What is the management approach for pancreatic neuroendocrine tumors (PNETs)?

Management of Pancreatic Neuroendocrine Tumors (PNETs)

Surgical resection is the primary treatment approach for localized pancreatic neuroendocrine tumors when possible, with specific management strategies tailored based on tumor size, functionality, and grade. 1, 2

Diagnostic Workup

• Initial biochemical assessment:

  • Plasma chromogranin A and urinary 5-hydroxyindoleacetic acid as baseline tests 1
  • Specific hormone tests based on suspected functional syndrome:
    • Insulinoma: insulin, C-peptide, glucose levels
    • Gastrinoma: gastrin levels
    • Glucagonoma: glucagon, blood glucose
    • VIPoma: VIP levels, electrolytes 1

• Imaging studies:

  • Multiphase CT or MRI to detect primary tumor and assess for metastases 1
  • Somatostatin receptor scintigraphy (SSRS) or preferably Gallium-68 PET/CT (most sensitive) 1, 2
  • Endoscopic ultrasound (EUS) for pancreatic tumors, especially small lesions 1

Management Based on Tumor Characteristics

1. Localized Resectable PNETs

Nonfunctioning PNETs:

• Tumors ≤1 cm:

  • Observation alone is acceptable for incidentally discovered tumors 1, 3
  • Regular imaging follow-up every 6 months 2

• Tumors 1-2 cm:

  • Surgical resection with consideration of lymph node dissection due to risk of lymph node metastases 1, 3
  • Risk of lymph node metastases increases significantly once tumor exceeds 15 mm 3

• Tumors >2 cm:

  • Formal surgical resection with lymph node dissection 1
  • Total removal of tumor with negative margins 1

Functioning PNETs:

• Surgical resection regardless of size to control hormone-related symptoms 2, 4
• Preoperative management:
  • Control hormone-related symptoms before surgery 1
  • For insulinomas: stabilize glucose with diet and/or diazoxide 1
  • For gastrinomas: proton pump inhibitors 1
  • For glucagonomas: manage hyperglycemia and diabetes 1
  • For VIPomas: correct electrolyte imbalances 1
  • Somatostatin analogs (octreotide/lanreotide) for symptom control in most PNET subtypes 1
    • CAUTION: Use somatostatin analogs with extreme caution in insulinomas as they can worsen hypoglycemia 1

Surgical Approach by Tumor Location:

• Gastrinomas:

  • Duodenal: duodenotomy with local resection/enucleation and periduodenal node dissection 1
  • Pancreatic head (exophytic/peripheral): enucleation with periduodenal node removal 1
  • Pancreatic head (deep/invasive): pancreatoduodenectomy 1
  • Distal pancreas: distal pancreatectomy 1

• Other PNETs:

  • Location-appropriate resection (pancreatoduodenectomy, distal pancreatectomy, or enucleation) 4

2. Advanced/Metastatic PNETs

Treatment options based on grade:

• G1-G2 (Ki-67 <20%) tumors:

  • Somatostatin analogs (octreotide/lanreotide) for SSTR-positive tumors 2
  • Targeted therapy with everolimus or sunitinib for progressive disease 2, 5
  • Cytoreductive surgery for selected patients with liver metastases 2, 4
  • Locoregional therapies (radiofrequency ablation, embolization) for liver metastases 2

• G3 (Ki-67 >20%) tumors:

  • Chemotherapy (temozolomide-based or platinum-based regimens) 2
  • Consider targeted therapy for well-differentiated G3 NETs 2

Special Considerations

1. Preoperative vaccination:

   • Patients who might require splenectomy should receive preoperative trivalent vaccine (pneumococcus, haemophilus influenzae b, meningococcus) 1

2. Follow-up after treatment:

   • Biochemical markers and imaging (CT or MRI) every 3-6 months 2
   • Longer follow-up periods (>5 years) are recommended due to the risk of late recurrence 2

3. Common pitfalls to avoid:

   • Using somatostatin analogs in insulinoma patients with negative somatostatin scintigraphy (can precipitate severe hypoglycemia) 1
   • Underestimating small tumors (1-2 cm), which may have malignant potential 1
   • Inadequate lymph node sampling during surgery for tumors >1.5 cm 3

The management of PNETs requires a multidisciplinary approach with treatment decisions based on tumor functionality, size, grade, and stage. Surgical resection offers the best chance for cure in localized disease, while a combination of systemic and locoregional therapies is needed for advanced disease.