Nutritional risk screening in malignant tumors: a study of 375 cancer inpatients

Malnutrition is a common complication in cancer patients. It often accelerates disease progression and affects treatment outcomes. Thus, in the early census of cancer patients, examination for possible nutritional risks and correcting potential causes of malnutrition are needed to improve patients’ quality of life. Our study included 375 patients diagnosed with cancer in Henan province and analyzed the relationship between nutritional risk and indicators like age, serum albumin, serum prealbumin, serum hemoglobin, tumor stage, tumor type, and inflammatory factors. We found that age, hemoglobin, and presence of gastrointestinal tumors were independent risk factors for nutritional risk. We also found significant correlation between inflammatory factors and nutritional risk in cancer patients, so as to provide new prediction indexes for clinical management of nutritional risk and dynamic changes of nutritional status.


Introduction
Cancer is a catabolic inflammatory disease that often causes malnutrition or even cachexia in severe cases [1]. Due to reduced food intake, abnormal nutrient metabolism, and the adverse effects of radiotherapy and chemotherapy, nutritional problems are often encountered during cancer treatment. A multi-center PreMiO study [2] in Italy found that 51% of cancer patients were malnourished, 9% are evidently malnourished, and 43% were at risk of malnutrition. The European Society for Clinical Nutrition and Metabolism guidelines point out that malnutrition during cancer treatment reduces quality of life, increases treatment side effects, and reduces response to treatment, thereby affecting patient survival [3]. Worse still, malnutrition may even cause patient death. Studies in the early 1930s found that about 20-50% of cancer deaths were not directly caused by the malignancy itself, but from malnutrition or cachexia [4]. Thus, nutritional screening and early intervention are important for prolonged survival and improved quality of life for cancer patients [5].

Patients
Patient recruitment was carried out among cancer patients admitted consecutively at the People's Hospital of Yanshi City during 1st April to 1st October 2016 and The First Affiliated Hospital of Xinxiang Medical University during 7th November to 24th November 2019. Inclusion criteria included the following: (1) patients with clear diagnosis and an expected hospital stay of > 3 days, (2) > 18 years, (3) informed consent to participate in the study, and (4) no radiotherapy and chemotherapy at the time of data collection. Exclusion criteria included the following: (1) end-stage patients, (2) patients with severe infection, (3) patients with severe liver or kidney failure, and (4) uncontrolled diabetes.

Collection of clinical data
Personal information (name, age, gender, height, weight, ethnicity, department, date of admission, primary diagnosis, co-existing comorbidities) were collected following after consent to participate in the study. Clinical data collected included serum albumin, serum pre-albumin, tumor stage, and presence of gastrointestinal tumors.

Nutrition risk screening
Using NRS 2002, the screening items included nutritional status score (0-3 points), disease severity score (0-3 points), and age score (> 70 years old added 1 point). Total score (0-7 points) was the sum of the 3. Total NRS score of ≥ 3 indicated malnutrition risk. NRS score of < 3 indicated no nutritional risk. Patients with risk scores of < 3 were reviewed weekly and if the rechecked result was ≥ 3 points, the patient was considered at nutritional risk and nutritional support recommended.

Serum specimen collection
Forty-eight patients were randomly selected at the First Affiliated Hospital of Xinxiang Medical University. Of these, 25 were not at nutritional risk (group A) and 23 cases were at nutritional risk (group B). Five milliliters of peripheral venous blood were collected using a coagulation tube. Serum was then collected by centrifugation at 3000 rpm for 10 min, at room temperature, and analyzed for the levels immune-related inflammatory factors, IL-6 and IL-8, using ELISA.

ELISA
Human IL-6 ELISA Kit and Human IL-8 ELISA Kit were purchased from Abison Biotechnology and ELISA done according to manufacturer instructions. In brief, purified standards and experimental samples were diluted and used to coat microtiter plates for 2 h at room temperature. Samples were then washed and 100 µL of detection antibody added into the wells followed by incubation at room temperature for 2 h. HRP-conjugated streptavidin (SA-HRP) was used at room temperature for 20 min in dark for antibody detection. The reaction was then stopped by adding 50-µl stop solution to each microwell. Within 30 min after adding the stop solution, absorbance was read at 450 nm on a microplate reader.

Statistical analysis
Measurement data were expressed as mean ± SD. The independent samples t-test compared differences between 2 groups. X2-test compared difference of composition ratios between groups. Multiple regression analysis compared basic parameter differences between the 2 groups. Spearman correlation analysis was used to analyze the correlation between 2 variables. P = < 0.05 was considered statistically significant.

Relationship between common indicators and nutritional risk
To identify nutritional risk factors, we divided the patients into 2 groups based on nutritional risk and analyzed their age, BMI, and serological factors ( Table 2). Mann-Whitney U test analysis of measurement data found no obvious differences in age, BMI, and serological test indexes between the nutritional risk group and the nonnutritional risk group. Logistics regression analysis of age, BMI, and related serological indicators found that age (p = < 0.01) negatively correlated with nutritional risk. BMI (p = < 0.01), albumin (p = < 0.01), and hemoglobin (p = < 0.05) positively correlated with nutritional risk. There was no obvious correlation between prealbumin and nutritional risk (Table 3).
To investigate correlation between gender, tumor stage, tumor type, and nutritional risk factors, we used univariate data analysis; the result of X2-test showed that tumor stage and whether gastrointestinal tumor or not had an obvious correlation with the occurrence of malnutrition risk (P < 0.001), while gender had no correlation with malnutrition risk (Table 4).

Relationship between inflammatory factors and nutritional risk
Patient's nutritional status is associated with metabolic changes and immune impairment [6]. Mounting evidence indicate that systemic inflammation is associated with the increased weight loss [7]. Pro-inflammatory factors may influence nutritional status by inhibiting appetite and altering gastrointestinal function, carbohydrate metabolism, and insulin resistance [8].
To explore the relationship between inflammatory factors and nutritional risk, we selected 48 cases from 375 patients randomly to express immune-related verification factors and divided them into group A (25 cancer patients without nutritional risk) and group B (23 cancer patients with nutritional risk). We then analyzed the levels of inflammatory factors IL-6 and IL-8 in the two groups and assessed the relationship between IL-6 and IL-8 and nutritional status of cancer patients. This analysis showed that the level of IL-6 and IL-8 in the serum of patients at nutritional risk was significantly higher than in patients without nutritional risk (Fig. 1).
Baseline characteristics and peripheral blood indicators with statistically significant differences between patients at nutritional risk and patients without nutritional risk were selected and correlation between IL-6 and IL-8 levels and peripheral blood indicators analyzed by Spearman correlation analysis (Table 5). This analysis revealed that IL-6 negatively correlated with serum albumin and serum prealbumin, and IL-8 positively correlated with serum albumin in  patients without nutritional risk (p = < 0.05). IL-6 negatively correlated with serum prealbumin in patients at nutritional risk (p = < 0.05). IL-8 was not associated with BMI, serum albumin, serum prealbumin, or gastrointestinal tumors in patients at nutritional risk. The Spearman correlation coefficient between IL-8 and serum prealbumin of patients at nutritional risk was − 0.341, but this was not statistically significant, probably due to the sample size (Table 6).

Discussion
Malnutrition is a risk factor for increased morbidity and decreased quality of life in cancer patients. Nutritional risk in cancer patients is related to many clinicopathological characteristics [2,9]. Some studies show that age is related to the occurrence of nutritional risk and elderly patients are more likely to have nutritional risks [6,10]. Moreover, multiple studies have reported that BMI is associated with malnutrition in cancer patients [11]. A BMI of < 20 kg/m2 has been found to have high sensitivity in the diagnosis of severe malnutrition in older cancer patients. Gastrointestinal cancer patients have a higher risk of malnutrition, probably due to loss of appetite and poor digestion and nutrient absorption. Studies show that patients with gastric cancer or upper gastrointestinal tumors (including esophageal cancer, gastric cancer, and duodenal cancer) had extremely high malnutrition risk rates (up to 94.6%) [12]. Inflammatory factors correlated with nutritional risk in cancer patients. Mounting evidence from basic biological studies suggest a correlation between malnutrition and inflammatory factors [13]. Past studies indicate that malnutrition risk is related to the levels of serum albumin and hemoglobin. Continued decline in a patient's serum total protein and serum albumin may indicate malnutrition [14]. There are few studies on the relationship between interleukins and nutritional risk.
To develop an easy index of predicting cancer patients' nutritional risk, we adopted indicators of patient clinical characteristics, including the impact of age, gender, BMI, tumor stage, and digestive tract tumor on the nutritional risk of patients with malignant tumors. No correlation was found between the gender, prealbumin, and nutritional risk. Age negatively correlated with nutritional risk, while BMI, albumin, and hemoglobin had positive correlation with nutritional risk. Moreover, we found that the serum levels of IL-6 and IL-8 were significantly elevated in patients at nutritional risk.
Nutritional status is significant for the immunity, treatment, and prognosis of tumor patients, but the evaluation of nutrition is usually not convenient. Previous studies have shown that the level of IL-6 and IL-8 appears to participate in the development of cancer-related cachexia in gastroesophageal malignancies [15] and is related to the quality of life (QOL) of tumor patients [16]. Our data show that malnutrition generally exists in cancer patients; IL-6 and IL-8 inflammatory factors may be used to evaluate dynamic changes in nutritional status in cancer patients. The original Fig. 1 Expression of IL-6 and IL-8 between the two groups finding of the study can effectively assist the evaluation of nutritional status of tumor patients through inflammatory indicators, which is of great significance for the nutritional evaluation and long-term management of tumor patients in the future.