Esophagectomy is one of the most invasive surgeries performed in patients with esophageal cancer; in addition to tumor resection, this surgery requires a wide operative field with lymph node dissection and resection. Because the function of the esophagus affects the metabolic, neuroendocrine, and immune systems, the nutritional status significantly deteriorates postoperatively because of hypermetabolism and digestion-absorption disorders [1
]. In addition, oral intake is considerably diminished after the operation because of the mechanical and functional gastrointestinal tract changes that cause swallowing disorders, early satiety, and postprandial dumping syndrome [9
Therefore, some patients treated surgically for esophageal cancer require supplemental nutritional management using enteral and parenteral nutrition to fulfill their nutritional requirements (NRs) during perioperatively. On the other hand, in order to shorten postoperative hospital stays, patients often get discharged after fulfilling NRs using enteral nutrition (EN) and parenteral nutrition (PN) only, despite still displaying inappropriate oral intake.
The most general algorithms for nutrition administration have recommended that oral intake, the physiological food administration route, be re-established as soon as possible and that it should take priority over EN and PN [10
]. Based on these guidelines, studies on nutrition administration in critically ill patients have questioned the nutrition quantity and timing of administration using EN and PN [12
]. Furthermore, several studies have addressed the topic of efficacious postoperative direct oral feeding as part of the “enhanced recovery after surgery (ERAS) protocol [16
]”. Several studies have reported that patients undergoing surgery for esophageal cancer resumed oral feeding at postoperative meal start [postoperative day (POD) 1] [17
], and the importance of oral intake is increasing. In the present study, we enrolled patients between June 2009 and December 2010, and some differences existed due to the current trends of nutritional support. As we had been in the process of shifting the major nutritional management from total parenteral nutrition (TPN) to gut (EN and oral), we secured TPN and EN routes (standardizing at the time) in almost all patients at our hospital, and nutrition management was primarily based on EN.
The cephalic phase responses (CPRs) can explain the benefits of oral intake because they prepare the gastrointestinal tract for digestion and absorption [19
]. However, no studies have assessed whether postoperative nutritional management including oral intake affects short-term and long-term outcomes in patients with esophageal cancer.
In this study, we re-analyzed the patients enrolled in our previous prospective study [22
] to investigate the relationship between postoperative oral intake and prognosis, because we obtained substantial follow-up data in these patients.
Our retrospective analysis of previous cases with postoperative nutritional management primarily based on the EN route suggested that the POI group demonstrated poor prognosis compared to the control group that could manage oral feeding (as a more physiological route). In this study, we revealed that assessing the oral intake at the fourth week postoperatively in patients treated surgically for esophageal cancer was not only a predictor of postoperative nutritional status but also a novel predictor of the postoperative prognosis. Hence, we believe that this study supports the validity of active nutritional management using oral intake.
In postoperative nutritional management, the most general algorithm of nutrition administration has recommended that oral intake should take priority over EN and PN [10
]. We followed these algorithms and prioritized oral intake for perioperative nutritional management.
In nutritional management for critically ill patients such as those undergoing surgical treatment for esophageal cancer, reports about the selection of nutrition administration and nutrient quantity within at the first week postoperatively exist [32
], and their results stated the importance of early EN administration and the criteria of energy administration. However, these studies referred to the exclusive use of EN and PN. Moreover, those studies contain no suggestions about a relation between oral intake postoperatively and prognosis. Currently, several studies address the topic of efficacious postoperative direct oral feeding as part of “ERAS protocol [16
]”. In patients undergoing surgery for esophageal cancer, although the effect of postoperative early oral intake on long-term weight has been reported [37
], its effect on postoperative prognosis is unknown. Therefore, our finding suggesting a direct relation between postoperative oral intake and prognosis of patients is important and novel.
Although patients in the POI group fulfilled NR as calculated at the fourth week postoperatively using EN by jejunostomy, they had a significantly worse nutritional status at the sixth month postoperatively and their prognosis was worse than that for control group patients. This suggests that the fulfilling of NR at the fourth week postoperatively by EN or PN was insufficient. Our study suggests that it is important for patients to attain an adequate oral intake to improve their prognosis.
Hospital stay of the patients in the POI group was longer than that of the control group because the POI group exhibited a markedly higher rate of postoperative complications, morbidity, and meal interruption. Thereby, the POI group had a large number of patients whose transition from EN or PN to oral intake was delayed. However, owing to lack of marginal significance in the results of the univariate Cox proportional hazards model for these factors, we did not use these factors in the multivariate Cox proportional hazards model. Hence, we consider that “oral-E/NR < 25%” was a valuable prognostic factor than postoperative complications because “oral-E/NR < 25%” synthetically signifies more postoperative parameters (e.g., complications and comorbidities associated with oral intake, the motivation of oral intake, and patient’s appetite).
The benefits of oral alimentation are explained in part by the action of the CPRs. The role of CPRs is to prepare the gastrointestinal tract for food digestion and absorption by promoting physiological changes before food intake [20
]. CPRs stimulate the vagus nerve [38
]; this results in the release of biological active substances (saliva [39
], gastric juice [40
], and exocrine pancreatic juices [41
]) and hormones (insulin and glucagon [42
]). Furthermore, CPRs lead to increase in stomach motility [21
], changes in cardiac function [21
], rise in blood pressure [21
], increase in the respiratory quotient (as described in a study using rats [43
]), and increase in the metabolic rate by postprandial thermogenesis [44
] as a non-secretory reaction. A randomized controlled trial and an animal experiment in colorectal surgery indicated that oral and sham feedings (using chewing gum) enhance the autonomic nervous system more than enteral and parenteral routes, reducing inflammatory-based complications and length of hospital stay [45
]. Additionally, in upper gastrointestinal surgery, oral feeding reduces the complications and length of stay more than enteral route [48
Our study focused on patients surgically treated for esophageal cancer, and the study subjects were substantially different from those in the abovementioned reports. However, it is conceivable that the same benefits of the oral route of alimentation apply to our patients. In this study, we identified a novel independent predictor of the treatment outcome.
The present study suggests that a smooth transition to oral intake enhances not only the perioperative nutritional status but also the prognosis. At present, EN using jejunostomy primarily involves perioperative nutritional management in patients treated surgically for esophageal cancer to ensure adequate caloric intake. Conversely, focusing on the medical staff’s efforts on fulfilling the NRs using EN and PN could account for a delay in the transition from EN or PN to oral intake. Recently, development of the rehabilitation techniques of speech-language-hearing therapists and care food has contributed toward the improvement in patients with poor oral intake. In addition, improvement in oral intake was possible despite postoperative complications (e.g., dysphagia or obstruction and mastication disorder). Thus, a multidisciplinary team should engage even those patients who fulfill the NRs using EN and PN so that they too can re-establish an adequate oral intake during the postoperative hospital stay.
We are aware of the limitations of our study. First, the study included a relatively smaller sample size, which may confound the overall conclusion of this study. However, the 117 patients were treated at a single facility by the same surgical and nutrient management teams. Accordingly, we considered that the patients received uniform treatment and avoided problems associated with non-uniform treatment in multicenter studies. Second, our study did not investigate the differences in the expected and actual nutrient intakes to be provided in the hospital during the perioperative period and those after discharge. In a future study, we believe it will be interesting to consider a diet survey after hospital discharge and compare the oral intake between study groups at the sixth or twelfth month postoperatively.