Malnutrition indicates chronic nutritional deficiencies in the body caused by insufficient food intake, impaired digestion and absorption, and excessive wastage during the process of ingesting nutrients. It is generally divided into four categories: primary malnutrition (chronic starvation, inadequate intake), secondary malnutrition (significant stress, disease, and excessive nutrient depletion), age-related malnutrition (frailty, sarcopenia), and mixed malnutrition. The risk of malnutrition elucidates the impact of undernutrition on adverse clinical events or outcomes in patients. Huang et al. retrospectively analyzed 597 older adult patients (> 60 years old) who underwent radical gastrectomy for gastric cancer. Approximately, 34.5% of the elderly patients presented postoperative malnutrition [12]. Skeie et al. retrospectively analyzed 6110 patients in Norway's National Gastric Cancer Surgery Registry using Global Leadership Initiative on Malnutrition (GLIM) criteria. They discovered that 35.4% of the patients had postoperative malnutrition, of whom 15.6% were severely malnourished [13]. Thus, the nutritional risk of patients after gastric cancer surgery is high, and they are prone to malnutrition. The reasons stem from two main aspects. The first is the influence of gastric cancer itself on the nutritional status of the body. Specifically, 1) gastric cancer affects the function of the stomach as a critical digestive organ, and severe gastric cancer damages the normal structure of the digestive tract; 2) cancer, as a consumption disease, accelerates the basal metabolism and nutrient consumption of patients; 3) the pain and psychological impact induced by gastric cancer leads to decreased appetite and intake of patients; and 4) the influence of gastric cancer on the body's microenvironment and intestinal flora causes the patient's absorption disorder. The second reason is related to the impact of surgery on nutritional status, as: 1) surgical removal of part or all of the gastric tissue inevitably harms the patient’s digestive function; 2) surgical stress and trauma worsen the patient’s psychological burden; 3) postoperative symptoms, such as abdominal distension and nausea, lead to loss of appetite; 4) postoperative chemotherapy and complications result in increased nutritional consumption and decreased intake, and boost incidences of malnutrition. Additionally, patients with malnutrition after gastric cancer surgery generally develop adverse body states such as low tissue protein levels, impaired immune function, and internal environment disturbances, which are prone to severe complications such as postoperative infection and poor anastomotic healing [14]. Malnourished patients have a decreased willingness and ability to exercise postoperatively, resulting in muscle atrophy and decreased intestinal motility [15]. All of the above tend to aggravate the malnutrition state of the patient, forming a vicious circle. Malnutrition is closely related to the survival rate and quality of life of patients with gastric cancer after surgery. Xiao et al. reported that nutritional deficiencies after gastric cancer surgery directly impact the treatment effect of patients and can easily lead to adverse clinical outcomes [16]. Hirahara et al. revealed that the peak period of malnutrition occurred three months after gastric cancer surgery [10]. Therefore, a comprehensive analysis of related clinical research and pathogenesis demonstrates that patients with gastric cancer have a higher risk of malnutrition after surgery and are prone to malnutrition, which in turn affects their mid-term and long-term prognosis. At present, the assessment of malnutrition in patients after gastric cancer surgery has remarkable lag and insufficient accuracy. Consequently, it is difficult to effectively screen high-risk patients during hospitalization or the perioperative period to achieve early warning and intervention.
The indicators affecting nutritional status were used as independent variables, and the nutritional status (whether or not malnutrition occurs) three months after surgery was the dependent variable. First, the difference variables were obtained by a simple difference test. Subsequently, variables statistically different and clinically believed to have a theoretical impact on the outcome were incorporated into multivariate logistic regression in combination with clinical theory. Finally, the variables for building the predictive model were derived. Statistical results and clinical mechanisms were considered in the entire model construction process. The variables in the model were not only those with relevant statistical results (all are independent risk factors for malnutrition after gastric cancer surgery, as determined by P < 0.05 using multivariate analysis), but also those that have a direct theoretical relationship with the outcome of malnutrition.
The TNM stage of gastric cancer was adopted as a standard to evaluate the degree of infiltration and metastasis of the tumor itself. A higher stage indicated a higher degree of malignancy. In patients with high TNM staging, digestion and absorption dysfunction occurs due to the severe invasion of the tumor into the stomach and surrounding lymph nodes. Cancer cells compete with normal cells in the body for nutrients and consume significant amounts of energy and protein. Besides, patients with a high TNM stage usually develop accompanying symptoms such as anorexia, pain, nausea, and vomiting, resulting in insufficient intake. Such patients require wider surgical resection and longer courses of postoperative chemotherapy, increasing the risk of postoperative malnutrition. Ravasco et al. suggested that the malignant degree of gastric cancer is a critical factor affecting the nutritional status of patients, and TNM staging is an effective clinical indicator to evaluate the degree of malignancy [17]. Lee et al. demonstrated that the malignant degree of gastric cancer is closely correlated with the occurrence of postoperative malnutrition and is an independent risk factor [18].
Cardiac function classification (NYHA) is an evaluation of patients' cardiac function from the perspective of clinical symptoms, especially for patients with chronic heart failure. Kinugawa et al. suggested that patients with chronic heart failure frequently suffer from malnutrition ascribed to changes in systemic metabolism and increased body consumption, with an incidence rate of 16%‒62% [19, 20]. Patients undergoing gastric cancer surgery are more likely to suffer from insufficient body intake, loss of appetite, and increased risk of postoperative malnutrition because of reduced intake, and exercise tolerance, especially if complicated with cardiac insufficiency. Sze et al. revealed that chronic heart failure aggravates the symptoms of gastrointestinal congestion and intestinal edema in patients with gastric cancer, impacts the absorption of nutrients, and increases the occurrence of malnutrition [21].
PAB is synthesized by hepatocytes and is so named because it is generally displayed in front of albumin by electrophoresis. Owing to its short half-life of only about 12 hours, it is more sensitive than albumin and transferrin in response to malnutrition. Aoyama et al. reported that prealbumin can be used as a representative indicator of postoperative nutritional status in patients with gastric cancer and is correlated with the recurrence rate and survival rate of gastric cancer patients [22]. Zu et al. confirmed that the level of prealbumin at admission is an independent risk factor for the long-term prognosis of gastric cancer patients [23].
The NLR is an indicator of the degree of inflammation in the body. From one perspective, the more intense the inflammatory response of gastric cancer patients, the greater the consumption of nutrients, and the more likely it is to aggravate stress trauma such as surgery, increase the chance of postoperative infection, and promote the occurrence of postoperative malnutrition status [24]. From another perspective, an increase in this index indicates an increase in neutrophils and/or a decrease in lymphocytes in gastric cancer patients. Neutrophils can drive tumor growth by producing soluble cytokines and various proteases [25]. Moreover, they boost tumor metastasis by inhibiting functions such as effector T cells and NK cells. A decrease in the number of lymphocytes implies a decrease in immune function and surveillance, making it easier for the tumor to metastasize [26]. The accelerated growth or metastasis of gastric cancer as a tumor directly affecting the digestive organs will directly aggravate the consumption of nutrients and obstruct digestion and absorption function.
Regarding anxiety grading, the SAS was employed to effectively evaluate and grade whether the patient has anxiety and its severity. Negative emotions such as anxiety can further affect the appetite of patients with gastric cancer through behavioral mechanisms, resulting in insufficient intake of nutrients [27]. Moreover, a state of anxiety can induce a state of stress in gastric cancer patients through neuroendocrine pathways, such as the hypothalamic-pituitary-adrenal axis [28]. Additionally, anxiety aggravates the body's inflammatory response, inhibits immunity, and influences the recovery of postoperative nutritional status in patients with gastric cancer [29]. Anxiety is an independent risk factor affecting the nutritional prognosis of cancer patients [30].
During the process of selecting variables for modeling in this study, the selected variables were required to meet multi-dimensional requirements, in addition to considering the statistical results and the mechanism of malnutrition after gastric cancer surgery. The selected variables can reflect not only the situation of the tumor itself (TNM staging) but also the cardiac function, nutritional reserve, the body’s inflammatory response and anxiety level of gastric cancer patients through related indicators (NYHA, PAB, NLR, and SAS scale grading), and the pathophysiological state of the whole body. Finally, joint prediction of malnutrition outcomes from multiple perspectives can improve model efficiency. With respect to the model display, the nomogram visually expresses the meaning of the model and quantifies risks concisely and effectively, which is convenient for clinical use.
In the design method of this study, the included patients were divided into the training set and validation set, and the internal and external joint verification after modeling was conducted with various methods to effectively evaluate the predictive ability and extrapolation of the model. The model discrimination was evaluated by the ROC curve, and the obtained AUC values of the two sets were 0.842 and 0.815, respectively. According to the standard of AUC prediction validity, the overall discrimination of the prediction model was excellent. Compared with the commonly used NRS2002 scale (AUC: 0.794), the model had higher validity in predicting malnutrition after gastric cancer surgery. The prediction accuracy of the model was confirmed by the calibration curve (visual observation, Brier value: 0.161, 0.195) and the Hosmer-Lemeshow goodness-of-fit test (training set and validation set, P > 0.05). The DCA curve demonstrated that the predicted probability of this model was in the range of 10%‒70%, the level of clinical net benefit was the highest, and that the model possessed acceptable clinical applicability. Meanwhile, the variables in the prediction model were clinical classification, laboratory indicators, or scoring scales commonly used in the clinic, which can be quickly mastered by doctors and nurses while being popularized and used by hospitals at all levels.
First, the variables in the model had a theoretical causal relationship with the outcome of malnutrition. Second, the pathophysiological states of the body represented by the cardiac function classification (NYHA), preoperative nutritional reserve index (PAB), inflammation degree (NLR), and anxiety state (SAS classification) in the model variables were clinically interventionable. The corresponding state was improved by lowering the cardiac load, increasing the preoperative nutritional reserve, reducing the body’s inflammatory response, and relieving anxiety, contributing to the increased risk of postoperative malnutrition. Therefore, the prediction model can provide not only early warning for high-risk patients with malnutrition after gastric cancer surgery but also theoretical support and practical guidance for early intervention in high-risk patients.
However, this study, as a retrospective analysis of a single center, still has some limitations. First, the number of cases is small, and the source is limited. Second, the established model needs to be verified by an in-depth prospective cohort study. Third, the selected indicators did not include an evaluation of the patients' families, including socioeconomic status, types of meals, and eating habits. Therefore, we expect to conduct a multi-center prospective study incorporating more innovative indicators to further improve the predictive performance of the model.