A Randomized Trial of Long-term Immunonutrition Oral Supplements Versus Standard Nutrition in Patients who Underwent Colorectal Cancer Surgery after Discharge: Interim Analysis of a Nationwide Multicentre Study in China

A Randomized Trial of Long-term Immunonutrition Oral Supplements Versus Standard Nutrition in Patients who Underwent Colorectal Cancer Surgery after Discharge: Interim Analysis of a Nationwide Multicentre Study in China | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Randomized Trial of Long-term Immunonutrition Oral Supplements Versus Standard Nutrition in Patients who Underwent Colorectal Cancer Surgery after Discharge: Interim Analysis of a Nationwide Multicentre Study in China Mandula Bao, Shaomu Cao, Fei Huang, Zhexue Wang, Pu Cheng, Qian Liu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7917373/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Enteral nutrition (EN) can prevent and treat postoperative malnutrition in patients with malignant tumors, thereby improving their short-term postoperative prognosis. However, there is currently a lack of long-term observational data on the impact of immunonutrition (IMN) on the immunotrophic status of patients with colorectal cancer (CRC) after discharge. Methods This was a multicentre, randomized, controlled noninferiority trial with two parallel intervention arms for patients with CRC (ChiCTR2300071078). Patients were included as study participants after screening. They were randomly assigned to receive an immunomodulatory oral formula (IMN group) or a standard nutritional oral formula (SN group). The ratio of the number of enrolled patients in the IMN and SN groups was 2:1. After the intervention, changes in nutritional and immunologic parameters, such as body mass index (BMI), patient-generated subjective global assessment (PG-SGA), transferrin (TFN), albumin (ALB), prealbumin (PA), glucose (GLU), lymphocyte absolute value (LAV), C-reactive protein (CRP), immunoglobulin G (IgG), IgM, and IgA, were the primary endpoints of the study. The secondary end points were the postoperative complications, including total, infectious and noninfectious complications. Results Interim data analysis is presented in this report. There were 416 patients enrolled from the main centre. Of these, 279 patients were in the IMN group, and 137 patients were in the control group. The patients in the two groups had similar demographics. With respect to nutritional parameters, after the intervention, the PG-SGA and serum ALB significantly differed between the two groups (P < 0.05). Moreover, compared with those in the control group, the LAV, IgG, and IgM in the IMN group were significantly increased after the intervention. Finally, although the incidence of postoperative infectious complications in the IMN group was lower than that in the SN group, there was no significant difference in the rate of postoperative total, infectious, or noninfectious complications between the two groups (P > 0.05). Conclusions Interim data show that long-term, continuous oral IMN after discharge can improve the nutritional status, enhance the immune response, and reduce the incidence of postoperative infectious complications in patients with CRC who have undergone radical surgery. Colorectal cancer Immunonutrition Postoperative intervention Postoperative complications Figures Figure 1 Figure 2 Figure 3 Introduction The 2024 Global Cancer Report, published by the World Health Organization (WHO), identifies colorectal cancer (CRC) as a major health issue, with an estimated 40,800 new cases and 19,600 deaths occurring annually[ 1 ]. In 2024, the National Cancer Center released the China Cancer Statistics, which revealed that in 2022, CRC was the second most commonly diagnosed malignant tumour in China and accounted for the fourth highest number of cancer-related deaths[ 2 ]. Numerous studies have shown that malnutrition is a prevalent health issue among patients with cancer[ 3 ]. A study by the Chinese Anti-Cancer Association revealed that a significant proportion of patients with cancer in China suffer from malnutrition, with 79.4% of patients experiencing some form of malnutrition and 58% exhibiting moderate to severe malnutrition. Patients with digestive tract tumours have the highest incidence of malnutrition[ 4 ]. Severe malnutrition can lead to an increased incidence of postoperative complications and mortality in patients with CRC, along with prolonged hospital stays and increased economic burden[ 5 – 7 ]. Malnutrition can occur for many reasons. First, cancer is known to disrupt metabolic balance and immunological competence, leading to a weakened response to surgical trauma and accelerating tumour recurrence, advancement, and tissue infiltration. Second, although patients with early CRC can be successfully treated with surgery, major surgical procedures are often followed by a catabolic state characterized by proteolysis, the breakdown of branched-chain amino acids, weight loss, and immunosuppression of multifactorial origin, which can exacerbate the risk of postoperative complications and prolong hospital stays[ 8 , 9 ]. Therefore, timely restoration of nutritional status and immune function in patients with CRC following surgery is crucial for their postoperative recovery[ 10 ]. Immunonutrition (IMN), or more precisely immune-modulating nutrition, is broadly defined as the provision of nutrients in amounts greater than normal dietary intake to modulate the activities of the immune system[ 11 , 12 ]. IMN not only supplies energy and protein (via nitrogen) but is also believed to regulate the inflammatory response and mitigate the adverse effects of postoperative immune system impairments[ 13 ]. Research has demonstrated that short-term perioperative IMN for patients with CRC undergoing surgery is effective at reducing catabolism and enhancing immunologic parameters. This randomized, controlled study involved 60 patients with CRC, who were divided into an immunonutrition support group (n = 30) and a control group receiving conventional enteral nutrition support (n = 30). The immunonutrition support group was administered immunonutritional agents 7 days prior to surgery, whereas the control group received only a conventional diet. The concentrations of PA and TFN in the immunonutrition group were higher than those in the control group (p < 0.05). Additionally, the postoperative IgG concentration in the immunonutrition group was significantly greater than that in the conventional nutrition group (13.35 ± 2.06 g/l vs. 9.59 ± 2.23 g/l; P < 0.05)[ 14 ]. Another study included 28 patients who were divided into an immunonutrition support group and a control group without nutritional support at a 1:1 ratio. The immunonutrition support group was given immunonutritional support from 6 days before surgery until the day before surgery and from the 3rd day to the 7th day after surgery. The control group received traditional nutritional support during the same period. The results revealed a significant increase in the number of CD4 lymphocytes on the day before surgery compared with the baseline parameters (p < 0.05) in the immunonutrition support group but not in the traditional group[ 15 ]. Although IMN therapy has been widely adopted in clinical practice and is endorsed by numerous authoritative institutions, including the European Society of Clinical Nutrition and Metabolism (ESPEN) and the Chinese Medical Association Branch of Parenteral and Enteral Nutrition (CSPEN), the existing studies on the effects of IMN on the nutritional and immune status of patients with CRC remain largely confined to the short-term perioperative period (typically ranging from one week before surgery to two weeks after surgery). Moreover, long-term observational data concerning the impact of IMN on CRC patients' immunotrophic status after discharge are lacking. Currently, a multicentre, large-scale, randomized controlled observational study is needed to determine whether long-term, continuous oral immunonutrition supplements after discharge can enhance the immunonutritional status, bolster the immune response, and consequently improve the prognosis for patients with CRC who have undergone radical surgery. Materials and Methods Trial Design A randomized, noninferiority, two-parallel-arm, interventional trial involving thirty-five Chinese medical centres led by the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, was conducted between April 2023 and February 2024. This trial was registered on www.chictr.org.cn (ChiCTR2300071078) after approval of the protocol by the local ethics committee. All patients were informed about the conditions of participation in the study and agreed to participate after signing the informed consent forms. Inclusion and Exclusion Criteria Patients who were diagnosed with colorectal adenocarcinoma and aged 18–75 years and who underwent radical colorectal surgery were recruited. The inclusion criteria also included a BMI ranging from 18.5–28 kg/m 2 , a haemoglobin (HB) concentration of no less than 90 g/L, an ALB concentration of no less than 2.5 g/dL, and no use of blood products within one week before inclusion in the study. The exclusion criteria specified CRC treated with radio- or chemotherapy and the intraoperative fashioning of a protective ileostomy, chronic inflammatory bowel diseases, renal insufficiency (creatinine [CR], ≥ 2 times the upper limit of normal; haemodialysis), cardiac insufficiency (New York Heart Association [NYHA], > 3), hepatic insufficiency (alanine aminotransferase [ALT], ≥ 2 times the upper limit of normal; total bilirubin [Tbil], ≥ 2 times the upper limit of normal value), severe respiratory insufficiency (partial pressure of arterial oxygen [PaO2], < 70 mmHg), current infection, hypothyroidism or hyperthyroidism, diabetes mellitus receiving medical and dietary treatment, and congenital or acquired immunodeficiency. Randomization and Blinding Randomization was carried out by each participating surgeon using https://edc-cloud.medsci.cn . Each patient received a participant number that assigned them to either the IMN group or the SN group and received one of the two nutritional formulas. The ratio of the number of enrolled patients in the IMN and SN groups was 2:1. The ratio of patients with colon cancer to those with rectal cancer was 1:1 to achieve effective cases that could be evaluated. The random assignment sequence was concealed until the procedure was allocated to the patients. Nutrition Support The nutritionist provided one-on-one instructions to all patients on taking the daily oral dose of enteral feed and recording it. Additionally, the daily intake and caloric count were meticulously calculated. IMN group: Patients in this group received nutrition education and guidance to receive 500 mL/day of postoperative oral supplementation in the form of an IMN-enriched enteral feed (IMPACT Oral®) added to the normal diet for thirty consecutive days starting from the day after discharge. IMPACT Oral® contains high levels of protein, arginine, omega-3 fatty acids and RNA. The detailed composition of the oral supplements is shown in the Supplementary Table. SN group: Patients in this group received nutrition education and guidance to supplement nutrition with the traditional protocol. Outcome Measures Demographics and disease-related data for each cohort at the time of surgery, such as sex, age, BMI, American Society of Anaesthesiology (ASA) score, major comorbidities, tumour site, TNM stage, previous abdominal surgery status, neoadjuvant chemotherapy status and mismatch repair (MMR) expression, were obtained. We also measured the following nutritional and immunologic parameters on the first day after discharge (defined as “baseline”), the day that patients started to take the IMPACT Oral® treatment, and the 30th day (defined as “endline”) after first intake: BMI, PG-SGA, TFN, ALB, PA, GLU, LAV, CRP, IgG, IgM, and IgA. The incidence of postoperative complications, ranging from baseline to endline, was meticulously documented, encompassing a spectrum of adverse events such as surgical site infections, abdominal abscess, anastomotic fistula and intestinal obstruction. Complications were defined as any deviation from the normal postoperative course and were divided into minor and major complications[ 16 ]. Minor complications, which could include events such as bedside wound infections, urinary tract infections, or postoperative ileus, are classified as Clavien–Dindo I–II. Major complications include life-threatening events and those necessitating surgical or endoscopic intervention or radiological intervention, such as anastomotic fistula, abdominal abscess, and pneumonia and are classified as Clavien–Dindo III–IV. Statistical Analyses The statistical analyses were conducted using SPSS 27.0 version for Windows (SPSS Inc., Chicago, IL, United States). The measurement data are presented as the means ± standard deviations (‾x ± s) and were analysed by Student’s t test. The data are presented as percentages, and comparisons between the IMN and SN groups were conducted using the chi-square (χ 2 ) test. A p value less than 0.05 is typically regarded as indicating a statistically significant difference, as it suggests that the observed result is unlikely to have occurred by chance alone. Results Patients Between April 2023 and February 2024, the study enrolled 511 patients and randomly allocated them into two groups (339 in the IMN group and 172 in the SN group) at the main centre. Thirty-five patients were excluded because they did not progress to surgery and did not meet the inclusion criteria, and forty-five patients were lost to follow-up. Consequently, 416 patients were included in the definitive interim analysis: 279 in the IMN group and 137 in the SN group. The patient flow chart depicted in Fig. 1 outlines the detailed steps involved in the patient therapy process. Fig. 1 Flowchart of the study population selection. Demographic Data As listed in Table 1, the t test revealed that the demographics of the patients in the IMN group were similar to those in the SN group, and no significant differences were found between the two groups in terms of sex (P=0.191), age (P=0.590), BMI (P=0.665), ASA score (P=1.131), major comorbidities (P=0.068) or tumour site (P=3.179). Furthermore, the overall difference in TNM stage between the IMN and SN groups was not significant (P=2.852). Finally, no significant differences in previous abdominal surgery status, neoadjuvant chemotherapy status, or MMR expression were detected between the two groups (P>0.05). Table 1. Demographics and disease-related data for each cohort IMN (n=279) SN (n=137) P-value Gender, n (%) 0.191 Male 171（61.3%） 87（63.5%） Female 108（38.7%） 50（36.5%） Age, mean (SD), year 59.66±9.86 57.71±10.03 0.590 BMI 24.27±4.06 24.10±3.20 0.665 ASA score, n (%) 1.131 I 34（12.2%） 14（10.2%） II 180（64.5%） 90（65.7%） III 59（21.1%） 28（20.4%） IV 6（2.2%） 5（3.6%） Morbidity, n (%) 0.068 Diabetes 37（13.3%） 13(9.5%) Hypertension 88（31.9%） 32(23.4%) Heart disease 8(2.9%) 3(2.2%) Respiratory disease 8(2.9%) 5(3.6%) Urological diseases 3(1.1%) 2(1.5%) Liver disease 16(5.7%) 6(4.4%) Other 41(14.7%) 24(17.5%) Tumor site, n (%) 3.179 Rectum 165（59.1%） 90（65.7%） Sigmoid colon 54（19.4%） 20（14.6%） Descending colon 7（2.5%） 2（1.5%） Transverse colon 11（3.9%） 3（2.2%） Ascending colon 42（15.1%） 22（16.1%） TNM stage, n (%) 2.852 Carcinoma in situ 14（5.0%） 8（5.8%） Stage I 42（15.1%） 29（21.2%） Stage II 95（34.1%） 42（30.7%） Stage III 117（41.9%） 52（38%） Stage IV 11（3.9%） 6（4.4%） Previous abdominal surgery, n (%) 0.216 Yes 71（25.4%） 32（23.4%） No 208（74.6%） 105（76.6%） Neoadjuvant chemotherapy, n (%) 0.822 Yes 45（16.1%） 27（19.7%） No 234（83.9%） 110（80.3%） MMR expression, n (%) 0.069 dMMR 16（5.7%） 7（5.1%） pMMR 263（94.3%） 130（94.9%） Notes: Abbreviations: BMI, body mass index; ASA, American Society of Anesthesiology; MMR, mismatch repair; Nutritional Parameters The nutritional parameters of the patients were analysed and are listed in detail in Table 2. No significant differences in BMI (P=0.665), PG-SGA (P=0.235), TFN (P=0.057), ALB (P=0.063), PA (P=0.090) or GLU (P=0.873) were detected between the two groups prior to the intervention. After the intervention, the BMI, TFN, PA and GLU in the two groups did not differ (P>0.05). However, as shown in Fig. 2, after the intervention, the PG-SGA scores and serum ALB concentrations significantly differed between the two groups (P<0.05), indicating that both the subjective overall assessment and objective nutritional index were significantly improved after oral IMN. Table 2. Comparison of nutritional parameters（`x±s） IMN (n=279) SN (n=137) t-value P-value BMI(kg/m2） baseline 22.98±3.14 22.77±3.09 0.434 0.665 endline 23.45±3.21 23.39±3.07 0.138 0.891 PG-SGA baseline 4.99±2.61 5.43±2.46 -1.193 0.235 endline 2.66±2.12 3.26±2.29 -2.014 0.045 TFN(mg/dL） baseline 190.26±36.15 198.71±42.38 -1.911 0.057 endline 259.89±65.11 262.99±66.68 -0.271 0.787 ALB(g/L） baseline 35.38±5.22 34.46±43.44 1.867 0.063 endline 43.11±3.87 42.01±4.02 2.552 0.011 PA(g/L） baseline 16.70±3.98 17.78±6.19 -1.704 0.090 endline 27.27±5.82 27.46±5.34 -0.228 0.820 GLU(mmol/L） baseline 6.18±1.94 6.21±1.48 -0.160 0.873 endline 5.88±1.68 6.04±1.33 -0.689 0.491 Notes: Abbreviations: BMI, body mass index; PG-SGA, patient-generated subjective global assessment; TFN, transferrin; ALB, albumin; PA, prealbumin; GLU, glucose; Fig. 2 After the intervention, the PG-SGA scores and serum ALB concentrations significantly differed between the two groups (P<0.05). Immunologic Parameters The immunologic parameters of the patients were analysed and are listed in detail in Table 3. Prior to the intervention, some immunologic parameters in the IMN group, such as LAV, IgG, and IgM, were similar to those in the SN group (P>0.05). Furthermore, compared with those in the SN group, LAV, IgG, and IgM were significantly increased in the IMN group after the intervention (P0.05). Table 3. Comparison of immunologic parameters（`x±s） IMN (n=279) SN (n=137) t-value P-value LAV(×10^9/L) baseline 1.23±0.50 1.21±1.01 0.380 0.704 endline 1.82±0.64 1.68±0.65 2.020 0.044 CRP(mg/L） baseline 5.91±4.84 5.44±4.26 0.949 0.343 endline 1.28±4.52 0.74±1.45 0.877 0.382 IgG (g/L) baseline 8.92±1.84 9.35±2.31 -1.764 0.079 endline 14.11±3.12 12.97±2.96 2.152 0.033 IgM (g/L) baseline 0.83±0.41 0.84±0.49 -0.320 0.749 endline 1.33±0.56 1.14±0.45 2.040 0.043 IgA (g/L) baseline 2.24±1.05 2.24±0.88 -0.035 0.972 endline 2.91±1.16 2.89±0.96 0.114 0.909 Notes: Abbreviations: LAV, lymphocyte absolute value; CRP, c-reactive protein; IgG, immunoglobulin G; Fig. 3 Compared with those in the SN group, LAV, IgG, and IgM were significantly increased in the IMN group after the intervention (P<0.05). Postoperative Complications The surgical complications of the patients were analysed and are listed in detail in Table 4. Although the total incidence of complications in the IMN group was significantly lower than that in the SN group (15.1% vs. 18.2%), the difference between the two groups was not statistically significant (P=0.405). Upon classification and comparison, the incidence of postoperative infectious or non-infectious complications in the IMN group did not significantly decrease compared with the control group (P>0.05). Even in the comparison of each individual complication rate, there were no significant differences between the two groups, such as respiratory tract infection (P=0.195), wound infection (P=0.605), urinary tract infection (P=0.734), intra-abdominal infection (P=0.458), anastomotic fistula (P=0.976), bleeding (P=0.735), intestinal obstruction (P=0.734) and wound dehiscence (P=0.804) Table 4. Detail of postoperative complications and outcomes IMN (n=279) SN (n=137) P-value Infectious complications, n (%) 23（8.2%） 16（11.7%） 0.259 Respiratory tract 2（0.7%） 3（2.2%） 0.195 Wound infection 13（4.7%） 8（5.8%） 0.605 Urinary tract 3（1.1%） 1（0.7%） 0.734 Intra-abdominal infection 5（1.8%） 4（2.9%） 0.458 Noninfectious complications, n (%) 19（6.6%） 9（6.8%） 0.927 Anastomotic fistula 8（2.9%） 4（2.9%） 0.976 Bleeding 3（1.1%） 2（1.5%） 0.735 Intestinal obstruction 3（1.1%） 1（0.7%） 0.734 Wound dehiscence 5（1.8%） 2（1.5%） 0.804 Total complication, n (%) 42（15.1%） 25（18.2%） 0.405 Discussion Malnutrition is a prevalent yet frequently underestimated issue among patients with digestive cancers[3]. Research has indicated that the incidence of nutritional risk and malnutrition in patients with gastrointestinal cancer can reach 84.3–90.0%, with malnutrition affecting 45–60% of patients with CRC, a rate that significantly increases after radical surgery[17,18]. Severe malnutrition significantly increases the risk of postoperative complications and mortality in patients with CRC. Studies have shown that patients with severe malnutrition have a mortality risk that is 2–5 times greater than that of patients with good nutritional status, and up to 20% of patients with CRC die directly from malnutrition rather than the cancer itself[5-7]. It also leads to extended hospital stays and heightened economic burdens. Therefore, nutritional therapy has become an important part of multidisciplinary comprehensive treatment for CRC. Standardized nutritional therapy has been shown to significantly increase the quality of life and prognosis for patients with cancer, as evidenced by studies indicating that targeted nutritional interventions can reduce complications, improve survival rates, and maintain body functions[19, 20]. The PG-SGA is a crucial instrument for evaluating the nutritional status of patients with cancer and integrates patient self-assessment with clinical observation to assess indicators such as weight changes, dietary intake, symptoms, activity levels, and physical condition. Based on the stratified results of the assessment, personalized nutritional therapy plans are developed for patients with cancer, thereby improving treatment outcomes and quality of life. A Brazilian study examined the correlation between PG-SGA scores and survival outcomes in 250 older patients with CRC. Individuals with severe malnutrition, classified as PG-SGA Class C, exhibited a significantly increased risk of mortality than those with a better nutritional status, classified as PG-SGA Class A[21]. In our study, the PG-SGA scores of patients in the IMN group were significantly lower than those of the control group after the intervention. These findings suggest that prolonged oral intake of IMN following surgery can decrease the incidence of malnutrition. Furthermore, serum albumin is among the primary indicators used to assess the nutritional status of patients with CRC after surgery. A retrospective analysis was conducted by the American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIPP). The study, which involved 30,676 patients who underwent CRC surgery, investigated the correlation between mild hypoalbuminaemia and postoperative complications and mortality and revealed that hypoalbuminaemia could significantly impact patient outcomes and survival rates. The results indicated that among the 30,676 patients with CRC, 5,230 had mild hypoproteinaemia (with levels less than 35 and greater than or equal to 30 g/l). Postoperative mortality was significantly associated with mild hypoproteinaemia after a 1:2 matching with patients who had normal albumin levels (≥35 g/l) (P<0.001). Additionally, mild hypoproteinaemia was significantly correlated with 11 postoperative complications, including deep vein thrombosis, pulmonary embolism, superficial and deep surgical site infections, pneumonia, septic shock, ventilation for more than 48 hours, blood transfusion, return to the operating room, stroke, and reintubation. Mild hypoalbuminaemia was also linked to an increased risk of overall complications (P<0.001) and longer total hospital stays (P<0.001). In conclusion, a slight decrease in serum albumin levels has been identified as a significant predictor of poor prognosis in patients undergoing surgery[22]. Our trial revealed that, after intervention, compared with those in the control group, the serum ALB concentration in the IMN group increased significantly (P<0.05). These findings suggest that long-term oral IMN following radical surgery in patients with CRC can significantly increase nutritional status, mitigate the risk of malnutrition and improve prognosis. Although early nutritional support has shown certain benefits postoperatively for patients with CRC and has been acknowledged by many physicians, there is limited improvement in postoperative immune function. With respect to continuous research and exploration, scholars have reported that the addition of certain special nutrients to standard EN formulas can achieve the desired effects. EN formulas containing these special nutrients can stimulate the body to maintain a moderate immune response state, regulate immune molecule responses, and control inflammatory responses to some extent, further enhancing the immune response function of the body and preserving the original physiological barrier function of the intestine. Currently, the special nutrients, widely known as IMN when clinically applied, mainly include omega-3 fatty acids, glutamine, arginine, dietary fibre, nucleosides, and RNA. Omega-3 fatty acids are essential polyunsaturated fatty acids that primarily consist of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which serve as critical nutrients for immune modulation. EPA and DHA, which are specific types of fatty acids, increase cell membrane fluidity, facilitate messenger transmission and receptor function on the cell membrane, decrease the production of inflammatory mediators, improve the body’s cellular immune response, and mitigate inflammation. Additionally, they exhibit biological effects such as inhibiting cancer cell proliferation, reducing tumour burden, and minimizing nutrient consumption[19-21]. Glutamine, the most abundant free amino acid in the body, is crucial for maintaining the integrity of the intestinal barrier and promoting the growth and differentiation of intestinal cells. It also plays a pivotal role in enhancing the immune responsiveness of lymphocytes and mononuclear macrophages, thereby supporting the body's defence mechanisms[8]. Arginine, as the sole substrate for nitric oxide (NO) synthesis, plays a crucial role in innate antimicrobial immunity, which is essential for the host’s first line of defence[23]. Arginine not only supports cardiovascular health by promoting vasodilation and improving blood flow but also contributes to immune regulation and cellular growth, as evidenced by its extensive use in biomedical research and applications. It also plays important roles in maintaining the physiological balance of the gastrointestinal tract and regulating the metabolism of many types of lymphocytes[24,25]. Moreover, an RNA supply is necessary to prevent T-lymphocytes from decreasing in number and to increase IL-2 levels and the CD4/CD8 ratio[12,26-28]. Many clinical and experimental studies have demonstrated the effectiveness of IMN, with the specific components mentioned above, in reinforcing the body’s cellular and humoral immunity. A meta-analysis conducted by Yue T et al.[29], which included 20 studies and 1,613 patients, revealed that omega-3 fatty acids significantly increased humoral immune function indices, such as IgA (standardized mean difference (SMD) = 0.54, 95% CI 0.10–0.99), IgM (SMD = 0.52, 95% CI 0.05–0.99), and IgG (SMD = 0.65, 95% CI 0.47–0.84), as well as T-cell immune function indices, including CD3+ (SMD = 0.73, 95% CI 0.54–0.92), CD4+ (SMD = 0.76, 95% CI 0.53–0.98), and the ratio of CD4+/CD8+ (SMD = 0.66, 95% CI 0.39–0.92). Xu J et al.[14] randomly divided sixty patients with gastrointestinal cancer into 2 groups, each of which was fed IMN or a conventional diet for 7 days before surgical procedures. Postoperative IgG levels were higher in the IMN group than in the control group. Huang Z et al.[30] conducted a retrospective study on 102 patients who underwent gastrointestinal surgery, including 52 patients who received an IMN diet and 50 patients who received a conventional nutrition diet during the perioperative period. Compared with control patients, patients fed the IMN diet exhibited notably elevated levels of IgA, IgG, IgM, complement C3, and complement C4 on both the 1 st and 7 th days post-operation (P<0.05). Our study further revealed that, after continuous oral IMN starting on the day of discharge from the hospital, significant improvements in LAV, IgG, and IgM levels were observed compared with those in the control group (P<0.05). The results indicated that the continuous use of IMN after surgery could enhance cellular and humoral immunity in the long term. Can long-term enhancement of the postoperative immune response and control of the inflammatory response benefit patients, thereby improving their prognosis? The answer is yes. It is widely recognized that lymphocytes are crucial components of the human immune system. When lymphocytes detect potential pathogens introduced via surgical trauma, they activate the body’s immune response and proliferate extensively to eliminate these pathogens, consequently reducing the risk of infection and facilitating recovery and wound healing. In addition, clinically, the key indicators for evaluating the body’s humoral immune status are primarily the immunoglobulins IgA, IgM, and IgG. Immunoglobulins are a unique category of proteins with antibody activity found in human serum and bodily fluids that possess antibacterial and antiviral properties and enhance the phagocytic capabilities of cells. They can also, with the aid of complement, neutralize and breakdown pathogenic microorganisms, playing a vital role in the body’s humoral immunity. IgG is particularly involved in antibacterial, antiviral, and antitoxic activities and contributes significantly to immune processes. The gastrointestinal tract is the primary site for the synthesis and secretion of IgA, an essential antibody in the immune response of the gastrointestinal mucosa. IgM antibodies are characterized by their high efficiency and potent bactericidal effects, especially against gram-negative bacteria such as Escherichia coli , and are the first to be produced during the humoral immune response to pathogens that grow and replicate in the body, leading to infections[31]. In our study, although IgA did not significantly increase compared with that in the control group, the long-term use of IMN in the IMN group led to increased components of cellular immunity (LAV) and humoral immunity (IgG and IgM). Although, as mentioned above, the immunologic parameters in the IMN group significantly increased compared to those in the control group after the intervention, it might be due to the insufficient sample size that this study failed to prove that continuous oral IMN after discharge could significantly reduce the incidence of postoperative infectious complications compared with the control group. However, this study has limitations. First, the scope of our investigation was limited because the sample size was inadequate to derive definitive conclusions. Second, with respect to the cellular immune response, our analysis was restricted to the absolute lymphocyte count; specific lymphocyte subsets were not examined. Other immune cells, including T cells, B cells, NK cells, and macrophages, were neither observed nor subjected to analysis. Third, our research focused on the influence of long-term postoperative IMN on the short-term prognosis of individuals diagnosed with CRC. There is a scarcity of observational studies that assess the effect of long-term postoperative IMN on the survival of such patients. We need to complete the data entry for the remaining 34 centres to increase the sample size. Ultimately, this comprehensive study will encompass observations on not only the effect of long-term postoperative IMN on the short-term prognosis of patients with CRC but also its impact on their continued survival. Conclusion An interim analysis revealed that long-term oral IMN postoperation, which includes specific components such as omega-3 fatty acids, glutamine, arginine, and RNA, can lead to an improvement in nutritional status and enhance the immune response in patients with CRC after discharge. Although it is necessary to conduct further studies involving more centres and larger sample sizes to substantiate the effect of sustained oral IMN on long-term survival, it is evident that such nutritional intervention can improve the nutritional status, enhance the immune response and improve the short-term prognosis of patients with CRC. Declarations Ethics approval The study was successfully approved by the Ethics Committee of National Cancer Center/ Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College. We solemnly declare that the entire study process was carried out in strict compliance with the relevant guidelines and regulations. All participants and/or their legal guardians have signed the informed consent form. Conflict of interest The authors declare no competing interests. Funding None. Author Contribution The study design and conceptualization were carried out by Mandula Bao, Fei Huang, Qian Liu, Zhaoxu Zheng; data collection was carried out by Mandula Bao, Shaomu Cao, Fei Huang, Zhexue Wang, Pu Cheng; analyses were carried out by Mandula Bao, Zhexue Wang, Pu Cheng; and the interpretation, drafting, and revising of the manuscript were done by Mandula Bao, Zhexue Wang, Pu Cheng. All authors approved the final version of the manuscript. Acknowledgement The authors are thankful to all the patients that participated in the present study. Data Availability Some, if not all, of the data utilized in the research process can be obtained from the corresponding data resources of the corresponding authors. References Bray F, Laversanne M, Sung H et al (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74(3):229–263 Han B, Zheng R, Zeng H et al (2024) Cancer incidence and mortality in China, 2022. J Natl Cancer Cent 4(1):47–53 Hu WH, Cajas-Monson LC, Eisenstein S et al (2015) Preoperative malnutrition assessments as predictors of postoperative mortality and morbidity in colorectal cancer: an analysis of ACS-NSQIP. Nutr J 14:91 Song C, Cao J, Zhang F et al (2019) Nutritional Risk Assessment by Scored Patient-Generated Subjective Global Assessment Associated with Demographic Characteristics in 23,904 Common Malignant Tumors Patients. Nutr Cancer 71(1):50–60 Chen Y, Liu BL, Shang B et al (2011) Nutrition support in surgical patients with colorectal cancer. World J Gastroenterol 7(13):1779–1786 Dobrila-Dintinjana R, Trivanovic D, Zelić M et al (2013) Nutritional support in patients with colorectal cancer during chemotherapy: does it work? Hepatogastroenterology 60(123):475–480 Barret M, Malka D, Aparicio T et al (2011) Nutritional status affects treatment tolerability and survival in metastatic colorectal cancer patients: results of an AGEO prospective multicenter study. Oncology 81(5–6):395–402 Daly JM, Lieberman MD, Goldfine J et al (1992) Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome. Surgery 112(1):56–67 Moore FA, Feliciano DV, Andrassy RJ et al (1992) Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a meta-analysis. Ann Surg 216(2):172–183 Gianotti L, Braga M, Nespoli L et al (2002) A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology 122(7):1763–1770 Grimble RF (2001) Nutritional modulation of immune function. Proc Nutr Soc 60(3):389–397 Calder PC (2003) Immunonutrition BMJ 327(7407):117–118 Uno H, Furukawa K, Suzuki D et al (2016) Immunonutrition suppresses acute inflammatory responses through modulation of resolvin E1 in patients undergoing major hepatobiliary resection. Surgery 160(1):228–236 Xu J, Zhong Y, Jing D et al (2006) Preoperative enteral immunonutrition improves postoperative outcome in patients with gastrointestinal cancer. World J Surg 30(7):1284–1289 Finco C, Magnanini P, Sarzo G et al (2007) Prospective randomized study on perioperative enteral immunonutrition in laparoscopic colorectal surgery. Surg Endosc 21(7):1175–1179 Clavien PA, Barkun J, de Oliveira ML et al (2009) The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 250(2):187–196 Gyan E, Raynard B, Durand JP et al (2018) NutriCancer2012 Investigator Group. Malnutrition in Patients With Cancer: Comparison of Perceptions by Patients, Relatives, and Physicians-Results of the NutriCancer2012 Study. JPEN J Parenter Enter Nutr 42(1):255–260 Hiramatsu K, Shindoh J, Hanaoka Y et al (2021) Postoperative Nutritional Status is Predictive of the Survival Outcomes in Patients Undergoing Resection of Stage III Colorectal Cancer. World J Surg 45(10):3198–3205 Hébuterne X, Lemarié E, Michallet M et al (2014) Prevalence of malnutrition and current use of nutrition support in patients with cancer. JPEN J Parenter Enter Nutr 38(2):196–204 Drissi M, Cwieluch O, Lechner P et al (2015) Nutrition care in patients with cancer: A retrospective multicenter analysis of current practice - Indications for further studies? Clin Nutr 34(2):207–211 Barao K, Abe Vicente Cavagnari M, Silva Fucuta P et al (2017) Association Between Nutrition Status and Survival in Elderly Patients With Colorectal Cancer. Nutr Clin Pract 32(5):658–663 Hu WH, Eisenstein S, Parry L et al (2019) Preoperative malnutrition with mild hypoalbuminemia associated with postoperative mortality and morbidity of colorectal cancer: a propensity score matching study. Nutr J 18(1):33 Xiong L, Teng JL, Botelho MG et al (2016) Arginine Metabolism in Bacterial Pathogenesis and Cancer Therapy. Int J Mol Sci 17(3):363 Evoy D, Lieberman MD, Fahey TJ 3rd et al (1998) Immunonutrition: the role of arginine. Nutrition 14(7–8):611–617 Klein D, Morris DR (1978) Increased arginase activity during lymphocyte mitogenesis. Biochem Biophys Res Commun 81(1):199–204 Di Fronzo LA, Cymerman J, O'Connell TX (1999) Factors affecting early postoperative feeding following elective open colon resection. Arch Surg 134(9):941–945 discussion 945-6 Franzè E, Dinallo V, Rizzo A et al (2017) Interleukin-34 sustains pro-tumorigenic signals in colon cancer tissue. Oncotarget 9(3):3432–3445 EuroSurg C (2016) EuroSurg: a new European student-driven research network in surgery. Colorectal Dis 18(2):214–215 Yue T, Xiong K, Deng J et al (2022) Meta-analysis of omega-3 polyunsaturated fatty acids on immune functions and nutritional status of patients with colorectal cancer. Front Nutr 9:945590 Huang Z, Wang Y (2022) Perioperative enteral immunonutrition with probiotics favors the nutritional, inflammatory, and functional statuses in digestive system surgery. Asia Pac J Clin Nutr 31(1):78–86 Lohse S, Derer S, Beyer T et al (2011) Recombinant dimeric IgA antibodies against the epidermal growth factor receptor mediate effective tumor cell killing. J Immunol 186(6):3770–3778 Additional Declarations No competing interests reported. Supplementary Files Supplementaryinformation.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7917373","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":545448397,"identity":"af2ad5d5-8a23-4f76-b541-dbd5a735388a","order_by":0,"name":"Mandula Bao","email":"","orcid":"","institution":"National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Mandula","middleName":"","lastName":"Bao","suffix":""},{"id":545448398,"identity":"a35b5bdb-c3f0-40ca-9bdd-6ee164e39d4a","order_by":1,"name":"Shaomu Cao","email":"","orcid":"","institution":"National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Shaomu","middleName":"","lastName":"Cao","suffix":""},{"id":545448399,"identity":"1d9984f1-ed25-4686-abac-8866f28d4b82","order_by":2,"name":"Fei Huang","email":"","orcid":"","institution":"National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical 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08:27:43","extension":"html","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":123143,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7917373/v1/b13ad926355f201b2f863c8f.html"},{"id":96156140,"identity":"d67a32b8-e909-4db2-b089-5910547989f9","added_by":"auto","created_at":"2025-11-18 08:27:43","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":133043,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the study population selection.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7917373/v1/4c867b0dec3d1c4ba00ef802.jpeg"},{"id":96251494,"identity":"ff86d20c-38a2-4f01-b1f8-d7f42ea084bf","added_by":"auto","created_at":"2025-11-19 07:39:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":204733,"visible":true,"origin":"","legend":"\u003cp\u003eAfter the intervention, the PG-SGA scores and serum ALB concentrations significantly differed between the two groups (P\u0026lt;0.05).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7917373/v1/293720b2984977c45cb4c84d.png"},{"id":96156148,"identity":"5edb1841-f582-4b75-b9a5-56e57292ba41","added_by":"auto","created_at":"2025-11-18 08:27:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":168735,"visible":true,"origin":"","legend":"\u003cp\u003eCompared with those in the SN group, LAV, IgG, and IgM were significantly increased in the IMN group after the intervention (P\u0026lt;0.05).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7917373/v1/8d91b749ec1d251d820df0a0.png"},{"id":104399565,"identity":"ef6c90e9-8a01-4e39-a76d-44708ced9c8a","added_by":"auto","created_at":"2026-03-11 12:06:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1296955,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7917373/v1/eb5b7b85-98a4-4bf6-b9d6-f8541b0390d3.pdf"},{"id":96156139,"identity":"a698b75d-c19e-410d-a57a-7a72224ef3e0","added_by":"auto","created_at":"2025-11-18 08:27:43","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15324,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryinformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-7917373/v1/1e91097812ee15099226f9fe.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Randomized Trial of Long-term Immunonutrition Oral Supplements Versus Standard Nutrition in Patients who Underwent Colorectal Cancer Surgery after Discharge: Interim Analysis of a Nationwide Multicentre Study in China","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe 2024 Global Cancer Report, published by the World Health Organization (WHO), identifies colorectal cancer (CRC) as a major health issue, with an estimated 40,800 new cases and 19,600 deaths occurring annually[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In 2024, the National Cancer Center released the China Cancer Statistics, which revealed that in 2022, CRC was the second most commonly diagnosed malignant tumour in China and accounted for the fourth highest number of cancer-related deaths[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNumerous studies have shown that malnutrition is a prevalent health issue among patients with cancer[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. A study by the Chinese Anti-Cancer Association revealed that a significant proportion of patients with cancer in China suffer from malnutrition, with 79.4% of patients experiencing some form of malnutrition and 58% exhibiting moderate to severe malnutrition. Patients with digestive tract tumours have the highest incidence of malnutrition[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Severe malnutrition can lead to an increased incidence of postoperative complications and mortality in patients with CRC, along with prolonged hospital stays and increased economic burden[\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Malnutrition can occur for many reasons. First, cancer is known to disrupt metabolic balance and immunological competence, leading to a weakened response to surgical trauma and accelerating tumour recurrence, advancement, and tissue infiltration. Second, although patients with early CRC can be successfully treated with surgery, major surgical procedures are often followed by a catabolic state characterized by proteolysis, the breakdown of branched-chain amino acids, weight loss, and immunosuppression of multifactorial origin, which can exacerbate the risk of postoperative complications and prolong hospital stays[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, timely restoration of nutritional status and immune function in patients with CRC following surgery is crucial for their postoperative recovery[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eImmunonutrition (IMN), or more precisely immune-modulating nutrition, is broadly defined as the provision of nutrients in amounts greater than normal dietary intake to modulate the activities of the immune system[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. IMN not only supplies energy and protein (via nitrogen) but is also believed to regulate the inflammatory response and mitigate the adverse effects of postoperative immune system impairments[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Research has demonstrated that short-term perioperative IMN for patients with CRC undergoing surgery is effective at reducing catabolism and enhancing immunologic parameters. This randomized, controlled study involved 60 patients with CRC, who were divided into an immunonutrition support group (n\u0026thinsp;=\u0026thinsp;30) and a control group receiving conventional enteral nutrition support (n\u0026thinsp;=\u0026thinsp;30). The immunonutrition support group was administered immunonutritional agents 7 days prior to surgery, whereas the control group received only a conventional diet. The concentrations of PA and TFN in the immunonutrition group were higher than those in the control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Additionally, the postoperative IgG concentration in the immunonutrition group was significantly greater than that in the conventional nutrition group (13.35\u0026thinsp;\u0026plusmn;\u0026thinsp;2.06 g/l vs. 9.59\u0026thinsp;\u0026plusmn;\u0026thinsp;2.23 g/l; P\u0026thinsp;\u0026lt;\u0026thinsp;0.05)[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Another study included 28 patients who were divided into an immunonutrition support group and a control group without nutritional support at a 1:1 ratio. The immunonutrition support group was given immunonutritional support from 6 days before surgery until the day before surgery and from the 3rd day to the 7th day after surgery. The control group received traditional nutritional support during the same period. The results revealed a significant increase in the number of CD4 lymphocytes on the day before surgery compared with the baseline parameters (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in the immunonutrition support group but not in the traditional group[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Although IMN therapy has been widely adopted in clinical practice and is endorsed by numerous authoritative institutions, including the European Society of Clinical Nutrition and Metabolism (ESPEN) and the Chinese Medical Association Branch of Parenteral and Enteral Nutrition (CSPEN), the existing studies on the effects of IMN on the nutritional and immune status of patients with CRC remain largely confined to the short-term perioperative period (typically ranging from one week before surgery to two weeks after surgery). Moreover, long-term observational data concerning the impact of IMN on CRC patients' immunotrophic status after discharge are lacking. Currently, a multicentre, large-scale, randomized controlled observational study is needed to determine whether long-term, continuous oral immunonutrition supplements after discharge can enhance the immunonutritional status, bolster the immune response, and consequently improve the prognosis for patients with CRC who have undergone radical surgery.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eTrial Design\u003c/h2\u003e\u003cp\u003eA randomized, noninferiority, two-parallel-arm, interventional trial involving thirty-five Chinese medical centres led by the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, was conducted between April 2023 and February 2024.\u003c/p\u003e\u003cp\u003eThis trial was registered on \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003ca href=\"http://www.chictr.org.cn\" target=\"_blank\"\u003ewww.chictr.org.cn\u003c/a\u003e\u003c/span\u003e\u003cspan address=\"http://www.chictr.org.cn\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (ChiCTR2300071078) after approval of the protocol by the local ethics committee. All patients were informed about the conditions of participation in the study and agreed to participate after signing the informed consent forms.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eInclusion and Exclusion Criteria\u003c/h3\u003e\n\u003cp\u003ePatients who were diagnosed with colorectal adenocarcinoma and aged 18\u0026ndash;75 years and who underwent radical colorectal surgery were recruited. The inclusion criteria also included a BMI ranging from 18.5\u0026ndash;28 kg/m\u003csup\u003e2\u003c/sup\u003e, a haemoglobin (HB) concentration of no less than 90 g/L, an ALB concentration of no less than 2.5 g/dL, and no use of blood products within one week before inclusion in the study.\u003c/p\u003e\u003cp\u003eThe exclusion criteria specified CRC treated with radio- or chemotherapy and the intraoperative fashioning of a protective ileostomy, chronic inflammatory bowel diseases, renal insufficiency (creatinine [CR], \u0026ge;\u0026thinsp;2 times the upper limit of normal; haemodialysis), cardiac insufficiency (New York Heart Association [NYHA], \u0026gt;\u0026thinsp;3), hepatic insufficiency (alanine aminotransferase [ALT], \u0026ge;\u0026thinsp;2 times the upper limit of normal; total bilirubin [Tbil], \u0026ge;\u0026thinsp;2 times the upper limit of normal value), severe respiratory insufficiency (partial pressure of arterial oxygen [PaO2], \u0026lt;\u0026thinsp;70 mmHg), current infection, hypothyroidism or hyperthyroidism, diabetes mellitus receiving medical and dietary treatment, and congenital or acquired immunodeficiency.\u003c/p\u003e\n\u003ch3\u003eRandomization and Blinding\u003c/h3\u003e\n\u003cp\u003eRandomization was carried out by each participating surgeon using \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://edc-cloud.medsci.cn\u003c/span\u003e\u003cspan address=\"https://edc-cloud.medsci.cn\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Each patient received a participant number that assigned them to either the IMN group or the SN group and received one of the two nutritional formulas. The ratio of the number of enrolled patients in the IMN and SN groups was 2:1. The ratio of patients with colon cancer to those with rectal cancer was 1:1 to achieve effective cases that could be evaluated. The random assignment sequence was concealed until the procedure was allocated to the patients.\u003c/p\u003e\n\u003ch3\u003eNutrition Support\u003c/h3\u003e\n\u003cp\u003eThe nutritionist provided one-on-one instructions to all patients on taking the daily oral dose of enteral feed and recording it. Additionally, the daily intake and caloric count were meticulously calculated.\u003c/p\u003e\u003cp\u003e IMN group: Patients in this group received nutrition education and guidance to receive 500 mL/day of postoperative oral supplementation in the form of an IMN-enriched enteral feed (IMPACT Oral\u0026reg;) added to the normal diet for thirty consecutive days starting from the day after discharge. IMPACT Oral\u0026reg; contains high levels of protein, arginine, omega-3 fatty acids and RNA. The detailed composition of the oral supplements is shown in the Supplementary Table.\u003c/p\u003e\u003cp\u003eSN group: Patients in this group received nutrition education and guidance to supplement nutrition with the traditional protocol.\u003c/p\u003e\n\u003ch3\u003eOutcome Measures\u003c/h3\u003e\n\u003cp\u003eDemographics and disease-related data for each cohort at the time of surgery, such as sex, age, BMI, American Society of Anaesthesiology (ASA) score, major comorbidities, tumour site, TNM stage, previous abdominal surgery status, neoadjuvant chemotherapy status and mismatch repair (MMR) expression, were obtained.\u003c/p\u003e\u003cp\u003eWe also measured the following nutritional and immunologic parameters on the first day after discharge (defined as \u0026ldquo;baseline\u0026rdquo;), the day that patients started to take the IMPACT Oral\u0026reg; treatment, and the 30th day (defined as \u0026ldquo;endline\u0026rdquo;) after first intake: BMI, PG-SGA, TFN, ALB, PA, GLU, LAV, CRP, IgG, IgM, and IgA.\u003c/p\u003e\u003cp\u003eThe incidence of postoperative complications, ranging from baseline to endline, was meticulously documented, encompassing a spectrum of adverse events such as surgical site infections, abdominal abscess, anastomotic fistula and intestinal obstruction. Complications were defined as any deviation from the normal postoperative course and were divided into minor and major complications[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Minor complications, which could include events such as bedside wound infections, urinary tract infections, or postoperative ileus, are classified as Clavien\u0026ndash;Dindo I\u0026ndash;II. Major complications include life-threatening events and those necessitating surgical or endoscopic intervention or radiological intervention, such as anastomotic fistula, abdominal abscess, and pneumonia and are classified as Clavien\u0026ndash;Dindo III\u0026ndash;IV.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analyses\u003c/h2\u003e\u003cp\u003eThe statistical analyses were conducted using SPSS 27.0 version for Windows (SPSS Inc., Chicago, IL, United States). The measurement data are presented as the means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations (\u0026oline;x\u0026thinsp;\u0026plusmn;\u0026thinsp;s) and were analysed by Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e test. The data are presented as percentages, and comparisons between the IMN and SN groups were conducted using the chi-square (χ\u003csup\u003e2\u003c/sup\u003e) test. A p value less than 0.05 is typically regarded as indicating a statistically significant difference, as it suggests that the observed result is unlikely to have occurred by chance alone.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBetween April 2023 and February 2024, the study enrolled 511 patients and randomly allocated them into two groups (339 in the IMN group and 172 in the SN group) at the main centre. Thirty-five patients were excluded because they did not progress to surgery and did not meet the inclusion criteria, and forty-five patients were lost to follow-up. Consequently,\u0026nbsp;416 patients were included in the definitive interim analysis: 279 in the IMN group and 137 in the SN group. The patient flow chart depicted in Fig. 1 outlines the detailed steps involved in the patient therapy process.\u003c/p\u003e\n\u003cp\u003eFig. 1\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFlowchart of the study population selection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDemographic Data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs listed in Table 1, the \u003cem\u003et\u003c/em\u003e test revealed that the demographics of the patients in the IMN group were similar to those in the SN group, and no significant differences were found between the two groups in terms of sex (P=0.191), age (P=0.590), BMI (P=0.665), ASA score (P=1.131), major comorbidities (P=0.068) or tumour site (P=3.179). Furthermore, the overall difference in TNM stage between the IMN and SN groups was not significant (P=2.852). Finally, no significant differences in previous abdominal surgery status, neoadjuvant chemotherapy status, or MMR expression were detected between the two groups (P\u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003eTable 1. Demographics and disease-related data for each cohort\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"559\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIMN (n=279)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSN (n=137)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP-value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 140px;\"\u003e\n \u003cp\u003eGender, n (%) \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.191\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e171（61.3%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e87（63.5%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e108（38.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e50（36.5%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003eAge, mean (SD), year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e59.66\u0026plusmn;9.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e57.71\u0026plusmn;10.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.590\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e24.27\u0026plusmn;4.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e24.10\u0026plusmn;3.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.665\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 140px;\"\u003e\n \u003cp\u003eASA score, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e1.131\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e34（12.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e14（10.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e180（64.5%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e90（65.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e59（21.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e28（20.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e6（2.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e5（3.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 140px;\"\u003e\n \u003cp\u003eMorbidity, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.068\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e37（13.3%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e13(9.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e88（31.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e32(23.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003eHeart disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e8(2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e3(2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003eRespiratory disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e8(2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e5(3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Urological diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e3(1.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e2(1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Liver disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e16(5.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e6(4.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e41(14.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e24(17.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 140px;\"\u003e\n \u003cp\u003eTumor site, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e3.179\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Rectum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e165（59.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e90（65.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Sigmoid colon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e54（19.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e20（14.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003eDescending colon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e7（2.5%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e2（1.5%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Transverse colon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e11（3.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e3（2.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Ascending colon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e42（15.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e22（16.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 140px;\"\u003e\n \u003cp\u003eTNM stage, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e2.852\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Carcinoma in situ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e14（5.0%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e8（5.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Stage I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e42（15.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e29（21.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Stage II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e95（34.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e42（30.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003eStage III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e117（41.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e52（38%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003eStage IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e11（3.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e6（4.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 140px;\"\u003e\n \u003cp\u003ePrevious abdominal surgery, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.216\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e71（25.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e32（23.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e208（74.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e105（76.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 140px;\"\u003e\n \u003cp\u003eNeoadjuvant chemotherapy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.822\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e45（16.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e27（19.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e234（83.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e110（80.3%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 140px;\"\u003e\n \u003cp\u003eMMR expression, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.069\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; dMMR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e16（5.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e7（5.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp; pMMR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e263（94.3%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 140px;\"\u003e\n \u003cp\u003e130（94.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNotes:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u0026nbsp;\u003c/strong\u003eBMI, body mass index; ASA, American Society of Anesthesiology;\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eMMR, mismatch repair;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNutritional Parameters\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe nutritional parameters of the patients were analysed and are listed in detail in Table 2. No significant differences in BMI (P=0.665), PG-SGA (P=0.235), TFN (P=0.057), ALB (P=0.063), PA (P=0.090) or GLU (P=0.873) were detected between the two groups prior to the intervention. After the intervention, the BMI, TFN, PA and GLU in the two groups did not differ (P\u0026gt;0.05). However, as shown in Fig. 2, after the intervention, the PG-SGA scores and serum ALB concentrations significantly differed between the two groups (P\u0026lt;0.05), indicating that both the subjective overall assessment and objective nutritional index were significantly improved after oral IMN.\u003c/p\u003e\n\u003cp\u003eTable 2. Comparison of nutritional parameters（`x\u0026plusmn;s）\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"560\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIMN (n=279)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSN (n=137)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003et-value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP-value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 133px;\"\u003e\n \u003cp\u003eBMI(kg/m2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e22.98\u0026plusmn;3.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e22.77\u0026plusmn;3.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.434\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.665\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003eendline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e23.45\u0026plusmn;3.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e23.39\u0026plusmn;3.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.891\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 133px;\"\u003e\n \u003cp\u003ePG-SGA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e4.99\u0026plusmn;2.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e5.43\u0026plusmn;2.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e-1.193\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.235\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003eendline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e2.66\u0026plusmn;2.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e3.26\u0026plusmn;2.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e-2.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 133px;\"\u003e\n \u003cp\u003eTFN(mg/dL）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e190.26\u0026plusmn;36.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e198.71\u0026plusmn;42.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e-1.911\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003eendline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e259.89\u0026plusmn;65.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e262.99\u0026plusmn;66.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e-0.271\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.787\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 133px;\"\u003e\n \u003cp\u003eALB(g/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e35.38\u0026plusmn;5.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e34.46\u0026plusmn;43.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e1.867\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.063\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003eendline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e43.11\u0026plusmn;3.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e42.01\u0026plusmn;4.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e2.552\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 133px;\"\u003e\n \u003cp\u003ePA(g/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e16.70\u0026plusmn;3.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e17.78\u0026plusmn;6.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e-1.704\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.090\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003eendline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e27.27\u0026plusmn;5.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e27.46\u0026plusmn;5.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e-0.228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.820\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 133px;\"\u003e\n \u003cp\u003eGLU(mmol/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e6.18\u0026plusmn;1.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e6.21\u0026plusmn;1.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e-0.160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.873\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003eendline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e5.88\u0026plusmn;1.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e6.04\u0026plusmn;1.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e-0.689\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e0.491\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNotes:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u0026nbsp;\u003c/strong\u003eBMI, body mass index; PG-SGA, patient-generated subjective global assessment; TFN, transferrin; ALB, albumin; PA, prealbumin; GLU, glucose;\u003c/p\u003e\n\u003cp\u003eFig. 2\u003c/p\u003e\n\u003cp\u003eAfter the intervention, the PG-SGA scores and serum ALB concentrations significantly differed between the two groups (P\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImmunologic Parameters\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe immunologic parameters of the patients were analysed and are listed in detail in Table 3. Prior to the intervention, some immunologic parameters in the IMN group, such as LAV, IgG, and IgM, were similar to those in the SN group (P\u0026gt;0.05). Furthermore, compared with those in the SN group, LAV, IgG, and IgM were significantly increased in the IMN group after the intervention (P\u0026lt;0.05), as shown in Fig. 3. In contrast, the CRP and IgA levels did not significantly differ either before or after the intervention (P\u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003eTable 3. Comparison of immunologic parameters（`x\u0026plusmn;s）\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"555\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIMN (n=279)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSN (n=137)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003et-value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP-value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 129px;\"\u003e\n \u003cp\u003eLAV(\u0026times;10^9/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e1.23\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e1.21\u0026plusmn;1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e0.380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.704\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003eendline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e1.82\u0026plusmn;0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e1.68\u0026plusmn;0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e2.020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.044\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 129px;\"\u003e\n \u003cp\u003eCRP(mg/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e5.91\u0026plusmn;4.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e5.44\u0026plusmn;4.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e0.949\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.343\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003eendline\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e1.28\u0026plusmn;4.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e0.74\u0026plusmn;1.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e0.877\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.382\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 129px;\"\u003e\n \u003cp\u003eIgG (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e8.92\u0026plusmn;1.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e9.35\u0026plusmn;2.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-1.764\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003eendline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e14.11\u0026plusmn;3.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e12.97\u0026plusmn;2.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e2.152\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 129px;\"\u003e\n \u003cp\u003eIgM (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e0.83\u0026plusmn;0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e0.84\u0026plusmn;0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.320\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.749\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003eendline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e1.33\u0026plusmn;0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e1.14\u0026plusmn;0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e2.040\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 129px;\"\u003e\n \u003cp\u003eIgA (g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003ebaseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e2.24\u0026plusmn;1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e2.24\u0026plusmn;0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e-0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.972\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003eendline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003e2.91\u0026plusmn;1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e2.89\u0026plusmn;0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.909\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNotes:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e LAV, lymphocyte absolute value; CRP, c-reactive protein; IgG, immunoglobulin G;\u003c/p\u003e\n\u003cp\u003eFig. 3\u003c/p\u003e\n\u003cp\u003eCompared with those in the SN group, LAV, IgG, and IgM were significantly increased in the IMN group after the intervention (P\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePostoperative Complications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe surgical complications of the patients were analysed and are listed in detail in Table 4. Although the total incidence of complications in the IMN group was significantly lower than that in the SN group (15.1% vs. 18.2%), the difference between the two groups was not statistically significant (P=0.405). Upon classification and comparison, the incidence of postoperative infectious or non-infectious complications in the IMN group did not significantly decrease compared with the control group (P\u0026gt;0.05). Even in the comparison of each individual complication rate, there were no significant differences between the two groups, such as respiratory tract infection (P=0.195), wound infection (P=0.605), urinary tract infection (P=0.734), intra-abdominal infection (P=0.458), anastomotic fistula (P=0.976), bleeding (P=0.735), intestinal obstruction (P=0.734) and wound dehiscence (P=0.804)\u003c/p\u003e\n\u003cp\u003eTable 4.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eDetail of postoperative complications and outcomes\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"570\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIMN (n=279)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSN (n=137)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP-value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003eInfectious complications, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e23（8.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e16（11.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.259\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003e\u0026nbsp; Respiratory tract\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2（0.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3（2.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.195\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003eWound infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e13（4.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e8（5.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.605\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003eUrinary tract\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3（1.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1（0.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.734\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003eIntra-abdominal infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e5（1.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4（2.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.458\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003eNoninfectious complications, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e19（6.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e9（6.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.927\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003eAnastomotic fistula\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e8（2.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4（2.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.976\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003eBleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3（1.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2（1.5%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.735\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003eIntestinal obstruction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3（1.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1（0.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.734\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003eWound dehiscence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e5（1.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2（1.5%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.804\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 279px;\"\u003e\n \u003cp\u003eTotal complication, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e42（15.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e25（18.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0.405\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eMalnutrition is a prevalent yet frequently underestimated issue among patients with digestive cancers[3]. Research has indicated that the incidence of nutritional risk and malnutrition in patients with gastrointestinal cancer can reach 84.3–90.0%, with malnutrition affecting 45–60% of patients with CRC, a rate that significantly increases after radical surgery[17,18]. Severe malnutrition significantly increases the risk of postoperative complications and mortality in patients with CRC. Studies have shown that patients with severe malnutrition have a mortality risk that is 2–5 times greater than that of patients with good nutritional status, and up to 20% of patients with CRC die directly from malnutrition rather than the cancer itself[5-7]. It also leads to extended hospital stays and heightened economic burdens. Therefore, nutritional therapy has become an important part of multidisciplinary comprehensive treatment for CRC. Standardized nutritional therapy has been shown to significantly increase the quality of life and prognosis for patients with cancer, as evidenced by studies indicating that targeted nutritional interventions can reduce complications, improve survival rates, and maintain body functions[19, 20].\u003c/p\u003e\n\u003cp\u003eThe PG-SGA is a crucial instrument for evaluating the nutritional status of patients with cancer and integrates patient self-assessment with clinical observation to assess indicators such as weight changes, dietary intake, symptoms, activity levels, and physical condition. Based on the stratified results of the assessment, personalized nutritional therapy plans are developed for patients with cancer, thereby improving treatment outcomes and quality of life. A Brazilian study examined the correlation between PG-SGA scores and survival outcomes in 250 older patients with CRC. Individuals with severe malnutrition, classified as PG-SGA Class C, exhibited a significantly increased risk of mortality than those with a better nutritional status, classified as PG-SGA Class A[21]. In our study, the PG-SGA scores of patients in the IMN group were significantly lower than those of the control group after the intervention. These findings suggest that prolonged oral intake of IMN following surgery can decrease the incidence of malnutrition. Furthermore, serum albumin is among the primary indicators used to assess the nutritional status of patients with CRC after surgery. A retrospective analysis was conducted by the American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIPP). The study, which involved 30,676 patients who underwent CRC surgery, investigated the correlation between mild hypoalbuminaemia and postoperative complications and mortality and revealed that hypoalbuminaemia could significantly impact patient outcomes and survival rates. The results indicated that among the 30,676 patients with CRC, 5,230 had mild hypoproteinaemia (with levels less than 35 and greater than or equal to 30 g/l). Postoperative mortality was significantly associated with mild hypoproteinaemia after a 1:2 matching with patients who had normal albumin levels (≥35 g/l) (P\u0026lt;0.001). Additionally, mild hypoproteinaemia was significantly correlated with 11 postoperative complications, including deep vein thrombosis, pulmonary embolism, superficial and deep surgical site infections, pneumonia, septic shock, ventilation for more than 48 hours, blood transfusion, return to the operating room, stroke, and reintubation. Mild hypoalbuminaemia was also linked to an increased risk of overall complications (P\u0026lt;0.001) and longer total hospital stays (P\u0026lt;0.001). In conclusion, a slight decrease in serum albumin levels has been identified as a significant predictor of poor prognosis in patients undergoing surgery[22]. Our trial revealed that, after intervention, compared with those in the control group, the serum ALB concentration in the IMN group increased significantly (P\u0026lt;0.05). These findings suggest that long-term oral IMN following radical surgery in patients with CRC can significantly increase nutritional status, mitigate the risk of malnutrition and improve prognosis.\u003c/p\u003e\n\u003cp\u003eAlthough early nutritional support has shown certain benefits postoperatively for patients with CRC and has been acknowledged by many physicians, there is limited improvement in postoperative immune function. With respect to continuous research and exploration, scholars have reported that the addition of certain special nutrients to standard EN formulas can achieve the desired effects. EN formulas containing these special nutrients can stimulate the body to maintain a moderate immune response state, regulate immune molecule responses, and control inflammatory responses to some extent, further enhancing the immune response function of the body and preserving the original physiological barrier function of the intestine. Currently, the special nutrients, widely known as IMN when clinically applied, mainly include omega-3 fatty acids, glutamine, arginine, dietary fibre, nucleosides, and RNA. Omega-3 fatty acids are essential polyunsaturated fatty acids that primarily consist of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which serve as critical nutrients for immune modulation. EPA and DHA, which are specific types of fatty acids, increase cell membrane fluidity, facilitate messenger transmission and receptor function on the cell membrane, decrease the production of inflammatory mediators, improve the body’s cellular immune response, and mitigate inflammation. Additionally, they exhibit biological effects such as inhibiting cancer cell proliferation, reducing tumour burden, and minimizing nutrient consumption[19-21]. Glutamine, the most abundant free amino acid in the body, is crucial for maintaining the integrity of the intestinal barrier and promoting the growth and differentiation of intestinal cells. It also plays a pivotal role in enhancing the immune responsiveness of lymphocytes and mononuclear macrophages, thereby supporting the body's defence mechanisms[8]. Arginine, as the sole substrate for nitric oxide (NO) synthesis, plays a crucial role in innate antimicrobial immunity, which is essential for the host’s first line of defence[23]. Arginine not only supports cardiovascular health by promoting vasodilation and improving blood flow but also contributes to immune regulation and cellular growth, as evidenced by its extensive use in biomedical research and applications. It also plays important roles in maintaining the physiological balance of the gastrointestinal tract and regulating the metabolism of many types of lymphocytes[24,25]. Moreover, an RNA supply is necessary to prevent T-lymphocytes from decreasing in number and to increase IL-2 levels and the CD4/CD8 ratio[12,26-28].\u003c/p\u003e\n\u003cp\u003eMany clinical and experimental studies have demonstrated the effectiveness of IMN, with the specific components mentioned above, in reinforcing the body’s cellular and humoral immunity. A meta-analysis conducted by Yue T et al.[29], which included 20 studies and 1,613 patients, revealed that omega-3 fatty acids significantly increased humoral immune function indices, such as IgA (standardized mean difference (SMD) = 0.54, 95% CI 0.10–0.99), IgM (SMD = 0.52, 95% CI 0.05–0.99), and IgG (SMD = 0.65, 95% CI 0.47–0.84), as well as T-cell immune function indices, including CD3+ (SMD = 0.73, 95% CI 0.54–0.92), CD4+ (SMD = 0.76, 95% CI 0.53–0.98), and the ratio of CD4+/CD8+ (SMD = 0.66, 95% CI 0.39–0.92). Xu J et al.[14] randomly divided sixty patients with gastrointestinal cancer into 2 groups, each of which was fed IMN or a conventional diet for 7 days before surgical procedures. Postoperative IgG levels were higher in the IMN group than in the control group. Huang Z et al.[30] conducted a retrospective study on 102 patients who underwent gastrointestinal surgery, including 52 patients who received an IMN diet and 50 patients who received a conventional nutrition diet during the perioperative period. Compared with control patients, patients fed the IMN diet exhibited notably elevated levels of IgA, IgG, IgM, complement C3, and complement C4 on both the 1\u003csup\u003est\u003c/sup\u003e and 7\u003csup\u003eth\u003c/sup\u003e days post-operation (P\u0026lt;0.05). Our study further revealed that, after continuous oral IMN starting on the day of discharge from the hospital, significant improvements in LAV, IgG, and IgM levels were observed compared with those in the control group (P\u0026lt;0.05). The results indicated that the continuous use of IMN after surgery could enhance cellular and humoral immunity in the long term.\u003c/p\u003e\n\u003cp\u003eCan long-term enhancement of the postoperative immune response and control of the inflammatory response benefit patients, thereby improving their prognosis? The answer is yes. It is widely recognized that lymphocytes are crucial components of the human immune system. When lymphocytes detect potential pathogens introduced via surgical trauma, they activate the body’s immune response and proliferate extensively to eliminate these pathogens, consequently reducing the risk of infection and facilitating recovery and wound healing. In addition, clinically, the key indicators for evaluating the body’s humoral immune status are primarily the immunoglobulins IgA, IgM, and IgG. Immunoglobulins are a unique category of proteins with antibody activity found in human serum and bodily fluids that possess antibacterial and antiviral properties and enhance the phagocytic capabilities of cells. They can also, with the aid of complement, neutralize and breakdown pathogenic microorganisms, playing a vital role in the body’s humoral immunity. IgG is particularly involved in antibacterial, antiviral, and antitoxic activities and contributes significantly to immune processes. The gastrointestinal tract is the primary site for the synthesis and secretion of IgA, an essential antibody in the immune response of the gastrointestinal mucosa. IgM antibodies are characterized by their high efficiency and potent bactericidal effects, especially against gram-negative bacteria such as \u003cem\u003eEscherichia coli\u003c/em\u003e, and are the first to be produced during the humoral immune response to pathogens that grow and replicate in the body, leading to infections[31]. In our study, although IgA did not significantly increase compared with that in the control group, the long-term use of IMN in the IMN group led to increased components of cellular immunity (LAV) and humoral immunity (IgG and IgM). Although, as mentioned above, the immunologic parameters in the IMN group significantly increased compared to those in the control group after the intervention, it might be due to the insufficient sample size that this study failed to prove that continuous oral IMN after discharge could significantly reduce the incidence of postoperative infectious complications compared with the control group.\u003c/p\u003e\n\u003cp\u003eHowever, this study has limitations. First, the scope of our investigation was limited because the sample size was inadequate to derive definitive conclusions. Second, with respect to the cellular immune response, our analysis was restricted to the absolute lymphocyte count; specific lymphocyte subsets were not examined. Other immune cells, including T cells, B cells, NK cells, and macrophages, were neither observed nor subjected to analysis. Third, our research focused on the influence of long-term postoperative IMN on the short-term prognosis of individuals diagnosed with CRC. There is a scarcity of observational studies that assess the effect of long-term postoperative IMN on the survival of such patients. We need to complete the data entry for the remaining 34 centres to increase the sample size. Ultimately, this comprehensive study will encompass observations on not only the effect of long-term postoperative IMN on the short-term prognosis of patients with CRC but also its impact on their continued survival.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAn interim analysis revealed that long-term oral IMN postoperation, which includes specific components such as omega-3 fatty acids, glutamine, arginine, and RNA, can lead to an improvement in nutritional status and enhance the immune response in patients with CRC after discharge. Although it is necessary to conduct further studies involving more centres and larger sample sizes to substantiate the effect of sustained oral IMN on long-term survival, it is evident that such nutritional intervention can improve the nutritional status, enhance the immune response and improve the short-term prognosis of patients with CRC.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval\u003c/p\u003e\n\u003cp\u003eThe study was successfully approved by the Ethics Committee of National Cancer Center/ Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College. We solemnly declare that the entire study process was carried out in strict compliance with the relevant guidelines and regulations. All participants and/or their legal guardians have signed the informed consent form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eThe study design and conceptualization were carried out by Mandula Bao, Fei Huang, Qian Liu, Zhaoxu Zheng; data collection was carried out by Mandula Bao, Shaomu Cao, Fei Huang, Zhexue Wang, Pu Cheng; analyses were carried out by Mandula Bao, Zhexue Wang, Pu Cheng; and the interpretation, drafting, and revising of the manuscript were done by Mandula Bao, Zhexue Wang, Pu Cheng. All authors approved the final version of the manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eThe authors are thankful to all the patients that participated in the present study.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eSome, if not all, of the data utilized in the research process can be obtained from the corresponding data resources of the corresponding authors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBray F, Laversanne M, Sung H et al (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74(3):229\u0026ndash;263\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHan B, Zheng R, Zeng H et al (2024) Cancer incidence and mortality in China, 2022. J Natl Cancer Cent 4(1):47\u0026ndash;53\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHu WH, Cajas-Monson LC, Eisenstein S et al (2015) Preoperative malnutrition assessments as predictors of postoperative mortality and morbidity in colorectal cancer: an analysis of ACS-NSQIP. Nutr J 14:91\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSong C, Cao J, Zhang F et al (2019) Nutritional Risk Assessment by Scored Patient-Generated Subjective Global Assessment Associated with Demographic Characteristics in 23,904 Common Malignant Tumors Patients. Nutr Cancer 71(1):50\u0026ndash;60\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen Y, Liu BL, Shang B et al (2011) Nutrition support in surgical patients with colorectal cancer. World J Gastroenterol 7(13):1779\u0026ndash;1786\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDobrila-Dintinjana R, Trivanovic D, Zelić M et al (2013) Nutritional support in patients with colorectal cancer during chemotherapy: does it work? Hepatogastroenterology 60(123):475\u0026ndash;480\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarret M, Malka D, Aparicio T et al (2011) Nutritional status affects treatment tolerability and survival in metastatic colorectal cancer patients: results of an AGEO prospective multicenter study. Oncology 81(5\u0026ndash;6):395\u0026ndash;402\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDaly JM, Lieberman MD, Goldfine J et al (1992) Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome. Surgery 112(1):56\u0026ndash;67\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMoore FA, Feliciano DV, Andrassy RJ et al (1992) Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a meta-analysis. Ann Surg 216(2):172\u0026ndash;183\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGianotti L, Braga M, Nespoli L et al (2002) A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology 122(7):1763\u0026ndash;1770\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGrimble RF (2001) Nutritional modulation of immune function. Proc Nutr Soc 60(3):389\u0026ndash;397\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCalder PC (2003) Immunonutrition BMJ 327(7407):117\u0026ndash;118\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUno H, Furukawa K, Suzuki D et al (2016) Immunonutrition suppresses acute inflammatory responses through modulation of resolvin E1 in patients undergoing major hepatobiliary resection. Surgery 160(1):228\u0026ndash;236\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXu J, Zhong Y, Jing D et al (2006) Preoperative enteral immunonutrition improves postoperative outcome in patients with gastrointestinal cancer. World J Surg 30(7):1284\u0026ndash;1289\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFinco C, Magnanini P, Sarzo G et al (2007) Prospective randomized study on perioperative enteral immunonutrition in laparoscopic colorectal surgery. Surg Endosc 21(7):1175\u0026ndash;1179\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eClavien PA, Barkun J, de Oliveira ML et al (2009) The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 250(2):187\u0026ndash;196\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGyan E, Raynard B, Durand JP et al (2018) NutriCancer2012 Investigator Group. Malnutrition in Patients With Cancer: Comparison of Perceptions by Patients, Relatives, and Physicians-Results of the NutriCancer2012 Study. JPEN J Parenter Enter Nutr 42(1):255\u0026ndash;260\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHiramatsu K, Shindoh J, Hanaoka Y et al (2021) Postoperative Nutritional Status is Predictive of the Survival Outcomes in Patients Undergoing Resection of Stage III Colorectal Cancer. 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Front Nutr 9:945590\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHuang Z, Wang Y (2022) Perioperative enteral immunonutrition with probiotics favors the nutritional, inflammatory, and functional statuses in digestive system surgery. Asia Pac J Clin Nutr 31(1):78\u0026ndash;86\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLohse S, Derer S, Beyer T et al (2011) Recombinant dimeric IgA antibodies against the epidermal growth factor receptor mediate effective tumor cell killing. J Immunol 186(6):3770\u0026ndash;3778\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Colorectal cancer, Immunonutrition, Postoperative intervention, Postoperative complications","lastPublishedDoi":"10.21203/rs.3.rs-7917373/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7917373/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eEnteral nutrition (EN) can prevent and treat postoperative malnutrition in patients with malignant tumors, thereby improving their short-term postoperative prognosis. However, there is currently a lack of long-term observational data on the impact of immunonutrition (IMN) on the immunotrophic status of patients with colorectal cancer (CRC) after discharge.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis was a multicentre, randomized, controlled noninferiority trial with two parallel intervention arms for patients with CRC (ChiCTR2300071078). Patients were included as study participants after screening. They were randomly assigned to receive an immunomodulatory oral formula (IMN group) or a standard nutritional oral formula (SN group). The ratio of the number of enrolled patients in the IMN and SN groups was 2:1. After the intervention, changes in nutritional and immunologic parameters, such as body mass index (BMI), patient-generated subjective global assessment (PG-SGA), transferrin (TFN), albumin (ALB), prealbumin (PA), glucose (GLU), lymphocyte absolute value (LAV), C-reactive protein (CRP), immunoglobulin G (IgG), IgM, and IgA, were the primary endpoints of the study. The secondary end points were the postoperative complications, including total, infectious and noninfectious complications.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eInterim data analysis is presented in this report. There were 416 patients enrolled from the main centre. Of these, 279 patients were in the IMN group, and 137 patients were in the control group. The patients in the two groups had similar demographics. With respect to nutritional parameters, after the intervention, the PG-SGA and serum ALB significantly differed between the two groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Moreover, compared with those in the control group, the LAV, IgG, and IgM in the IMN group were significantly increased after the intervention. Finally, although the incidence of postoperative infectious complications in the IMN group was lower than that in the SN group, there was no significant difference in the rate of postoperative total, infectious, or noninfectious complications between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003e Interim data show that long-term, continuous oral IMN after discharge can improve the nutritional status, enhance the immune response, and reduce the incidence of postoperative infectious complications in patients with CRC who have undergone radical surgery.\u003c/p\u003e","manuscriptTitle":"A Randomized Trial of Long-term Immunonutrition Oral Supplements Versus Standard Nutrition in Patients who Underwent Colorectal Cancer Surgery after Discharge: Interim Analysis of a Nationwide Multicentre Study in China","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-18 08:27:38","doi":"10.21203/rs.3.rs-7917373/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"99eec0ac-4599-4f4d-9450-d5134111efe9","owner":[],"postedDate":"November 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-27T17:39:51+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-18 08:27:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7917373","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7917373","identity":"rs-7917373","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}