Pediatric Chronic Pancreatitis

　　First, the causes of disease

　　1. Common Causes

　　Common causes of chronic pancreatitis can be divided into three categories:

　　(1) Obstructive: Congenital ductal abnormalities, injury, sclerosing cholangitis, idiopathic fibrous pancreatitis.

　　(2) Calcification: Hereditary pancreatitis, tropical pancreatitis, biliary fibrosis, hypercalcemia, hyperlipidemia.

　　(3) Mixed: Mitochondrial myopathy, inflammatory bowel disease, idiopathic.

　　2. Chronic Calcifying Pancreatitis

　　(1) Hereditary Pancreatitis: It is an autosomal recessive genetic disease. The gene for hereditary pancreatitis is located on the long arm of chromosome 7. The arginine at position 117 of trypsinogen is replaced by histidine, leading to self-digestion of the pancreas and triggering pancreatitis.

　　Pathological findings include pancreatic atrophy, fibrosis, and calcification, with almost all acinar cells atrophic, duct obstruction, and extensive fibrosis. Islet cells are intact.

　　(2) Tropical (Nutritional) Pancreatitis: Tropical (Nutritional) Pancreatitis is a common cause of chronic pancreatitis in children. It is seen in some populations with insufficient nutritional intake in tropical regions such as southern India, Indonesia, and the equatorial regions of Africa. The cause is malnutrition and consumption of cassava flour, which contains toxic glycosides. The clinical course is similar to that of other types of chronic pancreatitis.

　　3. Chronic obstructive pancreatitis

　　(1) Pancreatic divisum: Pancreatic divisum has an incidence rate of 5% to 15% in the general population and is the most common malformation of the pancreas. Due to the failure of the dorsal and ventral pancreatic primordia to fuse, the tail, body, and part of the head of the pancreas are drained through a relatively narrow accessory pancreatic duct, rather than through the main pancreatic duct. Many scholars believe that pancreatic divisum is related to recurrent pancreatitis. ERCP can be used to diagnose pancreatic divisum. Papillary sphincterotomy is helpful.

　　(2) Abdominal trauma: After abdominal trauma, latent injury to the pancreatic duct can lead to stricture, pseudocyst formation, and chronic obstruction.

　　4. Idiopathic fibrosis pancreatitis

　　Idiopathic fibrosis pancreatitis is rare and can have abdominal pain or obstructive jaundice. The gland can show diffuse fibrous tissue hyperplasia.

　　5. Other

　　Patients with hyperlipidemia types I, IV, and V can develop pancreatitis. Hyperlipidemia can occur transiently during pancreatitis, so the elevation of blood lipids during acute pancreatitis must be re-measured after improvement. Other causes include cholecystosis, cholangitis, inflammatory bowel disease, and others.

　　2. Pathogenesis

　　Chronic pancreatitis has two main pathological types: calcified and obstructive. Both types are rare in children. In children, chronic calcified pancreatitis is seen in hereditary pancreatitis and idiopathic pancreatitis. The pancreas is hard, and calcareous stones can be felt during surgery. Obstruction occurs when a sticky plug composed of various proteins such as digestive enzymes, mucopolysaccharides, and glycoproteins fuses in the lumen of the duct. Calcium carbonate precipitation forms intraductal stones. There is also speculation that toxic metabolites exacerbate pancreatic damage.

　　Chronic pancreatitis often complicates with absorption disorders and maldevelopment, as well as diabetes, pancreatic cancer, and other diseases. Acute pancreatitis with mild symptoms rarely has complications, while severe acute pancreatitis often has multiple complications. These include pancreatic abscess, pseudocyst, organ failure, and secondary infections in the abdomen, respiratory tract, and urinary tract during the course of the disease. The spread of infection can cause sepsis. A few cases may evolve into chronic pancreatitis. Chronic pancreatitis is mainly manifested by chronic abdominal pain and insufficient exocrine and endocrine function of the pancreas, and it is related to the occurrence of pancreatic cancer. The most common complications are the formation of pseudocysts and mechanical obstruction of the duodenum and common channel.

　　1. Abdominal pain

　　Most children with chronic pancreatitis have intermittent or chronic abdominal pain, the cause of which is not very clear, mainly manifested in the upper abdomen, costal region, or umbilical area, with pain in the back as well. Vomiting and fever are not common, and sometimes the pain can last for several weeks, with varying degrees of pain. However, as the disease progresses, the pain can gradually subside.

　　2. Absorption disorders and maldevelopment

　　This clinical manifestation is mainly due to postprandial abdominal pain, which limits the intake of food and leads to insufficient nutritional supply. In addition, the low function of the pancreas affects the absorption of fats and proteins, with steatorrhea more common than protein diarrhea. This is because the decrease in lipase is more obvious than that of protease in the early stage of the disease. Although severe steatorrhea occurs, the absorption disorder of fat-soluble vitamins is less common, and only the malabsorption of vitamin B12 is more obvious. Blood lipids and urinary amino acids are all increased.

　　3. Diabetes

　　Abnormal sugar metabolism is due to the damage to the release of insulin and glucagon, which sometimes occurs in the early stage of the disease. Diabetes is the most common clinical manifestation of tropical pancreatitis in adolescents, and it can also be seen in calcified pancreatitis and alcoholic pancreatitis. At the same time as the insulin secretion is reduced due to the injury of islet cells, the insulin release into the blood is reduced due to the fibrosis around the islet cells causing circulatory disorders.

　　4. Malignant tumors of the pancreas

　　For some patients with chronic pancreatitis, the incidence of pancreatic cancer is significantly increased, and the level of this risk varies with the cause. It may also be a natural progression of some chronic pancreatitis. To date, there are no reports of pancreatic malignant tumors in patients with hereditary pancreatitis.

　　5. Other

　　Chronic pancreatitis with ascites is rare, and pleural effusion is even rarer. Some may cause subcutaneous fat tissue necrosis due to leakage of pancreatic enzymes into the blood, forming macules and nodules. Some patients may have abdominal masses, which may be inflammatory masses of the pancreas, or pseudocysts or benign or malignant tumors of the pancreas.

　　1. Bile duct diseases

　　Avoid or eliminate bile duct diseases. For example, prevent intestinal ascaris, timely treat bile duct stones, and avoid acute attacks of bile duct diseases.

　　2. Alcoholism

　　People who are accustomed to drinking alcohol are damaged to the liver, pancreas, and other organs due to chronic alcoholism and malnutrition, and their ability to resist infection decreases. On this basis, acute pancreatitis can occur due to a single episode of alcohol abuse.

　　3. Overeating and overdrinking

　　It can lead to gastrointestinal dysfunction, causing normal intestinal activity and emptying to be impaired, obstructing the normal drainage of bile and pancreatic juice, and causing pancreatitis

　　First, laboratory examination

　　1. General laboratory examination

　　(1) Serum amylase can increase during the acute attack, but in most cases, due to the obstruction of pancreatic juice secretion, serum amylase does not increase.

　　(2) The microscopic examination of feces shows a large amount of fat droplets and undigested muscle fibers.

　　(3) In some cases, the urine sugar reaction and glucose tolerance test is positive.

　　2. Pancreatic exocrine function test

　　(1) Pancreozymin-secretin test (pancreozymin-secretin, P-S test): It is the only method to directly check the secretion function of the pancreas in patients with chronic pancreatitis who are not too severe. Before the test, a P-S sensitivity test is performed, the child is fasting for 12 hours, a muscle injection of metoclopramide and diazepam is given before the examination, the throat is anesthetized locally with 2% tetracaine, and the gastrointestinal duodenal tube is inserted under the supervision of a fluorescence screen. The gastric drainage hole is located in the antrum of the stomach, and the distal hole is located at the lower end of the descending duodenum. When the duodenal fluid becomes clear and shows an alkaline reaction, collect 10-20 minutes of duodenal fluid for experimental control. Slowly inject secretin 2-3U/kg intravenously, collect duodenal fluid once every 10 minutes, twice in total, and then slowly inject secretin 1-2U/kg intravenously, collect duodenal fluid once every 10 minutes, three times in total. This test is within the normal range.

　　After giving the children with the disease pancreatin or cholecystokinin, the amount of pancreatic juice excreted, the amount of bicarbonate, and the amount of pancreatic enzymes excreted may be lower than the normal value.

　　(2) Benzoyl-tryptophan-p-aminobenzoic acid test (BT-PABA test, bentiromide test): For 3 days before the examination, avoid taking drugs that may affect the examination, such as pancreatin, sulfonamides, vitamin B2, etc. For 1 day before the examination, fasting is required at night, and 15 mg/kg BT-PABA (about 5 mg/kg PABA) is taken orally, which can be taken with a normal breakfast, normal water intake is allowed, and 6 hours of urine is collected. The content of PABA in the urine is determined, and the result is expressed as the percentage of PABA excreted in the urine to the amount taken. Normally, the excretion rate of PABA in 6 hours urine is 60％～87％，with an average of 70％. The excretion rate of chronic pancreatitis children is less than 60％. This test is more accurate in the progressive stage (sensitivity about 70％), but the sensitivity is low in the early stage or mild chronic pancreatitis. False positives may occur in liver and gallbladder diseases, kidney diseases, and small intestinal diseases.

　　2, Imaging examination

　　1, Abdominal X-ray

　　It can be seen that there is calcification of the pancreas or pancreatic duct stones.

　　2, Ultrasound

　　It can be seen that there are changes such as calcification of the pancreas, pancreatic duct stones, expansion of the pancreatic duct, local or diffuse enlargement or atrophy of the pancreas, and pseudocysts of the pancreas.

　　3, CT scan

　　It can be seen that the outline of the pancreas is irregular, there are calcification foci in the pancreas, the expansion or irregularity of the pancreatic duct, atrophy of the glandular body.

　　4, Endoscopic retrograde cholangiopancreatography

　　Pancreatic ductography shows dilatation of the lumen or irregular bead-like shape, with possible calcification or stones, and pseudocysts can also be seen.

　　5, Pancreatic angiography

　　Through the splenic artery or superior mesenteric artery of the duodenum, segmental stenosis or occlusion of intrapancreatic arteries or aneurysms can be seen, and intrapancreatic veins can also be stenosed or occluded.

　　1, Diet

　　Therapeutic diet for chronic pancreatitis (the following information is for reference only, detailed consultation is required with a doctor)

　　1, Juice of melon and fruit. White radish juice, watermelon juice, tomato juice, pear juice: water chestnut juice, mung bean sprout juice, etc., can be taken. It has the effects of clearing heat and detoxifying, and can also supplement vitamins. It is suitable for patients with acute pancreatitis who are just allowed to consume low-fat fluid food after fasting.

　　2, Drink of yellow flower and purslane. 30 grams of cauliflower, 30 grams of purslane. After washing both, put them into a pot, add an appropriate amount of water, boil with strong fire, then change to gentle fire and cook for 30 minutes. Cool and store in a jar. It can be taken as tea, which has the effects of clearing heat, detoxifying and reducing inflammation. It is suitable for the initial stage of pancreatic炎 when starting to eat fluid food.

　　3, finger citron porridge. 15 grams of finger citron, 50 grams of glutinous rice. Boil the finger citron juice, remove the residue, add the appropriate amount of glutinous rice and water, cook into porridge, add a moderate amount of rock sugar when it is about to be done, and eat it when the porridge is done. It has the effects of regulating Qi, relieving pain, and invigorating the spleen and nourishing the stomach.

　　4, cinnamon, licorice, and white peony root. 20 grams of cinnamon, 40 grams of white peony root, 12 grams of licorice, 20 grams of ginger, 12 dates, boil the water, remove the residue, and add 100 grams of glutinous rice, cook into porridge, and take it in several doses. It can invigorate the spleen and calm the stomach.

　　5, cardamom porridge. 10 grams of cardamom, 10 grams of ginger, 50 grams of glutinous rice. First, cook the glutinous rice into porridge, then add the ground cardamom powder and ginger, and cook into porridge. It can regulate Qi, relieve pain, and dispel cold, and is used to treat acute pancreatitis with cold symptoms.

　　6, pork pancreas powder. Dry the pork pancreas with low heat and grind it into powder, fill it into capsules, and take it in several doses daily. It contains various pancreatic enzymes and can act as a substitute therapy, effective for patients with indigestion and steatorrhea.

　　7, hawthorn and lotus leaf tea. 30 grams of hawthorn, 12 grams of lotus leaf. Boil the two drugs in 2 bowls of clear water, reduce to 1 bowl, remove the residue and take it separately. It can promote digestion and assist digestion, and can treat chronic pancreatitis with indigestion.

　　8, seaweed and cassia seed tea. 20 grams of seaweed, 10 grams of cassia seed. Boil the two ingredients in 2 bowls of water, reduce to 1 bowl, take it all at once, and take it twice a day. It is beneficial for the alleviation of chronic pancreatitis.

　　9, dried ginger porridge. 3 grams of dried ginger, 3 grams of rhizoma galangal, 50 grams of glutinous rice. First, boil the dried ginger and rhizoma galangal in water, remove the residue and take the juice, then add the cleaned glutinous rice and cook into porridge. Take it in several doses. It has the effects of invigorating the spleen and warming the stomach.

　　10, Evodia fruit porridge. 2 grams of evodia fruit, 2 slices of ginger, 2 scallions, 50 grams of glutinous rice. Boil the glutinous rice in water, add the finely powdered evodia fruit and ginger, and chop the scallions, then cook into porridge. Take it in several doses daily. It has the effects of harmonizing the stomach and stopping vomiting, regulating Qi and relieving pain.

　　11, crucian carp porridge. 10 grams of amomum villosum, 10 grams of calamus, 10 grams of tangerine peel, one crucian carp, 10 grams of Sichuan peppercorn, 10 grams of pickled chili, scallions, garlic, and salt to taste. Clean the crucian carp, put the above medicine and spices in the abdomen, and cook into porridge as usual, and take it in several doses. It has the effects of dispelling cold, regulating Qi, and relieving pain, and is used for chronic pancreatitis.

　　Two, areca nut drink

　　Usage: Wash 10 grams of areca nut clean, boil in an appropriate amount of water for 30 minutes, then add 5 grams of amomum villosum and boil for another 5 minutes, remove the residue and take the juice. Effect: Promote Qi and dissolve stones, harmonize the middle, mainly for chronic pancreatitis with dampness and turbidity blocking, symptoms such as decreased appetite, abdominal distension, sticky and uncomfortable stool, greasy mouth, and heavy sensation all over the body.

　　Three, braised crucian carp

　　Usage: Remove the scales and internal organs of crucian carp (about 300 grams), wash it clean; wrap 10 grams of tangerine peel and 3 grams of amomum villosum in gauze, add 3 grams of table salt, scallions, and a moderate amount of vegetable oil. Add the above ingredients to a sufficient amount of water, cook together until soft, then remove the medicine bag and it can be eaten. Effect: Promote Qi, benefit fluid, and dry dampness, mainly for elderly chronic pancreatitis with symptoms such as abdominal distension and pain, and decreased appetite.

　　Four, others

　　Usage: Wash hawthorn 15 grams, malt 30 grams, and glutinous rice 100 grams, and then take them as is. Effect: Dissolve food and relieve accumulation, activate blood circulation, mainly for chronic pancreatitis with symptoms such as abdominal pain, loss of appetite, and discomfort in the chest and abdomen.

　　1. Treatment

　　The main goal of treatment is to alleviate symptoms and control complications.

　　1. Abdominal pain

　　During the acute phase of pain, the treatment methods are similar to those for acute pancreatitis. For children with chronic pancreatitis, pain control is important, but it can sometimes be difficult. Steroidal or non-steroidal anti-inflammatory drugs can be used; pancreatic enzyme supplementation to inhibit the secretion of cholecystokinin. During the intermission period, when patients have no obvious pain, symptomatic treatment can be administered.

　　If general analgesics are ineffective, sometimes analgesics are needed, but morphine类药物 is limited due to its ability to cause sphincter of Oddi spasm. For patients with mild symptoms, methods to limit pancreatic secretion can be used to alleviate pain, such as the application of large doses of pancreatic enzyme preparations to feedback-inhibit pancreatic secretion. Oral citrates and disodium EDTA (EDTA) can alleviate pancreatic calcification and pain, but the mechanism is unclear. If pain is difficult to control and drug treatment fails, endoscopic or surgical procedures can be performed to relieve pancreatic duct obstruction, but the efficacy of treatments such as resection of the celiac plexus or pancreas is not very certain.

　　2. Dietary treatment

　　Malabsorption is common in chronic pancreatitis, but the incidence rate in children is unclear. Treatment can be with pancreatic enzyme preparations, and a balanced diet supplemented with vitamins should be consumed.

　　The purpose of dietary treatment is to alleviate symptoms and improve the patient's overall condition. Appropriate restriction of fat intake can alleviate the patient's pain and steatorrhea. However, while considering symptom relief, it is important to ensure that children receive sufficient calories and protein for their development. Some children may benefit from a small and frequent meal schedule. The supplementation of pancreatic enzymes can also alleviate steatorrhea and protein diarrhea, and if symptoms do not improve during treatment, the dose can be increased. However, when the gastric pH is less than 4, the activity of pancreatic enzymes is limited, and enteric-coated pancreatic enzyme preparations can be used to improve the transmission of active enzymes. At the same time, acidifying agents, such as H2 receptor antagonists, should be added to maintain the pH of the digestive tract at approximately 4-5. If these methods do not improve steatorrhea, it should be considered whether there is an associated small intestinal mucosal disease. In patients with marked malnutrition, parenteral nutrition can supplement intestinal malabsorption. A diet low in fat, high in protein, and high in carbohydrates is recommended, and in some cases of malnutrition, where fat intake is limited in the diet, the use of medium-chain triglycerides may be considered.

　　3. Pseudocyst

　　Acute and chronic pancreatitis can both lead to pseudocystic lesions of the pancreas. Pseudocysts are cystic structures that are often limited to the lesser omentum sac, and they can communicate with the pancreatic duct, containing high concentrations of pancreatic enzymes. The occurrence of pseudocysts is often latent, and they are occasionally discovered in the upper abdomen when they become large, or they may cause abdominal pain, distension, and a feeling of fullness upon palpation. More often, they are detected during an ultrasound examination. Pseudocysts can cause compressive obstruction, and depending on the size and location of the cyst, they can cause obstruction of the pancreatic duct and other organs outside the pancreas (such as the bile duct, duodenum, and stomach). Pseudocysts can also lead to hemorrhage or infection, and if they rupture, they can cause peritonitis. Small pseudocysts can generally resolve spontaneously or persist for a long time without symptoms. If the cyst is large and has not shown a tendency to shrink after 6 weeks, drainage treatment should be considered. There are various methods of drainage, which can be performed under the guidance of ultrasound or CT, or by surgery.

　　4. Diabetes

　　When chronic pancreatitis is complicated with diabetes, it is usually mild, and ketosis acidosis is rare. If the content of urinary glucose is very high, treatment is needed, and a relatively small dose of insulin is required to maintain blood glucose levels. Many patients can control urinary glucose satisfactorily with oral hypoglycemic agents. If the effect of oral hypoglycemic agents is not significant, insulin can be used. Pancreatic-inflammatory diabetes patients are very sensitive to insulin, and some patients may experience severe hypoglycemia when applying a small amount of insulin, which may be due to the decreased secretion of glucagon from the pancreas. Patients with diabetes secondary to chronic pancreatitis are less likely to have cardiovascular complications, which is different from patients with idiopathic pancreatitis.

　　5. Biliary Obstruction

　　Obstruction of the distal common bile duct can cause cholestasis, jaundice, cholestatic liver cirrhosis, cholangitis, and other conditions. Sometimes these may be the initial symptoms, and chronic pancreatitis is discovered later, but they may also be symptoms caused after the onset of chronic pancreatitis. Treatment mainly focuses on draining the biliary system.

　　Chronic pancreatitis is usually treated with medical treatment. Patients with the following indications can be treated surgically:

　　(1) Intractable chronic abdominal pain.

　　(2) Common bile duct obstruction.

　　(3) Pancreatic duct obstruction and dilation.

　　(4) Pseudocysts and their complications.

　　It is often difficult to determine the effectiveness of treating abdominal pain in surgical treatment. For obstruction of the bile duct and pancreatic duct, ERCP can be first used for diagnosis. After diagnosis is clear, methods such as nasobiliary drainage and sphincterotomy can be used for treatment. If the pain decreases after ERCP treatment, it can be further predicted that the effect of drainage by surgical operation will be better. For stone obstruction of the common bile duct and pancreatic duct, the best treatment effect can be achieved if the stones can be surgically removed. For non-stone obstruction of the bile duct and pancreatic duct, methods such as sphincterotomy oroplasty are commonly used, or biliary-enteric anastomosis or pancreatic-enteric anastomosis can be applied. Partial resection of the pancreas is often used for localized lesions in the body and tail of the pancreas, and pancreatectomy with duodenectomy is used for lesions in the head of the pancreas. For severe persistent abdominal pain, subtotal pancreatectomy can be effective, but it can cause insufficient exocrine and endocrine function of the pancreas after surgery. For patients with complete loss of pancreatic function, pancreatic transplantation can have certain efficacy.

　　II. Prognosis

　　The prognosis of this disease is poor.