Ampullary carcinoma is a relatively rare malignant tumor, associated with a more favorable prognosis than adenocarcinomas of the adjacent pancreatic duct, common bile duct, or duodenum (1). Pancreatoduodenectomy (PD) was widely considered a safe, potentially curative surgical treatment method for ampullary neoplasm (2–4). As reported previously, many factors affect the postoperative outcomes of ampullary carcinoma after PD, including surgical technique factors (5, 6) and host- and disease-related risk factors (7, 8), such as advanced age, comorbidities, jaundice, advanced tumor stage, and adjuvant chemotherapy (9, 10).

Malnutrition was a common problem in patients with malignant tumor and closely related to the immunosuppression and inflammatory activity (11–14), also considered as an important risk factor of postoperative outcomes (7, 13, 15). Numerous studies have revealed that preoperative malnutrition increased the incidence of postoperative complications and affected the long-term survival of patients (13, 15, 16). However, the studies examining whether postoperative malnutrition affects the long-term survival of patients who underwent PD for ampullary carcinoma were lacking. The scored Patient-Generated Subjective Global Assessment (PG-SGA) proposed by Ottery (17), as a noninvasive nutrition measurement tool for oncology patients, was a modification of the Subjective Global Assessment (SGA) (18). The preoperative scored PG-SGA has been validated in colectomy and hepatectomy in many countries (19–21); however, the correlation of postoperative malnutrition assessed by the scored PG-SGA and postoperative outcomes in patients of ampullary carcinoma following PD is still unknown.

The aim of this study was to investigate the effect of preoperative and postoperative malnutrition on postoperative outcomes for ampullary carcinoma after PD.

In recent years, the prognostic factors of postoperative outcome after PD have been extensively studied. The postoperative outcomes of patients with malignant tumors after curative surgery were associated with the tumor characteristics, surgical factors, and host-related factors (2–4). Among them, preoperative malnutrition was also an important risk factor of postoperative outcomes for malignant tumor after radical surgery (7, 13). Preoperative malnutrition in patients who underwent PD was often caused by the decrease in oral food intake, absorption disorder, and gastrointestinal obstruction. Patients who underwent PD frequently experience impaired digestive function that can affect long-term nutritional status. The consequences of preoperative and postoperative malnutrition on postoperative outcomes include increased incidence of complications, prolonged hospital day, and poor survivals. However, the studies examining whether postoperative malnutrition affects the long-term survival of patients who underwent PD for ampullary carcinoma were lacking.

In our study, the incidence of postoperative complications was more higher in severely malnourished group than in well-nourished or moderately malnourished group. The multivariate Cox proportional hazards regression analysis showed that severe malnutrition (PG-SGA score > 9 scores) before operation and at 6 and 12 months after operation were independent prognostic factors in patients who underwent PD for ampullary carcinoma.

As previously reported (11, 28), malnutrition was common in hospitalized patients with malignant tumor. Song et al. (11) analyzed the nutritional status of 23,904 patients with 16 common malignant tumors; 13,826 participants (57.88%) were moderately or severely malnourished. Similarly, most of the patients with ampullary carcinoma had varying degrees of malnutrition before and after operation in our study. Before operation, 122 (23.9%) patients were classified into well-nourished group, 189 (37.0%) into moderately malnourished group, and 200 (39.1%) into severely malnourished group. Additionally, many patients still suffer from malnutrition after operation; the median PG-SGA scores were 5, 4, and 3 scores at 3, 6, and 12 months after PD, respectively.

The nutritional status of hospitalized patients could be assessed by various methods, included objective anthropometric measurements, and subjective measurements based on the clinical history and physical examination (29–31). Among the aforementioned, the PG-SGA was the widely recommended method for the assessment of nutritional status of the tumor patients (17, 19, 32). The scored PG-SGA consists of a quantitative score and a qualitative global assessment, which was more sensitive to a subtle changes in nutritional status than the SGA. The higher the PG-SGA score is, the greater the risk of malnutrition is. Many previous studies have demonstrated that the scored PG-SGA was an effective and reliable tool for nutrition evaluation. Additionally, the NRS-2002 was also the preferred subjective screening tool for nutritional risk. According to the previous study, the PG-SGA scale is simple and accurate and may be the most suitable method for evaluating the nutritional status of malignant tumor patients and was more sensitive to the nutritional status in the general population of cancer patients compared with the NRS-2002.

Malnourished patients with malignant tumor often coexists with systemic inflammatory response and immunosuppression (14, 33). As previously reported (34, 35), the malignant tumors incite a systemic inflammatory response, which often triggers the release of inflammatory cytokines and chemokines, such as tumor necrosis factor and IL-1 and IL-6. Meanwhile, the systemic inflammatory response induced profound catabolic effects on host metabolism, for instance, which caused the depletion of skeletal muscle and visceral function proteins. In addition, neutrophilia and lymphocytopenia were commonly involved in cancer-related inflammation (36–38). Patients with immunosuppression and inflammatory response have poor tolerance to operation, recover slowly after surgery, and more susceptible to postoperative complications. Previous reports have found a relationship between preoperative malnutrition and poor short-term outcome and long-term survival, which were consistent with our results. In our cohort, we found that the incidence of postoperative complications in malnourished group was significant higher than that in the well-nourished group, and the preoperative malnutrition was the independent risk factor of overall survival.

To date, the relationship between postoperative long-term nutritional status and survival remains unknown. Previous studies reported that malnutrition after gastrectomy significantly and adversely affects overall survival; nutritional interventions to lessen the impact of postoperative malnutrition can offer hope for prolonged survival. However, they could not completely adjust for the negative survival impact of patient backgrounds in the malnutrition group and excluded patients with gastric cancer recurrence. In our study, to control for the effects of confounding factors, propensity score matched analysis was performed to balance the clinicopathological variables between preoperative group A (well-nourished and moderately malnourished group) and group B (severely malnourished group). After PSM analysis, we revealed relationships between poor survival and malnutrition before and at 6 and 12 months after PD. The PG-SGA score >9 scores before operation and at 6 and 12 months after operation were independent prognostic factors in patients who underwent PD for ampullary carcinoma. However, the PG-SGA score >9 scores at 3 months after operation was not the independent prognostic factor in our study.

In addition, as previously reported, the loss of skeletal muscle (SM) and visceral functional proteins was considered as the important indication of nutritional status (31, 39). The SM and visceral functional protein depletion leads to changes in intra- and extracellular electrolyte regulations and reduction in the metabolically active tissue and often coexists with immunosuppression, which were the important mechanisms for increased postoperative complications and poor survival after PD. de Oliveira Pereira et al. (39) quantitatively calculated the body composition using computed tomography and assessed the nutritional status of hospitalized patients, and they found that the PG-SGA was closely correlated with the skeletal muscle index. Meanwhile, compared with the weight loss and BMI, the scored PG-SGA was a more sensitive and precise method to assess nutritional status of patients with malignant tumor. Laky et al. (31) showed that BMI and percentage of weight loss were not able to effectively detect malnutrition of patients with malignant tumor because they could be masked by edema and dehydration. Similarly, Wigmore et al. (40) found that the median BMI of 20 pancreatic cancer patients at diagnosis was 20.7 (range, 19.5–23.6) kg/m² despite a median weight loss of 14.2 (range, 10–20%) in the previous 6 months.

Besides, malnourished cancer patients were often accompanied by vitamin and microelement deficiency due to decreased oral food intake and impaired absorption. The deficiency of vitamin and microelement was closely related to symptoms such as nausea and vomiting and indigestion, which maybe the reason that the incidence of postoperative DGE after PD was more higher in malnourished group than in well-nourished group in our study. Regrettably, the incomplete data of vitamin and microelement test results makes it impossible to analyze its effect on postoperative DGE in this study.

These findings implied that nutritional status was associated with the postoperative outcomes of patients after PD. Therefore, preoperative and postoperative adequate nutritional support including oral or intravenous nutritional supplementation were considered important treatment means to improve the postoperative outcome of patients underwent PD. A retrospective multicenter study suggested that nutritional support before surgery might lead to better surgical outcome of resectable pancreatic cancer patients (41). Similarly, Adiamah and his colleagues found that preoperative immune modulating nutrition (IMN) had the significant impact on infectious complications and a tendency to shorten length of stay; preoperative IMN should be encouraged as a routine practice in patients undergoing surgery for gastrointestinal cancer (21).

This study has some limitations. First, it was retrospective and single-centered; thus, susceptible to the inherent problems of such design features, subject selection bias was unavoidable. In the future, prospective studies with larger sample sizes, and external validation of our findings in other populations, are essential.

Our study suggested that patients with ampullary carcinoma had varying degrees of malnutrition before and after operation. Malnutrition before and at 6 and 12 months after PD significantly affects the long-term survival of patients. Additionally, the preoperative malnutrition was related to postoperative complications after PD. Nutritional interventions to lessen the impact of postoperative malnutrition might offer hope for prolonged survival.

The original contributions presented in the study are included in the article/supplementary materials. Further inquiries can be directed to the corresponding authors.

All patients provided written informed consent to participate in the study, and the study was approved by the Ethics Committee of the local hospital (no. TJ-IRB20190418).

Conception and design: JJ, RQ, and GX. Administrative support: RQ and MW. Provision of study materials or patients: JJ and RQ. Collection and assembly of data: JJ, GX, and XW. Data analysis and interpretation: JJ. Manuscript writing: all authors. All authors contributed to the article and approved the submitted version.

This study was supported by grants from the National Natural Science Foundation of China (Nos. 81772950 and 81874205). This study was also supported by a grant from the National Natural Science Foundation of China Youth Fund (No. 81902499).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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