Glucagonoma Treatment
Surgical resection is the definitive treatment for glucagonoma, with the specific procedure determined by tumor location: distal pancreatectomy with splenectomy and peripancreatic lymph node resection for tail lesions (most common), or pancreatoduodenectomy for head lesions. 1, 2
Preoperative Management
Before surgical intervention, address the metabolic and systemic complications:
- Treat hyperglycemia and diabetes with appropriate measures including intravenous fluids 1
- Consider perioperative anticoagulation due to the hypercoagulable state associated with glucagonoma, which increases risk of thromboembolism and pulmonary emboli 2, 3
- Administer somatostatin analogues (octreotide or lanreotide) for symptom control, as glucagonomas are generally sensitive to these agents 1
- Consider total parenteral nutrition (TPN) given the severe weight loss commonly seen in these patients 1
- Provide preoperative trivalent vaccine (pneumococcus, haemophilus influenzae b, meningococcus) for all patients requiring splenectomy 1, 3
Surgical Approach by Tumor Location
For Tail Lesions (Most Common Site - 68%)
- Distal pancreatectomy with splenectomy and peripancreatic lymph node resection is the standard approach 4, 2, 5
- Splenectomy is mandatory for glucagonomas due to their typically malignant nature with regional lymph node involvement 4, 3
- For small (<2 cm) peripheral glucagonomas, enucleation or local excision with peripancreatic lymph dissection may be considered 2
For Head Lesions
- Pancreatoduodenectomy (Whipple procedure) with peripancreatic lymph node resection is required 2
Management of Metastatic Disease
Most glucagonomas are malignant, with 63% presenting with synchronous metastases 5:
- Pursue surgical excision of both primary tumor and liver metastases when feasible (staged or synchronous), as this provides both antisecretory and antitumor benefit 4, 5
- Surgery of metastases achieved 85.7% secretory response rate with complete resolution of necrolytic migratory erythema in 93.8% of cases 5
- Chemotherapy demonstrates substantial efficacy with 85.7% secretory response rate and longest time to next treatment (20.2 months) 5
- Liver-directed therapy (embolization, radiofrequency ablation) achieved 75% secretory response rate 5, 6
- Somatostatin analogues provide 60% secretory response rate and can normalize glucagon levels in metastatic disease 5, 7
- Peptide receptor radionuclide therapy (PRRT) and mTOR inhibitors (everolimus) are additional options for advanced disease 6
Prognosis and Surveillance
- Median overall survival is 17.3 years, even with metastases at diagnosis 5
- Ki-67 index >3% is associated with shorter survival (HR 5.27) 5
- Follow-up at 3-12 months post-resection, then every 6-12 months for up to 10 years with history, physical exam, biochemical markers (serum glucagon), and imaging 4
- Disease recurrence occurs in 21-42% of patients, most within 5 years but can occur beyond 10 years 4, 7
- Surgical resection is recommended for resectable locoregional or oligometastatic recurrence 4
Critical Clinical Pearls
- Necrolytic migratory erythema (NME) is present in 86.8% of cases and often the initial finding—prompt recognition allows earlier diagnosis before liver metastases develop 8, 5
- Complete resolution of NME occurs in 93.8% after successful surgery 5
- Metastases occur late, making early recognition potentially life-saving 8
- Curative-intent surgery should always be considered, even in the presence of metastases, given the prolonged survival and potential for symptom resolution 5