Gastrinoma is a functionally active tumor, more often localized in the pancreas or duodenum, secreting gastrin in excess quantities. Gastrinoma is clinically manifested by Zollinger-Addison syndrome: recurrent peptic ulcers, diarrhea and steatorrhea. In order to diagnose gastrinoma, the concentration of gastrin in the blood serum, provocative tests, transhepatic selective angiography with determination of the content of gastrin in the blood from the pancreatic veins, EGD, pancreatic ultrasound, etc. are carried out. Radical treatment consists in the complete removal of the tumor; if the operation is impossible, drug antiproliferative and symptomatic therapy is performed.
Meaning
Gastrinoma is a gastrin–secreting tumor that stimulates hyperproduction of hydrochloric acid, which leads to the development of recurrent ulcers of the duodenum and jejunum. Disease is found in about 1% of patients with peptic ulcers; in 85% of cases, the tumor is localized in the pancreas; in 10% of cases – in the antrum of the stomach and the descending part of the duodenum 12; extremely rarely – in other organs (spleen, liver, gallbladder, omentum, ovaries). In 60% of clinical cases, gastrinoma is detected in men. In almost 90% of cases, gastrinoma is a malignant metastatic tumor.
The pathology in which recurrent peptic ulcer disease is combined with gastrin-producing tumors was first described by Zollinger and Ellison in 1955, on the basis of which the tumor was named “gastrinoma”, and the disease itself is ulcerative diathesis ulcer syndrome (or according to the authors – Zollinger-Ellison syndrome). Pathology is of clinical interest for specialists in the field of endocrinology and gastroenterology.
Causes
In the development of gastrinoma, the role of unfavorable heredity is assumed, which is expressed by a tendency to multiple endocrine neoplasia (MEN) type I – the formation of benign or malignant tumors in several endocrine glands at once. The components of multiple endocrine adenomatosis type I are tumors of the pituitary gland, tumors from islet cells of the pancreas and hyperplasia of the parathyroid glands. In the structure of multiple endocrine neoplasia, gastrinoma occurs in 25% of cases.
Disease is a solitary node or multiple formations of grayish-brown or yellowish-gray color without a clear capsule. The size of the gastrinoma can reach from 1-3 mm to 1-3 cm in diameter. Gastrinoma develops from Langerhans islet cells and has the ability to secrete the polypeptide hormone gastrin in excessive amounts. In turn, hypergastrinemia promotes hyperplasia of the parietal cells of the stomach and stimulation of hydrochloric acid secretion, which leads to the formation of peptic ulcers, inactivation of pancreatic juice enzymes and changes in bile acids.
Gastrinoma symptoms
In 90% of cases with Zollinger-Ellison syndrome caused by gastrinoma, severe peptic ulcer disease develops, refractory to treatment. Multiple gastroduodenal ulcers occur very persistently, often recur, and do not respond well to anti-ulcer therapy. Ulcers can be found in the stomach, the bulb of the duodenum, often they have atypical postbulbar localization (in the jejunum). When the ulcer is punctured, gastrointestinal bleeding may occur, which is life-threatening.
The subjective manifestations of the ulcerative process are intense pain in the epigastrium, acid belching, heartburn. Esophagitis phenomena may occur, sometimes leading to narrowing of the esophagus.
Ingestion of a large amount of hydrochloric acid into the intestine leads to mucosal damage, increased motility of the small intestine and slowing down the absorption processes. As a result, severe diarrhea develops; the stool has an abundant watery character and contains a large amount of fat (steatorrhea). Diarrhea and steatorrhea accompany the course of gastrinoma in 50% of cases. With malignant gastrinoma, there is a significant decrease in body weight. In 60% of patients, gastrinoma metastases to the liver and other organs are detected.
Diagnostics
The assumption of the presence of gastrinoma may occur with frequently recurrent or multiple ulcers of the stomach and duodenum that are not amenable to intensive medical treatment. Conducting radiography of the stomach and EGDS allows you to identify multiple ulcerative lesions, giant sizes of ulcers (more than 2 cm), their atypically low location, hypertrophy of the folds of the gastric mucosa. At the same time, there is no connection of peptic ulcer disease with taking NSAIDs or helicobacter infection.
In this case, it is necessary to study the level of gastrin in the blood serum on an empty stomach, which with gastrinoma turns out to be increased by 5-30 times (with normal hyperthyroidism, gastritis, provocative functional tests are used (with meat broth, calcium or secretin intravenously). With gastrinoma, eating does not stimulate an increase in gastrin production, whereas the introduction of calcium or secretin causes a twofold increase in hormone production. The study of gastric juice obtained as a result of probing the stomach reveals an increase in the secretion of hydrochloric acid.
For the purpose of topical diagnosis of gastrinoma, CT, MRI, abdominal ultrasound, pancreas are performed. Selective abdominal angiography allows not only to visualize gastrinoma, but also to take blood from the pancreatic veins to determine the level of gastrin in it.
To exclude multiple endocrine neoplasia of type I, blood hormones (insulin, prolactin, cortisol, etc.) are examined, skull x-ray, CT or brain MRI is performed.
In the process of diagnosing gastrinoma, it is important to differentiate it with peptic ulcer of the stomach and duodenum, tumors of the small intestine, celiac disease, medullary thyroid cancer, which causes secretory diarrhea.
Gastrinoma treatment
A radical method of treating gastrinoma is surgical removal of the tumor, but this possibility appears only in a quarter of patients. Abdominal surgery uses various types of operations (taking into account the localization and prevalence of the tumor process): gastrinoma enucleation, pancreatoduodenal resection, distal pancreatic resection, subtotal pancreatic resection, etc. In some cases, selective embolization of gastrinoma is resorted to.
Previously widely performed gastrectomy is currently used only in cases of ineffectiveness of drug treatment of a common ulcerative process. Various types of gastric resections are of limited use, since they do not stop the development of the ulcerative process. In the presence of removable metastases in the liver, its resection is performed. Detection of multiple metastases of gastrinoma in lymph nodes, liver, bones requires chemotherapy.
A conservative approach to the treatment of gastrinoma when it is inoperable involves the appointment of antiproliferative drugs (octreotide), high dosages of H2 blockers (ranitidine, famotidine), proton pump blockers (lansoprazole, omeprazole).
Forecast
Radical removal of gastrinoma makes it possible to achieve a high 5-year survival rate (90%); in the absence of surgery, this indicator, taking into account the slow growth of the tumor, is about 60%; if metastases are detected, 20%. The death of patients may occur from tumor progression or profuse gastrointestinal bleeding. Patients with gastrinoma need the supervision of an oncologist, gastroenterologist, endocrinologist.