Vasoactive Intestinal Peptide-Secreting Tumor (VIPoma)

Forest Washington, MD
The Operative Review of Surgery. 2023; 1:182-188.

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Table of Contents

Pathophysiology
Presentation
Diagnosis
Treatment

References

Pathophysiology

Also Known as “VIP-Producing Neuroendocrine Tumor”, “Vasoactive Intestinal Peptide-Secreting Neoplasm”, or “VIP-Secreting Tumor of the Pancreas”

Definition 1

  • Vasoactive Intestinal Peptide (VIP) Secreting Neuroendocrine Tumor
  • Most Commonly Arise from Islet Cells of the Pancreas (75-90%) 2
  • *See Pancreatic Neuroendocrine Tumor (PNET)
  • Other Potential Sites: 2-5
    • Lung
    • Colon
    • Liver
    • Adrenal Gland or Sympathetic Ganglion – More Common in Infants and Pediatric Patients
      • Neuroblastoma
      • Ganglioneuroma
      • Pheochromocytoma
      • Paraganglioma

Distribution and Size

  • Most Common in Body or Tail of the Pancreas (70-75%) 6-8
  • Usually Solitary with Rare Multicentric Masses (5%) 9,10
  • Most are Large (> 3 cm) 6,11

Malignancy

  • Most are Malignant and Have Metastasized at the Time of Diagnosis (60-80%) 9
  • 5% Have Multiple Endocrine Neoplasia Type 1 (MEN-1) 12

Epidemiology

  • Median Age: 40-50 Years 2,13,14
    • Between Ages 2-4 Years in Children 4
  • More Common in Females (65%) 14

Distal Pancreatectomy Specimen with a Peripancreatic VIPoma (Arrow) 15

Presentation

VIPoma Syndrome

  • Also Known As:
    • Watery Diarrhea, Hypokalemia, and Achlorhydria (WDHA) Syndrome
    • Verner-Morrison Syndrome
    • Pancreatic Cholera
  • Classic Triad: 2,4
    • Watery Diarrhea
      • Profuse and Persists with Fasting (> 700 mL/Day but Can Be Over 6 L)
      • Tea-Colored Odorless Stools
      • Profound Diarrhea Can Lead to Electrolyte Imbalances and Non-Anion Gap Metabolic Acidosis
    • Hypokalemia
      • Due to Diarrhea, Aldosterone Synthesis, and Direct Excretion by Enterocytes
    • Achlorhydria (HCl)
      • Due to the Inhibition of HCl Secretion by Gastric Parietal Cells

Additional Symptoms 2,4,16-18

  • Flushing (15-30%)
  • Hyperglycemia (20-50%)
  • Hypercalcemia (25-50%)
  • Nausea and Vomiting
  • Lethargy
  • Weakness
  • Muscle Cramps
  • Weight Loss

Diagnosis

Diagnosis

  • Primary Diagnosis Made by Demonstrating High Serum VIP Levels (> 200 pg/mL) 19,20
  • Biopsy Not Required but Can Be Used for Grading 21

TNM Staging

Localization

  • Initial Imaging: Noninvasive (CT or MRI) 23,24
  • Somatostatin Receptor Imaging 23,24
    • Consider if Initial Imaging Fails to Localize
    • Options:
      • Somatostatin (Octreotide) Receptor Scintigraphy (SRS) – Classic Test Used
      • Functional PET Scan (Ga-68 DOTATATE) – Becoming More Prevalent with Higher Sensitivity
  • If Noninvasive Imaging Fails: Invasive Imaging
    • Endoscopic Ultrasound (EUS) – Generally Preferred Next Step 25
    • Selective Visceral Angiography

PNET on Imaging: (A) CT, (B) EUS, (C) SRS, (D) Functional PET 26

Treatment

Initial Medical Therapy 27-29

  • Aggressive Fluid Resuscitation
  • Electrolyte Replacement
  • Somatostatin Analogs (Octreotide/Lanreotide) May Be Needed to Control Diarrhea
  • Additional Agents for Refractory Diarrhea:
    • Glucocorticoids
    • Clonidine
    • Loperamide

Surgical Resection (Treatment of Choice) 2,30,31

  • Definitive Treatment: Surgical Resection
    • Head/Neck: Pancreaticoduodenectomy
    • Body/Tail: Distal Pancreatectomy (Concurrent Splenectomy if Malignancy is Suspected)
    • Entire Pancreas: Total Pancreatectomy
  • May Consider Enucleation for Small Tumors (< 2-3 cm) – Controversial Due to High Malignancy Rates
    • Additional Requirements: Single Lesion, ≥ 2-3 mm From the Main Pancreatic Duct, Well-Encapsulated, and No Local Invasion
  • Due to High Rates of Metastases, Surgical Resection is Often Not Feasible 9

Liver-Directed Therapy

  • Resection of Metastases if Able
  • Radiofrequency Ablation (RFA) or Cryoablation 32
  • Hepatic Artery Embolization 33,34

Additional Options in Surgically Unresectable Disease

  • Somatostatin Analogs (Octreotide/Lanreotide) to Decrease Hormonal Secretion and Control Symptoms 28,29
  • Other Molecular-Targeted Agents:
    • Everolimus 35
    • Sunitinib 36
  • Peptide Receptor Radionuclide Therapy (PRRT) 37,38
  • Chemotherapy 39,40
  • Radiation Therapy 41,42
    • Pancreatic Neuroendocrine Carcinomas Were Previously Considered to be Resistant to Radiation

References

  1. National Cancer Institute. NIH.
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