Gastrinom D37.78

Gastrin-producing, mostly solitary, mostly sporadically (75%) occurring tumor (non-ß-cell tumor of the pancreas) belonging to the family of neuroendocrine tumors of the gastrointestinal tract. 25% of gastrinomas appear as partial symptoms of MEN1 syndrome. At diagnosis, 50% of sporadic gastrinomas have already metastasized.

Sporadic gastrinomas (about 66% of gastrinomas)

Syndromal gastrinomas (about 25% of gastrinomas occur in the context of a MEN1 syndrome)

0.5-1.0/100,000 persons

Unknown; for partial symptom of MEN 1 (mutation of the gene MEN1 - menin gene -, a tumour suppressor gene mapped on gene locus 11q13.

At the time of diagnosis, patients are between 20-50 years old.

Sporadic gastrinomas (about 66% of gastrinomas) are tumours that are often located in the so-called "gastrinoma triangle" (bounded by the pancreatic head, duodenum and liver orifice).

50-60% of gastrinomas are localized in the pancreas (NET of the pancreas); 30-35% of gastrinomas occur in the duodenum

Syndromal gastrinomas in MEN1 syndrome (about 25% of the gastrinomas) are located 60% in the duodenum and 40% in the pancreas.

Gastrinoma is characterized by hypersecretion of gastric acid with fulminant recurrent ulcer formation, recurrent reflux disease and diarrhea (50% of cases).

The ulcers are localized in the stomach in 95% of cases, furthermore in the duodenum and less frequently in the jejunum. Clinically, dyspeptic symptoms (e.g. ulcer pain), diarrhoea, occasional dysphagia, nausea and vomiting are the most common.

About 50% of sporadic gastrinomas are diagnosed only after metastasis to the liver, abdominal lymph nodes or bones. Gastrinomas in the context of MEN1 often occur multiple times. Malignant gastrinomas are rarer in MEN I; the metastases are found in the liver and/or lymph nodes.

• Cave hypergastrinemia also under therapy with PPI, in autoimmune gastritis, H. p. gastritis, gastric outlet stenosis and renal insufficiency
• in the provocation test with secretin, increase in the gastrin level by more than 100%.
• endoscopic evidence of multiple, partly also atypically localized ulcers
• endosonography, MRT including MRCP and MR angio, PET-CT, spiral CT to visualize the tumor
• Somatostatin receptor scintigraphy

Elevated serum gastrin level (>1000 ng/l).

For further differentiation of hypergastrinemia, the secretin test is used: in gastrinoma, there is an increase in gastrin levels of more than 200 pg/l after injection of secretin (1 or 2 clinical units/kg body weight). (Note: in hypergastrinemia (<500 pg/l) with other causes, gastrin levels remain unchanged or fall after administration of secretin; the most frequent cause of elevated gastrin levels is therapy with acid-inhibiting drugs, e.g. with H2-receptor antagonists, proton pump inhibitors. These must be discontinued 1 week before diagnosis).

The secretin test is indicated for basal gastrin levels in the slightly elevated range (100-1000 pg/ml). In the case of very high basal gastrin levels (>1000 pg/ml), the diagnosis is almost certain if the patient has an appropriate clinical picture (note: high gastrin levels are also found in chronic atrophic gastritis type A).

Clinic with the recurrent history of ulcer; path. gastric test; imaging techniques.

Localization diagnostics:

Preoperative: In small tumours <1cm uncertain; endosonography, one-stop-shop-MRI including MRCP and MRT angiography); PET-CT (Ga-DOTATOC-PET-CT). Octreotide scan.

Intraoperative: Palpation, ultrasound and the possibility of an intraoperative histological freezing section should be kept available for a safe intraoperative diagnosis of gastrinoma.

Symptomatic:

Medicinal acid blockade with proton pump inhibitors (omeprazole, lansoprazole, pantoprazole). The necessary dose should be determined individually (basal acid secretion, measured in the morning before the next intake of the proton pump inhibitor, < 5 mmol/hour).

Inhibition of hormone secretion by somatostatin analogues, e.g. octreotide (Sandostatin®)

Possibly radionuclide therapy or chemotherapy

The goal of curative surgical resection should be pursued in all patients with sporadic CES without liver metastases or significant comorbidity. For curative surgery, complete resection of the primary tumor and systematic lymphadenectomy in the gastrinoma triangle should be performed.

Due to the high rate of metastasis (in 70% of cases) already at diagnosis, curative resection in sporadic gastrinomas is only possible in about 30% of cases.

Operative procedure for syndromic gastrinomas (in the context of a MEN1 syndrome). Here, the multilocal occurrence of the gastrinomas usually prevents a curative resection approach. This is also not absolutely necessary due to the low malignant potential of this genetic disease. Therapy of choice in this constellation is a life-long, acid-inhibiting therapy with proton pump inhibitors.

1. Perren A et al (2010): Classification and pathology of gastroenteropancreatic neuroendocrine tumors. Visceralmed 26: 234-240
2. Rinke A et al (2018) S2k guideline neuroendocrine tumors. Z Gastroenterol 56: 583-681
3. Ruszniewski P et al (2006) Well-differentiated gastric tumors/carcinomas. Neuroendocrinology 84:158-164
4. Scherübl H et al (2003) Neuroendocrine gastrointestinal tumors. Diagnosis and therapy. Dtsch Med Weekly 128: 81-83
5. Scherübl H et al (2011) Management of early gastrointestinal neuroendocrine neoplasms. World J Gastrointestinal test Endosc 3: 133-139