home Audience 12 Zollinger Ellison syndrome description of symptoms and treatment. Zollinger-Ellison syndrome: symptoms of the disease and its treatment. Application of instrumental diagnostic methods

Zollinger Ellison syndrome description of symptoms and treatment. Zollinger-Ellison syndrome: symptoms of the disease and its treatment. Application of instrumental diagnostic methods

GASTROENTEROLOGY

Y.V.VASILIEV, MD, Professor, Central Research Institute of Gastroenterology, Moscow

ZOLLINGER-ELLISON SYNDROME

The article is devoted to important issues of etiology, pathogenesis, clinical picture, diagnosis, treatment of Zollinger-Ellison syndrome.

Key words: Zollinger-Ellison syndrome, histamine H2 receptor antagonists, proton pump inhibitors

In 1955, American surgeons R.M. Zollmger and E. Ellison in their article reported on two patients with severe hypersecretion of gastric acid, primary peptic ulcerations of unusual localization and nonspecific islands of tumor cells in the pancreas. In their honor, this triad of clinical findings was named “Zollinger-Ellison syndrome.” Currently, it is the most common clinical syndrome in the differential diagnosis of benign ulcerations of the stomach and intestines.

Zollinger-Ellison syndrome is diagnosed in most cases in the presence of the following symptoms:

■ high hypersecretion and hyperchlorhydria of gastric juice (with almost normal pepsin secretion);

■ recurrent peptic ulcer of the gastrointestinal tract with a tumor arising from cells that do not produce insulin (non-p-cells) of the “islet apparatus” of the pancreas;

■ recurrent abdominal pain.

However, all three signs are not always present. For example, in addition to single ulcers of the gastrointestinal tract, multiple ulcers (20-55%), as well as malignancy with gastrin, may be observed.

The cause of the development of Zollinger-Ellison syndrome is the proliferation of gastrin-secreting endocrine cells. In some patients, hyperplasia of the endocrine pancreas may be due to the presence

tumors. In the course of studying tumor cells that were removed during surgery and placed in a nutrient medium, it was concluded that tumor culture cells and the medium predominantly contain gastrin with a molecular weight of 34 and a smaller amount of gastrin G-17 (^-17), and the concentration gastrin gradually decreased and after 2 weeks the hormone was not detected in the culture. This may be due to the gradual dedifferentiation of endocrine epithelial cells or increased fibroblast activity.

Gastrin-producing tumors that release large amounts of gastrin (2,000 pg/ml at a norm of 75 pg/ml) into the blood circulating through the blood vessels, leading to increased acid secretion with the formation of ulcers, are called “gastrinoma”. In most cases, they are localized in the pancreas (mainly in the body and tail), less often in the proximal part of the duodenum, and very rarely in the hilum of the spleen. Sometimes Zollinger-Ellison syndrome can be combined with an aberrant pancreas localized in the duodenum. Gastrinomas are characterized by hyperplasia and proliferation. The cells contain many acidophilic secretory granules and are often vacuolated.

Various forms of gastrin, identical to antral gastrin G-17, are found in blood serum. In the blood of patients with Zollinger syndrome

Ellison gastrin G-34 predominates with a large molecular weight (approximately 38,000), containing gastrin G-17. Compared to gastrin G-17, gastrin G-34 is physiologically less active. About 2% of serum gastrin in patients with Zollinger-Ellison syndrome is gastrin with a molecular weight of 21,000, and in mucus

Fragments of gastrin G-17 were found in the stable membrane.

Clinical manifestations. When diagnosing Zollinger-Ellison syndrome, it is important to analyze the symptoms and history of the disease, as well as prescribe laboratory tests and conduct instrumental examinations. Clinical symptoms of this disease may vary depending on the presence or absence of complications. Most patients complain of frequent, not always associated with food intake, periodic, sometimes pronounced, less often constant and minor pain in the pilo-roduodenal and/or epigastric region. Patients are also bothered by heartburn, belching, less often

Loose stools, nausea, vomiting of acidic stomach contents (occurring at a height of pain), dysphagia. Eating food can reduce the intensity of pain. Characterized by watery, profuse stools containing a significant amount of fat (steato-rhea). Diarrhea and steatorrhea indicate insufficiency of exocrine pancreatic function. Impaired absorption and the occurrence of steatorrhea are promoted by hypersecretion of hydrochloric acid, leading to damage to the gastric and intestinal epithelium, inactivation of intestinal enzymes, incl. lipolytic.

With the development of hypo- and normochromic anemia, a decrease in the level of albumin in the blood serum, the condition of patients worsens, and the loss of body weight increases. Almost all patients with Zollinger-Ellison syndrome experience an increase in serum gastrin concentrations. A high level of basal secretion (10 mEq/h or more) and a relatively weak increase in the secretion of gastric juice upon histamine administration (compared to the basal period) are some of the characteristic signs of Zollinger syndrome

Ellison. Many patients experience severe hypersecretion of gastric acid, but in some, the secretion of hydrochloric acid ranges from 150 to 300 mEq, with the release of 3,000-12,000 ml of gastric juice during the same period, mainly at night.

Islands of tumor cells are diagnosed in 10-48% of cases, due to their small size. In patients with Zollinger-Ellison syndrome, in 38-68% of cases a single duodenal ulcer is detected, and in 14-25% there are no ulcers. Ulcers are localized in the postbulbar part of the duodenum, sometimes in the stomach and jejunum, and in patients who have previously undergone gastrectomy for suspected duodenal ulcer, in the jejunum near the gastroenteroanastomosis.

Instrumental diagnostics. X-ray examination allows identifying ulcers in the upper gastrointestinal tract. When performing angiography, in 20% of cases it is possible to identify signs indicating the presence of a tumor of the islet apparatus of the pancreas. The scan reveals an enlarged pancreas. Endoscopic examination reveals a large amount of fluid in the stomach, swelling of the mucous membrane and thickening of its folds are observed. In some patients, erosions, esophagitis, peptic stricture of the esophagus, gastric and (or) duodenal ulcers are detected.

Laboratory diagnostics. The main way to diagnose “erased” forms of Zollinger-Ellison syndrome is to determine the level of gastrin in the blood serum using a radioimmunological method.

Laboratory diagnostic criteria are an increase in gastrin levels, the presence of a positive secretin test exceeding 200 pg/ml, and basal secretion of hydrochloric acid in the stomach exceeding 15 mEq/h (not previous gastric surgery); the presence of basal secretion of hydrochloric acid by parietal cells of the gastric mucosa (preceding gastric surgery); detection of a serum gastrin level of more than 1,000 pg/ml and a level of basal secretion of hydrochloric acid in the stomach of more than 15 mEq/h (not preceding gastric surgery); identifying the level of basal secretion of hydrochloric acid in the stomach exceeding 5 mEq (preceding gastric surgery).

GASTROENTEROLOGY

To make a diagnosis, food, secretin and calcium provocation tests are performed. Using the radioimmunological method, serum gastrin during a food test is determined 30, 15, 1 minute before and 15, 30, 45, 60, 90, 120 and 150 minutes after meals

One slice of bread, 200 ml milk, 50 g cheese, boiled egg (30 g protein, 20 g fat and 25 g carbonate). If the result is positive, the serum gastrin level increases (compared to the basal level). Hyperfunction and hyperplasia of G cells in the antrum of the stomach in Zollinger-Ellison syndrome are extremely rare.

When conducting a secretin test, serum gastrin is determined 10 minutes before the injection, then secretin is administered intravenously (at the rate of 2i/kg body weight), and gastrin levels are measured 1, 2, 5, 10, 20 and 30 minutes after administration. A positive result is considered to be an increase in serum gastrin by more than 200 pg/ml. False negatives occur in less than 5% of cases, and false positives do not occur.

Within 4 hours after intravenous administration of calcium gluconate at a dose of 5 mg/kg/h, blood samples are taken at 30-minute intervals to determine gastrin concentrations. When intravenous calcium is administered to patients with high levels of gastrin in the blood serum, there is a significant increase in acid production in the stomach.

When carrying out differential diagnosis, it should be taken into account that possible hypergastrinemia is often associated with diseases accompanied by normal or reduced secretion of hydrochloric acid in the stomach (chronic gastritis, stomach cancer, pheochromocytoma, pernicious anemia, conditions arising after a patient has undergone vagotomy) and an increase in secretion of hydrochloric acid in the stomach (gastritis combined with gastric outlet stenosis, renal failure, hyperfunction and/or hyperplasia of G-cells in the antrum of the stomach, short bowel syndrome).

Ulcers in Zollinger-Ellison syndrome may be complicated by penetration into adjacent organs and/or bleeding. The prognosis of patients depends on the level of inhibition or neutralization of hydrochloric acid in the stomach and elimination of hypergastrinemia. Tumor metastases to vital organs, postoperative complications and bleeding most often lead to death.

Drug therapy. The effectiveness of drug therapy is evidenced by the cessation of diarrhea and the disappearance of pain in the epigastric region. Drug therapy for Zollinger-Ellison syndrome has been ineffective for a long time. The use of antacid drugs only briefly alleviated the condition of patients. In 1977, it was noticed that with a single injection into the stomach through a tube of some antacid drugs containing aluminum (including Phosphalugel), the pH and concentration of gastrin in the blood serum significantly increased. In this regard, it was suggested that an increase in serum gastrin in patients with duodenal ulcers after the administration (taking) of antacid drugs is associated with an increase in intragastric pH, the state of the ulcer, vagal influences, individual reactivity of the body and other factors. A slight improvement in the condition of patients with Zollinger-Ellison syndrome who took antacid drugs is due to their effect on the level of acid secreted into the stomach by the parietal cells of the mucous membrane.

The use of other drugs in high doses led to complications, and in therapeutic dosages it was ineffective.

Gastrectomy (total gastrectomy) was used as a radical treatment. However, this operation had a fairly high operative mortality rate. After gastrectomy, patients often experienced reflux esophagitis and associated symptoms, as well as signs of dumping syndrome, a feeling of early satiety after eating, anemia.

Mia, diarrhea, weight loss. In patients with multiple tumors, endocrine neoplastic syndrome sometimes developed, combined with hyperparathyroidism.

The effectiveness of therapy for Zollinger syndrome

Allison increased significantly only with the advent of histamine H2 receptor antagonists, in particular cimetidine and ranitidine, which can significantly inhibit acid formation in the stomach. However, attempts to increase the standard dose of drugs were accompanied by the development of side effects and complications.

The incidence of side effects has decreased significantly with the advent of third-generation histamine H2 receptor antagonists (famotidine). It was observed that famotidine (Gastrosidin, Kvamatel) at a dose of 40 mg 2 times a day significantly improves the condition of patients with Zollinger-Ellison syndrome. The use of histamine H2 receptor antagonists and antacid drugs can not only reduce the level of acid in the stomach, but also increase the effectiveness of treatment.

Later it was found that proton pump inhibitors can suppress acid formation in the stomach for a longer period. Proton pump inhibitors are usually prescribed for the treatment of Zollinger-Ellison syndrome in any type of acid formation, but their use is especially indicated in cases of patients refractory to histamine H2 receptor antagonists (including in the absence of a sufficient level of inhibition of the release of hydrochloric acid by parietal cells of the gastric mucosa).

A test for a decrease in acid production and/or daily pH allows timely adjustment of the treatment regimen. In severe cases, it is more advisable to use proton pump inhibitors. With a moderate course of the disease, you can limit yourself to standard doses, but individually they are prescribed at a dose of up to 160 mg/day.

Omeprazole is the first drug from the group of proton pump inhibitors, synthesized

introduced in Sweden in 1979. Esomeprazole, an isomer of omeprazole, was developed somewhat later.

The bioavailability of omeprazole is 40-60%, binding to plasma proteins is 95%, the maximum concentration in plasma is observed after 1-3 hours, the half-life is 0.7 hours. Currently, omeprazole, in the form of monotherapy or in combination with antibiotics, is the standard drug for the treatment of patients suffering from acid-related diseases.

■ When carrying out differential diagnosis, it should be taken into account that diseases accompanied by normal or reduced secretion of hydrochloric acid in the stomach are often associated with possible hypergastrinemia.

Esomeprazole is the first proton pump inhibitor, an isomer of omeprazole, which has a similar mechanism of action and a more pronounced and persistent inhibitory effect on acid secretion by parietal cells of the gastric mucosa throughout the day. Compared to omeprazole, lansoprazole and rabeprazole, it causes less pronounced interindividual fluctuations in acidity. The creation of esomeprazole, which has constant pharmacodynamics and pharmacokinetics, made it possible to reduce the dependence of these indicators on metabolism in the liver with the participation of cytochrome P450, i.e. ensure the maximum possible area under the concentration-time curve.

Omeprazole, lansoprazole, pantoprazole and esomeprazole, unlike rabeprazole, are significantly metabolized by the cytochrome P450 enzyme system in individuals with the CYP2C19 gene and slightly - with the CYP2A4 gene. Esomeprazole (Nexium) effectively inhibits acid formation in the stomach, has a uniform composition and, unlike other proton pump inhibitors, has

GASTROENTEROLOGY

two isomers (K- and S-isomers), identical in chemical structure, but differing in properties, consists of one type of optical isomer molecules (^-isomer).

Esomeprazole is absorbed in the small intestine and then passes through the blood vessels to the stomach. The concentration of esomeprazole (via diffusion) is noted in the lumen of the secretory tubules of the parietal cell of the gastric mucosa. Conversion to sulfenamide (the active form of esomeprazole) allows it to bind to the thiol groups of cysteine in the proton pump, inhibit this enzyme and reduce the secretion of hydrochloric acid. Unlike other proton pump inhibitors, esomeprazole is metabolized more slowly in the liver, and its bioavailability is higher. After the first dose of the drug, a greater amount of the active substance reaches the parietal cells of the gastric mucosa, and as a result, a greater number of proton pumps are blocked. Increasing the bioavailability of esomeprazole (due to lower clearance compared to other proton pump inhibitors) allows increasing the concentration of this drug to inhibit the “work” of the parietal cell. This explains the more pronounced inhibitory effect of esomeprazole on the secretion of hydrochloric acid compared to other inhibitors of gastric secretion.

Thus, omeprazole and esomeprazole have the following advantages:

■ a relatively quickly onset effect of eliminating heartburn (burning) and/or pain in the chest and epigastric region, especially during the daytime in patients suffering from various acid-related diseases (ulcerative and gastroesophageal reflux disease, Zollinger-Ellison syndrome, non-steroidal gastropathy, etc.) ;

■ more intense inhibition of acid formation in the stomach over a longer period of time compared to histamine H2 receptor antagonists (ranitidine and famotidine) and antacid drugs;

■ high efficiency when used in various anti-Helicobacter therapy regimens and effectiveness in the treatment of patients with hypersecretion of hydrochloric acid.

The above advantages of omeprazole and esomeprazole determine the effectiveness of using these drugs in therapeutic doses in the treatment of acid-related diseases, incl. in the treatment of Zollinger-Ellison syndrome. In severe cases of Zollinger syndrome

Ellison, it is more advisable to use esomeprazole for the treatment of patients. The daily dosage of the drug is selected by the doctor taking into account the patient’s condition.

LITERATURE

1. Burchinsky G.I. Peptic ulcer / Guide to internal medicine. - M.: Medicine, 1965. - T. 4. - P. 183-236.

2. Vasiliev Yu.V. Diseases of the digestive system. Histamine H2 receptor blockers. - M.: Double Freig, 2002. - 93 p.

3. Howard J.J., Chremos A.N., Collen M.J., et al. Famotidine, a new potent, long-acting histamine H2-receptor antagonist; comparison with cimetidine and ranitidine in the treatment of Zollinger-Ellison syndrome // Gastroenterol.

1985. - Vol. 88. - P. 1026-1033.

4. Feurle G.E. The Action of Antacids on Serum Gastrin Concentrations in Man // Klin. Wschr. - 1977. - H. 55. - No. 21. - S. 1039-1042.

5. Lichtenberger L.M., Lechago J., Dockray G.J., Passaro E. Culture of Zollinger-Ellison Tumor Cells // Gastroenterology/ - 1975. - Vol. 68, 5(1). - P. 1119-1126.

6. McGuigan J.E. The Radioimmunoassay of Gastrin. Clinical Considerations // J. Amer. Med. Ass. - 1976. - Vol. 235.

4. - P. 405-406.

7. Metz D.S., Pisegna J.R., et al. Control of gastric acid Hypersecretion in the management of patients with Zollinger-Ellison syndrome // Wid. J. Surg. - 1993. - Vol. 17. - P. 463-468.

8. McTavish D., Backley M.M.T., Heel R.C. Omeprazole an updater review of its pharmacology and therapeutic use on acid-related disorders // Drugs. - 1991. - Vol. 2/2 (1).

9. Mignon M., Merrouchem M., Gardner J., et al. Rabeprazole therapy effective in Zollinger-Ellison syndrome and Idiopathic acid hypersecretion // Gut.-1999. - Vol. 44 (Suppl.1) - A125 (abstract no, TH 500).

Examination plan for suspected Zollinger-Ellison syndrome

Since only a small proportion of patients with ulcerative lesions of the gastrointestinal tract are caused by Zollinger-Ellison syndrome, this syndrome should be suspected only under certain conditions:

Duodenal ulcers associated with diarrhea, the cause of which has not been established.
Recurrent postoperative ulcers.
Multiple ulcerations.
Ulcers of the distal duodenum or jejunum.
Family history of ulcerative lesions.

Further in-depth examination to diagnose Zollinger-Ellison syndrome is carried out only in the above clinical situations.

The diagnosis of Zollinger-Ellison syndrome is made based on the study of serum gastrin levels. At the same time, a search is carried out for possible concomitant tumors within the framework of multiple endocrine neoplasia syndrome type I. The next stage after diagnosis is determining the specific location of the tumor (gastrinoma) to assess the possibilities of its surgical removal.

Suspicion of Zollinger-Ellison syndrome is confirmed by the following factors.

Evidence of gastric hypersecretion (basal secretion of hydrochloric acid is more than 15 mmol/h with an intact stomach and above 5 mmol/h with a resected stomach; it accounts for more than 60% of the maximum acid secretion, since parietal cells are already stimulated in the basal state by excessively produced gastrin).
Evidence of the presence of fasting hypergastrinemia, despite hyperchlorhydria (exceeding the normal level of serum gastrin, equal to 30-120 pg/ml, tens of times or more; antiserum is used, including all molecular forms of the peptide).
Establishing hypergastrinemia using a provocative secretin test (intravenous administration of secretin for 30 seconds at a dose of 2 units/kg, which usually causes inhibition of gastrin release, in gastrinoma leads to a paradoxical increase in its level in the blood - more than 100% of the basal level).

History and physical examination

The main symptoms of Zollinger-Ellison syndrome are abdominal pain, similar to manifestations of a peptic ulcer, as well as diarrhea and weight loss. In 25% of patients, the disease begins with gastrointestinal bleeding.

In 75% of cases, ulcers are located in the upper horizontal part of the duodenum, in 14% of cases - in its distal part and in 11% - in the jejunum.

Diarrhea develops in half of patients due to hypersecretion of hydrochloric acid and is accompanied by significant weight loss. Increased acidity leads to damage to the small intestinal mucosa, inactivation of pancreatic lipase and precipitation of bile acids, which causes steatorrhea. High gastrin levels lead to incomplete absorption of Na + and water, while intestinal motility increases.

Laboratory research

Mandatory general clinical examination methods

general blood analysis;
determination of blood group;
determination of the Rh factor;
stool occult blood test;
general urine analysis.

Changes in the results of general clinical examinations are not typical

Mandatory specialized laboratory tests

The concentration of gastrin in the blood serum is determined by radioimmunoassay if Zollinger-Ellison syndrome is suspected. The gastrin content in the blood serum in this disease is increased and amounts to 200-10,000 ng/l (the norm is less than 150 ng/l).

If basal gastrinemia of 200-250 ng/l is detected, provocative tests should be performed with intravenous calcium (5 mg/kg/h for 3 hours) or secretin (3 units/kg/h). The test is positive if the serum gastrin level increases 2-3 times compared to the basal level (the sensitivity and specificity of this test for detecting gastrinoma is about 90%).

The combination of elevated blood gastrin levels with increased basal hydrochloric acid production makes the diagnosis highly likely. However, the isolated detection of increased secretion of hydrochloric acid for the diagnosis of Zollinger-Ellison syndrome currently has only auxiliary value. Fractional study of gastric secretion (detection of hypersecretion of hydrochloric acid on an empty stomach more than 15 mmol/h or 5 mmol/h after partial resection of the stomach suggests the possibility of gastrinoma).

A nonspecific marker of neuroendocrine tumors is chromogranin A. Its level is more than 10 nmol/l (normal is less than 4.5 nmol/l) indicates the presence of multiple endocrine neoplasia. Its content of more than 75 nmol/l is observed in tumor metastases, which makes the prognosis assessed as unfavorable.

Radioimmune and enzyme immunoassay determination of the concentration of hormones in the blood plasma (parathyroid hormone, insulin, prolactin, somatotropin, luteinizing and follicle-stimulating hormones) is carried out to exclude type I multiple endocrine neoplasia syndrome.

Determination of glucose concentration in the blood (detection of a possible concomitant tumor producing glucagon). Determination of calcium and phosphorus content in the blood and urine (detection of possible pathology of the parathyroid glands).

Instrumental studies

Mandatory examination methods

FEGDS or X-ray examination of the upper gastrointestinal tract. If ulcers are detected, dynamic FEGDS is required.

Ultrasound of the pancreas (detection of gastrinoma), liver (the most common localization of metastases), kidneys, adrenal glands, thyroid gland in order to identify the primary focus, metastases, and concomitant pathology of other endocrine glands. X-ray (fluorography) of the chest to detect metastases.

A special method for diagnosing endocrine tumors of the digestive organs and their metastases is scintigraphy with octreotide labeled with radioactive 111In, which has the highest sensitivity and specificity compared to other methods for determining the localization of gastrinoma. Octreotide administered intravenously is detected at somatostatin receptors after 24-48 hours and allows visualization of the tumor with scintigraphy. Radioisotope octreotide can be used both for intraoperative detection of a tumor and its metastases, and for assessing the radicality of the operation.

Additional examination methods

Endoscopic ultrasonography can detect tumors in the head of the pancreas, the wall of the duodenum, and adjacent lymph nodes.

CT, magnetic resonance imaging (MRI), selective abdominal angiography, radiography and radioisotope bone scanning. Studies are carried out to determine the localization of gastrinoma, exclude multiple endocrine neoplasia type I and tumor metastases.

Differential diagnosis

If there is a characteristic clinical picture of ulcerative lesions of the gastrointestinal tract in combination with the above clinical situations, differential diagnostic measures are carried out to confirm the Zollinger-Ellison syndrome itself, as well as to identify its hereditary (as part of the multiple endocrine neoplasia syndrome) or acquired nature. A special place in the differential diagnosis is occupied by clarification of the benign or malignant nature of the identified tumor.

Indications for consultation with other specialists

In any case, when Zollinger-Ellison syndrome is detected, consultation with an endocrinologist and surgeon is necessary.

Zollinger-Ellison syndrome (ulcerogenic pancreatic adenoma, gastrinoma) is a tumor of the islet apparatus of the pancreas, characterized by the occurrence of peptic ulcers of the duodenum and stomach, which cannot be treated and is accompanied by persistent diarrhea.

The true incidence of Zollinger-Ellison syndrome has not been established. According to some data, it occurs in 0.1-1% of patients with gastric and duodenal ulcers. More often, the initial manifestations of this disease occur at the age of 30-60 years.

Causes and development of the disease

The syndrome is the result of the development of a tumor (gastrinoma) in the head or tail of the pancreas (85% of cases). In 15% of cases, the tumor is localized in the stomach or duodenum. Cases of multiple endocrine adenomatosis (multiple endocrine neoplasia) have been described.

About two-thirds of gastrinomas are malignant; In a third of patients, metastases are detected at the first visit to the doctor. Typically, malignant gastrinomas grow slowly, but sometimes they progress rapidly and give multiple metastases early on. Most often, gastrinomas metastasize to regional lymph nodes and the liver, as well as to the peritoneum, spleen, bones, skin and mediastinum.

The development of treatment-resistant peptic ulcers is the main manifestation of the disease in almost all patients. Ulceration is caused by the production of gastrin by the tumor, and accordingly, increased secretion of gastric juice, i.e. hydrochloric acid and enzymes. In the vast majority of patients, a single ulcer is localized in the duodenum and stomach (75%), as well as in the jejunum. There are also multiple ulcers of the stomach, duodenum and jejunum.

Complaints and symptoms

Clinical manifestations of the disease are pain in the upper abdomen, which have the same patterns in relation to food intake as with a regular duodenal and stomach ulcer, but unlike them, they are very persistent, are of great intensity and do not respond to antiulcer therapy.

Characterized by persistent heartburn and sour belching. An important symptom is diarrhea, caused by the entry of a large amount of hydrochloric acid into the small intestine and, as a result, increased motility of the small intestine and slower absorption. The stool is copious, watery, with a lot of fat. A significant decrease in body weight is possible, which is typical for malignant gastrinemia.

Ulcers of the stomach and duodenum with Zollinger-Ellison syndrome do not heal even with prolonged complex therapy. Many patients experience esophagitis, sometimes even with the formation of a narrowing (stricture) of the esophagus. When palpated, severe pain is detected in the upper abdomen and the projection area of the lower stomach.

In the case of a malignant course of the disease, tumor formations in the liver and its significant increase are possible.

Diagnostics

X-ray and endoscopic examination reveal an ulcer that does not differ from that of a normal duodenal ulcer. The main laboratory criterion for Zollinger-Ellison syndrome is hypergastrinemia (the gastrin content in the blood is increased to 1000 pg/ml or more, whereas with a normal peptic ulcer it does not exceed the upper limit of normal - 100 pg/ml).

The tumor itself is detected using ultrasound, computed tomography, and selective abdominal angiography. The most informative method is selective abdominal angiography with taking blood from the pancreatic veins and determining gastrin in it.

However, it is quite difficult to establish the localization of gastrinoma. In approximately half of patients with clinically and laboratory confirmed Zollinger-Ellison syndrome, the tumor cannot be found during surgery. Selective angiography can detect gastrinoma in 50%, CT in 30%, and ultrasound in 20% of cases.

Treatment

The main method of treatment is surgery with removal of a potentially malignant tumor.

Conservative treatment has the goal of significantly reducing gastric secretion and thereby achieving healing of the peptic ulcer. For this purpose, proton pump inhibitors are prescribed with a dosage increased by 2-3 times: Lansoprazole (per os 30-160) or Omeprazole (per os 20-120 mg/day).

Description:

Symptoms:

Clinical manifestations of the disease are pain in the upper abdomen, which have the same patterns in relation to food intake as with a regular ulcer of the duodenum and stomach, but unlike them, they are very persistent, have great intensity and do not respond to antiulcer therapy. Characterized by stubborn and sour. An important symptom is diarrhea, caused by the entry of a large amount of hydrochloric acid into the small intestine and, as a result, increased motility of the small intestine and slower absorption. The stool is copious, watery, with a lot of fat. A significant decrease in body weight is possible, which is typical for malignant gastrinemia.
Ulcers of the stomach and duodenum in Zollinger-Ellison syndrome do not heal even with prolonged appropriate therapy. Many patients experience symptoms, sometimes even with the formation of a narrowing of the esophagus. Palpation reveals severe pain in the upper abdomen and the projection area of the lower stomach; there may be a positive Mendelian sign (local pain in the projection of the ulcer). In the case of a malignant course of the disease, tumor formations in the liver and its significant increase are possible.
X-ray and endoscopic examination reveal an ulcer that is no different from an ulcer in a normal duodenal ulcer.
Relative laboratory criteria for Zollinger-Ellison syndrome are:
* hypergastrinemia (gastrin content in the blood is up to 1000 pg/ml or more, with a common peptic ulcer it does not exceed the upper limit of normal - 100 pg/ml);
* the acidity of the main secretion is more than 100 mmol/h.
The tumor is visualized using ultrasound, computed tomography, and selective abdominal angiography. The most informative method is selective abdominal angiography with taking blood from the pancreatic veins and determining gastrin in it.

Causes:

The syndrome occurs as a result of a tumor located in the head or tail of the pancreas (85% of cases). In 15% of cases, the tumor is localized in the stomach or is a manifestation of multiple endocrine adenomatosis (multiple endocrine neoplasia). The development of treatment-resistant peptic ulcers is associated with increased production of gastric juice and, accordingly, hydrochloric acid and enzymes.
In the vast majority of patients, it is localized in the duodenum, less often found in the stomach and jejunum. Multiple ulcers of the stomach, duodenum and jejunum are often observed.

Treatment:

For treatment the following is prescribed:

In most patients with Zollinger-Ellison syndrome, conventional conservative and surgical treatments for peptic ulcer disease are ineffective. Often after (with or without vagotomy) or vagotomy with pyloroplasty, ulcers very quickly recur.
In the past, many patients with gastrinoma underwent multiple operations, especially in cases where the diagnosis could not be established from the very beginning. Mortality was lowest in patients who immediately underwent gastrectomy. Therefore, for a long time it was considered the method of choice in the treatment of gastrinoma.
The creation of powerful drugs that suppress the secretion of hydrochloric acid and the development of accurate methods for topical diagnosis of gastrinomas have significantly expanded treatment options.
The clinical manifestations and severity of the disease vary, so the approach must be individualized. As with other malignancies, the ideal treatment is removal of the tumor.
H2 blockers reduce the secretion of hydrochloric acid, relieve symptoms and promote healing of ulcers. These drugs are effective in 80-85% of patients.
It is recommended to take the same drugs as for duodenal ulcer, but their doses should be 4-8 times higher. H2 blockers are prescribed for life, since even with a temporary cessation of their use, ulcer recurrence occurs. In approximately 25% of patients, ulcers do not respond to treatment with H2 blockers or recur during treatment. The dose of drugs is selected depending on the level of basal secretion of hydrochloric acid, measured within an hour before the next dose of the drug. This figure should not exceed 2.8 µmol/s (10 meq/h). H+,K+-ATPase inhibitors (omeprazole and lansoprazole) are most effective for suppressing the secretion of hydrochloric acid and treating ulcers in Zollinger-Ellison syndrome, including those with resistance to H2-blockers. The initial dose of omeprazole and lansoprazole is 60 mg once in the morning before breakfast. The dose is selected so that the basal secretion of hydrochloric acid does not exceed 2.8 μmol/s (10 mEq/h), and in operated patients - 1.4 μmol/s (5 mEq/h). For esophagitis, secretion may need to be reduced to 0.25 µmol/s (1 mEq/h). A third of patients need to take the drug 2 times a day. Sometimes, after the condition improves, it is possible to reduce its dose. In cases where it is not possible to identify the tumor or remove it, proximal selective vagotomy is sometimes resorted to. In some patients, this makes it possible to reduce the dose of H2 blockers and even stop them completely.
When choosing a treatment method, the clinical manifestations of the disease should be taken into account. Previously, such patients died mainly from complications of peptic ulcer disease. However, improved early diagnosis and successful anti-ulcer therapy have led to an increase in the life expectancy of patients, which is why the malignant properties of gastrinomas have increasingly begun to appear. Approximately half of the patients whose gastrinoma was not removed die from tumor invasion of surrounding tissues and neighboring organs. The optimal treatment method is complete removal of the tumor. During the operation, fiber-optic diaphanoscopy of the duodenum and lateral duodenotomy should be performed with a thorough examination of the mucosa. The benefits of intraoperative ultrasound remain to be determined. Complete removal of gastrinoma, leading to cure, is possible only in 30% of patients. Before the diagnosis is made, the location and size of the tumor is clarified, and surgery is performed, omeprazole or lansoprazole is prescribed. If there are contraindications, the tumor is inoperable, or if the patient refuses surgery, these drugs must be taken for life. To reduce the tumor mass and accompanying symptoms in gastrinomas prone to invasive growth, they tried to use a combination of streptozocin, fluorouracil and doxorubicin. Remission after chemotherapy occurs in less than 65% of patients and is never complete. The effectiveness of interferon alpha and octreotide is also low. In case of inoperable gastrinoma or the presence of metastases, omeprazole or lansoprazole is prescribed to prevent the formation of ulcers. Gastrectomy is performed less frequently. The effect of gastrectomy on the rate of tumor progression has not been proven.

Very often, doctors make false diagnoses due to the fact that some diseases are so similar in symptoms, but have completely different treatment methods. One of them is Zollinger-Ellison syndrome. This disease is very often confused with a duodenal or gastric ulcer.

What is Zollinger-Ellison syndrome?

Zollinger-Ellison syndrome is a pathological condition in which a tumor appears on various organs of the gastrointestinal tract as a result of increased gastrin secretion. Gastrin is a substance that regulates acidity and promotes the digestion and absorption of food. If the pH in the stomach is elevated, this can lead to stomach ulcers and more. Sometimes this disease cannot be treated.

There are also several types of Zollinger-Ellison syndrome, which are distinguished by the number of pathologies:

Single – 70% of cases. Found in the pancreas.
Multiple – 25% of cases. Located in the pancreas, thyroid gland, pituitary gland.

Symptoms of Zollinegra-Ellison disease

First of all, with Zollinegra-Ellison syndrome, a person loses body weight, which is associated with prolonged loose stools. Diarrhea occurs with an admixture of undigested food or fat. This symptom is accompanied by pain in the upper body and anal incontinence. This can lead to gastrointestinal bleeding, which in turn leads to stomach ulcers.

Important! Diarrhea is often the only symptom of Zollinger-Ellison syndrome.

Secondary symptoms of Zollinegra-Ellison syndrome:

nausea;
heartburn;
vomit.

Causes of pathology

The main reason for the formation of Zollinger-Ellison syndrome is increased stomach acidity, which occurs due to the abundant secretion of gastrin. It is provoked by stress, alcohol abuse, poor diet, sedentary lifestyle, poor quality food, etc. Also, the occurrence of pathology is often associated with a hereditary factor.

MEN type 1 (multiple endocrine neoplasia), or Wermer's syndrome as it is called, is an inherited autosomal dominant syndrome characterized by tumors or peptic ulcers. Zollinger-Ellison disease in most cases appears between the ages of 20 and 40 years, rarely at the age of 10 years.

Diagnostics

It is difficult to diagnose Zollinger-Ellison syndrome in the early stages because its symptoms are very similar to those of ulcers. Only laboratory tests can distinguish one disease from another. This can be done using selective abdominal angiography. The main objective of this method is to study blood vessels. By analyzing the blood content from the pancreatic veins, the level of gastrin can be determined. With Zollingea-Ellison syndrome, the gastrin content in the blood exceeds 1000 pg/ml, and with an ulcer it is only 100 pg/ml.

Tumors in Zollinger-Ellison syndrome can be seen after an ultrasound or computed tomography. Their location can be completely different, but identifying them is not so difficult. This is due to changes in the appearance and size of some gastrointestinal organs. For example, if a malignant tumor is located in the liver, then you can notice a significant increase in this organ.

Treatment of Zollinger-Ellison syndrome

First of all, you need to reduce the secretion of stomach acid. For this purpose, proton pump blocker drugs are prescribed. The mechanical actions of different types of blockers are almost the same: after they enter the stomach, they move to the small intestine, where they dissolve, and then penetrate through the membrane into the walls of the stomach, where, using various chemical processes, they lower the pH level in the organ.

In cases where treatment with medication alone is ineffective, surgical intervention has to be resorted to. However, the prognosis is not always favorable. Very often, malignant tumors can recur. Then the doses of proton pump inhibitor drugs are increased, and the medications themselves can be prescribed for life. Treatment of any type of tumor is accompanied by chemotherapy: a combination of streptozocin, fluorouracil and doxorubicin. They are intended to prevent the occurrence of metastases (tumor movement) and to reduce the risk of relapse.

Nutrition

When treating Zollinger-Ellison syndrome, it is important to adhere to diet No. 1. This diet is prescribed for almost all gastrointestinal diseases, since it does not irritate the walls of the stomach and the menu contains foods that do not increase the secretion of gastric juice. The temperature of cooked food should be warm, since hot or cold foods have a negative effect on the mucous membrane. You should also avoid smoked, fatty and fried foods. Food is boiled or steamed. It is prohibited to add various spices and herbs to food. It is recommended to eat frequently and in small portions. The daily menu should include:

dairy products: cottage cheese, milk, cheese, sour cream;
porridge: buckwheat, semolina, pearl barley, rice;
fruits: fresh or baked apples;
soups;
tea with milk.

Complications of the disease

With Zollinger-Ellison syndrome, tumors may move. They can spread to other tissues and organs, thereby causing new problems. Such tumors may be accompanied by:

ulcerative bleeding;
increase in ulcers;
perforation (the appearance of a through defect, when the contents of internal organs can escape into the abdominal cavity);
disruption of the passage of food through the gastrointestinal tract.

If the malignant tumor is not removed in time and the necessary therapy is not carried out, then everything can turn out to be fatal. In 50-80% of cases, from the moment of diagnosis, the patient can live 5 years. With a benign tumor there is absolutely no threat of death.

You need to monitor your health and try to prevent the disease from developing to a critical condition. To do this, at the first pain in the abdomen you need to contact a gastroenterologist.