: 0.51–1.57, P<0.001; I² =98.4%, P_{heterogeneity}<0.001) (Figure 4A). Two studies using radical gastrectomy showed a benefit of PN on the anal exhaust time (WMD =0.78 days, 95% CI: 0.39–1.16, P<0.001; I² =87.5%, P_{heterogeneity}=0.005). Two studies using other surgery methods showed a benefit of PN on the anal exhaust time (WMD =1.30 days, 95% CI: 0.89–1.71, P=0.001; I² =91.3%, P_{heterogeneity}=0.001) (Figure 4B).

Figure 4 Forest plot of the anal exhaust time (days). (A) Overall. (B) Subgroup analysis (radical gastrectomy and other). CI, confidence interval; WMD, weighted mean difference.

Nutritional variables

Seven RCTs presented data about the effect of PN on the albumin levels and the albumin levels were comparable between PN and EN after surgery (18-23,25) (WMD =−1.50 g/L, 95% CI: −2.99 to 0.00, P=0.05; I² =92.8%, P_{heterogeneity}<0.001) (Figure 5A). Five studies using radical gastrectomy showed no benefit of PN on albumin level (WMD =−2.04 g/L, 95% CI: −4.11 to 0.02, P=0.052; I² =95.1%, P_{heterogeneity}<0.001). Two studies using other surgery methods also showed no benefit of PN on albumin level (WMD =−0.29 g/L, 95% CI: −1.32 to 0.73, P=0.57; I² =0.00%, P_{heterogeneity}=0.54) (Figure 5B).

Figure 5 Forest plot of the nutritional variables. (A) Overall of albumin. (B) Subgroup analysis of albumin (radical gastrectomy and other). (C) Overall of prealbumin. (D) Subgroup analysis of prealbumin (radical gastrectomy and other). (E) Overall of CD4/CD8 ratio. (F) Subgroup analysis of CD4/CD8 ratio (radical gastrectomy and other). CI, confidence interval; SMD, standardized mean difference; WMD, weighted mean difference.

Six RCTs presented data about the effect of PN on the prealbumin levels and the prealbumin levels were higher with PN than EN after surgery (18,20-23,25) (WMD: −2.71 g/L, 95% CI: −4.72 to −0.70, P=0.008; I² =99.3%, P_{heterogeneity}<0.001) (Figure 5C). Four studies using radical gastrectomy showed no benefit of PN on prealbumin level (WMD =−3.86 g/L, 95% CI: −8.08 to 0.35, P=0.07; I² =99.6%, P_{heterogeneity}<0.001). Two studies using other surgery methods also showed no benefit of PN on prealbumin level (WMD =−0.55 g/L, 95% CI: −1.56 to 0.47, P=0.29; I² =93.2%, P_{heterogeneity}<0.001) (Figure 5D).

Finally, four studies presented data on the CD4/CD8 ratio and higher CD4/CD8 ratio in PN compared with EN (18,20,22,25) (WMD =−0.13, 95% CI: −0.26 to 0.00, P=0.049; I² =73.5%, P_{heterogeneity}=0.01) (Figure 5E). Three studies using radical gastrectomy showed no benefit of PN on CD4/CD8 ratio (WMD =−0.12, 95% CI: −0.33 to 0.09, P=0.25; I² =82.0%, P_{heterogeneity}=0.004). Another study showed a benefit of PN on CD4/CD8 ratio (WMD =−0.12, 95% CI: −0.22 to −0.02, P=0.03) (Figure 5F).

Adverse events

Seven RCTs reported data about post-complications, such as diarrhea, surgical site infection, blood loss, etc. (13,20-25). The results suggest that no differences in surgical complications between EN and PN [rate difference (RD) =0.07, 95% CI: −0.09 to 0.24, P=0.38; I² =85.7%, P_{heterogeneity}<0.001] (Figure 6A). Five studies using radical gastrectomy showed no benefit of PN on surgical complications (RD =0.12, 95% CI: −0.10 to 0.34, P=0.30; I² =87.2%, P_{heterogeneity}<0.001). Two studies showed no benefit of PN on surgical complications (RD =−0.03, 95% CI: −0.26 to 0.20, P=0.78; I² =74.2%, P_{heterogeneity}=0.049) (Figure 6B).

Figure 6 Forest plot of the anal adverse events. (A) Overall. (B) Subgroup analysis (radical gastrectomy and other). CI, confidence interval; RD, rate difference.

Publication bias

No publication bias was observed when considering the length of hospital stay (Begg’s test, P=0.90; Egger’s test, P=0.35), anal exhaust time (Begg’s test, P>0.99; Egger’s test, P=0.81), albumin level (Begg’s test, P=0.23; Egger’s test, P=0.17), prealbumin level (Begg’s test, P=0.26; Egger’s test, P=0.22), CD4/CD8 ratio (Begg’s test, P=0.73; Egger’s test, P=0.76), AE (Begg’s test, P=0.76; Egger’s test, P=0.46), suggesting that these results were robust.

Sensitivity analysis

The sensitivity analyses suggested that the length of hospital stay, anal exhaust time, nutritional variables (albumin level, prealbumin level and CD4/CD8 ratio) and adverse events were robust (Figures S1-S6).

Discussion

This meta-analysis of RCTs suggests that compared with EN, PN could shorten the hospital stay and anal exhaust time, and improve the prealbumin level with comparable complications. Thus, the results support the use of PN in patients with gastric cancer after surgery.

The meta-analysis by Zhao et al. (26) suggested that early PN in patients with gastrointestinal cancer improved immune function, reduced inflammatory reaction, and improved recovery. In the present meta-analysis, PN was better than EN to improve prealbumin, which is a marker of nutritional status. Prealbumin has a shorter plasma half-life than albumin and is considered a more sensitive marker of nutritional status than albumin (27,28). Previous studies have demonstrated that EN is associated with fewer complications, earlier postoperative evacuation times, shorter hospital stays, lower costs, and more stable blood glucose control. EN appears to be particularly beneficial for patients with gastric cancer who also have diabetes mellitus, due to its ability to maintain more stable glucose levels (13). However, in the present meta-analysis, the length of hospital stay was shorter with PN, representing an overall better condition of the patients. Indeed, the length of hospital stay after surgery is influenced by complications, recovery, and nutritional status, among others.

Still, beyond the nutritional status, PN and EN could have other advantages. Indeed, Yao et al. (29) reported that EN was better than PN for improving insulin sensitivity after gastric surgery, again supporting the use of EN in diabetic patients. Besides, no differences were observed between PN and EN regarding the delayed hypersensitivity response, polymorphonuclear cells, interleukin-2 (IL-2) receptor levels, and total lymphocytes (25). Nevertheless, although interesting, these outcomes were reported by only one study, and no meta-analysis could be performed on them. Thus, future studies are necessary to determine the effects of PN in a comprehensive manner.

It is known that PN is associated with a risk of overfeeding, and it has been suggested that overfeeding during PN is associated with complications (30,31). In this meta-analysis, overfeeding as an outcome could not be analyzed because of unavailable data, but the data showed that there were no differences in overall complications between PN and EN and that the infectious complications were less frequent with PN, possibly due to a better nutritional status. It is supported by previous studies that suggested that the risks of PN are exaggerated (11,12,32).

The strength of this meta-analysis is the exclusive use of data from RCTs that compared PN and EN. Still, this study has several limitations. First, the number of included studies was limited, resulting in variability in reported outcomes and potentially compromising the reliability of the findings. Second, some included studies had relatively small sample sizes, which may lead to an overestimation of treatment effects. Third, only English-language databases were searched, which may have led to omission of relevant studies published in other languages and introduced potential language bias. Fourth, some studies enrolled patients with digestive cancers other than gastric cancer, and subgroup data specific to gastric cancer were not always available, which may dilute the specificity of the results. Last, while five studies were assessed as having a low risk of bias in the randomization process, four were rated as unclear risk. Although sensitivity analyses indicated that the pooled results for both primary and secondary outcomes were robust, the inclusion of studies with unclear risk of bias may have introduced some uncertainty to the overall findings. Therefore, caution is warranted in interpreting these findings. Larger, well-designed studies focusing exclusively on gastric cancer populations are needed to validate these conclusions.

Conclusions

This meta-analysis demonstrated that compared with EN, PN shortens the hospital stay and anal exhaust time, and improves the prealbumin level with comparable complications. As an important method of nutrition support for several diseases, treatment of PN could be used in association with gastric cancer after surgery.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-242/rc

Peer Review File: Available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-242/prf

Funding: This study was supported by Key project of TCM Science and Technology Development Plan of Jiangsu Province in 2020 (No. ZD202005).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-2025-242/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424. [Crossref] [PubMed]
2. Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021. CA Cancer J Clin 2021;71:7-33. [Crossref] [PubMed]
3. Chiu W, Lin TY, Chang YC, et al. An Update on Gene Therapy for Inherited Retinal Dystrophy: Experience in Leber Congenital Amaurosis Clinical Trials. Int J Mol Sci 2021;22:4534. [Crossref] [PubMed]
4. Smyth EC, Verheij M, Allum W, et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016;27:v38-49. [Crossref] [PubMed]
5. Smyth EC, Nilsson M, Grabsch HI, et al. Gastric cancer. Lancet 2020;396:635-48. [Crossref] [PubMed]
6. Rosania R, Chiapponi C, Malfertheiner P, et al. Nutrition in Patients with Gastric Cancer: An Update. Gastrointest Tumors 2016;2:178-87. [Crossref] [PubMed]
7. Mulazzani GEG, Corti F, Della Valle S, et al. Nutritional Support Indications in Gastroesophageal Cancer Patients: From Perioperative to Palliative Systemic Therapy. A Comprehensive Review of the Last Decade. Nutrients 2021;13:2766. [Crossref] [PubMed]
8. Hsu PI, Chuah SK, Lin JT, et al. Taiwan nutritional consensus on the nutrition management for gastric cancer patients receiving gastrectomy. J Formos Med Assoc 2021;120:25-33. [Crossref] [PubMed]
9. Baskar S, Schoeneich R, Grewal US. In-hospital Outcomes Between Total Parenteral Nutrition and Enteral Feeding in Esophageal and Gastric Cancer: A Nationwide Analysis. Anticancer Res 2025;45:2453-7. [Crossref] [PubMed]
10. Comerlato PH, Stefani J, Viana LV. Mortality and overall and specific infection complication rates in patients who receive parenteral nutrition: systematic review and meta-analysis with trial sequential analysis. Am J Clin Nutr 2021;114:1535-45. [Crossref] [PubMed]
11. Chowdary KV, Reddy PN. Parenteral nutrition: Revisited. Indian J Anaesth 2010;54:95-103. [Crossref] [PubMed]
12. Griffiths RD. Too much of a good thing: the curse of overfeeding. Crit Care 2007;11:176. [Crossref] [PubMed]
13. Wang J, Zhao J, Zhang Y, et al. Early enteral nutrition and total parenteral nutrition on the nutritional status and blood glucose in patients with gastric cancer complicated with diabetes mellitus after radical gastrectomy. Exp Ther Med 2018;16:321-7. [Crossref] [PubMed]
14. Swartz MK. PRISMA 2020: An Update. J Pediatr Health Care 2021;35:351. [Crossref] [PubMed]
15. Aslam S, Emmanuel P. Formulating a researchable question: A critical step for facilitating good clinical research. Indian J Sex Transm Dis AIDS 2010;31:47-50. [Crossref] [PubMed]
16. Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019;366:l4898. [Crossref] [PubMed]
17. Higgins JPT, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions version 6.1 (updated September 2020). London: Cochrane Collaboration. 2020.
18. Li B, Liu HY, Guo SH, et al. The postoperative clinical outcomes and safety of early enteral nutrition in operated gastric cancer patients. J BUON 2015;20:468-72.
19. Li G, Gu R, Wen X, et al. The effect of early enteral nutrition on hyperthermic intraoperative intraperitoneal chemotherapy-induced mucosal permeability following gastrectomy. JPEN J Parenter Enteral Nutr 2012;36:213-8. [Crossref] [PubMed]
20. Liu H, Ling W, Cao H. Effects of immune-enhanced enteral nutrition and parenteral nutrition on immune and nutritional function in elderly patients with gastric cancer after total gastrectomy. Journal of Shanghai Jiao Tong University 2011;31:1000-4. (Medical Science).
21. Li B, Liu HY, Guo SH, et al. Impact of early enteral and parenteral nutrition on prealbumin and high-sensitivity C-reactive protein after gastric surgery. Genet Mol Res 2015;14:7130-5. [Crossref] [PubMed]
22. Huang D, Sun Z, Huang J, et al. Early enteral nutrition in combination with parenteral nutrition in elderly patients after surgery due to gastrointestinal cancer. Int J Clin Exp Med 2015;8:13937-45.
23. Kim HU, Chung JB, Kim CB. The comparison between early enteral nutrition and total parenteral nutrition after total gastrectomy in patients with gastric cancer: the randomized prospective study. Korean J Gastroenterol 2012;59:407-13. [Crossref] [PubMed]
24. Okamoto Y, Sakaguchi T, Ikematsu Y, et al. Early enteral nutrition with arginine compensates for negative nitrogen balance in patients undergoing curative total gastrectomy. J Med Invest 2023;70:325-33. [Crossref] [PubMed]
25. Braga M, Gianotti L, Gentilini O, et al. Early postoperative enteral nutrition improves gut oxygenation and reduces costs compared with total parenteral nutrition. Crit Care Med 2001;29:242-8. [Crossref] [PubMed]
26. Zhao Y, Wang C. Effect of ω-3 polyunsaturated fatty acid-supplemented parenteral nutrition on inflammatory and immune function in postoperative patients with gastrointestinal malignancy: A meta-analysis of randomized control trials in China. Medicine (Baltimore) 2018;97:e0472. [Crossref] [PubMed]
27. Ingenbleek Y, Young VR. Significance of transthyretin in protein metabolism. Clin Chem Lab Med 2002;40:1281-91. [Crossref] [PubMed]
28. Keller U. Nutritional Laboratory Markers in Malnutrition. J Clin Med 2019;8:775. [Crossref] [PubMed]
29. Yao K, Zhang X, Huang Z, et al. Influence of early enteral nutrition (EEN) on insulin resistance in gastric cancer patients after surgery. Asia Pac J Clin Nutr 2013;22:537-42. [Crossref] [PubMed]
30. Gessouroun A, DiNizo D. Con - The Harms of Overfeeding Early in Critical Illness. J Cardiothorac Vasc Anesth 2024;38:1431-3. [Crossref] [PubMed]
31. Reintam Blaser A, Rooyackers O, Bear DE. How to avoid harm with feeding critically ill patients: a synthesis of viewpoints of a basic scientist, dietitian and intensivist. Crit Care 2023;27:258. [Crossref] [PubMed]
32. Jeejeebhoy KN. Enteral and parenteral nutrition: evidence-based approach. Proc Nutr Soc 2001;60:399-402. [Crossref] [PubMed]