Enriched enteral nutrition may improve short-term survival in stage IV gastric cancer patients: A randomized, controlled trial

Highlights

• A diet enriched with arginine, glutamine, and omega-3 fatty acids has beneficial effects.

• Enriched enteral nutrition may decrease risk of dying in gastric cancer patients.

• Postoperative enriched enteral nutrition has rather short-term effect.

• Further effort is needed to assess the magnitude of the effect.

Abstract

Objective

The aim of the study was to determine whether the postoperative use of enteral nutrition enriched with arginine, glutamine, and omega-3 fatty acids influences survival in patients diagnosed with stomach cancer. For the purpose of the study, the second wave of the trial performed in 2003 to 2009 was done.

Methods

Ninety-nine patients who underwent surgery for gastric cancer (27 F, 72 M, mean age: 62.9 y) met the inclusion criteria. Of those, 54 were randomized to standard and 45 to enriched enteral nutrition (EEN). In all patients, short- and long-term (5 y) survival was analyzed.

Results

Analysis of the overall survival time did not reveal differences between groups (P = 0.663). Until the end of the third month, however, there were nine deaths in the standard enteral nutrition group and no deaths in the EEN group (16.7% versus 0.0%, P = 0.004). The univariate analyses suggested that the EEN group may have lower risk, especially during the first year after intervention. A significant reduction in the risk of death was seen during the early period after surgery (first 6 mo) in the EEN group in stage IV patients (hazard ratio = 0.25, P = 0.049). The use of enriched enteral diet did not influence, however, the risk of dying when patients were analyzed together.

Conclusions

The study does not support the beneficial effect of enriched enteral nutrition in long-term survival; however, the positive impact on the stage IV patients suggests the need for further, more detailed studies.

Introduction

Cancer remains one of the leading causes of death worldwide, and its burden has been growing in recent decades, reaching 21.4 million cases and 13.2 million deaths [1]. Although new therapeutic options are being researched worldwide, the majority of treatment strategies still rely on available treatments and other interventions expected to improve patients' life expectancy in curable and incurable conditions. One of the most effective modalities that shows benefits is clinical nutrition. Although the strategy to enrich cancer patients’ diets with some nutrients was discussed due to the concept of “feeding of cancerous cells,” clinical nutrition is no longer blamed for the stimulation of tumor growth; moreover, it is considered to be a crucial part of anticancer therapy, as stated in European Society for Clinical Nutrition and Metabolism guidelines [2]. Clinical nutrition has been evolving in recent decades and should no longer be considered only as a way of delivering nutrients, as it has been recognized as a form of therapy. The concept of pharmaconutrition is based on the assumption that some nutrients may exert therapeutic effects by immunomodulation or liver protection. Immune intervention in particular has raised high hopes not only for defense mechanism enhancement, but also for stimulation of anticancer actions.

Several studies have showed that perioperative use of enteral and, to some extent, parenteral formulas containing arginine, glutamine, and omega-3 fatty acids reduced the frequency of postoperative complications and improved survival in both well-nourished and malnourished cancer patients treated surgically [3], [4], [5]. Beneficial effects were also observed when immunodiets were used both pre- and postoperatively, especially in malnourished gastric and pancreatic cancer patients [6], [7], [8], [9]. Although some researchers expressed doubts about the real value of immunointervention, metaanalyses supported its beneficial effect in surgical population [10], [11]. The use of immune-enhancing diets has even become a part of surgical guidelines and recommendations [12].

There is an agreement to use enriched diets in malnourished patients, especially before surgical intervention, though there is still a discussion regarding the role of this diet when introduced postoperatively.

The discussion about the possibility of an enriched diet's beneficial effects on the risk of dying encouraged us to run a second wave of the study, which was primarily focused on postoperative complications in patients treated surgically due to cancer [9]. The aim of the current investigation was to determine whether the postoperative use of enteral nutrition enriched in glutamine, arginine, and omega-3 fatty acids influences survival in patients diagnosed with stomach cancer.