Consensus guidelines on nutritional therapy for patients with biliary tumors

Source: Journal of Clinical Hepatobiliary Diseases 1 Background 1.
1 The incidence of malignant tumors of the biliary system Malignant tumors of the biliary system refer to the general term for malignant tumors that occur in the intrahepatic bile duct, left hepatic duct, right hepatic duct, common hepatic duct and common bile duct, including intrahepatic Cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder carcinoma and ampullary carcinoma
.

Among them, extrahepatic cholangiocarcinoma is also called cholangiocarcinoma
.

Although malignant tumors of the biliary system are not common in the world, their incidence is increasing year by year, and the degree of malignancy is relatively high
.

At present, the incidence of cholangiocarcinoma ranks 6th among malignant tumors of the digestive system and 2nd among malignant tumors of the hepatobiliary system, accounting for 3% of all malignant tumors of the digestive system [1]
.

More than 80% of malignant tumors of the biliary system are adenocarcinoma, 80%-95% are gallbladder cancer, and the peak age of onset is 70 years old [2-3]
.

The incidence of malignant tumors of the biliary system varies greatly in geography and ethnicity: the incidence is very high in Southeast Asia and the Americans, while the incidence in the United States and other countries is quite low
.

The incidence of malignant tumors of the biliary system in China is increasing year by year.
According to the report of China National Cancer Center in 2014, the incidence of gallbladder cancer in China is 3.
82/100,000, and the mortality rate is 2.
86/100,000[4]
.

Tumors of the biliary system have an insidious onset, lack of specific symptoms and effective early diagnosis methods, and only 25% of patients have the opportunity to undergo surgical resection
.

Most of the patients seek medical treatment because of upper abdominal pain, right upper abdominal mass and jaundice.
When this triad appears, the disease is mostly in the advanced stage, often accompanied by obstructive jaundice, liver failure and biliary infection, and the physical status and quality of life are poor
.

Regardless of whether or not they can undergo surgical resection, the prognosis of patients with cholangiocarcinoma is very poor.
The overall 5-year survival rate is only 5% to 10%, and there has been no significant improvement in 30 years [5]
.

Therefore, the palliative and supportive treatment of malignant tumors of the biliary system is particularly important, and its main purpose is to improve the quality of life and prolong survival time as much as possible
.

1.
2 Malignant tumors of the biliary system and malnutrition Because the incidence of malignant tumors of the biliary system is low and there are many types of tumors, there is no large-scale epidemiological survey to report the incidence of malnutrition, and there are only a few case studies
.

A case-control study compared the nutrition-related indicators of 153 patients with gallbladder cancer and 153 patients with gallbladder stones.
It was found that gallbladder cancer had a greater impact on the nutritional status of patients than gallbladder stones.
There were more patients with anorexia and weight loss, and their BMI , Serum albumin and hemoglobin levels are lower than those of patients with gallbladder stones [6]
.

Hilar cholangiocarcinoma is the most common type of cholangiocarcinoma.
It is difficult to operate and has a higher incidence of complications
.

Guo Jian et al.
[7] analyzed the data of 53 patients with hilar cholangiocarcinoma and found that the preoperative malnutrition rate was as high as 52.
4%
.

Miyata et al.
[8] evaluated the nutritional status of 71 patients with intrahepatic cholangiocarcinoma who underwent hepatectomy and found that the preoperative malnutrition rate was 43%.
A high preoperative control nutritional status (CONUT) score is a poor overall survival prognosis An independent predictor of the disease, but it was not found to be associated with postoperative complications
.

The biliary system is responsible for the important functions of collecting, concentrating and transporting bile to the intestine.
It is also the only pathway for the body to transport bile.
Once a tumor occurs in a certain part of the biliary tract, it can lead to poor bile drainage and obstructive jaundice
.

At this time, the nutritional metabolism of the body is mainly affected by the following aspects: (1) Reduced intake: lack of bile in the intestines suppresses appetite and slows down gastric emptying.
Obstructive jaundice can also cause abnormal liver function, which can cause abdominal distension and appetite.
Decrease and reduced food intake; (2) Absorption disorder: Bile plays an important role in the absorption of lipids.
The lack of bile in the intestine affects the absorption of lipids, leading to a deficiency of essential fatty acids; (3) Metabolism: Biliary tumors can also pass various mechanisms Causes abnormal carbohydrate, amino acid and fat metabolism
.

At the same time, comprehensive anti-tumor treatments, including surgery, drainage of obstructive jaundice, radiotherapy and chemotherapy, will also have an adverse effect on the nutritional status of patients
.

2 Evidence 2.
1 Indications 2.
1.
1 Indications for perioperative nutritional therapy Patients with malignant tumors of the biliary tract often have nutritional risks or malnutrition before surgery, and the operation is difficult, wide-ranging, and time-consuming, and co-infections are common
.

Patients with hilar cholangiocarcinoma with poor preoperative nutritional status (PG-SGA ≥4 points) have a higher postoperative complication rate than well-nourished patients.
Nutritional treatment before surgery can reduce the occurrence of complications [7, 9]
.

Therefore, perioperative patients with the following conditions need nutritional therapy[10-12]: (1) undergoing complex biliary tract surgery and there is nutritional risk (NRS 2002 score ≥ 3 points); (2) repeated biliary infections undergoing reoperation; (3) There is malnutrition before operation (more than 10% of body weight loss within 6 months; BMI<18.
5 kg/m2; serum albumin<3 g/dL); (4) No oral intake of food within a short period of time after operation; ( 5) Postoperative anastomotic leakage, gastrointestinal dysfunction, and severe infection
.

2.
1.
2 Indications for nutritional therapy for patients with radiotherapy and chemotherapy Indications for nutritional therapy for patients with radiotherapy and chemotherapy: (1) Receiving radiotherapy and chemotherapy, unable to eat, and reduced intake; (2) Malnutrition or inability to digest or absorb nutrients for a long time [13]
.

2.
1.
3 Nutritional treatment indications for end-stage patients.
Maintaining the nutritional status of patients at this stage is no longer important.
It should be combined with ethics, humanities, and family wishes, etc.
, while fully respecting the rights of patients and taking into account the rational use of medical resources.
As a prerequisite, determine the nutritional treatment plan
.

2.
2 Evaluation and diagnosis tools ADA, the Chinese Anti-Cancer Association Cancer Nutrition and Supportive Treatment Professional Committee all recommend NRS 2002 for nutritional risk screening, and PG-SGA for nutritional assessment of malignant tumors
.

Malnutrition is a risk factor for increased complications and increased mortality in cancer patients.
Therefore, nutritional assessment of patients with hilar cholangiocarcinoma and nutritional therapy for malnourished patients have become one of the key links in improving preoperative preparations[9 , 14]
.

2.
3 Energy requirements The energy requirements of patients with malignant tumors of the biliary system can be referred to other tumors of the digestive system
.

It is recommended that the total daily energy expenditure (TDEE) of perioperative patients is 30 kcal/(kg·d) for bedridden patients and 35 kcal/(kg·d) for ambulatory patients; if the intake is less than 60% of the target requirement , You need enteral nutrition and/or parenteral nutrition
.

50%~70% of the total energy comes from carbohydrates, and 30%~50% is provided by lipids; protein requirements increase from 1.
0~1.
2 g/(kg·d) (0.
15~0.
2 g nitrogen) before surgery to postoperative 1.
2~1.
8 g/(kg·d) (0.
2~0.
3 g nitrogen); sugars usually need to be taken in 3~4 g/(kg·d) to meet the demand, not less than 2 g/(kg·d) , The total amount should not be less than 100 g; lipids should be 1.
5~2.
0 g/(kg·d), but not more than 2 g/(kg·d); at the same time, ensure that the daily intake of minerals and vitamins is appropriate
.

If total parenteral nutrition is adopted, the energy supply of bedridden patients should be reduced to 25 kcal/(kg·d), and for ambulatory patients, 30 kcal/(kg·d)[10]
.

2.
4 Nutritional treatment pathways Nutritional treatment pathways include intravenous and enteral (oral, tube feeding) routes
.

The selection principle of nutritional therapy for biliary malignant tumors is basically the same as that of other malignant tumors, but it also has its characteristics [11]
.

(1) Biliary tract surgery is mostly limited to the upper gastrointestinal tract, and the bowel below the jejunum is less affected
.

Therefore, for patients who need postoperative nutritional therapy, it is recommended to add a T-tube jejunum or jejunostomy during the operation, and enteral nutrition can be started after the intestinal function is restored in the early postoperative period [12]
.

(2) For patients with preoperative malnutrition, especially with moderate or higher obstructive jaundice (total bilirubin> 171 μmol/L), it is recommended to place a tube through the mouth or nasal jejunum or through a T-tube jejunum.
Ways of enteral nutrition
.

(3) For patients with poor liver function reserves, large-scale hepatectomy or severe obstructive jaundice, biliary stent drainage or percutaneous hepatic biliary drainage (PTCD) for biliary decompression should be actively performed to improve the liver as soon as possible.
Function to promote the metabolism and absorption of nutrients
.

(4) PTCD is a widely used clinical method to treat malignant biliary obstruction
.

A large amount of bile is lost after PTCD, which seriously affects the patient's digestive function and body fluid balance.
How to reuse bile, restore the enterohepatic circulation of bile, and combine enteral nutrition to improve the nutritional status of patients has attracted much attention
.

A number of randomized case-control studies or retrospective analysis showed that patients with malignant obstructive jaundice who underwent PTCD, received bile reinfusion combined with enteral nutrition significantly improved gastrointestinal function compared with those who did not undergo bile reinfusion, including reduction of diarrhea and gastric emptying Reduced incidence of delay, increased tolerance of enteral nutrition, etc.
; nutritional status (BMI, triceps skinfold thickness, upper arm circumference), biochemical indicators (serum prealbumin, retinol binding protein, transferrin) Improved, and the body's inflammatory cytokine levels are lower, the hospital stay and the time of central venous catheter extubation are shortened [15-16]
.

In terms of the choice of the route of bile reinfusion, nasojejunal tube, jejunostomy tube or direct oral administration has no difference in improving the nutritional status of patients or reducing complications, but direct oral administration often involves more serious gastrointestinal reactions, and routine use is not recommended
.

2.
5 Preparations and formulas Early postoperative eating for patients with hilar cholangiocarcinoma can effectively reduce the incidence of complications such as infection, abdominal distension and urinary retention, and speed up the recovery of patients after surgery [17]
.

Cohort studies have shown that early postoperative nutritional therapy and dietary guidance for patients with biliary malignant tumors can improve gastrointestinal function, improve nutritional status, reduce gastrointestinal complications, shorten incision healing time, shorten hospitalization days, and reduce postoperative mortality Rate [18-19]
.

Early eating can also improve plasma prealbumin and albumin levels, which is a feasible diet management strategy
.

In addition to dietary guidance, patients with malignant tumors of the biliary system who started enteral nutrition early after surgery (2 hours after surgery) have early recovery of intestinal function, low incidence of biliary fistula, rapid recovery of postoperative body temperature, and low hospitalization costs
.

Perioperative supplementation of intestinal probiotics can effectively reduce the occurrence of postoperative complications and shorten the length of hospital stay
.

A randomized study of 54 patients undergoing hepatectomy for biliary tract cancer found that the incidence of infectious complications in the enteral nutrition and probiotic group was 19%, which was significantly lower than the 52% in the enteral nutrition group only [ 20]
.

Another prospective randomized double-blind study found that the incidence of postoperative infection in the probiotic group (26.
1%) was significantly lower than that in the placebo group (69.
6%).
The antibiotic treatment time in the probiotic group was shortened by an average of 6 days, and the probiotic group did not Died, while 6 cases died in the control group [21]
.

In the absence of contraindications to enteral nutrition, postoperative total parenteral nutrition can increase mortality, abdominal infection and gastrointestinal complications, and prolong hospital stay
.

Therefore, patients with hilar tumors without contraindications for enteral nutrition do not routinely use parenteral nutrition
.

However, when fasting patients cannot enteral nutrition on an empty stomach, parenteral nutrition is recommended
.

A randomized controlled study found that patients with biliary system tumors given total parenteral nutrition (1000 ml/d, 700 kcal) during the fasting period is conducive to maintaining body mass and improving body composition
.

For patients who need pancreaticoduodenectomy, administering immune-enhancing formula enteral nutrition (750 ml/d) for 5 consecutive days before surgery can effectively reduce the incidence of incision infection and reduce the incidence of postoperative sepsis [22]
.

The clinical benefit of routine supplementation of glutamine (Gln) after surgery for patients with malignant tumors of the biliary system is not clear
.

Gln is an important amino acid for synthesizing protein and muscle, and at the same time has the function of protecting the intestinal mucosa and regulating immunity.
When diseases and nutritional status are not good, the body's demand increases
.

However, a prospective randomized controlled double-blind study showed that in patients with malignant tumors of the biliary system who underwent pancreaticoduodenectomy, compared with the control group, patients who supplemented with Gln 0.
2 g/(kg·d) after surgery were hospitalized There are no significant differences in time, nutritional status, biochemical indicators, and the incidence of postoperative complications [23]
.

Therefore, after surgery for malignant tumors of the biliary system, the clinical benefit of using Gln as a routine nutritional supplement is not clear
.

2.
6 The implementation follows the five-step treatment model proposed by the Chinese Anti-Cancer Association Cancer Nutrition Therapy Professional Committee [24]
.

3 Recommendations ■ Patients with malignant tumors of the biliary system should undergo routine nutritional assessment during the perioperative period, and PG-SGA is recommended
.

(A)■ Patients with malnutrition before surgery are actively given preoperative nutritional therapy, which can effectively reduce complications and reduce the infection rate of the biliary system after surgery
.

(A)■ When the situation permits, start oral eating as soon as possible after the operation, and give proper nutritional treatment
.

(B)■ Patients without contraindications should be given enteral nutrition.
When enteral nutrition cannot be used and enteral nutrition cannot meet the target energy of 60%, parenteral nutrition should be started
.

(A)■ The clinical benefit of routine supplementation of Gln after surgery for malignant tumors of the biliary system is not clear (A), and supplementation of probiotics can effectively reduce the incidence of postoperative complications
.

(B)■ After PTCD in patients with malignant obstructive jaundice, bile reinfusion combined with enteral nutrition can significantly improve the nutritional status and reduce the occurrence of complications
.

(B) Writer: Li Wei (Tumor Center of Jilin University First Hospital) Consensus expert group members (ordered by surname strokes): Yu Shiying (Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology), Shi Hanping (Beijing, Capital Medical University) Shijitan Hospital), Cong Minghua (Tumor Hospital of Peking Union Medical College, Chinese Academy of Medical Sciences), Zhuang Zehao (First Affiliated Hospital of Fujian Medical University), Liu Lingxiang (First Affiliated Hospital of Nanjing Medical University), Jiang Hua (Sichuan Academy of Medical Sciences, Sichuan Provincial People Hospital), Xu Hongxia (The Third Affiliated Hospital of Army Military Medical University), Li Duo (Qingdao University Nutrition and Health Research Institute), Li Tao (Sichuan Cancer Hospital), Li Wei (Jilin University First Hospital), Zhang Xiaotian (Peking University Cancer Institute) Hospital), Chen Wei (Peking Union Medical College Hospital, Chinese Academy of Medical Sciences), Tao Yexuan (Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine), cite this article Chinese Anti-Cancer Association Cancer Nutrition Professional Committee, Chinese Medical Association Parenteral and Enteral Nutrition Branch .
Consensus on nutritional therapy for patients with biliary tract tumors[J].
Journal of Clinical Hepatobiliary Diseases, 2021, 37(9): 2058-2061.
Editor of this article: Wang Ying, public number editor: Xing Xiangyu