The metabolite butyrate produced by gut microbiota inhibits cachexia-associated skeletal muscle atrophy by regulating intestinal barrier function and macrophage polarization.

OBJECTIVE: Cachexia, marked by muscle atrophy, poses substantial challenges for prevention and treatment. This study delves into the unclear role of butyrate, a gut microbiota metabolite, in cachexia by examining gut microbiota and short-chain fatty acid (SCFA) profiles in human and mouse fecal samples. METHODS: We analyzed cachexia-associated gut microbiota and SCFA profiles using 16S rRNA sequencing and metabolomic techniques. Mouse cachexia models were developed with C26 cells, and LPS was used to induce muscle cell atrophy in C2C12 cells. We evaluated butyrate's in vivo effects on intestinal health, muscle preservation, inflammation, and macrophage activity. In vitro studies focused on butyrate's influence on macrophage polarization and the subsequent effects on muscle cells. RESULTS: Both cachexia patients and mice exhibited gut microbiota imbalances, irregular butyrate concentrations, and a decline in butyrate-producing bacteria. In vivo tests showed that butyrate counteract cachexia-induced muscle atrophy by adjusting the Akt/mTOR/Foxo3a and Fbox32/Trim63 pathways. These butyrate also bolstered intestinal barrier integrity, minimized endotoxin migration, and mitigated oxidative stress. Furthermore, butyrate curtailed inflammation and macrophage penetration in muscles. In vitro experimental results demonstrate that butyrate inhibit macrophage polarization towards the M1 phenotype and promote polarization towards the M2 phenotype. Both M1 and M2 macrophages influence the aforementioned pathways and oxidative stress, participating in the regulation of muscle cell atrophy. CONCLUSION: Our study delineates the intricate interplay between gut microbiota dysbiosis, butyrate fluctuations, and cachexia progression. Butyrate not only reinforces the intestinal barrier but also orchestrates macrophage polarization, mitigating muscle atrophy and averting cachexia-induced muscle deterioration. Concurrently, the M1 and M2 macrophages play pivotal roles in modulating skeletal muscle cell atrophy. This highlights the potential of utilizing the gut-derived metabolite butyrate as a promising therapeutic approach for addressing cachexia-related issues.

Sarcopenia and myosteatosis diagnostic tool for gastrointestinal cancer: creatinine to cystatin C ratio as evaluation marker.

OBJECTIVE: This study aimed to develop a simplified diagnostic tool for assessing sarcopenia and myosteatosis in gastrointestinal cancer patients, focusing on the creatinine to cystatin C ratio (CCR) as an evaluation marker. METHODS: 955 patients were split into training (n = 671) and validation (n = 284) cohorts. Using logistic regression, risk factors for sarcopenia and myosteatosis were identified. The predictive capacity of the developed model was examined. The association between CCR and muscle imaging parameters, along with its impact on clinical outcomes, was analyzed. RESULTS: No significant differences were observed in baseline traits between cohorts. CCR emerged as a significant risk factor for both sarcopenia and myosteatosis. Nomograms for diagnosing these conditions demonstrated strong predictive ability, with AUC values indicating high accuracy (sarcopenia AUC: 0.865-0.872; myosteatosis AUC: 0.848-0.849). The clinical utility of the nomograms was confirmed through decision curve analysis. CCR showed significant association with muscle imaging parameters and was a reliable indicator for assessing the risk of sarcopenia, myosteatosis, and cachexia. Moreover, CCR was able to differentiate between patient survival and disease progression rates. CONCLUSION: A diagnostic tool for sarcopenia and myosteatosis in gastrointestinal cancer patients was developed, with CCR being a pivotal biomarker for disease diagnosis and prognosis prediction.

Mitophagy-mediated inflammation and oxidative stress contribute to muscle wasting in cancer cachexia.

Cancer cachexia is commonly seen in patients with malignant tumors, which usually leads to poor life quality and negatively affects long-term prognosis and survival. Mitochondria dysfunction and enhanced autophagy are well-established to play an important role in skeletal muscle wasting. However, whether mitophagy is engaged in the pathogenesis of cancer cachexia requires further investigation. This study comprised a clinical study and animal experimentation. Clinical data such as CT images and laboratory results were obtained and analyzed. Then mice model of cancer cachexia and mitophagy inhibition were established. Data including skeletal muscle mass and function, mitochondria structure and function, inflammatory factors as well as ROS concentration. Mitophagy was enhanced in cancer cachexia patients with increased inflammatory factors. Greater disruption of skeletal muscle fiber and mitochondria structure were seen in cancer cachexia, with a higher level of inflammatory factors and ROS expression in skeletal muscle. Meanwhile, ATP production was undermined, indicating a close relationship with mitophagy, inflammation, and oxidative stress in the skeletal muscle of cancer cachexia mice models. In conclusion, mitophagy is activated in cancer cachexia and may play a role in skeletal muscle atrophy, and inflammation and oxidative stress might participate in mitophagy-related skeletal muscle injury.

Evaluation and management of body composition changes in cancer patients.

Wasting in cancer patients has long been recognized as a condition that adversely affects cancer patients' quality of life, treatment tolerance, and oncological outcomes. Historically, this condition was mainly evaluated by changes in body weight. However, this approach is not quite accurate because body weight is the overall change of all body compartments. Conditions such as edema and ascites can mask the severity of muscle and adipose tissue depletion. Changes in body composition assessment in cancer patients have historically been underappreciated because of the limited availability of measurement tools. As more evidence highlighting the importance of body composition has emerged, it is imperative to apply a more precise evaluation of nutritional status and a more targeted approach to provide nutritional support for cancer patients. In this review, we will discuss the modalities for evaluating body composition and how to manage body composition changes in cancer patients.

Development and application of the Cancer Cachexia Staging Index for the diagnosis and staging of cancer cachexia.

OBJECTIVE: The current tools for evaluating cancer cachexia are either too simple to reflect the far-reaching effects of cachexia or too complicated to be used in daily practice. This study aimed to develop a cancer cachexia staging index (CCSI) that is both practical and comprehensive. METHODS: Patients with gastrointestinal cancers were prospectively included in the study. Clinical data including weight change, body composition, systematic inflammation, nutrition, and function status were entered into regression models to determine the best variable combination as well as their respective cutoff values and score distribution in the CCSI. The CCSI's ability to predict outcomes and evaluate the consequences of cachexia for patients were then assessed. RESULTS: Clinical information and test results from 10 568 patients were used to develop a CCSI composed of subjective and objective measures. Subjective measures included body mass index-adjusted weight loss grade, rate of weight loss, inflammation (neutrophil-to-lymphocyte ratio and C-reactive protein level), and prealbumin level. Objective measures included appetite status and physical status. Patients were diagnosed and stratified by the total CCSI score into 3 subgroups: no cachexia, mild or moderate cachexia, and severe cachexia. The CCSI grades showed good survival discrimination and were independently predictive of survival in multivariate analysis. Compared with the traditional Fearon criteria for diagnosing cancer cachexia, the CCSI was more accurate in predicting postoperative complications (net reclassification index [NRI], 2.8%; 95% CI, 0.0104-0.0456%), death (NRI, 10.68%; 95% CI, 0.0429-0.1708%), recurrence (NRI, 3.71%; 95% CI, 0.0082-0.0685%), and overall survival (NRI, 8.5%; 95% CI, 0.0219-0.1533%). The CCSI also had better discriminative ability than Fearon criteria in discriminating nutritional status, body composition, and systematic inflammation in patients with or without cachexia. A more detailed evaluation of a randomly selected subgroup (n = 1566) showed that CCSI grades had good discrimination of appetite and food intake status, physical function and muscle strength, symptom burden, and quality of life. CONCLUSIONS: The CCSI is a comprehensive and practical evaluation tool for cancer cachexia. It can predict postoperative outcomes and survival. The CCSI stages showed good discrimination when evaluating patients with cancer in terms of nutritional status, physical function, systematic inflammation, body composition, symptom burden, and quality of life.

Association of longitudinal changes in skeletal muscle mass with prognosis and nutritional intake in acutely hospitalized patients with abdominal trauma: a retrospective observational study.

Background: The objective of this study was to explore whether longitudinal changes in skeletal muscle mass, from hospital admission to 3 weeks post-trauma, are associated with poor prognosis and nutritional intake in acutely hospitalized patients with abdominal trauma. Methods: A single-center retrospective observational review was conducted on 103 patients with abdominal trauma admitted to the Affiliated Jinling Hospital, Medical School of Nanjing University between January 2010 and April 2020. Skeletal muscle mass was assessed by abdominal computed tomography (CT) performed within 14 days before surgery and on post-trauma days 1-3 (week 0), 7-10 (week 1), 14-17 (week 2), and 21-24 (week 3). The skeletal muscle index (SMI) at L3, change in SMI per day (ΔSMI/day), and percent change in SMI per day (ΔSMI/day [%]) were calculated. The receiver-operating characteristic (ROC) curve was used to evaluate the discriminatory performance of ΔSMI/day (%) for mortality. Linear correlation analysis was used to evaluate the associations between ΔSMI/day (%) and daily caloric or protein intake. Results: Among the included patients, there were 91 males and 12 females (mean age ± standard deviation 43.74 ± 15.53 years). ΔSMI4-1/d (%) had a ROC-area under the curve of 0.747 (p = 0.048) and a cut-off value of -0.032 for overall mortality. There were significant positive correlations between ΔSMI4-1/d (%) and daily caloric intake and protein intake (Y = 0.0007501*X - 1.397, R2 = 0.282, R = 0.531, p < 0.001; Y = 0.008183*X - 0.9228, R2 = 0.194, R = 0.440, p < 0.001). Δ SMI/day (%) was positively correlated with daily caloric intake ≥80% of resting energy expenditure in weeks 2, 3, and 1-3 post-trauma and with protein intake >1.2 g/kg/d in weeks 3 and 1-3 post-trauma. Conclusion: Loss of skeletal muscle mass is associated with poor prognosis and nutritional intake in patients admitted to hospital with abdominal trauma.

Tumor-derived semaphorin 3D promoting cancer cachexia via regulating hypothalamic pro-opiomelanocortin neurons.

Cachexia is very common in cancer patients and predicts a poor prognosis; however, the molecular basis for progress in these individuals remains unclear, especially the effect of tumors on the hypothalamus energy regulation center. To investigate the regulatory pathway of tumors associated with hypothalamic pro-opiomelanocortin (POMC) neurons known as appetite-inhibiting neurons, we conducted observations both on patients and mice models. Results showed that the highly expressed exocrine semaphorin 3D (SEMA3D) both in cachexia patients and mice was positively related to the expression of POMC and its proteolytic peptide. Compared with the control group, mice inoculated with the SEMA3D-knockout C26 cell line decreased the activity of POMC neurons resulting in a 1.3-fold increase in food intake, a 22.2% increase in body weight, and reduced skeletal muscle and fat catabolism. The effect of SEMA3D on cachexia progression can be partially alleviated by knocking-down POMC expression in the brain. In terms of mechanism, SEMA3D enhances the activity of POMC neurons by activating the expression of NRP2 (membrane receptor) and PlxnD1 (intracellular receptor). Our research revealed the overexpression of SEMA3D in tumors works as an activator of POMC neurons, which may play a vital role in suppressing appetite and promoting catabolic metabolism.

Development and validation of a cancer cachexia risk score for digestive tract cancer patients before abdominal surgery.

BACKGROUND: Cancer cachexia is prevalent in digestive tract cancer patients and has significant impacts on prognosis; it is vital to identify individuals who are at risk of cancer cachexia to allow for appropriate evaluation and treatment. This study evaluated whether digestive tract cancer patients with a risk of cancer cachexia and who had a risk of adverse survival could be identified before abdominal surgery. METHODS: This large-scale cohort study involved patients who underwent abdominal surgery between January 2015 and December 2020 to treat digestive tract cancer. Participants were allocated to the development cohort, the validation cohort, or the application cohort. Univariate and multivariate analyses of the development cohort were performed to detect distinct risk variables for cancer cachexia to create a cancer cachexia risk score. The performance of the risk score across all the three cohorts was assessed through calculating the area under the receiver operating characteristic curve (AUC), as well as calibration and decision curves. We tested how well the score predicted survival outcomes in the application cohort. RESULTS: A total of 16 264 patients (median 64 years of age; 65.9% male) were included, with 8743 in the development cohort, 5828 in the validation cohort, and 1693 in the application cohort. Seven variables were identified as independent predictive factors and were included in the cancer cachexia risk score: cancer site, cancer stage, time from symptom onset to hospitalization, appetite loss, body mass index, skeletal muscle index, and neutrophil-lymphocyte ratio. The risk score predicting cancer cachexia owns a good discrimination, with the mean AUC of 0.760 (P < 0.001) in the development cohort, 0.743 (P < 0.001) in the validation cohort, and 0.751 (P < 0.001) in the application cohort, respectively, and had an excellent calibration (all P > 0.05). The decision curve analysis revealed net benefits of the risk score across a range of risk thresholds in the three cohorts. In the application cohort, compared with the high-risk group, the low-risk group experienced significantly longer overall survival [hazard ratio (HR) 2.887, P < 0.001] as well as relapse-free survival (HR 1.482, P = 0.01). CONCLUSIONS: The cancer cachexia risk score constructed and validated demonstrated good performance in identifying those digestive tract cancer patients before abdominal surgery at a higher risk of cancer cachexia and unfavourable survival. This risk score can help clinicians to enhance their capabilities to screen for cancer cachexia, assess patient prognosis, and strengthen early decision-making on targeted approaches to attune cancer cachexia for digestive tract cancer patients before abdominal surgery.

Loss of body weight and skeletal muscle negatively affect postoperative outcomes after major abdominal surgery in geriatric patients with cancer.

OBJECTIVES: Malnutrition characterized by the involuntary loss of body weight and skeletal muscle can be the result of both aging and malignancy. As a result, geriatric patients could face an increased nutritional risk. This study aimed to investigate the nutritional and functional status of geriatric patients and their association with postoperative complications. METHODS: Patients who underwent abdominal surgery for digestive cancer in our center between January 2020 and August 2021 were included in the study. Computed tomography scans were collected to evaluate muscle mass and density. Changes in body weight, muscle strength, physical performances, nutritional risk, and status were evaluated upon admission. Postoperative outcomes collected included postoperative length of stay, complications, and 30-d readmission. RESULTS: A total of 1513 patients were included for the analysis. Of these, 72.8% were at risk for malnutrition (70.3% in the non-geriatric group and 75.4% in the geriatric group; P = 0.031), and 28.9% had malnutrition according to the Subjective Global Assessment (26.0% in the non-geriatric group and 31.8% in the geriatric group; P = 0.016). Compared with younger patients, geriatric patients have decreased muscle mass (skeletal muscle index, 44.8 versus 47.4; P < 0.001) and skeletal muscle density. Significant weight loss and loss of skeletal muscle occurred concurrently in 18.8% of the patients and were more frequent in the geriatric group (22.3% versus 14.7%; P < 0.001). In multivariate analysis, an age of 65 y or older (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.07-1.86; P = 0.014), a serum albumin level ≤4.11 g/dL (OR, 1.35; 95% CI, 1.03-1.77; P = 0.03), skeletal muscle loss (OR, 1.69; 95% CI, 1.28-2.24; P < 0.001), declined functional status (OR, 1.5; 95% CI, 1.14-1.98; P = 0.004), systematic inflammation (OR, 1.71; 95% CI, 1.09-2.8; P = 0.026), and significant weight loss (OR, 1.4; 95% CI, 1.06-2.85; P = 0.017) were independent predictors of overall postoperative complications. Although there was a trend of interactions between advanced age, skeletal muscle loss, and significant weight loss, multivariate analysis showed none of the interactions were significantly predictive of overall postoperative complications. CONCLUSIONS: Geriatric patients are at greater risk for malnutrition. Their declined nutritional and functional status together with advanced age could increase the risk for postoperative complications. Nutrition evaluation should be part of the preoperative workup, and timely interventions should be initiated if needed, especially in geriatric patients.

Postoperative Loss of Skeletal Muscle Mass Predicts Poor Survival After Gastric Cancer Surgery.

BACKGROUND: Skeletal muscle mass deterioration is common in gastric cancer (GC) patients and is linked to poor prognosis. However, information regarding the effect of skeletal muscle mass changes in the postoperative period is scarce. This study was to investigate the link between postoperative loss of skeletal muscle mass and survival following GC surgery. METHODS: Patients who underwent GC surgery between January 2015 and December 2016 were recruited into the study. Computed tomography at L3 vertebral level was used to examine skeletal muscle index prior to surgery and about 6 months after surgery. Skeletal muscle index changes were categorized as presence or absence of ≥5% loss. Overall survival (OS) and disease-free survival (DFS) were analyzed, and Cox proportional hazard models used to identify their predictors. RESULTS: The study comprised of 318 gastric cancer patients of which 63.5% were male. The group's mean age was 58.14 ± 10.77 years. Sixty-five patients experienced postoperative skeletal muscle index loss ≥5% and had poorer OS (P = 0.004) and DFS (P = 0.020). We find that postoperative skeletal muscle index loss ≥ 5% predicts OS [hazard ratio (HR): 2.769, 95% confidence interval (CI): 1.865-4.111; P < 0.001] and DFS (HR: 2.533, 95% CI: 1.753-3.659; P < 0.001). CONCLUSIONS: Loss of skeletal muscle mass postoperatively is linked to poor survival following GC surgery. Further studies are needed to determine whether stabilizing or enhancing skeletal muscle mass after surgery improves survival.

Validation of GLIM malnutrition criteria in cancer patients undergoing major abdominal surgery: A large-scale prospective study.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) is a new framework to evaluate nutritional status. It has been validated mostly by retrospective studies, which often failed to follow the framework as recommended due to their retrospective nature. This study aims to validate GLIM with a large prospective study and investigate its role in predicting short-term surgical outcomes. METHODS: Patients who underwent abdominal surgery for digestive cancer in our center were prospectively included between January 2020 and December 2020. Data collected included demographic information, clinical and pathological information, lab results, and computed tomography scans. Muscle strength, physical performances, quality of life and cancer symptom burden were evaluated upon admission. Multiple tools for nutritional risk screening were used. Nutritional status was evaluated with Subjective Global Assessment (SGA) and GLIM. Postoperative outcomes collected included return of gastrointestinal function, postoperative length of stay, complications, 30-day readmission and 30-day mortality. RESULTS: A total of 1115 patients were evaluated with GLIM criteria. Inter-rater reliability was good [k = 0.76, 95% confidence interval (CI): 0.72-0.80]. The accuracy of GLIM diagnosis compared to the semi-gold standard SGA varied with the screening method used. GLIM with MNA-SF screening [area under the curve (AUC): 0.78] and GLIM without screening (AUC: 0.77) were the two most accurate protocols, and there was no significant difference between the two from a clinical perspective. GLIM can predict preoperative nutritional status, functional status, symptom burden and quality of life. It can also predict complications after surgery [odds ratio (OR) = 2.31, 95% CI: 1.67-3.21], especially infection related complications (OR = 2.19, 95% CI: 1.38-3.49) and wound healing related complications (OR = 2.54, 95% CI: 1.38-4.71). CONCLUSIONS: GLIM malnutrition criteria showed good inner-rater reliability and moderate agreement with SGA. GLIM can be used to predict preoperative nutritional status, functional status, cancer related symptoms, and quality of life. It can also predict postoperative outcomes especially complications that are related to infection and wound healing. In surgical candidates, the screening process could potentially be skipped so that GLIM assessment can be faster, more accessible, and more sensitive.

Nutrition and exercise prehabilitation in elderly patients undergoing cancer surgery.

Surgical resection is the primary and most effective treatment for cancer patients. While such a traumatic intervention often accompanies different degrees of postoperative risk largely depending on the patient's health status. Due to the high prevalence of malnutrition or low cardiorespiratory fitness in elderly cancer patients, prehabilitation is an optimal program to reduce postoperative complications and enhance recovery from surgical trauma. An increasing body of evidence suggests that improving nutrition and taking aerobic exercise or strength training prior to major surgery can help reduce postoperative morbidity, mortality, or length of stay. However, there are still controversies regarding the manner, intensity, or duration of preoperative nutrition and exercise training in elderly patients, as well as the impact on delaying cancer treatment. This article reviews the impact of prehabilitation on improving postoperative outcomes in the multi-modal or single-modal pathway, aiming to maximize its effectiveness and increase medical practitioners' attention on enhancing the physical condition of the elderly cancer patients preoperatively.

Low skeletal muscle mass predicts poor clinical outcomes in patients with abdominal trauma.

OBJECTIVE: The aim of this study was to investigate whether low skeletal muscle mass is associated with clinical outcomes in patients with abdominal trauma. METHODS: Patients presenting to our institution with abdominal trauma from January 2010 to April 2020 were retrospectively included. Low skeletal muscle mass was defined, using computed tomography, as skeletal muscle index (SMI) at the third lumbar vertebra below the lowest sex-specific quartile within 1 wk of admission. Clinical outcomes such as complications, hospital stay, and hospital cost were recorded, and univariate and multivariate analyses were performed. RESULTS: Among 684 patients, 451 were eligible. Of these, 112 (24.8%) were classified as having low skeletal muscle mass, based on SMI diagnostic cutoff values (42.08 cm2/m2 for men and 37.35 cm2/m2 for women). Low skeletal muscle mass was significantly associated with longer hospital length of stay, longer intensive care length of stay, higher cost, higher frequency of mechanical ventilation, longer duration of vasopressor use, and higher incidence of massive transfusion and overall complications (P < 0.05). Subgroup analysis showed that pneumonia, acute gastrointestinal dysfunction, cholecystitis, digestive tract fistula, gastric fistula, and intestinal fistula were significantly associated with low skeletal muscle mass (P < 0.05). Multivariate analysis showed that low skeletal muscle mass was an independent risk factor for overall complications (odds ratio [OR], 2.44; 95% confidence interval [CI], 1.33-4.49; P = 0.004), hospital length of stay (OR, 3.49; 95% CI, 1.96-6.20; P < 0.001), and hospital cost (OR, 2.67; 95% CI, 1.48-4.80; P = 0.001). CONCLUSIONS: Low skeletal muscle mass could be an independent predictor of poor clinical outcomes in patients with abdominal trauma.

Oral nutritional supplements, physical activity, and sarcopenia in cancer.

PURPOSE OF REVIEW: Sarcopenia is prevalent in cancer patients and can occur as a result of cancer as well as cancer-related therapies. It is related to high postoperative complications, long hospitalization, slow recovery as well as low tolerance to chemotherapy. Patients with sarcopenia also have poor oncological outcomes. Oral nutritional supplements (ONS) and physical activity have shown great potentials in managing this debilitating condition. We summarized the recent developments in the assessment of sarcopenia and its management with ONS and physical activity. RECENT FINDINGS: Many methods were developed to evaluate sarcopenia including muscle quality/quantity measurement and functional tests. Recent studies have shown that ONS and physical training can be used in managing sarcopenia, especially when used together as part of a multimodal intervention. However, barriers such as low awareness and lack of training and support for both patients and healthcare workers still exist and need attention. SUMMARY: Recent findings highlighted the benefits of identifying sarcopenia and managing those at risk. The details of a multimodal protocol, such as components of nutritional substrates, the intensity of physical exercise, and the use of medication need to be further looked into for an optimum approach. Education and training programs need to be developed to overcome the barriers in managing sarcopenia.

Post-discharge oral nutritional supplements with dietary advice in patients at nutritional risk after surgery for gastric cancer: A randomized clinical trial.

BACKGROUND & AIMS: Malnutrition frequently occurs and deteriorates in patients after surgery for gastric cancer, especially after hospital discharge, which has been consistently associated with negative outcomes. However, information regarding the impact of post-discharge nutritional interventions is poorly described. The aim of this study was thus to evaluate the impact of post-discharge oral nutritional supplements (ONS) with dietary advice compared with dietary advice alone on nutritional outcomes, including body mass index (BMI) and skeletal muscle index (SMI), sarcopenia prevalence, chemotherapy tolerance, the 90-day readmission rate, and quality of life in patients at nutritional risk after surgery for gastric cancer. METHODS: Three hundred and fifty-three patients who underwent surgery for gastric cancer and were at nutritional risk (Nutritional Risk Screening 2002 [NRS 2002] score ≥3 points) in our institution were randomly assigned to receive either ONS with dietary advice or dietary advice alone (control) for 3 months after discharge. The primary endpoints were nutritional outcomes and sarcopenia prevalence; the secondary endpoints included chemotherapy tolerance, the 90-day readmission rate, and quality of life. RESULTS: Three hundred and thirty-seven patients completed the study and were included in the analyses, consisting of 171 in the ONS group and 166 in the control group. The average daily intake of ONS in the intervention group was 370 mL. After 3 months of the intervention, the patients who received ONS and dietary advice had significantly less weight loss and higher BMI and SMI than those given dietary advice alone (P < 0.05). The incidence of sarcopenia was significantly lower in the ONS group than in the control group (P < 0.05). Similar number of patients in the two groups underwent postoperative chemotherapy, but the patients who received ONS and dietary advice had significantly less chemotherapy modifications, including delay, dose reduction, or termination (P < 0.05). The two groups had no significant differences in the 90-day readmission rate (P > 0.05). Regarding the quality of life, the patients who received ONS and dietary advice reported significantly less fatigue and appetite loss than those given dietary advice alone (P < 0.05), but the two groups showed no significant differences in the other outcomes (P > 0.05). CONCLUSIONS: Post-discharge ONS with dietary advice in patients at nutritional risk after surgery for gastric cancer improved nutritional outcomes, skeletal muscle maintenance, chemotherapy tolerance and some quality of life variables. These findings strongly support the concept of the introduction of post-discharge ONS with dietary advice to this patient cohort.