Hepatobiliary disease including hepatitis, pancreatitis, cholecystitis, alcoholic liver disease, cirrhosis, hepatocellular carcinoma and pancreatic cancer in East Asia is prevalent and accounts for half of the total global incidence. And 5–20% of them will undergo high risk hepatobiliary surgery each year for both benign and malignant disorders.1

The liver, gallbladder and pancreas are the main organs of nutritional metabolism, including protein synthesis, glycogen storage, fat digestion and detoxification. These functions become damaged to a greater or lesser extent in patients with diseases, resulting in various metabolic disorders, and their disturbed nutritional condition is associated with disease progression. Most patients present with significant weight loss due to anorexia and malabsorption, and are expected to have a period of inadequate oral intake up to 10 days after surgery.23 Malnutrition of different degrees will occur in at least more than half of these patients.4

Therefore, essential nutritional support and nutrition therapy for patients with hepatobiliary and pancreatic diseases undergoing surgery is very important, as it may improve clinical outcome.56 However, considering the nutrient metabolism abnormalities during the perioperative period, the nutritional support and fluid therapy could become complex. How to implement rational fluid therapy and nutritional support after surgery and effectively protect organ function is crucial for postoperative recovery.7

Perioperative nutrition is a well recognized aspect of care in recent years and has been shown to reduce the incidence of complications and to reduce hospital stay.8 Although clinical research has shown that early delivery of nutrition via the gastrointestinal tract after severe injury can reduce septic morbidity and mortality in critically injured patients,910 evidence suggests that routine post-operative enteral nutritional support may lead to increased incidence of gastric stasis.11 Currently the effects of nutritional supplements given to initiate enteral nutrition (EN) or peripheral nutrition (PN) are still debated. The aim this study was to examine the safety and efficacy of parenteral nutrition fluid (MG-TNA®) in patients undergoing surgery for hepatobiliary and pancreatic disease.

During a 5-month period, a total of 32 patients were enrolled. However, 2 patients failed to meet the inclusion criteria and failed the screening test as well. As a result, 30 patients completed the study and were included in the full analysis set. Mean age was 57.23±10.77 and male to female ratio was 2 to 1 (Table 1). Most patients underwent surgery due to malignant disease. Liver resection was the most common operation performed (43.3%) (Table 1). There was a significant decrease in serum prealbumin and CK on the third postoperative day (p<0.0001). Although not significant, serum transferrin levels tended to decrease (p=0.0519) (Fig. 2). During the study period, patient vital signs, physical examination and laboratory results revealed no adverse effects. Also, there was no mortality case.

Metabolic alterations of hepatobiliary disease are characterized by hyperdynamic changes, hypermetabolism, and catabolism. Hyperdynamic changes raise energy expenditure through increasing cardiac output and activation of the sympathetic nervous system, decreasing systemic vascular resistance, and so on.12 Hypermetabolic defined as resting energy expenditure (REE) >120% compared with the expected value. Studies have reported 30% of patients with ascites, cirrhosis or hepatocellular carcinoma are considered hypermetabolic.13 Catabolism is another significant metabolic alteration. Isotope techniques have been used to demonstrate that patients with hepatobiliary disease have a significantly higher urea production compared with controls, indicating both increased protein catabolism and diminished muscle protein synthesis. Abnormal metabolism of carbohydrate and fat also occur with hepatobiliary disease.12 This may result from cortisol and catecholamine increased, while glucose clearance and oxidation diminished. In hepatobiliary disease, glucose intolerance occurs in 40–90% of cases, and insulin is required in as many as 80% of patients. Not only does hepatobiliary disease cause metabolism change occurred, hepatobiliary surgery transiently aggravated the changes.12 After liver resection, patients appear to have increased level of aminotransferase, caused by surgical trauma, damage of liver cell and liver ultrastructure, and release of inflammatory mediators.14

A decreased level of nutrients can affect many systems and functions including respiratory failure, cardiac and neurological dysfunction, and insulin resistance. Hypo/hyperglycemia, hypocalcaemia and hypophoshataemia particularly after major resection should not be ignored and require correction.12 Malnutrition adversely affects the prognosis of these hepatobiliary patients, and poor nutritional status in patients undergoing surgery is well known to increase postoperative morbidity by deteriorating various organ functions and the immune system of the patients.15 If patients are unable to maintain adequate intake via the mouth, artificial nutrition is used to improve nutritional status.

Perioperative nutritional support composes with pre-operative and postoperative nutrition. At present, the view about pre-operative nutritional therapy is that the treatment should be provide to hepatobiliary patients with serious malnutrition or who prepare to have major surgical treatment with mild to moderate malnutrition. The main purpose is to improve the nutritional status of the patients, to improve their operation tolerance, reduce or avoid postoperative complications and mortality.1617 Postoperative nutrition should be provide to patients who have accepted with preoperative nutritional therapy, or who have severe malnutrition and/or complications after surgery. Patients fasting more than 1 week also need postoperative nutrition support.12

EN improves nutritional status and liver function, enhanced immunocompetence, decreased clinical infection rates, maintained gut structure and function, potentially attenuate catabolic stress responses in patients after surgery and prolongs survival.17 However, postoperative total enteral feeding is associated with complications such as diarrhea, abdominal distention, and abdominal cramps. These symptoms worsen with increasing caloric intake and can lead to discontinuance of enteral feeding. Nutritional treatment strategy accepted by majority practitioners is that EN support should be actively applied, if the gastrointestinal anatomy and function allows. Otherwise PN should be applied until gastrointestinal function recovery.18

PN is an intravenous administration of nutrients delivered into a large-diameter vein or a peripheral vein.2 If the patients enduring diffuse peritonitis, intestinal obstruction intractable vomiting, paralysis of intestine or intractable diarrhea, PN should be supply first until gastrointestinal function resume. PN offers the possibility of increasing or ensuring nutrient intake in patients in whom normal food intake is inadequate and EN is not feasible.212

However, parenteral nutrition can be complicated by many metabolic problems, which may arise from inadequate or excessive amounts, or from inappropriate composition of nutrients. The most severe complications are cholestatic liver disease and bone disease.19 Also catheter-related and infectious complications can occur.19 In our study, there were no complications in patients receiving PN partially because of peripheral administration of PN.

Demirer et al.20 reported a potential beneficial effect of soybean oil/olive oil based lipid emulsions for use in PN regarding inflammatory response and oxidant capacity in the treatment of patients. In their study, decrease from baseline in serum prealbumin and transferrin levels was observed on the 4^th postoperative day in all groups receiving PN which was similar to the results of our study.20

At present, most experts believe that PN combined with EN should be considered when EN cannot satisfy the energy needs for patients who has indications of nutritional support.21 There is also some evidence that nutritional supplementation with immunonutrient formulas containing arginine, fish oil lipid emulsion with omega-3 fatty acids, dextrose, and structured triglyceride may offer a benefit in terms of preserved liver function and better clinical outcome leading to improved wound healing, decreased infectious morbidities and shorter hospital stay. Concomitant administration of glutamine-enriched early EN and PN proved to be a potent protectant against intestinal mucosal barrier injury after liver transplantation.202223

However, there are limitations to this study. The small size of the study cohort, the single arm nature of this study and short administration period of the peripheral nutrition fluid may have limited the results of this study. Future multi-arm studies with a larger cohort with longer administration of peripheral nutrition fluid are needed.

In conclusion, administration of peripheral nutrition fluid (MG-TNA®) during the postoperative period in patients undergoing surgery for hepatobiliary and pancreatic disease proved to be safe and may improve the nutritional state of the patient.