Gastrinoma

Introduction to gastrinoma Gastrinoma, Zhuo-Ai syndrome, is a clinical syndrome characterized by refractory or unusual peptic ulcer, high gastric acid secretion, and non- islet cell tumor. The cause of gastrinoma is unknown and may be derived from the 1 cells of the pancreas. Because gastrinoma is more common in pancreatic tissue, less common in other tissues outside the pancreas, and the tumor is small, sometimes accurate positioning of the tumor is difficult, but in recent years, with the improvement of B-ultrasound, CT or MRI diagnostic techniques, it is tumor Positioning creates good conditions. If the tumor has no distant metastasis, the tumor can be cured after resection. basic knowledge The proportion of illness: 0.0005%--0.0009% Susceptible people: no specific population Mode of infection: non-infectious Complications: gastrointestinal bleeding, perforation of ulcer disease, diarrhea

Gastrinoma etiology

Abnormal gastrin secretion (40%)

Due to the nutritional effects of gastrin, the gastric mucosa is hypertrophied, and the wall cell volume can reach 3-6 times that of normal people, resulting in excessive secretion of gastric acid and gastric juice. Gastrinoma is seen almost anywhere in the abdominal cavity, and is not limited to the pancreas as previously thought. In addition to the pancreas (21%-65%), the duodenum is also a high-risk area (33% to 38%).

Genetic factors (10%)

Multiple type I endocrine tumors are autosomal gene abnormalities with high penetrance. This gene is located on chromosome 11, and all patients with multiple type I endocrine tumors may involve 3 organs (parathyroid, islet and pituitary), but There is not always a clinical manifestation of excessive hormones. Patients with multiple type I endocrine tumors with hyperparathyroidism usually develop gastrinoma.

Pathogenesis

Gastrin: The gastrin which is biologically active in gastrinoma and gastric antrum mucosa is mainly 17-peptide gastrin (G17), while the gastrin in the blood of patients with gastrin has 34 amino acids. Larger configuration (G34), gastrin in the blood circulation of healthy people and general peptic ulcer patients is also this type, sulfur in the serum of gastrinoma patients and normal people (gastrin II) and no Sulphur (gastrin I) two configurations, the serum sulphur gastrin (59%) in patients with this disease is higher than ordinary duodenal ulcer and gastric ulcer patients and normal people (37%), there is evidence It is indicated that the detection of the specificity of the gastrin antibody in the serum of G17 gastrin in patients with metastatic gastrinoma is higher in normal and non-metastatic gastrinoma patients, except for the detection of specific gastrin antibody in the serum of patients with metastatic gastrinoma. G17 and G34, there are other smaller and larger gastrin in serum and gastrinoma in patients with gastrinoma, including gastrin component 1, which is a slightly larger configuration than G34. Two species are smaller fragments, namely the 1 to 13 fragment of the amino terminus of G17 and the carboxy terminal 14 peptide amide (microgastrin), before It has no biological activity, while the latter has the same immunogenicity and biological activity as G17. High concentrations of unspliced progastrin and other gastric secretions can also be found in plasma and gastrinoma tissues of gastrinoma patients. Precursor, in addition, there are a large number of glycine-extended, non-bioactive gastrin and progastrin in plasma and gastrinoma tissues of patients with gastrinoma, which constitute some of the main gastrinoma patients. Immunogenic gastrin in tissues and blood circulation.

The total number of gastric parietal cells in gastrinoma patients is significantly increased, estimated to be at least 3.6 times that of normal people, 2.3 times that of patients with common duodenal ulcer. The hypertrophic effect of hypergastrin on wall cells increases the total number of parietal cells. Enhances the ability of the stomach to secrete hydrochloric acid. Gastric pheochromocytosis in the stomach of patients with gastrin and small multi-center non-invasive gastric carcinoids composed of chromaffin cells may represent a high level of blood circulation to gastrin. Nutritional effects.

Gastrinoma prevention

Stomach disease is a common disease. It includes various gastritis, such as superficial gastritis, atrophic gastritis, ulcer disease, and good and malignant tumors in the stomach. Clinical experience has proven that stomach disease can be prevented. Pay attention to the Ten Commandments in your life.

First, stop long-term mental stress

Long-term mental stress affects the autonomic nervous system through the cerebral cortex, causing vasoconstriction of the gastric mucosa, gastric dysfunction, excessive secretion of gastric acid and pepsin, leading to gastritis and ulceration, clinically seen long-term anxiety and depression, gastric ulcer and The incidence of duodenal ulcers is significantly higher.

Second, stop overworked

No matter whether you are engaged in physical labor or mental work, you should not be overworked. Otherwise, it will cause insufficient blood supply to the digestive organs and disorder of gastric mucosal secretion, which will lead to various stomach diseases.

Third, quit eating and hunger

The hunger and satiety is very harmful to the stomach. When the hunger is empty, the gastric acid and pepsin secreted by the gastric mucosa can easily damage the stomach wall, causing acute, chronic gastritis or ulceration. Overeating will cause the stomach wall to over-expand, food. Staying in the stomach for too long, it is also easy to cause acute, chronic gastritis or ulcers, and even acute gastric dilatation, gastric perforation.

Fourth, abstain from alcoholism

Alcohol can cause congestion and edema in the gastric mucosa, and even ulceration and ulceration. Long-term drinking also damages the liver, causing alcoholic cirrhosis. Pancreatitis is also associated with alcoholism, which in turn increases the damage to the stomach.

Fifth, quit smoking and smoldering

Smoking causes vasoconstriction of the gastric mucosa, which reduces the synthesis of prostaglandins in the gastric mucosa. Prostaglandins are a protective factor of the gastric mucosa, which reduces the damage of the gastric mucosa. Smoking also stimulates the secretion of gastric acid and pepsin. Addiction to tobacco is an important cause of various stomach diseases.

Six, ring tea coffee

Both strong tea and coffee are central stimulants. Through nerve reflex and direct influence, the gastric mucosa can become congested, secretory dysfunction, mucosal barrier destruction, and ulcer disease. In addition, attention should be paid to foods with strong gastric irritability. edible.

Seven, quit eating and gorging

Chewing slowly is beneficial to the digestion of food. When eating, it is swallowed. If the food is not fully chewed, it will increase the burden on the stomach. The study also found that the secretion of saliva increases when chewing slowly, and the role of protecting the gastric mucosa can avoid bad stimulation. Damage to the gastric mucosa.

Eight, quit sleeping and eating

Sleeping food not only affects sleep, but also stimulates gastric acid secretion and easily induces ulcers.

Nine, do not talk about hygiene

It has been found that Helicobacter pylori infection is the culprit leading to the pathogenesis of gastritis, ulcers and stomach cancer. It can be transmitted through tableware, dental tools, kissing, etc. Therefore, it is hygienic, and it is possible to prevent Helicobacter pylori infection by using other people's tableware and dental appliances. Thereby, various stomach diseases can be prevented.

X. Drugs for supervision

Many drugs can damage the gastric mucosa, causing erosive gastritis and hemorrhagic gastritis and gastric ulcer. Among them, there are three commonly used drugs that can damage the gastric mucosa: one is antipyretic analgesics such as aspirin, phenylbutazone , indomethacin, etc.; one type is hormonal drugs such as prednisone, dexamethasone; and one type is antibacterial drugs such as erythromycin, etc., pay attention to the application of these drugs, strictly in accordance with the doctor's advice to avoid Causes damage to the stomach.

Gastrinoma complications Complications, gastrointestinal bleeding, perforation, diarrhea

About one-fourth of patients have gastrointestinal bleeding, about one-fifth of patients have perforation of ulcer disease, 20% to 30% of patients have diarrhea, mostly watery stools, sometimes steatorrhea, and it is not uncommon to have other endocrine tumors. .

Gastrinoma symptoms Common symptoms Zhuo-Ai syndrome liver metastasis liver failure diarrhea high gastrinemia peptic ulcer steatorrhea

The most common clinical manifestation of gastrinoma patients is peptic ulcer, which is found in 90% to 95% of patients with gastrinoma. The clinical symptoms are often similar to those of patients with common peptic ulcer, but the symptoms are persistent and progressive. The response to treatment is poor. The distribution of upper gastrointestinal ulcers in gastrinoma patients is similar to that of common peptic ulcers. About 75% of patients with gastrinoma are located in the first segment of the duodenum. Gastric ulcers are rare. 1/2 to 2/3 of gastrinomas are malignant. The most reliable indicator of the malignancy of gastrin is their biological behavior, that is, whether the tumor has metastasis, but histological changes and biological activities are not obvious. In connection, malignant gastrinoma is usually painless and slow to grow. However, in a small number of patients with gastrinoma, the tumor grows rapidly and has extensive metastasis earlier, which can be transferred to regional lymph nodes, liver, spleen, bone. Mediastinal, peritoneal surface and skin, duodenal gastrinoma usually metastasize to local lymph nodes, less metastasis to the liver, prospective studies have shown that lymph node metastasis and liver metastases in patients with gastrinoma clinical process differences, Surgery found that only patients with local lymph node metastasis and no liver metastasis rarely died due to tumor invasion, and their survival period often reached or exceeded 25 years without tumor progression tendency. In fact, lymph node metastasis of gastrinoma patients and surgery were not found. The clinical course of patients with tumors is similar. On the contrary, the life expectancy of patients with liver metastasis is significantly shortened, averaging about 8 years, often leading to liver failure due to the progressive growth of tumors.

Serum HCG and , subunit levels are often increased in patients with metastatic gastrinoma, serum -HCG levels are increased in 20% of patients with malignant gastrinoma, and -HCG levels are significantly elevated in patients with gastrinoma with extensive metastasis Increased, while serum -HCG levels did not increase in patients with benign gastrinoma.

Patients with gastrinoma often have single or multiple ulcers. Compared with common peptic ulcers, gastrin ulcers can be located in the second, third or fourth part of the duodenum, even in the jejunum. Sexual investigations showed that 14% of the ulcers were located in the distal part of the duodenum, 11% were located in the jejunum, and patients with gastrinoma were often moderately large or small (less than 10 mm in diameter), but a few ulcers were larger and the diameter exceeded 20mm, prosthetic proximal or distal ulcer is prone to occur after surgery, and often accompanied by serious complications such as bleeding and (or) perforation, gastrinoma patients may have reflux esophagitis, esophageal ulcer and esophageal stricture, by Peptic reflux disease caused by gastrinoma patients is more common and serious.

More than one third of patients with gastrinoma develop diarrhea, and can precede the symptoms of peptic ulcer for 8 years. About 7% of patients with gastrinoma develop diarrhea without ulcer disease. The diarrhea is mainly due to the upper digestive tract. A large amount of hydrochloric acid causes the gastric juice in the stomach to reduce or eliminate diarrhea. The gastrin in the circulation may directly affect the secretion and absorption of the small intestinal mucosa. Especially the gastrin in the blood vessels can increase the intestinal secretion K and Reducing the absorption of water and sodium by the jejunum can cause diarrhea. The serum gastrin and gastric acid secretion rate of normal duodenal ulcer patients are normal. They usually do not have diarrhea, which is the basis for the theory.

A small number of patients with gastrin have steatorrhea, and the mechanism of causing steatorrhea is related to the following factors:

1. Lipase is easily acidified by a large amount of hydrochloric acid in the upper small intestine, which is irreversible and inactivated. After the lipase is inactivated, the triacylglycerol cannot be hydrolyzed into diglyceride, monoglyceride and fatty acid, resulting in fat absorption disorder.

2. The low pH in the small intestine makes certain primary bile acids insoluble and lipid micelle formation reduced, while the latter is necessary for the absorption of fatty acids and monoglycerides.

Gastrinoma patients may have malabsorption of vitamin B12, which is not related to internal factors. Although the function of gastric secretion is normal, the low pH in the small intestine affects the function of internal factors to promote the absorption of vitamin B12 in the distal jejunum. When the pH is adjusted to 7, this function is restored.

Gastrin tumor examination

Laboratory inspection

1. Determination of gastric acid secretion: Most (79%) patients with gastrinoma have a basic gastric acid secretion rate of >15mmol/h, and can be as high as 150mmol/h. Some people think that comparing the amount of basal gastric acid secretion and the maximum amount of gastric acid secretion after stimulation can diagnose the stomach. It is useful for normal tumors, but patients with common ulcers and even some normal people sometimes have high rate of acid secretion, while 1/2 to 2/3 of patients with gastrinoma have a lower basal acid secretion than the maximum amount of acid. %, so its value is still suspicious. At present, many medical institutions no longer use this technology, and some other diagnostic methods have basically replaced this test.

2. Gastrin determination: The most sensitive and specific method for the diagnosis of gastrinoma is to determine the serum gastrin concentration. In normal ulcers and normal people, the average fasting serum gastrin level is 50-60pg/ Ml (or less), high limit of 100 ~ 150pg / ml, fasting serum gastrin levels in patients with gastrinoma often > 150pg / ml, the average level is close to 1000pg / ml, sometimes as high as 450,000pg / ml, Clinically, patients with peptic ulcer symptoms and high gastric acid secretion, when the concentration of fasting serum gastrin is significantly increased (>1000pg/ml), the diagnosis of gastrinoma can be established, there are reports of gastrin patients fasting serum stomach When the level of hormone is >1500pg/ml, it should be highly suspected to be metastatic gastrinoma.

If there is a history of hypergastrinemia or urinary calculi in the past or present, unexplained diarrhea, multiple ulcers, or patients with distal duodenal or jejunal ulcers suspected of gastrinoma, should be detected Serum gastrin levels; patients with a family history of endocrine diseases, especially multiple type I endocrine neoplasia, recurrent ulcers after surgery, and drug-treated ulcer symptoms can not be improved.

It should be noted that some diseases that lead to decreased gastric acid secretion can also cause an increase in serum gastrin, such as pernicious anemia. Patients with pernicious anemia are comparable to serum gastrin in patients with gastrinoma, but the pH of gastric contents in patients with pernicious anemia is even Under the maximum stimulation, it will not be less than 6. Infusion of 0.1 mmol/L hydrochloric acid in patients with pernicious anemia can lower the serum gastrin level to approximately normal, which helps to distinguish from gastrinoma.

Film degree exam

1. X-ray barium meal examination: radiographic abnormalities have certain value for the diagnosis of gastrinoma, gastric folds often prominent and the stomach contains a lot of liquid, but similar large stomach folds are also seen in patients with giant hypertrophic gastritis, gastric lymphoma or Other invasive diseases, other X-ray signs of gastrinoma include: thickening of mucosal folds in the duodenum and part of the jejunum, dilatation of the duodenum, separation of the small intestines, and a large amount of fluid in the small intestine. It causes irregular flocculent sedimentation of the tincture. The upper digestive tract barium meal examination generally does not show pancreatic gastrinoma, but tumors protruding from the duodenal wall are often found.

2. Excitation test: Several gastrin challenge tests have been used to diagnose gastrinoma. These tests have the greatest value for patients with insignificant serum gastrin increase, such as patients with highly suspicious gastrinoma and serum gastrin. If the concentration of the hormone is a critical value or a slight increase (150-1000pg/L), the stimulation test is necessary to establish or exclude the diagnosis. The main stimulation tests are: secretin stimulation test; calcium challenge test; standard meal stimulation. The test, each test requires multiple determinations of serum gastrin concentration.

(1) Secretin stimulation test: It is the most valuable stimulation test for patients with gastrinoma. In normal people or patients with common duodenal ulcer, serum gastrin levels can be slightly reduced after intravenous injection of secretin. Invariant or slightly increased, on the contrary, in patients with gastrinoma, intravenous injection of secretin often induces an extremely high concentration of serum gastrin. Currently, pure porcine secretin 2U/kg is intravenously injected within 30 minutes, and serum samples are used. Radioimmunoassay, after intravenous injection of secretin in patients with gastrinoma, the serum gastrin concentration increased at least 200pg/L at least rapidly (within 2-10min), then gradually returned to the pre-injection level, after intravenous injection of secretin. More than 95% of gastrinomas have a positive reaction, and false positives in this trial are rare.

(2) Calcium challenge test: In the calcium challenge test, the radioimmunolabeled gastrin in the blood sample was measured 30 minutes before the injection of the calcium agent, and the radioimmunolabeled gastrin in the blood sample was measured every 30 minutes after the start of the experiment. A total of 9 times, 80% of patients with gastrinoma showed increased gastrin release after infusion of calcium, and the concentration of most gastrinoma patients increased significantly (increase >400pg / L), while normal or ordinary There is only a slight increase in ulcers. The highest gastrin concentration is usually achieved at the beginning of the injection. The sensitivity and specificity of the calcium challenge test are worse than the trypsin challenge test. If the gastrinoma test does not have a secretin challenge test. A positive reaction generally does not respond to the calcium challenge test.

(3) Standard meal stimulation test: standard meal includes 1 piece of bread, 200ml milk, 1 boiled egg, 50g cheese (including 20g fat, 30g protein, 25g sugar), 15min before feeding, 0min and every 1min after feeding Blood samples were taken for gastrin values until 90 min after ingestion.

Gastrin in patients with gastrinoma is characterized by fasting gastrinemia (over 150 pg / L), rapid and significant increase in serum gastrin (increased by more than 200 pg / L) after intravenous injection of secretin, calcium A significant increase in serum gastrin after the infusion (increased by more than 400 pg/L). The most common error in the interpretation of fasting serum gastrin levels is the diagnosis of gastrinoma after the discovery of hypergastrinemia. It should be noted that gastric acid deficiency or hypochlorhydria is more common than gastrinoma, causing hypergastrinemia. Once there is fasting gastrinemia, it should be determined whether it is high gastric acid secretion or gastric acid deficiency or hypoacidity. The above examination should be completed before any initiation of the challenge test (such as the secretin challenge test). If hypergastrinemia is caused by gastric acid deficiency or hypoacidity, there is no need for further examination of gastrinoma. The gastrin challenge tests of the three diseases are listed in Table 1.

3. Tumor localization: Gastrinoma must be located after the diagnosis of gastrinoma is confirmed. However, it is often difficult or even difficult to locate the position of gastrinoma. About 40% to 45% of patients have exact Clinical and laboratory evidence, but tumors were not found during surgery. Somatostatin receptor scintigraphy has higher sensitivity than other imaging methods and is usually the preferred method. Although CT is less sensitive to primary tumors, However, it is widely used because it is easy to implement, and can also be used to detect abdominal metastases.

If there is a significant liver metastases, surgery or percutaneous biopsy is feasible. The bone metastases only occur in those patients with liver metastases. Accurate detection can be obtained by somatostatin receptor scintigraphy, if no tumors or metastases are found. The lesion is clinically highly suspicious, and either endoscopic or double-slice CT scans can be used.

If these methods are not able to locate the tumor, the patient can perform angiography. In recent years, it has been suggested that selective angiography can detect about 1/3 of gastrinoma with clinical and biochemical evidence (about 60% can be found by surgery). However, angiography can not distinguish between intratumoral tumors and adjacent duodenal wall tumors. Selective abdominal and hepatic artery angiography is the best means to identify and determine intrahepatic metastasis of gastrinoma. CT scan can show about 30. % of gastrinomas, with low sensitivity for ultrasound, only 15% positive, it is reported that combined use of selective angiography and CT can detect gastrinoma in 44% of patients with gastrinoma and 80% Gastrinoma, which was later located in the operation, but visceral angiography and CT could not diagnose tumors less than 1.5 cm in diameter. The positive rate of gastrinoma on MRI was not high, and its value was about the same as that of abdominal ultrasound. The positive rate of MRI in the diagnosis of intrahepatic metastatic gastrinoma is inferior to selective angiography and CT, and it can not be detected in tumors less than 1cm in diameter. The tumor display rate of more than 3cm is only 30%. Recently, it is considered that the new type of magnetic Vibration imaging technology has great value in gastrinoma localization. Upper gastrointestinal endoscopy can detect gastrinoma located in the proximal duodenal wall. Combined with the above several techniques, it is more than a single method. effective.

Gastrin concentration gradients of portal vein and its branches have been used for portal gastrin localization by portal vein sampling, but the technique is difficult. Some scholars believe that the positive rate of this test is similar to CT, while other scholars report that when When all imaging examinations were negative, it found approximately 63% of lesions. Recently, it has been reported that selective gastroduodenal, spleen, and superior mesenteric artery are injected with secretin to localize gastrinoma, according to the organ after injection. The distribution of gastrin is different in the arterial gastrin, and the selective secretin arterial injection test can be used for the localization of gastrinoma that can not be found by CT, ultrasound and selective angiography.

Diagnosis and diagnosis of gastrinoma

The clinical manifestations of gastrinoma, especially primary gastrinoma, are indistinguishable from common ulcers, but there are some clinical conditions that can highly suggest the diagnosis of gastrinoma: the distal segment of the duodenum; Multiple ulcers of the digestive tract; usually ulcer treatment is ineffective; rapid recurrence after ulcer surgery; patients with peptic ulcer and diarrhea or diarrhea that is difficult to explain; patients with a typical family history of peptic ulcer; patients with parathyroid or pituitary tumors History or related family history; patients with peptic ulcer with urinary calculi; Helicobacter pylori-negative peptic ulcer without a history of non-steroidal anti-inflammatory drugs; with high gastric acid secretion or high gastrinemia or both .

Differential diagnosis

1. Peptic ulcer: peptic ulcer with a single ulcer or stomach, duodenum has an ulcer (complex ulcer) more common, gastric or duodenal multiple ulcers are relatively rare, such as the following conditions should be highly suspect Gastrinoma:

(1) Duodenal ampullary ulcer.

(2) Peptic ulcer is still ineffective after conventional doses of antisecretory drugs and regular course of treatment.

(3) ulcers rapidly relapse after surgical treatment of ulcers.

(4) Unexplained diarrhea.

(5) Personal or family history of parathyroid or pituitary tumors.

(6) Significantly high gastric acid secretion and hypergastrinemia.

2. Gastric cancer: The similarity between this disease and gastrinoma is poor medical treatment and intra-abdominal metastasis, but gastric cancer rarely combined with duodenal ulcer, no high gastric acid and high gastrin secretion characteristics, gastroscopic biopsy pathology Histological examination has a differential diagnostic value.

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