Gastrointestinal | Gastric Secretion: The Cephalic & Gastric Phase.
Mechanism of HCL Secretion
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Describes a syndrome characterized by severe hypergastrinemia, gastric hypersecretion and upper gastrointestinal peptic ulcer. Hypergastrinemia in this disease is related to a hormonally active tumor-gastrinoma. However, for millions of people, the actual incidence of the disease is much higher, which is related to the significant complexity of the diagnosis. It is known that a correct diagnosis can be established for an average of 5-7 years after the first symptoms appear. Patients account for 1% of all patients with duodenal ulcer [1,2]. Generally, the regulation of gastrin secretion is carried out through a negative feedback mechanism: the release of hydrochloric acid will inhibit the function of gastrin secretion by cells in the antrum. However, hydrochloric acid does not affect the tumor's gastrin production, leading to uncontrolled hypergastrinemia. The incidence of this infection in gastrinoma patients is 24% (active infection is 11%), which is much lower than the general population and patients with peptic ulcer disease.
Usually, tumors not only form and secrete gastrin, but also secrete other hormones: pancreatic polypeptide, somatostatin, corticotropin, glucagon, insulin, vasoactive intestinal peptide, but in most cases these substances The effect is not manifested clinically. Tumors can be single or more commonly multiple, ranging in size from 2 to 21. In the vast majority of patients (about 81%), the tumor is located in the so-called pancreas (body and tail), duodenum, and the junction of the gallbladder and the common hepatic duct [4, 5]. Traditionally, it has been described as an endocrine tumor of the pancreas, but about one-third of gastrinomas are located in the duodenal wall or peripancreatic lymph nodes. In addition, tumors can be located in the splenic hilum and stomach wall.
The cases may be malignant, but their histological heterogeneity often makes it difficult to distinguish malignant tumors from benign tumors. Under a light microscope, tumors may resemble carcinoids, especially if they develop from the small intestine or stomach. Malignant gastrinomas usually grow slowly. Metastasis occurs in regional lymph nodes, liver and peritoneum, spleen, bones, skin, and mediastinum.
The patient's gastrinoma is a component of multiple endocrine tumor type 1 (Vermeer's syndrome, -1). In most of these patients, in addition to gastrinoma, hyperplasia of the parathyroid glands and an increase in serum calcium are also observed. In addition, multiple endocrine neoplasia can manifest as pancreatic or pancreatic islet cells (cellular adenoma, glucagonoma, ), adrenal cortex, pituitary and thyroid islet cell hyperplasia or hyperplasia (Scheme 1). In 48% of cases, the tumor is malignant and most often metastasizes to the liver.
The most important sign of gastrinoma observed in 91-96% of patients is the appearance of gastrointestinal ulcers. In about 76% of patients, ulcers occur in the proximal duodenum and stomach. Ulcers can be located in the jejunum distal to the duodenum (up to 26% of cases). The ulcer is usually single, but there may be multiple, especially in positioning behind the ball. The clinical symptoms of gastrinoma ulcers are similar to common peptic ulcers, but are characterized by persistent abdominal pain that does not respond well to traditional anti-ulcer treatments. Ulcers often recur and complications develop: bleeding, perforation, stenosis. Complications of ulcers are difficult and are the main cause of death for patients. About half of patients develop esophagitis [1, 2, 4]. Duodenal ulcer with a liver mass.
Diarrhea is a characteristic of the disease and occurs in 31-66% of patients. In addition, diarrhea is the first symptom in 26-41% of patients and the only symptom in 7-19% of patients. Obviously excessive secretion of hydrochloric acid can cause damage to the jejunal mucosa, which leads to increased small intestinal peristalsis, increased secretion of potassium ions, and slower absorption of sodium and water. At low values, pancreatic enzymes (especially lipase) will be inactivated, and bilesalts will precipitate and micelle formation will be impaired. As a result, the absorption of fat and monoglycerides decreases, and steatorrhea and weight loss occur.
Perform gastric secretions and endocrine examinations every 6 to 13 months, including hormone studies.
One third of patients develop local lymph node metastasis. In the initial treatment, 11-21% of patients have found metastasis of gastrinoma in the liver, and then bone metastasis has occurred. The presence of liver metastases usually determines the patient's poor prognosis, but Ellison also described several patients with liver metastases who survived 16 to 21 years after total gastrectomy. The 11-year survival rate of patients with no tumors found after successful tumor removal or during surgery is 61-111%. For unresectable tumors, the 5-year survival rate is 41%. The survival rate of patients with type 1 multiple endocrine tumors is generally higher than that of patients alone. This is associated with brighter clinical symptoms, which leads to earlier diagnosis and the start of antisecretory therapy. All patients with severe esophagitis should be suspected (based on-3-4 grades), especially those with persistent duodenal ulcers or diarrhea of unknown origin (Scheme 2). Gastric ulcers are impossible: such ulcers are observed in less than 5% of gastrinoma patients.
Aspiration studies of gastric secretions are very important for diagnosis: in patients, the basic production of hydrochloric acid per hour is 16 or more. Sometimes more than 111. After gastric or duodenal ulcer surgery, the diagnosis level is> 5. Only 11% of patients with peptic ulcer disease have a value of more than 16, while in the case of -71% of patients occur. Another feature is that when used, the base production of hydrochloric acid is 61% or more of the maximum value. However, it should be remembered that both high acid production and a small gap between basal acid and maximum hydrochloric acid can be observed in both peptic ulcer patients and healthy individuals.
When measured on an empty stomach by the radioisotope method, 1 can reach 451'1. However, after extensive resection of the small intestine, serum gastrin levels will increase in diseases such as pernicious anemia, chronic atrophic gastritis, pheochromocytoma, and renal failure. Sometimes (less than 1% of cases) with duodenal ulcer disease, hypergastrinemia may occur due to hyperfunction and/or hyperplasia of gastric antrum cells. In this case, during the biopsy, an increase in gastrin content in the gastric antral mucosa was found. A gastrin level exceeding 261 is considered to have important diagnostic significance, while a gastrin level exceeding 1111 is unconditional.
If the gastric juice secretion is high, but the serum gastrin level is between 111 and 1111, a stimulus test should be used to diagnose gastrinoma. Test with secretin, calcium or standard breakfast. When testing with secretin, intravenous injection of Kabi secretory protein at a dose of 2. The gastrin level was measured twice before the injection and every 5 minutes thereafter for 31 minutes (alternative option: 2, 5, 11, 16 and 21 minutes after the injection). The operation of calcium-containing samples is as follows: 11% calcium gluconate solution is administered intravenously at a dose of 5, for 3 hours; gastrin is measured before calcium is introduced, and measured every 31 minutes for 4 hours, which is the same as the sample with secretin Compared with calcium samples, it is more harmful to patients, so it is not recommended to use it as the initial test. When testing with a standard breakfast, the gastrin activity is measured on an empty stomach, and every 16 minutes for 1.5 hours after eating. The characteristic is that after taking calcium solution, the content of gastrin increases sharply, after the injection of secretin, the content of gastrin increases abnormally, and after the test breakfast, the increase of gastrin does not exceed 51% (Table 1) . The test with secretin has the greatest diagnostic value. 88% of patients were positive. The indication for the calcium test is a negative secretin Builth Wells limpia obtained test result (14% of patients). Unfortunately, the calcium test can only identify another 4% of gastrinoma patients. Therefore, in 9% of patients, both provocation tests are negative.
To choose the correct treatment strategy, it is important to determine whether gastrinoma is isolated or exists within the framework of type 1 multiple endocrine tumors (see Protocol 1). In the latter case, most patients have a family history of hyperparathyroidism first and then gastrinoma. However, patients with signs of hyperparathyroidism have been described years after the detailed clinical presentation of. Research on hormonal spectroscopy, sella radiography, and computer tomography of the pituitary gland will help confirm the diagnosis. Establishing its location is no more difficult than laboratory diagnosis of gastrinoma. This is due to the small stomach tumor. Tumors smaller than 1 mm may be malignant and metastasize to local lymph nodes, liver. It is usually difficult to detect tumors smaller than 1 cm. In addition, endoscopic ultrasonography, transillumination during diagnostic laparotomy, and intraoperative ultrasonography can find that 81% of tumors with a size of 1 cm or larger are located in the triangle area of gastrinoma. A bone scan can identify bone metastases.
In established local gastrinomas, tumor resection is performed. This may occur in 21% of patients with solitary gastrinoma. The main indications for surgical treatment are: the tumor has been localized and there is no type 1 metastasis of multiple endocrine tumors. However, even in such patients, remission can be observed within 5 years in less than 31% of cases after tumor resection [7, 8]. Therefore, for most patients, symptomatic treatment is necessary: the use of antisecretory therapy to relieve the symptoms of the disease and achieve scarring of duodenal and jejunal ulcers. In patients after partial gastrectomy or vagus nerve transection, a more severe course is observed. According to Zollinger, the worst operation is partial gastrectomy. After such an operation, more active antisecretory therapy is necessary.
The main component of conservative treatment is effective continuous antisecretory therapy using endoscopy and checking gastric secretions under continuous supervision. To this end, two groups of drugs are used: histamine 2-receptor blockers and proton pump inhibitors. Before the advent of these drugs, the only way to inhibit gastric juice secretion was to perform total gastrectomy [4, 9]. Several times higher than duodenal ulcer [1, 12]. In particular, ranitidine is used at a dose of 1.5-9/day. The medication must be taken more frequently: every 4 to 6 hours. According to the recommendations of the National Institutes of Health, the goal of 2 blocker therapy is to reduce to less than 12. Unfortunately, even at high doses, with the help of 2 blockers, it is difficult to achieve this target (may be insufficient for scar ulcers and indented esophagitis). In addition, in most cases, the dose needs to be increased every year [12, 14]. Therefore, at present, 2-blockers are only used for intravenous administration during surgery, during postoperative periods, and when oral medication is not possible. Compared with 2-blocker, it blocks the final stage of hydrochloric acid secretion, and has a stronger and longer lasting antisecretory effect. With these drugs, it can be easily reduced to 12, and usually can reach a level of no more than 2. The use of proton pump inhibitors does not require increasing the daily dose over time, and the dose can usually be slightly reduced. However, lansoprazole has more binding sites in parietal cells, which explains its higher activity under experimental conditions [16, 18]. Clinical studies using a 25-hour meter show that omeprazole (dose 21-181 mg/day) and lansoprazole (dose 31-185 mg/day) in patients have similar curves and average values during the day . (1.8-6.4 units and 2.1-6.4 units respectively) [18, 19]. Although there have been publications indicating that the daily dose of proton pump inhibitors can be prescribed in one dose, dividing it into two doses can improve the effectiveness of the treatment.
The treatment needs to be carefully selected and monitored. The goal of treatment for patients who have not undergone surgery is to reduce to less than 5. Patients with esophagitis or gastric surgery (except for total gastrectomy) need to more significantly inhibit gastric acid production (up to less than 1) [2, 4, 20, 13, 20]. The initial dose of omeprazole or lansoprazole is 61 mg/day. Then drug treatment: under the control of gastric secretion studies, the daily dose is increased by 22-31 every 1-2 weeks until the desired level is reached. Perform gastric secretion studies approximately 1 hour before taking the next dose. It is recommended to use a 25-hour meter to assess the appropriate intake frequency. After 3 months, further follow-up examinations were performed, including gastric intubation. The absence of recurrence of the ulcer during this period may indicate a possible tumor removal. Dynamic observations (clinical studies, endoscopy, gastroscopy, gastric intubation) are performed 2-4 times in the first year, and then twice a year. If it is zero and less than 5, the dose can be carefully reduced, but if it is equal to or greater than 5, the drug dose must remain unchanged. Failure to comply with the prescribed treatment plan or regular follow-up examinations are indications for total gastrectomy. Patients usually tolerate this surgery well, but in the future they will need intramuscular injections of vitamin 13, iron and calcium.
It is unpredictable and difficult to control with antisecretory drugs. In patients with acid production of less than 1, there are cases of ulcer perforation and bleeding after complete gastrectomy. Systematic endoscopy can prevent this situation.
If the gastrinoma metastasizes, in addition to antisecretory therapy or total gastrectomy, the administration of streptozotocin and 5-fluorouracil can also reduce the size of the tumor and reduce the level of serum gastrin. This type mainly requires removal of the parathyroid glands. In some postoperative patients, the levels of gastrin and gastric secretions normalize [2, 11, 22].
No surgical treatment. These patients require continuous treatment with proton pump inhibitors under the control of endoscopy and gastric secretion studies. Mechanism of HCL Secretion