Pancreatic surgery is complicated and difficult, involving multiple organ resection and reconstruction of digestive system. Surgical trauma and stress, digestive tract reconstruction, postoperative gland loss, serious postoperative complications will affect nutritional status, postoperative recovery and clinical outcomes of patients.
Moreover, due to the special pathophysiological changes of pancreatic and duodenal diseases, many patients will have clinical manifestations such as pain, jaundice and digestive tract obstruction before operation, and produce nutrition-related secondary symptoms such as anorexia, fatigue and progressive weight loss, resulting in high nutritional risk, cancer-related sarcopenia and malnutrition. These preoperative nutrition disorders are all related to serious postoperative complications such as pancreatic fistula and infection. So nutritional problems should be considered through the whole perioperative period and a whole-course nutrition management strategy is required.
Whole-course nutrition management refers to a systematic, standardized, personalized and quantitative nutrition strategy that dynamically adjusts nutrition intervention according to indicators such as disease severity, nutritional status, demand and intake of patients from admission to discharge and should contain standardized rational nutrition support process consisting of 3 steps: nutritional screening, nutrition assessment, and nutrition intervention.[4,5] In 2019, 2 prospective randomized controlled trials (RCT) in the fields of general medicine and oncology showed that the whole-course nutrition management could improve the clinical outcomes, including reducing all-cause mortality and adverse reactions of radiotherapy and chemotherapy, and improving quality of life and psychological state.[6,7] However, perioperative whole-course nutrition management is a new concept which has never been mentioned in the field of surgery and no prospective research published at present.
This article reviews the current situation, consensus and controversy of perioperative nutrition management in pancreatic surgery, expecting to provide necessary guidance for clinical research and practice.
Database search strategy
We searched PubMed and Google Scholar for English articles and Wanfang database for Chinese articles that were published between 2000 and 2020 with key words such as pancreas, pancreatic surgery, pancreatectomy, pancreatoduodenectomy, nutrition support, nutrition therapy, nutrition management, perioperative, postoperative, and complication. We aimed to review the current situation, consensus and controversy of perioperative nutrition management in pancreatic surgery and provide necessary guidance for clinical research and practice.
Nutritional screening and choice of screening tool
Nutritional screening is a process of judging patients’ nutrition-related risks by using validated nutritional screening tools. It can identify patients who may benefit from a nutritional intervention preoperatively. In 2020, ESPEN consensus on perioperative nutrition support recommended that nutritional screening should be done at least 10 days before operation, so as to help discover nutrition problems and start nutrition care in time. Numerous screening tools have been validated in hospitalized patients, yet there is still lack of consensus and controversy of perioperative nutrition management in pancreatic surgery.
At present, nutritional risk screening 2002 (NRS2002) is the first choice for adult inpatients recommended by many guidelines due to its evidence-based character and convenient conduction process. NRS2002 contains 3 parts: nutritional status impairment score, disease severity score and age score. When the total score is ≥3, there is a “nutritional risk”, and it is necessary to make a nutrition care plan. A single-centre cross-sectional survey in China showed that the prevalence of nutritional risk of patients underwent pancreatoduodenectomy was as high as 69.7%. When the total score is ≥5, it can be defined as “high nutrition risk”.[11,12] NRS2002 has been validated prospectively by RCTs and cohort studies with the conclusions that patients at nutritional risk would benefit from nutrition support, including patients undergoing major abdominal surgery and pancreatic surgery.[13,14] In China, nutrition risk has been stipulated by the government policy to be the indication for the reimbursement of parenteral and enteral nutrition agents by medical insurance. In the recent published Chinese national survey, among 96 pancreatic surgeons, 66.7% would choose NRS2002 for preoperative nutritional screening.
In 2018, the American Society for Enhanced Recovery proposed a new screening tool named perioperative nutrition screen (PONS). The PONS determines nutrition risk based on body mass index (BMI), recent changes in weight, recent decrease in dietary intake, and preoperative albumin level. It was designed as a modified version of another validated screening tool called malnutrition universal screening tool (MUST), which was recommended to be used in community by ESPEN, yet there is still no high-grade validation of this newly created tool.
Nutrition assessment and further evaluation
Nutrition assessment is a process of further evaluation the nutritional status of hospitalized patients with nutritional risk. It consists of 2 parts: basic assessment and malnutrition assessment. Every patient at nutritional risk needs basic assessment, which contents nutrition-related medical history, dietary survey, physical examination (height, weight, etc), and laboratory examination (liver and kidney function, blood glucose, blood fat, electrolyte, acid-base balance, etc). All of these are routinely collected, and are necessary for making nutrition treatment plans and implementing monitoring.
Malnutrition assessment involves the diagnosis and severity classification of malnutrition, but there are no global unified criteria at present. In 2019, a diagnostic consensus was published called “Global Leadership Initiative on Malnutrition (GLIM)”, which contains 2 parts: phenotypic criteria (3 components: body weight loss, low BMI and reduced muscle mass) and etiologic criteria (2 components: food intake or assimilation reductions and disease burden or inflammation), and fulfilling at least 1 component in each part is necessary to diagnose malnutrition. In China, the prevalence of malnutrition diagnosed by GLIM in patients underwent pancreatoduodenectomy was as high as 56.6%. Cohort studies have found that malnutrition diagnosed by GLIM has a significant correlation with poor outcomes.[21,22] In 2020, a cohort study based on Chinese data pointed out that nutritional support can reduce the incidence of infection complications of malnourished patients diagnosed by GLIM, and this difference is particularly significant for cancer patients and major surgery patients.
Other malnutrition assessment tools, such as subjective global assessment (SGA) and patient generated SGA (PG-SGA), have different recommendations from different guidelines. At present, researches in the fields of liver transplantation and gastrointestinal surgery have confirmed that SGA has obvious correlation with adverse outcomes.[24,25] 2017 ESPEN guidelines in surgery and 2018 International Study Group on Pancreatic Surgery (ISGPS) consensus on nutrition support recommended grade C by SGA as one of the indications of preoperative nutrition support.[5,26] However, in 2017, ESPEN guidelines on definition and terminology only suggested SGA to be used as a tool to assist nutrition assessment, but not a mandatory one. After the publishing of GLIM, it might be replaced gradually. In the national survey in China, only 9.4% of pancreatic surgeons would choose this tool to evaluate the nutritional status. To sum up, there is still a lack of high-quality research evidence for diagnosis of malnutrition based on GLIM, SGA and PG-SGA in pancreatic surgery.
Application of body composition assessment
Nutrition assessment includes the assessment of human body composition, which mainly contains 2 parts: lean body mass or muscle evaluation and fat evaluation. Sarcopenia is characterized by progressive muscle loss and functional decline, and is significantly related to postoperative chemotherapy intolerance, postoperative pancreatic fistula, early postoperative recurrence, prolonged hospital stay and short survival. According to different assessment criteria, the prevalence of sarcopenia in pancreatic cancer patients was 21.3% to 86.3%.[27–29] Sarcopenic obesity is a subtype of sarcopenia and is a combination of muscle loss and visceral fat increase. The incidence and mortality of pancreatic fistula after operation in patients with muscular dystrophy obesity were significantly higher than those in normal patients.
The assessment methods include the evaluation of muscle mass and muscle function. The former includes dual-energy X-ray absorption, bioelectrical impedance, CT and MRI images, and anthropometry such as calf circumference and upper limb circumference. The latter includes muscle strength measurement such as grip strength and exercise performance measurement such as pace rate. At present, most of the literatures retrieved in the field of pancreatic surgery are retrospective cohort studies, and the results all show that the above measurement indexes are significantly correlated with postoperative pancreatic fistula, mortality and readmission rate. Because of the limitation of the measurement method and the lack of uniform measurement and cut-off in China, it cannot be widely used in clinical practice, but it provides a direction for clinic al research of pancreatic surgery.
Preoperative nutritional support
Patients in pancreatic surgery have rates of high nutritional risk and malnutrition before operation, so some patients may benefit from preoperative nutritional support. In 2018, ISGPS recommended the nutrition support indications as follows: (1) Weight loss is more than 15% within 6 months; (2) BMI < 18.5 kg/m2; (3) SGA Grade C; (4) NRS 2002 > 5 points; (5) Albumin < 30 g/L with normal liver and kidney function. These indications are mostly derived from the studies of major abdominal surgery, but no data in pancreatic surgery has been published. In 2019, guidelines for perioperative care for pancreatoduodenectomy from ERAS Society only took weight loss of more than 15% and BMI of less than 18.5 kg/m2 as indications of preoperative nutritional support. Meanwhile, the American Society for Enhanced Recovery recommended positive PNOS result as the indication of preoperative clinic or dietician nutrition intervention.
Among these indications, weight loss is the most reliable and widely used indication. With regard to the degree of weight loss, a survey from the United States in 2015 pointed out that 71% of patients with pancreatic head cancer will lose more than 3% of their weight at the time of diagnosis, 42% of them will lose more than 10%. The weight loss is related to the outcome. Albumin is a sensitive biochemical marker and a strong predictor of surgical risk/mortality, so it is an important part in PNOS. However, the American College of Gastroenterology (ACG) Guidelines suggested that albumin be treated as an inflammatory response marker rather than the change of nutritional status. Referring to NRS2002 score, a prospective cohort study of abdominal surgery proved that preoperative nutritional support can reduce infection complications and total complications in patients with NRS2002 ≥ 5 scores. In the field of pancreatic surgery, only one bi-centre retrospective cohort study has been published, showing that preoperative nutritional support for patients with NRS2002 ≥ 5 could significantly reduce the incidence of postoperative pancreatic fistula.
Most patients with pancreatic surgery at nutritional risk can start nutritional support with fortified diet and oral nutritional supplement (ONS). For patients with high nutritional risk or malnutrition, if these routes cannot meet the target, enteral nutrition (tube feeding), supplementary parenteral nutrition (SPN) or total parenteral nutrition should begin. 2017 ESPEN guideline recommended preoperative nutritional support for 10 to 14 days. Most Chinese studies recommend the duration should be at least 7 days.[10,35] The diet and formula of ONS should supply high protein, that means at least 1.2 g/kg/d protein should be provide, and for some preoperatively malnourished patients, the protein should reach up to 1.5 to 2.0 g/kg/d, and the calorie should reach at least 70% of physiological demand, often 25 kcal/kg/d.[5,17]
Intraoperative nutritional management
Role of the operation procedures
Operation procedures in pancreatic surgery, such as pancreaticoduodenectomy, total pancreatectomy and drainage operation of chronic pancreatitis, involve digestive tract resection and reconstruction, which will affect the metabolic and nutritional status. According to recent literatures, most studies focused on pancreaticoduodenectomy, and there are some high-quality RCTs and meta-analysis, including the comparison between pylorus-preserving pancreaticoduodenectomy and standard procedure, between pancreatogastrostomy and pancreaticojejunostomy,[37,38] between loop anastomosis and Roux-en-Y anastomosis, between laparoscopic and open surgery, and between robotic and laparoscopic surgery. However, there is no study on the relationship between surgical procedures and their direct influence towards nutrition, and no special nutrition-related parameters were reported. In these studies, the parameter indirectly related to nutrition was the incidence of delayed gastric emptying (DGE), which was considered to be the most common reason for changing nutrition management strategy after operation and no significant difference was found between cohorts.
Therefore, in order to reduce the influence of operation procedure on postoperative nutrition status, it does not rely on the operation procedure itself, but on the quality of operation, which depends on the experience of the surgeons and the volume of the hospital.
Placement of feeding tubes intraoperatively
Feeding tubes include jejunostomy, nasojejunostomy tube (NJT) and nasogastrotomy (NGT). Due to the application of ERAS and development of endoscopic technology, most pancreatic surgeons do not choose to place feeding tubes routinely during operation, but choose to place them when necessary after operation.[26,43,44] According to the national survey, 8.3% of surgeons routinely performed jejunostomy, which was similar to the data published in Europe (12%). However, jejunostomy is an invasive procedure with a risk of complications. 30.3% of surgeons routinely choose NJT, which was considered as the best route, but the probability of tube withdrawal (34%–40%) was higher than that of jejunostomy, and there was also the problem of poor patient comfort.[46,47] In 2018, ISGPS recommended to place a feeding tube for patients with one of the following indications: (1) preoperative malnutrition; (2) high risk of postoperative complications; (3) unplanned second operation.
Postoperative nutritional management
There are many RCTs, cohort studies and meta-analysis in the field of pancreatic surgery, which confirm that the strategy of ERAS including early oral feeding after surgery is safe and feasible.[48–50] Compared with tube feeding, oral feeding has the advantages of safety and physiology, and it also avoids the complications related to the tube and the psychological burden of patients on the indwelling tube. An RCT on early diet after gastrointestinal surgery including pancreatic surgery showed that taking food at will on the first day after surgery did not increase the incidence of complications compared with fasting and jejunostomy, and could improve the function of digestive tract. With the practice of ERAS and the improvement of surgical skill, it is possible for patients to recover their diet early after pancreatic procedures, which was also recommended as the first choice of nutritional support in domestic and foreign guidelines.
There are 2 problems in oral feeding, one is the patient's tolerance. Some cohort studies found that the patients’ tolerance for oral intake was 50%-82% on the first day after operation, and the tolerance for solid diet was 55%-86% on the second to third days after operation, which did not increase the incidence of related complications, but complications would obviously affect the patients’ tolerance[54,55]; The second problem is calorie and protein targeting. At present, there are few studies focusing on this problem. It is difficult to reach the target of calorie and protein only by oral feeding in the early postoperative period, especially within 5 days after operation. In most studies, the calorie was often below 1000kcal per day, but compared with the control group of parenteral nutrition, it did not increase the incidence of adverse events.
Therefore, if patients are at good nutritional status before operation, it can be considered not to apply enteral nutrition (tube feeding) and parenteral nutrition support, and at least 50% of energy and protein intake target should be gradually reached within 7 days after operation. While patients with high nutritional risk or malnutrition before operation should start enteral nutrition (tube feeding) or parenteral nutrition support early after operation.
Postoperative enteral nutrition (tube feeding) includes 2 situations. One is that patients with indwelling nutrition tube during operation can start enteral nutrition within 24 hours after operation. Compared with parenteral nutrition, there is evidence that it can reduce the rate of infection complications, postoperative pancreatic fistula and delayed gastric emptying; the second situation is postoperative placement of feeding tube, which is mainly used when oral feeding is insufficient. The feeding tubes include NGT, NJT, PEG/J, etc, and many factors should be considered such as application reasons, estimated nutrition support duration, technic of tube placement and patient tolerance. NGT is not the choice because of its high possibility of reflux and aspiration, PEG/J is an invasive procedure, and more studies suggested choosing NJT.[59,60]
Though at present, most guidelines recommend oral feeding to be started on the first day after pancreatic surgery, and PN is not a routine recommendation, PN is still the most preferred nutrition support route in China on the first day after operation (78.1%). However, due to the influence of pancreaticoduodenectomy on digestive tract, the interruption rate of postoperative enteral nutrition is high, which easily leads to insufficient intake.[61,62] Some RCT studies have not found the difference between EN and PN in postoperative outcomes,[63,64] and a meta-analysis showed that PN could significantly reduce the mortality and the incidence of infection complications for patients with preoperative malnutrition. Therefore, although postoperative PN is not a routine recommendation, it is necessary to choose SPN or TPN when oral or tube feeding is intolerant, oral or tube feeding fails to meet nutrient requirements, and when postoperative complications affect gastrointestinal function.[66,67]
At present, retrospective studies showed that the energy targeting rate of EN combined with PN was 93.4%, which could improve the liver function, reduced the incidence of complications and shortened the length of stay compared with TPN.[68,69] So, in the field of pancreatic surgery, EN combined with PN can be used as the choice of nutritional support after pancreatic surgery for at least 4 days, but there is still a lack of high-quality report.
Surgical trauma will lead to insulin resistance in the early postoperative period, which makes the metabolism of nutrients difficult. At the same time, the catabolism increases, which will produce endogenous heat of about 1400 kcal/d. Therefore, for patients with good nutrition status before operation, nutrition targeting is not emphasized within 3 days after operation. Goal-oriented liquid therapy and oral administration of clear or liquid diet are sufficient to meet the needs of patients and stabilize the internal environment. At 4 to 7 days after operation, it can gradually start diet or diet combined with ONS with the target energy of 25kcal/kg/d and protein of 1.5 g/kg/d. If the oral route fails to reach 50% of the demand for 7 days after operation, EN or PN should be considered, and if there is contraindication of EN, start TPN immediately. For patients with high nutritional risk or malnutrition before operation, EN can be started as early as possible after operation, PN can be selected according to the nutritional targeting, so as to reduce adverse outcomes.[71,72] During the progress of transition of various nutritional support routes, the amount of nutrients and liquid should be accurately calculated to prevent over-feeding.
Nutritional management under severe postoperative complications
Postoperative pancreatic fistula
Postoperative pancreatic fistula (POPF) is a common complication after pancreatic surgery. According to 2016 ISGPS diagnostic criteria, the incidence of grade B and grade C pancreatic fistula in large pancreatic centres in China is about 20%, and one quarter of them are grade C pancreatic fistula. It was recommended to start EN or PN for grade B and grade C fistulas, and started oral feeding for biochemical leaks. In 2018, this organization issued a recommendation on nutritional support for pancreatic surgery, which proposed to select individualized strategy for patients with pancreatic fistula of grade B and grade C, not only considering the grade, but also considering the severity. For patients with stable biochemical leakage and mild pancreatic fistula, there is not enough evidence to support the need to avoid oral feeding. For severe pancreatic fistula patients, artificial nutrition is needed because of poor tolerance to oral feeding.
There are high-quality studies to evaluate the effect of different nutrition routes on pancreatic fistula. For oral feeding, one RCT in Japan in 2015 compared oral feeding with TPN, and the results showed that oral feeding did not prolong the time of pancreatic fistula and hospitalization. Another RCT in Taiwan, China in 2019 compared oral feeding with EN by gastrojejunal tube. The results showed that oral feeding did not prolong the healing time of pancreatic fistula and had significant advantages in shortening length of stay and reducing hospital costs. Both studies are aimed at grade B and C POPF after pancreaticoduodenectomy.[75,76] For the choice of artificial nutrition, an RCT study involving pancreaticoduodenectomy in 2012 pointed out that compared with TPN group, the 30-day pancreatic fistula healing rate and healing time were better in EN group by NJT.
Therefore, when POPF occurs, the choice of nutritional support routes should take into account the classification and severity of POPF, the functional status of digestive tract and the nutritional demands. Personalized management should be implemented.
Gastric emptying disorder
DGE is the most common complication after pancreaticoduodenectomy with the prevalence of 15% to 35%. DGE is the most important indication for restarting parenteral and enteral nutrition support after pancreatic surgery. According to the definition of ISGPS classification, patients with grade A DGE can resume oral feeding within 2 weeks after operation, while patients with grade B and C DGE often need artificial nutritional support. It has been pointed out in the review literature that it is difficult for surgeons to choose NJT or PEG/J when DGE occurs, mainly because the procedures are invasive, and secondly because the surgeons are uncertain about the duration of DGE.
In the Chinese national survey, when DGE occurs, 72.9% of doctors will start enteral nutrition through PEG/J or NJT, among which 50% would choose SPN at the same time, and only 24% would use TPN. Some case control studies suggested that enteral nutrition support by NJT should be the first choice of nutritional support when DGE occurred.[79,80] There are few high-quality studies on the timing of placing NJT after DGE, and it has been reported in a review that it is more appropriate to place NJT 7 days after DGE occurs.
Postoperative exocrine insufficiency
Diagnosis of PEI
Pancreatic exocrine insufficiency (PEI) is a common complication after pancreatic surgery. The incidences of PEI are about 60–100% after pancreaticoduodenectomy, 0–40% after pancreatectomy and 10% after middle segment pancreatectomy.
Clinical manifestation is an important part of diagnosing PEI, including 2 aspects. One is symptoms secondary to the presence of undigested food in the intestinal lumen (fatty diarrhoea, flatulence, and dyspeptic symptoms) and the other is symptoms associated with the loss of nutrients (weight loss, fat-soluble vitamin deficit). However, due to the compensatory ability of pancreas, the clinical manifestation only exists when less than 10% of functional pancreatic tissue remains. Therefore, it is necessary to focus the diagnosis of asymptomatic PEI through objective examination, but it is seldom carried out in China. Fecal elastase-1 (FE-1) test is the most commonly used test, but some studies have pointed out that FE-1 has poor correlation with postoperative steatorrhea, and its diagnostic value is not clear. 13C-labelled mixed triglyceride breath test (13C-MTG) could be used as an alternative method, but it still needs further study. At present, there are no good examination that could reflect the poor absorption of carbohydrate and protein caused by insufficient pancreatic exocrine secretion.
Treatment of PEI
Although the incidence of PEI is high, the diagnosis and treatment rates are low at present. Studies have shown that pancreatic enzyme replacement therapy (PERT) is significantly related to the survival data after pancreaticoduodenectomy, especially for the subgroup with pancreatic duct diameter larger than 3 mm. PERT should be used for life after total pancreatectomy and used routinely for at least 6 months after pancreaticoduodenectomy. When PEI-related symptoms appear in patients with distal pancreatectomy, PERT should be applied.[88–90]
The recommended initial dose of PERT is 40,000 to 50,000 units of lipase for each dinner and 10,000 to 20,000 units of lipase for snacks. The commonly used monitoring indicators are symptom changes such as frequency of steatorrhea and weight change. 13C-MTG can be used as an objective index when available.
Because of the important physiological function of fat, it is not recommended to use low-fat diet routinely. If fat indigestion still exists after applying enough PERT, fat intake can be reduced on the premise of ensuring sufficient carbohydrate and protein supply. At present, diet control is mostly based on clinical experience, and there is no good research evidence.
Postoperative endocrine insufficiency
Endocrine insufficiency after pancreatectomy mainly refers to postoperative diabetes, also known as type 3c diabetes mellitus, pancreatogenic diabetes mellitus, brittle diabetes mellitus or refractory diabetes mellitus. Due to surgical resection, the number of islet cells decreases, and when more than 50% islet β cells lose, the risk of postoperative diabetes will increase. The incidence of newly onset diabetes after pancreaticoduodenectomy is 15% to 41%,[92,93] and it is 8% to 54% after distal pancreatectomy. Preoperative chronic pancreatitis and preoperative impaired glucose tolerance are reported to be risk factors of new onset diabetes after operation.
Brittle diabetes after total pancreatectomy seriously affects postoperative nutritional status and is related to poor prognosis. A retrospective study revealed that with the cooperation of strict blood glucose control and nutritional support, it would take at least 3 months to stabilize blood glucose level and restore nutritional status after total pancreatectomy. Long-term blood glucose control can refer to the treatment of type I diabetes, and continuous subcutaneous insulin pump and continuous blood glucose monitoring will benefit patients.[96,97] Adequate patient education and timely consultation in endocrinology department are all necessary contents. The target of postoperative blood glucose control is 7.2 mM and glycosylated haemoglobin is below 7.0%.
Total pancreatectomy with islet auto transplantation may be an effective method to prevent postoperative diabetes, which is suitable for patients with chronic pancreatitis and some benign tumours requiring total pancreatectomy. However, the technology is complex and the postoperative exogenous insulin dependence rate is high. Further study is needed.
Since this is a narrative review, there are some limitations. The search and evaluation of literature are relatively rough and not like systemic review and meta-analysis, no data collection and re-analysis were conducted in the article. However, we tried our best to provide a framework in this field, and provided a perspective for future research and review. So we could conclude that the concept of rational nutrition support should run through the whole course of perioperative nutrition management. There are still problems and controversies in pancreatic surgery. The evidence level of recent reports is not high and a prospective study is urgently needed.
The concept of rational nutrition support should run through the whole course of perioperative nutrition management. There are still problems and controversies in pancreatic surgery. The evidence level of recent reports is not high and prospective study is urgently needed.
Conception and design of the manuscript, data analysis, and manuscript writing: JW, JX; administrative support: JW; data collection: JX. All authors approved the final version of the manuscript.
This work was supported by the Capital Characteristic Clinical Project Supported by Beijing Municipal Science & Technology Commission (No. Z181100001718216) and Beijing Hospital Nova Project (No. BJ-2020-082).
Conflicts of interest
No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. The authors declare no conflict of interest.
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