What is the primary treatment for a patient with gastrinoma?

Treatment for Gastrinoma

The primary treatment for gastrinoma is surgical resection when feasible, combined with proton pump inhibitors to control gastric acid hypersecretion, with the surgical approach determined by tumor location and imaging findings. 1

Medical Management of Acid Hypersecretion

Proton pump inhibitors (PPIs) are the treatment of choice for controlling gastric acid hypersecretion and preventing peptic complications in all gastrinoma patients. 1

• Higher doses of PPIs may be required in patients with complicated disease 1
• PPIs substantially improve quality of life in patients with Zollinger-Ellison syndrome 2
• This medical therapy should be initiated immediately upon diagnosis, regardless of whether surgery is planned 1

Surgical Management Based on Tumor Location

The surgical approach is determined by preoperative imaging localization and intraoperative findings 1:

Occult Gastrinoma (No Visible Tumor on Imaging)

• Either observation or exploratory surgery with duodenotomy and intraoperative ultrasound 1
• If tumor identified during surgery: enucleation or local resection with removal of periduodenal lymph nodes 1

Duodenal Gastrinomas

• Duodenotomy with intraoperative ultrasound 1
• Local resection or enucleation of tumors 1
• Periduodenal lymph node dissection (mandatory, as the majority of gastrinomas are located in the duodenum) 1, 3

Pancreatic Head Gastrinomas

• Exophytic or peripheral tumors not adjacent to pancreatic duct: Enucleation with periduodenal lymph node removal 1
• Deeper or invasive tumors, or those near the main pancreatic duct: Pancreatoduodenectomy 1

Distal Pancreatic Gastrinomas

• Distal pancreatectomy with or without splenectomy 1
• The role of routine splenectomy is debated, though it facilitates lymph node retrieval 1
• Alternative: Warshaw technique (resection of splenic vessels with splenic preservation) achieves comparable lymph node retrieval 1

Preoperative Considerations

• All patients who might require splenectomy should receive preoperative trivalent vaccine (pneumococcus, haemophilus influenzae b, meningococcus group c) 1
• Evaluate all gastrinoma patients for MEN1 syndrome with appropriate testing 4, 3
• Somatostatin receptor scintigraphy (preferably Gallium-68 PET) is the standard for tumor localization 3
• Multiphase CT and MRI scans should be obtained for optimal detection 3
• Endoscopic ultrasound has sensitivity up to 83% for pancreatic gastrinomas 3

Management of Metastatic/Unresectable Disease

Approximately 60% of gastrinoma patients develop metastases, with likelihood correlated to primary tumor size 4, 3:

First-Line Antiproliferative Therapy

• Somatostatin analogues: Lanreotide autogel 60-120 mg/month or octreotide LAR 10-30 mg/month 3

Additional Treatment Options

• Liver-directed therapies for hepatic metastases: radiofrequency ablation, UAE, TACE, SIRT 3
• Peptide receptor radionuclide therapy (PRRT) with lutetium-177 DOTATATE for progressive disease 3
• Chemotherapy for well-differentiated tumors (G1/G2): streptozotocin plus doxorubicin/5-FU as second-line option 2
• Chemotherapy for poorly differentiated tumors (G3): etoposide plus cisplatin 2
• Everolimus may be used off-label for uncontrolled symptoms in refractory progressive disease 3
• Liver transplantation may be considered in young adults with stable liver-only disease and high tumor burden 3

Important Caveats

• Surgery is the only chance for cure, though recurrence is frequent (biochemical recurrence in 65% and morphological recurrence in 40% at 2 years) 5
• Liver metastases are associated with decreased survival 6
• Overall prognosis is relatively good with median survival above 10 years and 5-year survival above 80% in surgically resected patients 5
• Gastrinomas are subepithelial tumors arising from deeper layers, making standard mucosal biopsies non-diagnostic 3