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. 2024 Nov 16;24:412. doi: 10.1186/s12876-024-03510-6

Impact of perioperative immunonutrition on postoperative outcomes in pancreaticoduodenectomy: a systematic review and meta-analysis of randomized controlled trials

Gaofeng Zhang 1, Bing Zhao 1, Tengang Deng 1, Xiaofei He 1, Yongpin Chen 1, Changtao Zhong 1, Jie Chen 1,✉
PMCID: PMC11569618  PMID: 39550568

Abstract

Background

This systematic review and meta-analysis aimed to evaluate the impact of perioperative immunonutrition on postoperative outcomes in patients undergoing pancreaticoduodenectomy (PD).

Methods

Conducted a comprehensive search in PubMed, Embase, Cochrane Library, Medline, and Web of Science databases to identify all randomized controlled trials (RCTs) on the topic of immunonutrition and PD. Subsequently screened literature, extracted data, and assessed the risk of bias in the included studies, and finally conducted a meta-analysis using RevMan 5.3 software.

Results

The analysis included a total of 10 RCTs with 574 patients, among whom 288 were in the immunonutrition group and 283 in the control group. The meta-analysis revealed a significantly lower incidence of postoperative infection-related complications (OR = 0.45; 95% CI: 0.27–0.74; P = 0.002) and severe postoperative complications (OR = 0.61; 95% CI: 0.38–0.98; P = 0.04) in the immunonutrition group compared to the control group. Additionally, patients in the immunonutrition group had a significantly shorter length of hospital stay (MD= -1.87; 95%CI -3.29 - -0.44; P = 0.01). However, the analysis revealed no statistically significant difference in the overall complication rate between the two groups (P = 0.67). Furthermore, the incidence of specific complications and perioperative mortality rates also did not demonstrate any statistically significant differences (all P > 0.05).

Conclusions

Perioperative immunonutrition in PD patients can reduce postoperative infection-related complications, but more high-quality RCTs are needed for further validation.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12876-024-03510-6.

Keywords: Pancreaticoduodenectomy, Immunonutrition, Prognosis, Meta-analysis

Introduction

Pancreaticoduodenectomy (PD) is the surgical approach of choice for the management of tumors located in the pancreatic head, ampulla of Vater, distal bile duct, and duodenum [1]. Despite its clinical efficacy, the complexity of PD, which entails multi-organ resection and subsequent gastrointestinal reconstruction [2], results in a postoperative complication rate ranging from 25–55% [3]. Numerous patients undergoing this surgical procedure frequently encounter nutritional risks and impaired immune function during the perioperative period [4, 5], which may result in a heightened incidence of complications, including pancreatic fistula, bile duct fistula, hemorrhage, infection, and delayed gastric emptying. Consequently, the implementation of enhanced recovery after surgery (ERAS) is crucial for optimizing the perioperative management of patients undergoing pancreaticoduodenectomy [6]. Nutritional support constitutes an essential component of the ERAS protocol [7], permeating the entire rehabilitation process preoperatively, intraoperatively, and postoperatively. It plays a pivotal role in facilitating the rapid recovery of patients and mitigating postoperative complications [8].

Immunonutrition constitutes a therapeutic strategy designed to modulate dysregulated immune responses through the supplementation of specific nutrients [9]. Beyond addressing nutrient deficiencies, this approach can selectively activate immune cells to enhance their functionality [10], regulate cytokine production and release [11], mitigate inflammatory processes [12], and preserve the integrity of the intestinal mucosal barrier [13]. Frequently utilized immunonutritional agents encompass arginine, glutamine, omega-3 polyunsaturated fatty acids, nucleotides, and various other immunomodulatory compounds.

Existing research indicates that enteral immunonutrition support can significantly enhance immunological markers and clinical outcomes in patients undergoing gastrointestinal surgery [14]. However, the efficacy of perioperative immunonutrition support in patients undergoing PD remains a subject of ongoing debate [15, 16]. A systematic review conducted by Guan et al. [17] suggests that immunonutrition is associated with a reduced incidence of infectious complications and a shorter duration of hospital stay. However, the meta-analysis incorporated only four studies, and it did not include data from Miyauchi et al. [15] and Ashida et al. [18], potentially impacting the comprehensiveness and accuracy of the current conclusions. Therefore, we undertook a new meta-analysis by systematically searching multiple databases to elucidate the efficacy of perioperative immune nutritional support in patients undergoing PD and to furnish more precise evidence-based guidelines for the perioperative management of these patients.

Materials and methods

Literature retrieval strategy

This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [19]. Published randomised controlled studies comparing perioperative immunonutritional support in PD patients in PubMed, EMbase, The Cochrane Library and Web of Science were searched by computer. The search period is from the database’s inception to May 1, 2024. The search keywords include: (“pancreatic cancer” or “pancreatic tumor” or “pancreaticoduodenectomy”, “pancreatic surgery”) and (“nutrition” or “immunonutrition”). Meanwhile, manually search the reference citations of the included literature to avoid missing any potentially relevant studies.

Inclusion and exclusion criteria

Inclusion criteria: (1) Study design: published randomized controlled trials (RCTs) on immune nutritional support for PD patients during the perioperative period. (2) Study patients: all PD patients who received perioperative immune nutritional support, with no restrictions on the duration of nutritional support. (3) Intervention: the experimental group received immune nutritional support during the perioperative period, while the control group received conventional nutrition. (4) Outcome indicators: the primary outcome indicators were the incidence of complications and infectious complications, length of stay, and perioperative mortality rate; the secondary outcome indicators were incidence of wound infection, abdominal abscess, pneumonia, bacteremia, urinary tract infection, pancreatic fistula, delayed gastric emptying and intra-abdominal hemorrhage, etc.

Exclusion criteria include: (1) Non-randomized controlled trials, such as reviews, systematic reviews, case reports, and retrospective case-control studies; (2) Non-clinical trials, such as animal and cell experiments; (3) literature without an interest outcome indicator or with insufficient or unavailable data; and (4) literature with incomplete or duplicated information.

Literature screening and data extraction

Two researchers independently screened the literature and extracted the data according to the inclusion and exclusion criteria. In case of disagreement, they resolved the issue through discussion. The extracted data included: author names, publication year, country, sample size, gender, age, specific measures of immunonutrition and outcome measures.

Risk of bias assessment of included studies

Two researchers independently assessed and examined the included studies based on the Cochrane Collaboration ‘s bias risk assessment tool [20] to ensure consistency and check for bias risk. Seven projects were considered, including random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcomes assessment, incomplete outcome data, selective reporting, other bias. Each project is divided into high risk, low risk or unclear risk.

Statistical analysis

The data were analyzed using RevMan 5.3 software. The raw data were input and subsequently underwent transformation. Mean differences (MD) and odds ratios (OR) were used as effect size for continuous and dichotomous data, respectively. For continuous data provided in the form of median and range or quartile, we estimate the mean and standard deviation using the methods described by Hozo et al. [21] or Luo et al. [22]. All effect measures were provided with 95% confidence intervals (CI). The I2 statistic was used to examine the heterogeneity of each study. If I2 ≤ 50%, the fixed effect model was used for meta-analysis. If I2 > 50%, a random effects model was used for meta-analysis. When more than five studies were included, a funnel plot was used to assess potential publication bias. P < 0.05 is considered to indicate a significant overall effect.

Result

Process and results of literature search

Through a literature search, 335 studies were initially identified. First, 79 duplicate studies were excluded, and then 233 studies were excluded based on their titles and abstracts for not meeting the inclusion criteria. After full-text review of the remaining 23 studies, 13 studies were excluded, including 2 without full-text availability, 3 as duplicate publications of the same study population, 4 studies included other gastrointestinal tumors, 3 were non-RCT studies, and 1 lacked the clinical indicators of interest. Ultimately, 10 RCTs [5, 15, 16, 18, 23–28] met the inclusion criteria. The specific literature search process and results are shown in Fig. 1.

Fig. 1.

Fig. 1

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RISMA flow chart of the literature selection

Main characteristics and bias risk assessment results

The analysis included 10 studies [5, 15, 16, 18, 23–28] with a total of 574 patients, of which 288 were in the immunonutrition group and 286 were in the control group. The immunonutrition components in these studies mainly consisted of arginine, Omega-3 polyunsaturated fatty acids, RNA, or a combination of these immunomodulators. Six studies [15, 16, 25–28] used immunonutrition preoperatively, two studies [5, 23] used it postoperatively, and two studies [18, 24] used it in the perioperative period. There were no significant differences between the immunonutrition and control groups across the included studies in terms of sample size and age. The main characteristics of the included studies are summarized in Table 1.

Table 1.

Main characteristics of the 10 studies included in the meta-analysis

Author Year Country Number Age(year) Immunonutrition protocol
Immune-nutrition Control Immune-nutrition Control
Tumas 2020 Lithuania 30 40 62.6 ± 10.5 63.0 ± 8.7 5 days of preoperative immunonutrition ( L-arginine and polyunsaturated fat )
Miyauchi 2019 Japan 30 30 67.8 ± 9.3 67.6 ± 7.5 Perioperative oral supplementation with arginine, omega-3 fatty acids, and RNA (oral IMPACT; Ajinomoto Pharma Co., Ltd, Tokyo, Japan)
Ashida 2019 Japan 11 9 64 ± 11 69 ± 6 7 days of preoperative oral enriched in eicosapentaenoic acid (EPA) enriched nutrition
Gade 2016 Denmark 19 16 68 (50–81) 69 (53–79) 7 days of preoperative oral immunonutrition, Oral Impact Powder® (Nestle, Vevey, Switzerland)
Hamza 2015 UK 17 20 63 (58–69) 67 (63–70) 14 days of preoperative immune-enhancing feed that contained arginine, omega-3 polyunsaturated fatty acid, and mRNA (IMPACT [Novartis Medical Nutrition, Horsham, West Sussex, UK])
Aida 2014 Japan 25 25 66.4 ± 1.5 65.1 ± 1.9 5 days of preoperative oral supplementation containing arginine, u-3 fatty acids, and RNA (oral IMPACT; Ajinomoto Pharma Co., Ltd, Tokyo, Japan)
Suzuki 2010 Japan 20 10 61.9 ± 3.8 66 ± 3 Perioperative oral supplementation with arginine, omega-3 fatty acids, and RNA (oral IMPACT; Ajinomoto Pharma Co., Ltd, Tokyo, Japan)
Jo 2006 Korea 32 28 56.8 ± 9.4 56.9 ± 10.3 5 days of preoperative immunonutrition (L-arginine 6.04 g/day and polyunsaturated fat 4 g/day)
Gianotti 2000 Italy 71 73 61.1 ± 11.9 59.8 ± 12.2 7 days of postoperative enteral diet enriched with arginine, omega-3 fatty acids, and RNA
Carlo 1999 Italy 33 35 63.1 ± 13.1 61.7 ± 12.0 Average 12 days of postoperative enteral diet enriched with arginine, omega-3 fatty acids, and RNA (Impact®, Novartis Nutrition, Bern, Switzerland)
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The quality of included studies was assessed using the Cochrane Collaboration Network Bias risk tool for assessing risk of bias. Six studies reported randomization sequences generated by computer programs, while the methods used in the remaining studies were unclear. Eight studies reported allocation concealment schemes, including sealed envelopes and central randomization. Blinding of participants and personnel was described in seven studies, and due to objective outcomes, all studies were considered to have blinded outcome assessors. No evidence of selective outcome reporting or other sources of bias was found. Risk of bias assessment of included studies is presented in Fig. 2.

Fig. 2.

Fig. 2

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Quality assessment of the included studies

Effect of immunonutrition on postoperative complications

Eight studies [5, 15, 18, 23, 24, 26–28] compared the overall incidence of postoperative complications. These studies included a total of 494 patients (with 243 in the immunonutrition group and 251 in the control group). The heterogeneity among these studies was low (I2 = 20%), so a fixed-effects model was used for the pooled analysis. The result showed no significant difference in overall complication between the two groups (OR = 0.94; 95% CI: 0.64–1.39; P = 0.77) (Fig. 3). The funnel plot for this outcome were all symmetrically distributed, uggesting no publication bias (Supplementary Fig. 1).

Fig. 3.

Fig. 3

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Forest plot compare the overall postoperative complications of immunonutrition group and control group

Seven studies [5, 15, 16, 18, 23, 25, 27] were conducted to compare the occurrence of postoperative infection-related complications. A total of 409 patients were included in these studies (207 in the immunonutrition group and 202 in the control group). There was low heterogeneity among the studies (I2 = 0%), so a fixed-effect model was used for pooled analysis. The results indicated that the incidence of postoperative infection-related complications in the immunonutrition group was significantly lower than that in the control group (OR = 0.45; 95% CI: 0.27–0.74; P = 0.002) (Fig. 4). Based on the funnel plot, there is no indication of publication bias (Supplementary Fig. 2).

Fig. 4.

Fig. 4

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Forest plot compare the postoperative infection-related complications of immunonutrition group and control group

Six studies [5, 15, 16, 18, 23, 24] compared the incidence of severe postoperative complications (Clavien-Dindo Classification ≥ 3). These studies included a total of 412 patients (200 in the immunonutrition group and 212 in the control group). The heterogeneity among the studies was low (I2 = 0%), so a fixed-effects model was used for the pooled analysis. The pooled showed that the incidence of postoperative severe complications was significantly lower in the immunonutrition group than in the control group (OR = 0.61; 95% CI: 0.38–0.98; P = 0.04) (Fig. 5). Publication bias is not evident from the funnel plot presented (Supplementary Fig. 3).

Fig. 5.

Fig. 5

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Forest plot compare the severe postoperative complications of immunonutrition group and control group

We conducted a comparative analysis of the incidence of specific complications between the two groups. The results of the meta-analysis indicated no statistically significant differences between the immunonutrition group and the control group in terms of abdominal abscess (OR = 0.60; 95% CI: 0.29–1.25; P = 0.17), sepsis (OR = 0.53; 95% CI: 0.14–1.95; P = 0.34), wound infection OR = 0.70; 95% CI: 0.35–1.38; P = 0.30), cholangitis (OR = 0.25; 95% CI: 0.05–1.23; P = 0.09), pulmonary infection (OR = 0.57; 95% CI: 0.18–1.85; P = 0.35), urinary tract infection (OR = 0.62; 95% CI: 0.08–4.78; P = 0.65), delayed gastric emptying (OR = 0.99; 95% CI: 0.53–1.86; P = 0.98), pancreatic fistula (OR = 0.89; 95% CI: 0.53–1.48; P = 0.65), weight loss (MD=-0.35; 95%CI -1.02 – -0.32; P = 0.31), and systemic inflammatory response syndrome (SIRS) duration (MD=-0.39; 95%CI -0.83 – -0.05; P = 0.08), as presented in Table 2.

Table 2.

Meta-analysis of specific complication rate

Complications Number of studies Number of patients Heterogeneity (I2) Effect model Meta-analysis results
immunonutrition Control OR 95% CI P
Abdominal abscess 6 198 191 0% fixed-effect 0.60 0.29–1.25 0.17
Sepsis 3 55 50 0% fixed-effect 0.53 0.14–1.95 0.34
Wound infection 7 222 215 0% fixed-effect 0.70 0.35–1.38 0.30
Cholangitis 3 110 99 0% fixed-effect 0.25 0.05–1.23 0.09
Pulmonary infection 6 189 188 0% fixed-effect 0.57 0.18–1.85 0.35
Urinary tract infection 3 134 138 0% fixed-effect 0.62 0.08–4.78 0.65
Delayed gastric emptying 5 191 191 0% fixed-effect 0.99 0.53–1.86 0.98
Pancreatic fistula 8 239 230 0% fixed-effect 0.89 0.53–1.48 0.65
Weight loss 3 80 95 0% fixed-effect -0.35* -1.02–0.32 0.31
SIRS duration 3 75 65 87% random-effect -0.39* -0.83–0.05 0.08
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* Mean differences (MD) as effect size; SIRS: systemic inflammatory response syndrome

Effect of immunonutrition on hospital stay and mortality

Four studies [5, 23, 26, 28] compared the length of hospital stay between the two groups of patients. There was low heterogeneity among the studies (I2 = 0%), so a fixed-effect model was used for pooled analysis. The results showed that the length of hospital stay in the immunonutrition group was significantly shorter compared to the control group (MD= -1.87; 95%CI -3.29 - -0.44; P = 0.01) (Fig. 6).

Fig. 6.

Fig. 6

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Forest plot compare the hospital stay of immunonutrition group and control group

Four studies [5, 23, 26, 28] compared perioperative mortality between the two groups. Heterogeneity among studies was low (I2 = 0%), so a fixed-effect model was used for pooled analysis. The results indicated no significant difference in perioperative mortality between the immunonutrition group and the control group (MD = 1.51; 95%CI 0.39–5.85; P = 0.55) (Fig. 7).

Fig. 7.

Fig. 7

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Forest plot compare the perioperative mortality of immunonutrition group and control group

Discussion

This systematic review and meta-analysis sought to evaluate the efficacy of immunonutrition in patients with PD. By performing a more exhaustive literature search, we enhanced and expanded upon prior meta-analyses on this subject. Our findings corroborate that immunonutrition significantly decreases the incidence of postoperative infection-related complications (OR = 0.45; 95% CI: 0.27–0.74; P = 0.002) and reduces hospital length of stay (MD= -1.87; 95%CI -3.29 - -0.44; P = 0.01) in PD patients. Additionally, our study is the first to demonstrate that immunonutrition can lower the incidence of severe postoperative complications (OR = 0.60; 95% CI: 0.37–0.96; P = 0.03). However, our meta-analysis revealed that immunonutrition does not appear to significantly influence overall complication rates or mortality in patients undergoing PD. Furthermore, we did not detect a significant effect of immunonutrition on any specific complications.

Currently, it is estimated that between 52% and 88% of patients undergoing pancreatic cancer resection are at risk of developing moderate to severe malnutrition prior to surgery [29], attributable to compromised pancreatic endocrine and exocrine functions, as well as preoperative fasting [30]. Following PD, the release of inflammatory mediators and pancreatic enzymes can elicit a systemic inflammatory response [31], which accelerates the depletion of endogenous energy reserves and results in the loss of essential nutrients, thereby disrupting immune system regulation [32]. Consequently, this cascade may culminate in postoperative complications, including a series of catabolic stress responses, postoperative infections, and even deterioration of organ function [33]. Therefore, enhancing the nutritional status [34] and modulating the immune system to control excessive inflammatory responses postoperatively in patients undergoing PD holds significant importance in perioperative management [35].

The immune nutrients currently commonly used in clinical practice mainly include arginine, glutamine, nucleotides, and polyunsaturated fatty acids [5, 27]. Arginine is a semi-essential amino acid that participates in catabolic metabolism, plays an important role in the synthesis of repairing collagen, and improves immune function by enhancing the activity of T cells [36]. In addition, arginine can reduce inflammatory responses by inhibiting the production of cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) [37]. Glutamine is a conditionally essential amino acid that may be depleted in the body during periods of stress or infection [38]. It has immunomodulatory functions, such as stimulating lymphocyte proliferation and promoting the production of cytokines [39]. Omega-3 fatty acids have anti-inflammatory properties that promote wound healing and enhance adaptive immune responses [40]. Exogenous nucleotides can enhance immune function by promoting the maturation, activation, and proliferation of lymphocytes, increasing antibody production [41] and strengthening cellular immunity [42].

Despite previous meta-analyses [17, 43] that have examined the prognosis of immunonutrition in patients post-pancreaticoduodenectomy (PD), these studies have faced limitations due to either the incompleteness or inappropriateness of the included literature. Consequently, there is a need for a comprehensive meta-analysis to synthesize existing evidence and yield more definitive conclusions. In this study, we conducted a meta-analysis incorporating data from 10 randomized controlled trials, encompassing a total of 574 patients. Our findings provide further evidence that immunonutrition may enhance outcomes by reducing the incidence of postoperative infectious complications and decreasing the length of hospital stay for patients following pancreaticoduodenectomy (PD). Notably, our research also identified that immunonutrition is associated with a reduction in the incidence of severe postoperative complications (OR = 0.61; 95% CI: 0.38–0.98; P = 0.04), a novel finding that has not been previously reported in existing meta-analyses.

This meta-analysis comprehensively assessed the impact of immunonutrition therapy during the perioperative period in patients undergoing PD. However, several limitations persist. Firstly, the difficulty in acquiring original data precluded the possibility of conducting subgroup analyses based on patients’ preoperative nutritional status and the specific types of immunonutrition administered. Secondly, the majority of the included studies did not report the total hospitalization costs for both the immunonutrition and control groups, rendering it challenging to ascertain the cost-effectiveness of immunonutrition in the context of PD. Third, while there are variations in the formulations of immunonutrition products across different brands, the primary components remain largely consistent. Fourth, none of the included studies incorporated long-term follow-up, thereby precluding the possibility of conducting a meta-analysis on long-term complications. Finally, the potential bias introduced by commercial funding cannot be fully evaluated in this meta-analysis due to the limited number of commercially funded studies included.

Conclusions

In conclusion, the present body of evidence indicates that perioperative immunonutrition in patients undergoing PD may reduce the incidence of postoperative infectious and severe complications, as well as shorten the duration of hospital stay. Nonetheless, further validation through rigorous, multi-center, large-sample, high-quality RCTs is required.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1 (120.3KB, docx)

Acknowledgements

No.

Author contributions

G.F.Z, J.C, B.Z, T.G.D, designed and conducted the research and analyzed data; extracted data were checked by J.C; G.F.Z, X.F.H, Y.P.C, and T.C.Z wrote the manuscript; J.C had primary responsibility for final content. All authors read and approved the final manuscript.

Funding

There are no funding sources to declare.

Data availability

The data analysed during this study can be found within the published article.

Declarations

Ethics approval and consent to participate

All patient data in the study were obtained from published studies and therefore did not require ethical approval.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  • 1.Jabłońska B, Mrowiec S. The role of Immunonutrition in patients undergoing pancreaticoduodenectomy. Nutrients. 2020;12:2547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Xiang Y, Wu J, Lin C, Yang Y, Zhang D, Xie Y, et al. Pancreatic reconstruction techniques after pancreaticoduodenectomy: a review of the literature. Expert Rev Gastroenterol Hepatol. 2019;13:797–806. [DOI] [PubMed] [Google Scholar]
  • 3.Kokkinakis S, Kritsotakis EI, Maliotis N, Karageorgiou I, Chrysos E, Lasithiotakis K. Complications of modern pancreaticoduodenectomy: A systematic review and meta-analysis. Hepatobiliary Pancreat Dis Int. 2022;21(6):527-537. [DOI] [PubMed]
  • 4.Pappas S, Krzywda E, McDowell N. Nutrition and pancreaticoduodenectomy. Nutr Clin Pract. 2010;25:234–43. [DOI] [PubMed] [Google Scholar]
  • 5.Di Carlo V, Gianotti L, Balzano G, Zerbi A, Braga M. Complications of pancreatic surgery and the role of Perioperative Nutrition. Dig Surg. 1999;16:320–6. [DOI] [PubMed] [Google Scholar]
  • 6.Melloul E, Lassen K, Roulin D, Grass F, Perinel J, Adham M, et al. Guidelines for Perioperative Care for Pancreatoduodenectomy: enhanced recovery after surgery (ERAS) recommendations 2019. World J Surg. 2020;44:2056–84. [DOI] [PubMed] [Google Scholar]
  • 7.Wobith M, Weimann A. Oral nutritional supplements and Enteral Nutrition in patients with gastrointestinal surgery. Nutrients. 2021;13:2655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Kubota T, Shoda K, Konishi H, Okamoto K, Otsuji E. Nutrition update in gastric cancer surgery. Ann Gastroenterol Surg. 2020;4:360–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Kavalukas S, McClave SA. Immunonutrition vs standard nutrition for patients with cancer. Nutr Clin Pract. 2023;38:924–31. [DOI] [PubMed] [Google Scholar]
  • 10.Grimm H, Kraus A. Immunonutrition–supplementary amino acids and fatty acids ameliorate immune deficiency in critically ill patients. Langenbecks Arch Surg. 2001;386:369–76. [DOI] [PubMed] [Google Scholar]
  • 11.Mc MC. M. The role of Immunonutrition in patients. Nutrients. 2023;15. [DOI] [PMC free article] [PubMed]
  • 12.Zapatera B, Prados A, Gómez-Martínez S, Marcos A. Immunonutrition: methodology and applications. Nutr Hosp. 2015;31(Suppl 3):145–54. [DOI] [PubMed] [Google Scholar]
  • 13.Cerantola Y, Hübner M, Grass F, Demartines N, Schäfer M. Immunonutrition in gastrointestinal surgery. Br J Surg. 2011;98:37–48. [DOI] [PubMed] [Google Scholar]
  • 14.Shen J, Dai S, Li Z, Dai W, Hong J, Huang J, et al. Effect of Enteral Immunonutrition in patients undergoing surgery for gastrointestinal Cancer: an updated systematic review and Meta-analysis. Front Nutr. 2022;9:941975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Miyauchi Y, Furukawa K, Suzuki D, Yoshitomi H, Takayashiki T, Kuboki S, et al. Additional effect of perioperative, compared with preoperative, immunonutrition after pancreaticoduodenectomy: a randomized, controlled trial. Int J Surg. 2019;61:69–75. [DOI] [PubMed] [Google Scholar]
  • 16.Aida T, Furukawa K, Suzuki D, Shimizu H, Yoshidome H, Ohtsuka M, et al. Preoperative immunonutrition decreases postoperative complications by modulating prostaglandin E2 production and T-cell differentiation in patients undergoing pancreatoduodenectomy. Surgery. 2014;155:124–33. [DOI] [PubMed] [Google Scholar]
  • 17.Guan H, Chen S, Huang Q. Effects of Enteral Immunonutrition in patients undergoing pancreaticoduodenectomy: a Meta-analysis of Randomized controlled trials. Ann Nutr Metab. 2019;74:53–61. [DOI] [PubMed] [Google Scholar]
  • 18.Ashida R, Okamura Y, Wakabayashi-Nakao K, Mizuno T, Aoki S, Uesaka K. The Impact of Preoperative Enteral Nutrition Enriched with eicosapentaenoic acid on postoperative hypercytokinemia after pancreatoduodenectomy: the results of a double-blinded Randomized Controlled Trial. Dig Surg. 2019;36:348–56. [DOI] [PubMed] [Google Scholar]
  • 19.Mj P, Je M, Pm B, Tc IB, Cd H. M, The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg (London England). 2021;88. [DOI] [PubMed]
  • 20.Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5:13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2018;27:1785–805. [DOI] [PubMed] [Google Scholar]
  • 23.Gianotti L, Braga M, Gentilini O, Balzano G, Di Zerbi A. Carlo V Artif Nutr after Pancreaticoduodenectomy: Pancreas. 2000;21:344–51. [DOI] [PubMed] [Google Scholar]
  • 24.Tumas J, Jasiūnas E, Strupas K, Šileikis A. Effects of Immunonutrition on Comprehensive Complication Index in patients undergoing pancreatoduodenectomy. Medicina. 2020;56:52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Suzuki D, Furukawa K, Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, et al. Effects of perioperative immunonutrition on cell-mediated immunity, T helper type 1 (Th1)/Th2 differentiation, and Th17 response after pancreaticoduodenectomy. Surgery. 2010;148:573–81. [DOI] [PubMed] [Google Scholar]
  • 26.Jo S, Choi S, Heo J, Kim E, Min M, Choi D, et al. Missing effect of glutamine supplementation on the Surgical Outcome after Pancreaticoduodenectomy for Periampullary tumors: a prospective, randomized, Double-blind, controlled clinical trial. World j surg. 2006;30:1974–82. [DOI] [PubMed] [Google Scholar]
  • 27.Hamza N, Darwish A, O’Reilly DA, Denton J, Sheen AJ, Chang D, et al. Perioperative Enteral Immunonutrition modulates systemic and mucosal immunity and the inflammatory response in patients with Periampullary Cancer Scheduled for Pancreaticoduodenectomy: a Randomized Clinical Trial. Pancreas. 2015;44:41–52. [DOI] [PubMed] [Google Scholar]
  • 28.Gade J, Levring T, Hillingsø J, Hansen CP, Andersen JR. The effect of preoperative oral immunonutrition on complications and length of Hospital stay after elective surgery for pancreatic Cancer–A Randomized Controlled Trial. Nutr Cancer. 2016;68:225–33. [DOI] [PubMed] [Google Scholar]
  • 29.Afaneh C, Gerszberg D, Slattery E, Seres DS, Chabot JA, Kluger MD. Pancreatic cancer surgery and nutrition management: a review of the current literature. Hepatobiliary Surg Nutr. 2015;4:59–71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Poulia KA, Sarantis P, Antoniadou D, Koustas E, Papadimitropoulou A, Papavassiliou AG, et al. Pancreatic Cancer and Cachexia-metabolic mechanisms and Novel insights. Nutrients. 2020;12:1543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Long Z-D, Lu C, Xia X-G, Chen B, Xing Z-X, Bie L, et al. Personal predictive model based on systemic inflammation markers for estimation of postoperative pancreatic fistula following pancreaticoduodenectomy. World J Gastrointest Surg. 2022;14:963–75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Giger U, Büchler M, Farhadi J, Berger D, Hüsler J, Schneider H, et al. Preoperative immunonutrition suppresses perioperative inflammatory response in patients with major abdominal surgery-a randomized controlled pilot study. Ann Surg Oncol. 2007;14:2798–806. [DOI] [PubMed] [Google Scholar]
  • 33.Jotheeswaran R, Singh H, Kaur J, Nada R, Yadav TD, Gupta V, et al. Role of inflammatory and nutritional markers in predicting complications after pancreaticoduodenectomy. Surgery. 2022;172:1502–9. [DOI] [PubMed] [Google Scholar]
  • 34.Karagianni VT, Papalois AE, Triantafillidis JK. Nutritional status and nutritional support before and after pancreatectomy for pancreatic cancer and chronic pancreatitis. Indian J Surg Oncol. 2012;3:348–59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Xu X, Zheng C, Zhao Y, Chen W, Huang Y. Enhanced recovery after surgery for pancreaticoduodenectomy: review of current evidence and trends. Int J Surg. 2018;50:79–86. [DOI] [PubMed] [Google Scholar]
  • 36.Wu G, Meininger CJ, Knabe DA, Bazer FW, Rhoads JM. Arginine nutrition in development, health and disease. Curr Opin Clin Nutr Metab Care. 2000;3:59–66. [DOI] [PubMed] [Google Scholar]
  • 37.Efron DT, Barbul A. Modulation of inflammation and immunity by arginine supplements. Curr Opin Clin Nutr Metab Care. 1998;1:531–8. [DOI] [PubMed] [Google Scholar]
  • 38.Kim H. Glutamine as an immunonutrient. Yonsei Med J. 2011;52:892–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Cruzat V, Macedo Rogero M, Noel Keane K, Curi R, Newsholme P. Glutamine: metabolism and Immune function, supplementation and clinical translation. Nutrients. 2018;10:E1564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Shahidi F, Ambigaipalan P. Omega-3 polyunsaturated fatty acids and their health benefits. Annu Rev Food Sci Technol. 2018;9:345–81. [DOI] [PubMed] [Google Scholar]
  • 41.Kepp O, Loos F, Liu P, Kroemer G. Extracellular nucleosides and nucleotides as immunomodulators. Immunol Rev. 2017;280:83–92. [DOI] [PubMed] [Google Scholar]
  • 42.de Toro-Martín J, Arsenault BJ, Després J-P, Vohl M-C. Precision Nutrition: a review of Personalized Nutritional approaches for the Prevention and Management of metabolic syndrome. Nutrients. 2017;9:913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Fan Y, Li N, Zhang J, Fu Q, Qiu Y, Chen Y. The Effect of immunonutrition in patients undergoing pancreaticoduodenectomy: a systematic review and meta-analysis. BMC Cancer. 2023;23:351. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

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Supplementary Materials

Supplementary Material 1 (120.3KB, docx)

Data Availability Statement

The data analysed during this study can be found within the published article.

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