A Pilot Study to Determine the Effect of Individualized Enteral Nutrition Management Based on Prognostic Nutrition Index on Surgical Patients With Oral Malignancies

Abstract

This study aimed to assess the effect of individualized enteral nutrition management based on the prognostic nutrition index (PNI) on surgical patients with oral malignancies. This quasi-experimental pilot study consecutively included patients diagnosed with oral malignancies who underwent radical surgery in Ningbo No. 2 Hospital between January 2020 and May 2023. The primary outcome was PNI. A total of 71 patients with oral malignancies were enrolled, and 35 patients received PNI-based individualized enteral nutrition management. The PNI group displayed significantly higher PNI than the routine enteral nutrition support group (1st week postoperatively: 39.86 ± 3.86 vs. 37.29 ± 4.23, p < 0.001. 2nd weeks postoperatively: 44.17 ± 4.36 vs. 40.72 ± 3.40, p < 0.001). The surgical suture removal time and length of hospital stay (both p < 0.001) in the PNI group were significantly shorter than in the routine enteral nutrition support group. At 1 month postoperatively, the PNI group had significantly higher scores of QoL (p = 0.002) than the routine enteral nutrition support group. The individualized enteral nutrition management based on the PNI could improve the nutritional status of postoperative patients with oral malignancy, which could facilitate postoperative rehabilitation and improve overall QoL.

Introduction

Oral malignancy is one of the common malignancies of the head and neck that occurs in the lips, tongue, mouth floor, palate, gingiva, buccal mucosa, and alveolar mucosa (1). The International Agency for Research on Cancer (IARC) 2020 statistics show oral malignancy ranks 10th among systemic malignant tumors (2). Radical tumor treatment with local tissue reconstruction is the main treatment modality for oral malignancy, but due to the special anatomical site of the oral cavity, postoperative mastication and swallowing function are impaired, which is prone to the problem of malnutrition. Malnutrition causes postoperative complications such as delayed wound healing and infection and prolonged hospital stay, with adverse effects on patients’ clinical outcomes and quality of life (QoL) (3). Relevant research data show that the incidence rate of malnutrition in oral malignancy patients is as high as 80% (4), and it is of great significance for oral malignancy patients to recognize their nutritional status at an early stage and to take corresponding interventions in time (5).

Chen et al. (6) formulated a multidisciplinary cooperation scheme of precise enteral nutrition care that included one attending physician, one resident, one responsible nurse, and one nutritionist working together to analyze the patient’s condition and implement and manage enteral nutrition. Zhang et al. (7) proposed a progressive nutritional guideline sheet in the postoperative enteral nutrition management of patients with oral malignancy that achieved a certain clinical efficacy, with specific quantification of the daily amount, concentration, and frequency of enteral nutrition, etc. In that study, the nutritionist used routine nutritional screening and subjective comprehensive evaluation methods to conduct individualized nutritional assessments and analyze the nutritional problems (including chewing and swallowing issues, gastrointestinal tolerance, wound healing status, dietary history, food allergies, and laboratory test results) in conjunction with the surgical condition and comorbidities. Then, the nutritionists developed personalized nutritional prescriptions. The responsible nurse was responsible for the specific implementation of the nutrition plan, while the attending physician and resident physician oversaw the implementation of the nutritional prescription (7). In the study by Zhang et al. (7), the nutritional assessment did not judge the degree of malnutrition and lacked graded and targeted nutritional support and intervention, often failing to meet the individual nutritional needs of different patients. Nevertheless, these two previous studies showed that precision enteral nutrition management can improve postoperative recovery.

It has been shown that personalized nutritional intervention through objective monitoring of sensitive markers of nutritional levels can effectively prevent and control disease progression and promote rapid recovery of the organism (8). Serum albumin reflects the nutritional status and defense ability of the organism and can judge the prognosis of patients with tumors (9). Lymphocytes can participate in the recognition and elimination of malignant tumor cells in the body, reflecting the nutritional and immune status of the body, and are a very important component in the immunity against carcinoma cells (10). The prognostic nutrition index (PNI) is calculated by serum albumin and the number of lymphocytes in the body, which objectively reflects the nutritional and immune status of the patient and is of great significance in the evaluation of the nutritional status, surgical risk, and prognosis of cancer patients (11–13). For instance, Zhang et al. (11) demonstrated in their study that decreased PNI was associated with platinum treatment resistance, poor overall survival (OS), and progression-free survival (PFS) in ovarian cancer patients. Similarly, Go et al. (12) observed that patients with diffuse large B cell lymphoma and low PNI levels were more susceptible to treatment-related toxicity, resulting in treatment discontinuation and shorter OS. Furthermore, the meta-analysis conducted by Li et al. (13) revealed an association between a low PNI and poor OS in pancreatic cancer patients.

This pilot study introduced an individualized nutrition intervention scheme based on the PNI for patients with oral malignant tumors and aimed to assess the effect of individualized enteral nutrition management based on the PNI on surgical patients with oral malignancies.

Materials and Methods

Study Design and Population

This quasi-experimental pilot study consecutively included postoperative patients who were diagnosed with oral malignancy and received radical surgery at Ningbo No. 2 Hospital between January 2020 and May 2023. This study was a pilot study to provide data for the planning of the multicenter implementation of individualized enteral nutrition management.

The inclusion criteria were: 1) patients whose age was ≥ 18 years old; 2) patients who were histologically confirmed with oral carcinoma, including gingival cancer, soft and hard palate cancer, tongue cancer, cancer of the mouth floor, carcinoma of the jaws, lip cancer, and buccal cancer; 3) patients who initially received radical repair and reconstruction surgery. The exclusion criteria were: 1) patients who received radiotherapy or chemotherapy before surgery; 2) patients with preoperative history of infection or blood transfusion; 3) patients with a history of clinically uncontrolled cardiac, hepatic, or renal disease or combined with digestive systemic diseases such as gastrointestinal obstruction, esophagogastric fundal varices, and upper gastrointestinal bleeding; 4) patients combined with immune system diseases or hematologic diseases; 5) patients with diabetes mellitus; 6) patients with cognitive or communication disorders. This study was approved by the Medical Ethics Committee of Ningbo No. 2 Hospital (Grant No. PJ-NBEY-KY-2019-090-01), and all patients provided written informed consent.

Intervention

The patients included between January 2020 and February 2022 underwent routine enteral nutrition support. The patients included between March 2022 and May 2023 underwent individualized enteral nutrition management based on the PNI.

Establishment of Multidisciplinary Nutrition Support Team

A multidisciplinary nutrition support team (NST) was established to carry out the whole nutritional management of oral malignancy patients. It was led by nurses in the department of stomatology and further consisted of dental nursing staff, stomatologists, dietitians, and others if necessary. All diagnostic and therapeutic strategies were established based on the decisions after the discussions by the NST. Briefly, after admission, Nutritional Risking Screening 2002 (NRS2002) was completed by the nursing staff and attending physicians. Dietitians completed the patient-generated subjective global assessment (PG-SGA) nutritional assessment, formulated and further provided enteral nutritional support regimens. Nurses were responsible for the implementation of the enteral nutrition support scheme, condition monitoring, and patient education.

Routine Enteral Nutrition Support

An Individualized enteral nutrition support scheme was formulated according to the patient’s condition, target energy, and protein amount.

The calculation was conducted as below: Ideal body mass = (height − 105) kg; Daily target energy value = ideal body mass × (25-30) kcal/kg/d; Daily target protein requirement volume = ideal body mass × (1.2-2.0) g/kg/d.

The patients were implanted with nasogastric tubes for enteral nutrition on the first day after surgery. The nutrients prepared an enteral nutrition solution containing rich minerals, trace elements, and water-soluble and fat-soluble vitamins with a total concentration of 25% and volume of 100 ml, reaching 100 kcal calories. Ordinarily, the solution consisted of whey protein hydrolysates 3.7 g, fat 3.2 g, carbohydrate 13.3 g, and dietary fiber (DF) 1 g. If patients have mild gastrointestinal intolerance such as diarrhea, more easily absorbed short peptide enteral nutrition preparations, with a 25% concentration of 100 ml (100 kcal) of nutrition solution containing 3.6 g of whey protein hydrolysates, 1.6 g of fat and 17.5 g of carbohydrates were conducted. The concentration, speed, frequency, and total volume of daily infusion of enteral nutrient solution were incrementally increased from 10% to 25% of total concentration, speed from 100 ml/h to 350 ml/h, frequency from 3 to 7 times/per day, total volume from 500 ml/per day to a maximum volume of 1500-2200 ml/per day, and caloric intake was incrementally increased from 200 kcal/per day to 1500-2200 kcal/per day. 75% of the target energy value was achieved by the end of the first week. Enteral nutrition was started on the second day with a water-soluble vitamin component of 2 g/per day. After enteral nutrition solution intake reaches 25% of whole concentration, add compound whey protein powder (90% protein content) appropriately and gradually. Whey protein powder added amount = (daily protein requirement - the total amount of protein in enteral nutrition preparation)/90%, with 5 g/times, two to three times a day as the starting amount, and gradually increase to the target protein requirement.

Individualized Enteral Nutritional Management Based on the PNI

Preoperatively, all patients were given oral nutritional supplementation (ONS) with 25-30 kcal/kg/d energy and assessed the nutritional status with PNI. PNI = serum albumin (g/L) + total number of lymphocyte (10⁹/L) × 5.

On the first day after the operation, patients were implanted with the nasogastric tube and received precision nutrition intervention according to the PNI grade, followed by routine PNI assessment every 3 days until discharged from the hospital to adjust nutrition regimens. The details of nutrition interventions according to PNI grades were: a. Routine enteral nutrition support was given to those with PNI ≥ 50, which was the same as the regimen in the routine enteral nutrition support group. b. Those with PNI ≥45 and <50 were given dietary homogenate enteral nutrition support according to option based on the precise nutritional dietary regimen formulated by the dietitian, and when the concentration of nutrient solution reached 15%, the intake of compound whey protein powder (with protein content of 90% or more) was increased in advance on the basis of gradual gastrointestinal tract adaption to the dietary nutrients. The added amount of whey protein powder = (daily protein requirement - actual protein intake from enteral nutrition preparations)/90%. Increase the intake of whey protein powder gradually with 5 g per dose, 3-5 times/per day. The target protein requirement was based on ideal body mass × (1.5-2) g/kg/d. Also, supplement glutamine immuno-nutrient to start at 0.1 g/kg/d and gradually increase to 0.3-0.4g/kg/d, and add to enteral nutrient solution for intake in 3-4 times. c. For those given PNI ≥40 and <45, on the basis of scheme b, increase the infusion volume of enteral nutrition based on the original precision regimen of the routine enteral nutrition support group, 50-150 mL per dose, 200-500 mL per day, and intake in 3-5 times. d. Those who were given PNI <40 were given the combined application of parenteral nutrition in addition to the enteral nutrition solution in regimen c, intravenous infusion of fat milk injection, compound amino acid injection, water-soluble and fat-soluble vitamins, and other nutrients (Figure 1).

Figure 1. Perioperative nutritional management process for oral malignancy patients.

Outcome

The primary outcome was PNI. The secondary outcomes were hemoglobin, surgical suture removal time, length of hospital stay, QoL, and the occurrence of gastrointestinal complications. The hemoglobin Hb (g/L) and PNI values were compared between the two groups of patients before surgery, 7 days, and 14 days after surgery. Gastrointestinal complications during perioperative enteral nutrition included nausea and vomiting, diarrhea, and abdominal distension. The Chinese version of the European Organization for Research and Treatment of Cancer QoL Core Scale (EORTCQLQ-30) (14) was used to assess the patient’s QoL in the preoperative period and one month after operation. The scale includes five functional subscales of social, cognitive, somatic, role, and emotional functioning, three symptom subscales of pain, fatigue, nausea, and vomiting, as well as six individual tests and one overall QoL. Each score was linearly converted to a 100-point scale by polarization, where higher scores on the functional scales and overall QoL indicated better functional status and QoL, and higher scores on the single tests and symptom indicators indicated more severe symptoms. The scale has a Cronbach’s reliability of 0.63 to 0.91 and a validity of 0.70 to 0.90. Members of the NST team did measurements. Surgical suture removal time was defined as the number of days of suture removal counted when all intraoral and extraoral surgical sutures were removed. Length of hospital stay was defined as the hospitalization days of patients at discharge.

Covariates

Potential confounders were age, gender, body mass index (BMI), tumor node metastasis classification (TNM), Hb and PNI in the preoperative period, tumor location, and intraoperative bleeding volume. Tumor location was obtained from preoperative auxiliary examination and intraoperative rapid section examination and diagnosis, and intraoperative bleeding volume was obtained from the surgeon’s statistics of the total amount of incisional bleeding volume during the whole procedure of the patient’s surgery. Tumor node metastasis classification was divided into stages I-III (15).

Statistical Analysis

The study was initially designed to determine the difference between PNI and routine enteral nutrition support. The sample size was calculated based on the sample size estimation formula for the comparison of two means: $$n_1=n_2={\left(z_{\alpha }+z_{\beta }\right)}^2\times {2\sigma }^2/{\delta }^2$$

Using two-sided testing, α = 0.05, β = 0.10, z_α=1.960, z_β=1.282, σ = 12, and δ = 10, based on a previous study (16), the sample size was 30. Considering a drop-out rate of 20%, at least 36 patients were needed.

The statistical analysis was performed using SPSS Statistics version 25.0 (IBM, Armonk, NY, USA). Continuous data with a normal distribution were described as mean ± standard deviations (SD) and analyzed using Student’s t-test and ANOVA; otherwise, they were presented as medians (interquartile range, IQR) and analyzed using the Wilcoxon rank-sum test and Kruskall-Wallis H test. Categorical data were described as n (%) and analyzed using the chi-square test or Fisher’s exact test. Additionally, we used a generalized estimating equation (GEE) model (using the AR (1) working correlation matrix) to estimate the differences in values of Hb and PNI at each time point between the two groups and the time trend after treatment. Two-sided P-values <0.05 were considered statistically significant.

Results

A total of 71 patients (18 females) with oral malignancies enrolled, and 35 patients were included between March 2022 and May 2023. They underwent individualized enteral nutrition management based on the PNI (Figure 1). There were no significant differences in age, BMI, TNM stage, tumor location, PNI, and intraoperative bleeding volume between the two groups (all p > 0.05) (Table 1).

Table 1. Baseline characteristics.

Variables	PNI-based individualized enteral nutrition management group (n = 35)	Routine enteral nutrition support group (n = 36)	P-value
Age (mean ± SD)	62.63 ± 10.29	60.14 ± 9.21	0.286
Body mass index (BMI) [M (P25, P75)]	23.39 (21.29,25.81)	22.49 (20.04,24.78)	0.245
Gender
Male	27 (77.14)	26 (72.22)	0.634
Female	8 (22.86)	10 (27.78)
TNM Stage
I	7 (20.00)	7 (19.44)	0.929
II	12 (34.29)	11 (30.56)
III	16 (45.71)	18 (50.00)
Tumor location
Palate, soft palate	5 (14.29)	1 (2.78)	0.133
Guancia	7 (20.00)	4 (11.11)
Oropharynx or tongue	20 (57.14)	23 (63.89)
Gingiva	3 (8.57)	8 (22.22)
Intraoperative bleeding volume [M (P25, P75)]	300 (200,400)	400 (200,400)	0.508
PNI	48.96 ± 4.91	50.30 ± 4.74	0.245

PNI: prognostic nutrition index.

At 1st and 2nd week postoperatively, patients with individualized enteral nutrition management group based on the PNI had significantly higher levels of postoperative PNI than those with routine enteral nutrition support (1 week postoperatively: 39.86 ± 3.86 vs. 37.29 ± 4.23, p < 0.001. At 2 wk postoperatively: 44.17 ± 4.36 vs. 40.72 ± 3.40, p < 0.001, and the levels of Hb were not statistically different between the two groups (p > 0.05) (Table 2 and Figure 2).

Figure 2. Changes in the prognostic nutrition index (PNI) over time. Orange: individualized enteral nutrition management based on the PNI. Blue: standard management.

Table 2. Comparison of the main study indexes between the two groups.

Variables	PNI-based individualized enteral nutrition management group (n = 35)	Routine enteral nutrition support group (n = 36)	P-value (time)	P-value (group)	P-value (interaction)
Hemoglobin
Preoperative period	133.89 ± 16.41	137.64 ± 13.40	<0.001	0.294	0.704
One week after surgery	105.66 ± 15.43	102.22 ± 16.70
Two weeks after surgery	111.83 ± 14.76	107.75 ± 14.58
prognostic nutrition index
Preoperative period	48.96 ± 4.91	50.30 ± 4.74	<0.001	<0.001	0.241
One week after surgery	39.86 ± 3.86	37.29 ± 4.23
Two weeks after surgery	44.17 ± 4.36	40.72 ± 3.40

The surgical suture removal time [14 (12, 15) vs. 18 (15, 19) days, p < 0.001] and length of hospital stay [20 (17, 22) vs. 23 (21, 27) days, p < 0.001] in patients in PNI group were significantly shorter than those in the routine enteral nutrition support group. There were no significant differences when comparing the rate of gastrointestinal complications (p = 0.674) (Table 3).

Table 3. Occurrence of nasal feeding and gastrointestinal complications.

	PNI-based individualized enteral nutrition management group	Routine enteral nutrition support group	P-value
N (cases)	35	36
Surgical suture removal time (days)	14(12,15)	18(15,19)	<0.001
Length of hospital stay (days)	20(17,22)	23(21,27)	<0.001
Gastrointestinal reactions (cases)	3(8.57)	2(5.56)	0.674

After one month postoperatively, patients with individualized enteral nutrition management group based on the PNI had considerably higher scores of somatic functioning, role functioning, emotional functioning, and overall QoL [60.00 (60.00, 80.00) vs. 40.0 0(40.00, 60.00), p = 0.002] than the routine enteral nutrition support group and significantly lower fatigue than those with routine enteral nutrition support (all p < 0.05) (Table S1).

Discussion

This study showed that PNI-based individualized enteral nutrition management significantly improved PNI, shortened the surgical suture removal time and length of hospital stays, and improved the overall QoL in postoperative patients with oral malignancies. This management model may provide a reference for other postoperative nutritional management patients after surgery and dynamically adjust the regimen according to clinical disease differences and surgical modalities to improve patient treatment and prognosis and facilitate rapid postoperative recovery of patients in the future.

Recent studies emphasize that rational supplements of nutrition contribute to the recovery of patients. For instance, glutamine supports can improve cellular energy and protein metabolism, promote protein synthesis, reduce the occurrence of infectious complications, shorten the length of hospital stay, and have a positive effect on the prognosis of patients (17–19). Apart from the considerations of supplemented nutrient compositions, the additional consumptions should also be taken into account. For instance, 300-500 ml of dietary homogenate was increased one day on the basis of gradual adaptation of the gastrointestinal tract (20). However, the rational assessment of the energy requirements of patients with cancer remains a challenge in clinical practice (21). For instance, while supplements of necessary nutrition are needed to avoid malnutrition and muscle loss, inaccurate estimation of energy requirements may lead to the gain of adipose tissue instead of muscle (22–24). Thus, a dynamic and accurate estimation is the foundation of nutritional supplements. This study put forward the PNI-based nutritional intervention, which was under individualized management and dynamically monitored according to patient status.

The results of this study further demonstrated that this individualized enteral nutrition management could improve the postoperative nutritional status of oral malignancy patients and promote rapid rehabilitation after surgery. What’s more, the increased intake of enteral nutrition was not associated with the increased risk of gastrointestinal adverse reactions with the management of the multidisciplinary nutritional team, which further emphasized the importance of individualized management. While most studies focused on the predictive value of PNI to the survival of patients (25–27), PNI-guided nutritional interventions have also been demonstrated to improve patients’ immune function, meet their nutritional needs, facilitate postoperative rehabilitation, improve somatic function, and improve their QoL (28, 29). In accordance with previous results, this study also demonstrated that the PNI-based routine enteral nutrition support efficiently improved the nutritional status and immune function of the patients and reduced their fatigue symptoms. Thus, this study further provided evidence that PNI-guided nutritional interventions were a powerful tool to overcome the malnutrition of the patients by using a quasi-experimental model.

This study also had several limitations. Firstly, this study was a pilot study to provide data for the planning of the multicenter implementation of individualized enteral nutrition management. A larger multicenter study will be conducted later. Secondly, this was a non-randomized study with a limited sample size, which may not fully prove the superiority of this regimen. The sample size was too small to allow reliable subgroup analyses, and it was probably underpowered to detect differences in some variables. Thirdly, the follow-up period was short. Fourthly, limited nutritional assessment models were applied in this study. However, this study emphasized the importance of individualized and dynamic nutritional management in patients with oral malignancy. The reduced adverse effects and increased recovery and quality of life further rationalized the further exploration of our management in clinical practice.

In conclusion, PNI-based individualized management may be a powerful postoperative nutritional regimen and improve the nutritional status of postoperative oral malignancy patients.

Ethics Approval

This work has been carried out in accordance with the Declaration of Helsinki (2000) of the World Medical Association. This work was approved by the Medical Ethics Committee of Ningbo No. 2 Hospital (Grant No. PJ-NBEY-KY-2019-090-01). Informed consent was obtained from all participants.

Consent for Publication

Not applicable.

Authors’ Contributions

CD, HG, and BX carried out the studies, participated in collecting data, and drafted the manuscript. LC and HG performed the statistical analysis and participated in its design. CD and YD participated in the acquisition, analysis, or interpretation of data and drafted the manuscript. All authors read and approved the final manuscript.

Abbreviations
PNI	=	prognostic nutrition index
Hb	=	hemoglobin
QoL	=	quality of life score
IARC	=	International Agency for Research on Cancer
GEE	=	generalized estimating equation

Disclosure Statement

The authors declare that they have no competing interests.

Availability of Data and Materials

The data presented in this study are available in the article.

Additional information

Funding

This work was supported by the Medical and Health Science and Technology Project of Zhejiang Province (2019KY586) and the Project of Ningbo Leading Medical & Health Discipline.