ZES

Question 1

General findings

Answer 1

A gastrinoma (Zollinger-Ellison syndrome) is a gastrin-secreting neuroendocrine tumor that is most often localized to the duodenum and pancreas. Most gastrinomas occur sporadically, but some are associated with other endocrine neoplasias (e.g., pituitary adenomas, parathyroid adenomas, insulinomas). Although some gastrinomas are benign, more than half of all gastrinomas are malignant. Gastrinomas release high levels of gastrin, which then increases the production of gastric acid. Patients typically present with recurrent, therapy-resistant peptic ulcer disease and diarrhea. Patients with gastrinomas have low gastric pH and elevated serum gastrin. Furthermore, serum gastrin levels increase with the administration of secretin (positive secretin stimulation test). Surgical resection of the tumor is indicated in patients with localized disease. Proton pump inhibitors (PPIs) and octreotide may be used to control acid secretion.

Question 2

Etiology

Answer 2

1. Gastrinomas are assumed to arise from endocrine cells of the gut (mostly the duodenum) or the pancreas.
2. Most gastrinomas occur sporadically .
3. Some gastrinomas occur in association with multiple endocrine neoplasia type 1 (MEN 1) . (25%)

✔Tumor location
Duodenum (∼ 70% of cases)
Pancreas (∼ 25% of cases): typically the head
Ectopic locations (5–15% of cases): e.g., liver, peripancreatic lymph nodes, ovaries
∼ 60% of gastrinomas are malignant (but slow-growing)

NB
1. I gastrinomi associati a MEN 1 sono piccoli e multipli e se minori di 2 cm associati a prognosi migliore e alta resecabilità. Sono duodenali (1 e 2 segmento)

2.I gastrinomi duodenali sono piccoli e multipli mentre i gastrinomi pancreatici tendono ad essere maggiori di 1 cm

Question 3

Pathology

Answer 3

Gastrinomas are neuroendocrine tumors of the GI tract that secrete gastrin.
Hypergastrinemia → stimulation of parietal cells → gastric acid hypersecretion, which leads to:
Peptic ulcer disease
Inactivation of pancreatic enzymes → diarrhea, steatorrhea → malabsorption (The high volume of gastric acid that is produced decreases intestinal pH. Pancreatic lipases, which require an alkaline environment to function, are inactivated and can no longer emulsify fats. Moreover, gastrin acts directly on the intestine and prevents sodium and water reabsorption, resulting in secretory diarrhea.)

Question 4

Diagnostics

The presence of multiple, large (> 2 cm) ulcers in atypical locations (e.g., the jejunum) should raise suspicion of gastrinoma!
Low gastric pH along with gastrin levels > 1000 pg/mL is virtually sufficient to diagnose gastrinoma. If gastrin levels are less than 1000 pg/mL, a secretin stimulation test must be performed!💥

Answer 4

Best initial test: esophagogastroduodenoscopy💥
Important to rule out H. pylori infection and malignant ulcers
Typically reveals multiple ulcers and thick gastric folds
↓ Gastric pH
Confirmatory tests
↑ Serum gastrin (in a fasting serum sample)
A gastrin level > 1000 pg/mL (or 10-fold increase in gastrin levels) is conclusive evidence of a gastrinoma.👓

If serum gastrin levels increase (> 100 pg/mL) but are not more than 1000 pg/mL, a secretin stimulation test should be performed.
✔Secretin stimulation test (if fasting serum gastrin test is inconclusive)
A two-fold increase in gastrin above the basal level is indicative of a gastrinoma.
No increase or only a very slight increase is observed in cases of secondary hypergastrinemia.
Imaging: only after diagnosis is confirmed to localize the tumor

CT/MRI scan, somatostatin receptor scintigraphy (octreotide scan👓) and/or endoscopic ultrasonography
The presence of multiple, large (> 2 cm) ulcers in atypical locations (e.g., the jejunum) should raise suspicion of gastrinoma!

Low gastric pH along with gastrin levels > 1000 pg/mL is virtually sufficient to diagnose gastrinoma. If gastrin levels are less than 1000 pg/mL, a secretin stimulation test must be performed!

Question 5

Clinica

Answer 5

Most patients manifest with recurrent, therapy-resistant peptic ulcer disease.

1.Abdominal pain
2.Diarrhea and steatorrhea
Dyspeptic symptoms (e.g., heartburn)
Upper gastrointestinal bleeding
3.Weight loss
Possible symptoms of other endocrine neoplasias (See MEN 1.)

Question 6

Treatment

In approximately 50% of cases, the tumor has already metastasized at the time of diagnosis!

Answer 6

• Reduce acid production
• PPIs (e.g., omeprazole), H2 antagonists (e.g., ranitidine)
• Octreotide (a somatostatin analog) may be used in refractory cases.
• Nonmetastatic disease: surgical resection of the gastrinoma
• Metastatic disease: chemotherapy (doxorubicina, 5-fluorouracile)