Effect of perioperative individualized nutrition intervention on pancreatic surgery outcomes: a prospective single-center study

Abstract

Background

There is currently a lack of reports on prospective randomized controlled trials (RCTs) focused on personalized nutritional support in pancreatic surgery. This study aimed to evaluate the impact of perioperative individualized nutritional intervention on the outcomes of patients undergoing pancreatic surgery within the framework of enhanced recovery after surgery (ERAS).

Methods

This prospective cohort study enrolled 96 patients, randomly divided into a trial group and a control group in a 1:1 ratio. The primary endpoint was the change in body composition, including body cell mass (BCM), fat-free mass (FFM), skeletal muscle mass (SMM), and phase angle (PA). Secondary outcomes included time to first postoperative flatus, time to first bowel movement, length of hospital stay, and nutritional indicators.

Results

No significant differences were observed in the demographic characteristics between the two groups. The ratio of actual total calorie intake to recommended daily intake in the trial group was significantly higher than the control group (87.01% vs. 69.50%, P < 0.001). The ratio of actual protein intake to recommended daily intake was significantly higher in the trial group than the control group (96.18% vs.76.29%, P < 0.001). In body composition data, significant differences were found between the two groups in the ratio of BCM, FFM, and SMM at the study endpoint compared to admission. Additionally, a significant difference between the two groups was present in the ratio of BCM, FFM, and SMM at the third postoperative day (POD 3) compared with those at admission. While no significant differences were found between the groups in time to first flatus and time to first stool, the trial group had a significantly shorter postoperative hospital stay compared to the control group (15.9d vs. 20.4d, P = 0.046). Nutritional index analysis revealed a statistically significant difference in the ratio of serum total protein at the study endpoint compared POD 3 (P < 0.05), but no significant differences were found in serum prealbumin, albumin, and hemoglobin.

Conclusions

Personalized nutritional interventions throughout the perioperative period improved patients’ nutritional status and reduced the length of postoperative hospital stay.

Introduction

The detection rate of pancreatic diseases has been increasing due to changes in people’s lifestyles, advances in science and technology, and the rapid development of imaging equipment in recent years. Surgery remains a critical method for treating pancreatic-related diseases. Before admission, most patients undergoing pancreatic surgery experience clinical symptoms such as pain, jaundice, and gastrointestinal obstruction. These symptoms are often accompanied by secondary nutritional issues, including anorexia, fatigue, and progressive weight loss, leading to high nutritional risk, muscle loss, and malnutrition. Pancreatic surgery involves the resection of multiple organs and the reconstruction of the digestive system. The most common postoperative complications include pancreatic fistula, biliary fistula, gastrointestinal anastomotic fistula, and infection. These complications negatively influence the patient’s metabolism and nutritional status, affecting their postoperative recovery and clinical outcomes [1, 2]. Nutritional issues are present at all stages of the disease, and a wide range of nutritional impairments are associated with abnormal body composition phenotypes [3, 4].

Epidemiological surveys reveal a high proportion of nutritional risk among pancreatic surgery patients, with a 78.5% incidence rate among those undergoing surgery for pancreatic tumors [5]. Additionally, studies on patients with common malignant tumors indicate that pancreatic cancer patients have the highest patient-generated subjective global assessment (PG-SGA) scores compared to those with other tumors [6]. Therefore, nutritional therapy is crucial in the comprehensive treatment of pancreatic surgery patients. However, a 2019 international survey of pancreatic surgeons from multiple countries found that 44% of physicians did not perform preoperative nutritional evaluations, and their perioperative nutritional practices were not standardized [7]. Another study reported a lack of unified standards for the indications, pathways, and timing of perioperative nutritional support for pancreatic and duodenal resection among pancreatic surgeons in tertiary hospitals in China [8]. Consequently, there are significant differences between the theory and practice of nutritional management and enhanced recovery after surgery (ERAS) strategies. To promote a unified perioperative nutritional management strategy for pancreatic surgery in China and to provide a basis for the standardized implementation of nutritional support, the Pancreatic Surgery Group of the Surgery Branch of the Chinese Medical Association and the Parenteral and Enteral Nutrition Branch of the Chinese Medical Association formulated the “Chinese Expert Consensus on Perioperative Whole Process Nutrition Management in Pancreatic Surgery (2020 Edition),” emphasizing the urgent need for prospective studies on perioperative nutrition management strategies in pancreatic surgery [9].

In such cases, personalized nutritional treatment should be applied as early as possible, when intervention measures are most effective, and can prevent irreversible and difficult-to-treat states [10]. The foundation of individualized nutritional therapy is evidence-based medicine, which considers various factors such as the patient’s age, gender, disease type, stage of disease progression, gastrointestinal function, nutritional needs, surgical, method, intraoperative nutritional management, perioperative blood glucose fluctuations, fluid demand, postoperative insulin resistance, gastric emptying disorders, pancreatic fistula, severity of pancreatic fistula, abdominal infection, pancreatic exocrine dysfunction, and feeding tolerance. Proper selection and regular monitoring of a nutritional plan can prevent complications related to insufficient or excessive nutritional treatment, thereby improving clinical outcomes of patients [11, 12]. However, there is currently a lack of prospective randomized controlled trials (RCTs) on personalized nutritional support in pancreatic surgery.

This prospective cohort study was conducted following the Chinese Expert Consensus on the Whole Process of Individualized Nutritional Management in Pancreatic Surgery (2020 Edition) to explore the impact of perioperative individualized nutritional intervention on the outcomes of patients undergoing pancreatic surgery within the framework of ERAS.

Materials and methods

This prospective study was approved by the Biomedical Ethics Committee of the Joint Support Force 900th Hospital (permission No. 2022-025 from 2022-07-19). All participants provided written informed consent. The trial design has been registered with the China Clinical Trial Registration Center - World Health Organization International Clinical Trial Registration Platform Level 1 Registration Institution (chictr. org. cn) (ChiCTR230077719).

Eligibility assessment and randomization

All tumor patients with a Nutritional Risk Screening (NRS) score of ≥ 3, based on NRS 2002 [13], and who were scheduled for pancreatic surgery underwent a qualification assessment. Pancreatic surgical patients included those who had undergone pancreaticoduodenectomy, partial pancreatectomy, or pancreatic tumor enucleation. Partial pancreatectomy encompassed procedures such as pancreatic head resection, mid-pancreatic resection, and distal pancreatectomy. Among the eligible patients, those unsuitable for body composition measurement, patients with a prior history of pancreatectomy or those requiring a second surgery during the current hospitalization, were excluded from the study.

A total of 96 patients were included in this study and were randomly divided into a trial group and a control group in a 1:1 ratio (Fig. 1). Randomization uses random number generating function to generate random numbers. Patients didn’t know which group they were assigned to, but the researchers did. Stratified factors included gender, age, American Society of Anesthesiologists (ASA) score, body weight, body mass index (BMI), NRS 2002 score, PG-SGA, operation duration, blood loss, and surgical method, which were categorized into three types: pancreaticoduodenectomy, partial pancreatectomy, and pancreatic tumor enucleation.

Fig. 1

Flowchart of the trial

Intervention

We provided nutritional intervention throughout the perioperative period. The trial group, based on the ERAS and following the “Chinese Expert Consensus on Whole Process Nutritional Management in Pancreatic Surgery Perioperative Period (2020 Edition)” [9], developed preoperative (Fig. 2) and postoperative (Fig. 3) nutritional support protocols. The Harris-Benedict (HB) formula was used to calculate the target total energy for patients receiving individualized nutrition therapy based on an ideal body weight. The target protein intake was determined based on an ideal body weight of 1.2–1.5 g/kg, and personalized nutritional plans were created and implemented for each patient considering factors such as age, gender, constitution, organ function, actual energy expenditure, metabolic changes, and disease stage. For instance, if liver function was abnormal, liver-appropriate nutritional supplements were selected; if kidney function was impaired, kidney-appropriate supplements were chosen. In cases of electrolyte imbalance, electrolyte supplementation was adjusted accordingly. For elderly patients, fluid intake was carefully controlled, and if the digestive function was poor, short-peptide enteral nutrition supplements were provided. In cases of chyle leakage, long chain fatty acids were avoided, and a “low-fat, high medium chain fatty acids, high protein” nutritional strategy was implemented. Meanwhile, the control group received traditional nutritional treatment before and after surgery based on the physician’s clinical experience, the patient’s condition, and dietary habits. These patients were allowed a free diet or were given oral enteral or intravenous nutrition, supplemented with carbohydrates, fat, amino acids, complex vitamins, and inorganic salts. Food diary data were collected from all patients using “24-hour dietary recalls,” in which enrolled patients were asked about the types and amounts of all foods consumed in the past day or in the previous 24 h. The population of each protocol used for final analysis accounts for 50% each.

Fig. 2

Preoperative nutritional support process for the nutrition intervention group. Abbreviations: NRS2002, nutritional risk screening 2002; BMI: body mass index. PG-SGA: patient-generated subjective global assessment; ONS, oral nutritional supplements; EN, enteral nutrition; SPN, supplemental parenteral nutrition; TPN, total parenteral nutrition

Fig. 3

Flowchart of postoperative nutritional support. Abbreviations: NRS2002, nutritional risk screening 2002; ONS, oral nutritional supplements; EN, enteral nutrition; PN, parenteral nutrition; SPN, supplemental PN; TPN, total PN

Outcome measurements

We collected data on patientcharacteristics, including gender, age, ASA score, body weight, BMI, NRS2002 score, PG-SGA score, operation duration, blood loss, and surgical procedure. During the intervention period, total calorie and protein intake were recorded through diaries before surgery, at the third postoperative day (POD 3), and at discharge. The recommended daily intake of total calories and protein was estimated based on previously established guidelines [7]. The primary endpoint was the change in body composition, including body cell mass (BCM), fat-free mass (FFM), skeletal muscle mass (SMM), and phase angle (PA), which were measured by bioimpedance with an InBody S-10 device (Biospace, Seoul, South Korea). Secondary outcomes included the time to first postoperative flatus, time to first bowel movement, length of hospital stay, and the evaluation of nutritional indicators through blood samples.

Sample size calculation and statistical analysis

The sample size was calculated using RAOSOFT (Raosoft, Inc., Seattle, WA, USA; www.raosoft.com), targeting a total of 100 patients. To ensure 90% confidence in detecting 80% of the effect size, 30 patients were required in each group, assuming a 0.05 probability of error in a two-sided test.

All analyses were performed on individuals who met the inclusion criteria. In both groups, patients who withdrew consent or discontinued participation were classified as “drop-out.” Patients who decided to forgo surgical treatment before the procedure were categorized as “given up operation” patients. If the scope of surgical resection was altered during surgery based on the patient’s condition, those patients were labeled as “pancreas not involved” cases. Patients who lacked data at the study endpoint due to the novel coronavirus disease 2019 (COVID-19) pandemic were considered “follow-up loss.” Patients, whose postoperative condition worsened, resulting in death, were categorized as “death cases”. Ultimately, data of 60 patients were included and subjected to statistical analysis.

All statistical analyses were conducted using SPSS software, version 21.0 (SPSS Inc., Chicago, IL, USA). Continuous variables with non-normal distribution were represented as medians (P25, P75) and analyzed using non-parametric tests. Continuous variables with normal distribution were presented as mean ± standard deviation (Mean ± SD) and analyzed using an independent sample t-test. Categorical variables were presented as n (%) and analyzed using the chi-square test or Fisher’s exact tests. P < 0.05 was considered statistically significant.

Results

There were no significant differences between the two groups in baseline characteristics, including gender, age, ASA score, body weight, BMI, NRS2002 score, PG-SGA score, operation duration, blood loss, and the expected surgical approach (Table 1).

Table 1 Baseline characteristics and surgical procedures

Nutritional outcomes and changes in body composition

The actual total calorie intake in both groups was lower than the recommended daily intake. However, the ratio of actual calorie intake to recommended intake was significantly higher in the trial group compared to the control group (87.01% vs. 69.50%, P = 0.000001). Similarly, the actual protein intake in both groups was below the recommended daily intake, but the ratio of actual protein intake to recommended intake was significantly higher in the trial group than in the control group (96.18% vs.76.29%, P = 0.000014).

Body composition analysis revealed statistically significant differences between the two groups in the ratios of BCM, FFM, and SMM at the study endpoint compared to admission, although the difference in PA was not statistically significant. Additionally, statistically significant differences were observed between the two groups in the ratios of BCM, FFM and SMM at POD 3 compared to admission, but again, the difference in PA was not statistically significant (Table 2). Figure 4 shows the changes in hydration status during different perioperative assessments in the two groups. Perioperative hydration levels in both groups ranged between 72.7% and 74.3%, indicating stable fluid balance and reliable body composition analysis.

Table 2 Comparison in nutritional outcomes between the two groups

Using independent samples T-test for normal continuous variables and values are reported Mean ± SD.

Fig. 4

Changes in hydration in the different perioperative assessments in two groups (ratio of total body water to fat-free body mass: n.v. 72.7—74.3%). Using independent samples T-test for normal continuous variables and values are reported Mean ± SD

Postoperative course

The trial group experienced earlier times for the first postoperative flatus and defecation compared to the control group, although the difference was not statistically significant. However, the trial group had a significantly shorter postoperative hospital stay compared to the control group (15.9 days vs. 20.4 days, P = 0.046) (Table 3).

Table 3 Comparison of postoperative course between the two groups

Postoperative nutrition indexes

We monitored nutritional indicators at the study endpoint and POD 3. The trial group had a higher ratio of serum total protein (TP) at POD 3 compared to the control group (P < 0.05). However, there were no significant differences in the levels of serum prealbumin (SPA), albumin (ALB), or hemoglobin (HGB) between the two groups (Table 4).

Table 4 Comparison of nutritional indicators between the two groups

Discussion

Patients undergoing pancreatic surgery are at higher nutritional risk compared to other patients, with nutritional challenges persisting throughout the entire treatment process [14]. Malnutrition is an independent risk factor for prolonged hospital stays, higher readmission rates, increased healthcare costs, decreased quality of life, and higher mortality in patients with malignant tumors [15]. Research has shown that individualized nutrition management is more effective than non-individualized approaches in improving postoperative nutritional status [16]. Moreover, comprehensive nutrition management enhances clinical outcomes, reduces all-cause mortality and adverse reactions, and improves quality of life and mental well-being [17,18,19].

However, there is an urgent need for prospective studies on perioperative nutrition management strategies in pancreatic surgery. In this study, based on the ERAS concept and the “Consensus of Chinese Experts on Whole Process Nutrition Management in Pancreatic Surgery Perioperative Period (2020 Edition),“we provided personalized nutritional treatment tailored to each patient’s age, gender, constitution, organ function, actual energy consumption, metabolic changes, and disease stage. Our findings revealed that patients in the trial group had significantly higher total energy and TP intake compared to the control group (P < 0.01). We believe that this is due to the fact that on the one hand, personalized nutritional treatment has improved the attention of physicians to nutritional therapy, making nutrition therapy more timely and standardized, and on the other hand, individualized nutrition therapy has solved the confusion of patients who dare not eat and do not know how to eat.

Studies have shown that more sensitive and accurate methods than the conventional ones should be used for nutritional status evaluation, such as body composition phenotyping [20]. Data, such as BCM, FFM, SMM, and PA, can be obtained through body composition phenotyping. Among these, BCM is a stable nutritional variable that is less influenced by non-nutritional factors [21]. FFM is widely recognized as an indicator of nutritional status and is closely linked to clinical outcomes in surgical and critically ill patients [22]. SMM can serve as an effective indicator of nutritional risk, with its decline negatively impacting clinical outcomes in surgical patients [23, 24]. Additionally, skeletal muscle content can predict survival in patients with malignant tumors and can guide treatment planning [25]. Beyond nutritional status evaluation and prognosis prediction, PA is associated with muscle quality, strength, function, inflammatory and oxidative stress biomarkers, and the severity of musculoskeletal and respiratory diseases [26]. Assessing body composition through these parameters is essential for evaluating nutritional status and the impact of nutritional interventions [27]. In this study, body composition analysis demonstrated significant improvements in BCM, FFM, and SMM, though PA did not show direct improvement. This may be attributed to the short data collection period, which was limited to the hospitalization period. Interestingly, we observed that BCM, FFM, and SMM values in the trial group were higher than their preoperative values at POD 3. This result may be since all patients enrolled in this study were at nutritional risk and had indications for nutritional treatment. Consequently, the trial group received nutritional support before surgery, and early postoperative nutritional intervention based on the ERAS strategy, which improved their nutritional status by POD 3 and reduced endogenous consumption.

Another key finding of this study is that although there was no statistically significant difference between the groups in terms of major surgical complications, the trial group had a significantly shorter hospital stay compared to the control group, with the difference being statistically significant. This aligns with evidence from Liu et al. [28]. and Wu et al. [29]. which suggests that nutritional support in pancreatic surgery patients improves outcomes by reducing complications and shortening hospital stays. Our results are consistent with these previous studies. However, there was no statistically significant difference between the two groups in terms of the time to first postoperative flatus and defecation. Earlier research has shown that chewing gum can promote early recovery of intestinal function after abdominal surgery, and it is now a routine postoperative practice. Chewing gum works on the principle of “sham feeding,” which simulates eating, stimulates oral receptors, and activates the vagus nerve, leading to increased secretion of gastrointestinal hormones, and enhanced intestinal peristalsis. Additionally, chewing gum reflexively promotes gastrointestinal activity and increases levels of gastrin and motilin, thereby aiding the recovery of gastrointestinal function [30, 31].

TP, ALB, SPA, and HGB are commonly used biochemical indicators to assess patients’ nutritional status and the effectiveness of nutritional interventions [32]. When adequate energy is provided, supplementing with exogenous amino acids or proteins can effectively promote protein synthesis in the body. The main findings of this study regarding postoperative protein levels are as follows: First, the TP level at the study endpoint was higher than at POD 3, and the values in the trial group were significantly higher than those in the control group (P < 0.001), indicating the beneficial regulatory effect of individualized nutritional support on postoperative TP levels. Second, by the study endpoint, the levels of SPA, ALB, and HGB were all greater than or equal to those at POD 3, though the differences between the trial and control groups were not statistically significant (P > 0.05). There were no significant changes in HGB and ALB levels between the study endpoint and POD 3, which might suggest that nutritional support did not significantly alter HGB and ALB. However, considering that the half-life of HGB is about 120 days and that of ALB is 19–21 days, the decrease in HGB and ALB due to surgical catabolic effects may be delayed. Postoperative nutritional support may have contributed to only minor changes by the study endpoint compared to POD 3. The lack of significant difference between the trial and control groups suggests that individualized nutritional support might not have an immediate positive effect on these parameters. However, it is important to note that the postoperative hospitalization time for patients in the trial group was 15.9 days, approximately five days shorter than the 20.4 days in the control group, which indicates that nutritional intervention reduced the metabolic losses caused by surgery in pancreatic surgery patients. Compared to ALB and HGB, SPA has a much shorter half-life of approximately 1.9 days [33], making it a better marker for reflecting nutritional status. Our findings show significant improvement in SPA levels at the study endpoint compared to POD 3, although the difference between the trial and control groups was not statistically significant. The control group also underwent detailed nutritional risk screening and evaluation at the three testing time points, which likely increased patient awareness of dietary importance and emphasized the role of nutritional support to patients and their families. Furthermore, the sample size in this study was small, which might have influenced the results. While TP has a longer half-life, it represents a summary indicator of all proteins in the blood. Although no statistically significant differences were found in SPA, ALB, and HGB between the two groups, the TP level in the trial group was significantly higher than or equal to that in the control group.

Limitations Several limitations of this study need to be acknowledged. The most significant issue is the high dropout rate, with over 25% of enrolled patients lost to follow-up. The COVID-19 caused a global outbreak and significant public health concern, leading to strict measures to minimize personnel contact to prevent cross-infection [34]. These restrictions not only hindered data collection but also increased the number of patients lost to follow-up and decreased their willingness to cooperate. Additionally, in recent years, the incidence and mortality rates of pancreatic cancer have been rising. While surgical resection remains the only curative treatment for pancreatic cancer, advances in surgical technology have not significantly improved long-term survival rates [35]. Consequently, acceptance of surgical treatment is low, and many patients refuse surgery, contributing to the high dropout rate and refusal of therapy. As a result, the number of patients ultimately included in the analysis was relatively low. We plan to include more patients in our future research to evaluate the impact of personalized nutritional therapy on the clinical outcomes of pancreatic surgery patients. Another limitation is that this study focused on assessing the effects of individualized nutritional therapy on nutritional status and body composition. In future studies, we aim to include multiple outcome measures, such as postoperative C-reactive protein (CRP), to provide a more comprehensive evaluation of the therapy’s impact. This study can only provide a reference for the improvement of nutritional status and body composition based on this nutritional treatment, and does not constitute an in-depth analysis of the interaction between nutrients.

As is well known, the risk of malnutrition in patients undergoing pancreaticoduodenal surgery is higher than in those undergoing other digestive system surgeries [36]. To minimize surgical bias, we divided the patients into three subgroups (pancreaticoduodenectomy, partial pancreatectomy, and pancreatic tumor enucleation) for analysis. In the pancreaticoduodenectomy subgroup, there were statistically significant differences between the trial and control groups in the ratios of BCM, FFM, and SMM at the study endpoint compared to admission, although the difference in PA was not statistically significant. Similarly, in the partial pancreatectomy subgroup, significant differences were observed between the two groups in the ratios of BCM, FFM, and SMM at the study endpoint compared to admission, but the difference in PA remained statistically insignificant. In the pancreatic tumor enucleation subgroup, no statistically significant differences were found between the two groups in the ratios of BCM, FFM, SMM, or PA at the study endpoint compared to admission. These results may be attributed to the small number of patients in the pancreatic tumor enucleation subgroup (Data are provided in the Supplementary Materials section).

Conclusions

In conclusion, our study demonstrates that personalized nutritional interventions during the perioperative period increased actual total calorie and protein intake, shortened hospital stays, and improved body composition in terms of BCM, FFM, and SMM. This study highlights that nutritional therapy is a complex process that cannot be effectively managed using traditional approaches alone. It requires standardized, precise nutritional interventions, real-time analysis of specific parameters, and ongoing adjustments to nutritional therapy plans, as recommended by the latest guidelines. Our research, based on the ERAS principles and aligned with the Chinese Expert Consensus on Whole Process Nutritional Management in Pancreatic Surgery Perioperative Period (2020 Edition), aims to provide prospective randomized controlled trial data that support the recommendations in the Chinese Expert Consensus on Perioperative Nutritional Management for Pancreatic Surgery (2020 Edition).This study seeks to enhance the level of evidence for these recommendations and to offer a framework for personalized nutritional interventions for pancreatic surgery patients throughout the perioperative period, thereby providing valuable insights for the clinical practice of ERAS in pancreatic surgery.