Diagnosis

Gastrinoma

Etiology

Cause [zof][adw]

• 80% sporadic arise from enteroendocrine G-cells

• 20-30% in association with multiple endocrine neoplasia type 1 (MEN1):

  • Dysregulation of the MEN1 pathway, chromosomal instability, and alterations in key signaling pathways

Other causes of hypergastrinemia [aui]

• Appropriate (physiological) hypergastrinemia

  • Chronic atrophic gastritis/pernicious anemia

  • Gastric acid antisecretory agents (proton pump inhibitors)

  • Chronic renal failure

  • Pangastritis H. pylori infection

  • Postacid-reducing surgery/vagotomy

• Inappropriate hypergastrinemia with hyperchlorhydria

  • Antral predominant H. pylori infection

  • Gastric outlet obstruction

  • Antral G cell hyperfunction/hyperplasia

  • Chronic renal failure

  • Short bowel syndrome

  • Retained gastric antrum syndrome

  • Juvenile polyposis of the stomach

  • Zollinger–Ellison syndrome

Pathophysiology [adw]

1. Elevated gastrin independent of luminal pH --> sustaining persistent acid hypersecretion:

   • G-cells autonomously secrete gastrin

   • Ectopic secretion of gastrin

2. Hydrochloric acid production --> Hyperchlorhydria:

   • Refractory peptic disease

   • Gastroesophageal reflux

   • Diarrhea

3. Acid-mediated inactivation of pancreatic enzymes and bile salts:

   • Impairs lipid digestion and absorption

Anatomic location [zof][ub1]

• Duodenum (30%)

• Pancreas (60%)

• Stomach/liver (10%)

Complications [adw]

• Metastatsis

• GI bleeding

• GI perforation

Epidemiology

Incidence per 100.000 [1uf][hsn][fcs][rda][wga][sgy][ub1]

Approach

• Blood test: chromogranin A

• Gastroscopy

• Secretin stimulation test (performed off PPIs) demonstrating an increase in serum gastrin of >120 pg/ml has a sensitivity of 94% and specificity of 100% [aui]

• Fasting hypergastrinemia (and hyperchlorhydria) in the absence of antisecretory therapy (sensitivity: 98–100%) [aui]

  • Fasting gastrin >1000 pg/ml (normal <100 pg/ml)

  • Gastric pH ≤ 2

• Somatostatin PET-CT

• CT scan

• MRI

WHO classification [adw]

1. Grade 1: Low-grade, well-differentiated tumor exhibiting benign or uncertain behavior at diagnosis: mitotic count <2 per 10 high-power fields and Ki-67 index of <3%.

2. Grade 2: Low-grade, well-differentiated tumor with intermediate proliferative activity: mitotic count 2 to 20 per 10 HPF and Ki-67 index of 3% to 20%.

3. Grade 3: High-grade, poorly differentiated carcinoma with aggressive clinical behavior: mitotic count >20 per 10 HPF and Ki-67 index of >20%.

TNM-classification [adw]

1. Primary tumor (T):

   • T1: Tumor ≤2 cm, confined to the pancreas; tumor invades the mucosa or submucosa of the duodenum only and is ≤1 cm in greatest dimension

   • T2: Tumor >2 cm but ≤4 cm, confined to the pancreas; Tumor invades the muscularis propria of the duodenum or is >1 cm in greatest dimension

   • T3: Tumor >4 cm or invading adjacent structures (excluding major vessels); duodenal tumor invades the pancreas or peripancreatic adipose tissue

   • T4: Tumor invades adjacent organs, visceral peritoneum, or large vessels

2. Regional lymph nodes (N):

   • N0: No regional lymph node involvement

   • N1: Regional lymph node metastasis present

3. Distant metastasis (M): 

   • M0: No distant metastasis

   • M1: Distant metastasis present (commonly the liver, but may also include bones or lungs)

Treatment

1. Medication: [zof][adw]

   • Lifelong high-dose proton pump inhibitors (PPIs are preferable to H2 receptor blockers due to their higher potency and longer duration of action)

2. Surgical resection: [adw]

   • The only curative treatment in the absence of unresectable metastatic disease

3. Chemotherapy is an option for patients with widespread metastasis: [adw]

   • Streptozotocin and 5-fluorouracil or doxorubicin

Differential diagnoses

Achlorhydria, Acute pancreatitis, Arteriovenous malformation, Brain damage, Esophageal varices, Esophagitis, Gastric outlet obstruction, Gastritis, Gastrointestinal obstruction, Gastrointestinal perforation, Mallory-Weiss tear, Pernicious anemia, Ulcer disease