VIPoma: Clinical manifestations, diagnosis, and management

Author:: Emily Bergsland, MD
Section Editors:: Kenneth K Tanabe, MD; David C Whitcomb, MD, PhD
Deputy Editor:: Shilpa Grover, MD, MPH, AGAF

Literature review current through: Dec 2022. | This topic last updated: Nov 02, 2021.

INTRODUCTION — VIPomas are rare functioning neuroendocrine tumors that secrete vasoactive intestinal polypeptide (VIP) [1,2]. This topic will review the clinical manifestations, diagnosis, and management of VIPomas. An overview of the clinical manifestations, diagnosis, and management of pancreatic neuroendocrine tumors and other functioning pancreatic neuroendocrine tumors are discussed in detail, separately. (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine neoplasms" and "Surgical resection of sporadic pancreatic neuroendocrine tumors" and "Metastatic well-differentiated pancreatic neuroendocrine tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion" and "Metastatic gastroenteropancreatic neuroendocrine tumors: Local options to control tumor growth and symptoms of hormone hypersecretion" and "Insulinoma" and "Somatostatinoma: Clinical manifestations, diagnosis, and management" and "Glucagonoma and the glucagonoma syndrome" and "Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis" and "Management and prognosis of the Zollinger-Ellison syndrome (gastrinoma)".)

EPIDEMIOLOGY — VIPomas are detected in 1 in a million people per year [3]. The majority of VIPomas arise within the pancreas, and are classified as functioning pancreatic neuroendocrine (islet cell) tumors. In adults, VIPomas are intrapancreatic in over 95 percent of cases. However, other VIP-secreting tumors have been reported, including lung cancer, colorectal cancer, ganglioneuroblastoma, pheochromocytoma, hepatoma, and adrenal tumors. In children, VIPomas rarely arise in the pancreas [4]. Instead, VIP-secreting tumors typically occur in the sympathetic ganglia (eg, ganglioneuroblastomas or ganglioneuromas) and the adrenal glands [5-7]. (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine neoplasms", section on 'Classification and nomenclature'.)

VIPomas are usually diagnosed between 30 and 50 years of age in adults and between two and four years of age in children. Symptomatic pancreatic VIPomas are usually solitary, more than 3 cm in diameter, and occur in the tail of the pancreas in 75 percent of patients. Approximately 60 to 80 percent of VIPomas have metastasized by the time of diagnosis [8,9]. VIPomas usually occur as isolated tumors, but in 5 percent of patients they are part of the multiple endocrine neoplasia syndrome type 1 (MEN1) and occur in association with parathyroid and pituitary tumors, gastrinoma, and other tumors [10,11]. (See "Multiple endocrine neoplasia type 1: Clinical manifestations and diagnosis".)

PATHOPHYSIOLOGY — The VIPoma syndrome is caused by excessive, unregulated secretion of vasoactive intestinal polypeptide (VIP) by the tumor. However, other substances, such as prostaglandin E2, may occasionally be secreted by the tumors [12]. VIP is a 28 amino acid polypeptide that binds to high affinity receptors on intestinal epithelial cells, leading to activation of cellular adenylate cyclase and cAMP production. This results in net fluid and electrolyte secretion into the lumen, resulting in secretory diarrhea and hypokalemia [12,13]. Other biologic actions of VIP including vasodilation, inhibition of gastric acid secretion, bone resorption, and enhanced glycogenolysis are responsible for flushing as well as laboratory findings of hypochlorhydria, hypercalcemia, and hyperglycemia in patients with VIPomas (table 1). (See "Vasoactive intestinal polypeptide" and 'Clinical features' below and "Physiology of gastric acid secretion".)

CLINICAL FEATURES

Clinical manifestations — The majority of patients with VIPoma have VIPoma syndrome, which is also called the pancreatic cholera syndrome, Verner-Morrison syndrome, and the watery diarrhea, hypokalemia, and hypochlorhydria or achlorhydria (WDHA) syndrome. VIPoma syndrome is characterized by watery diarrhea that persists with fasting. Stools are tea-colored and odorless with stool volumes exceeding 700 mL/day. In 70 percent of patients, stool volume can exceed 3000 mL per day [14-16]. Abdominal pain is mild or absent. Associated symptoms include flushing episodes in 20 percent of patients and symptoms related to hypokalemia and dehydration, such as lethargy, nausea, vomiting, muscle weakness, and muscle cramps (table 1). (See "Clinical manifestations and treatment of hypokalemia in adults".)

Laboratory findings — Patients with VIPoma have secretory diarrhea with a low osmotic gap (<50 mOsm/kg) (calculator 1) [17]. Hypochlorhydria occurs in 75 percent of patients and can result in iron and B12 deficiency. Other findings may include hyperglycemia and hypercalcemia (table 1). Hypercalcemia may be due to coexistent hyperparathyroidism as part of the MEN1 syndrome or to hyperalbuminemia caused by dehydration. In patients with dehydration, the serum total calcium concentration is increased, but the serum ionized (or free) calcium concentration is normal. (See "Diagnostic approach to hypercalcemia", section on 'Confirm hypercalcemia' and "Approach to the adult with chronic diarrhea in resource-abundant settings".)

DIAGNOSIS — The diagnosis of a VIPoma is suspected in patients with unexplained high-volume secretory diarrhea (>700 mL/day). The diagnosis is established by a serum vasoactive intestinal polypeptide (VIP) concentration >75 pg/mL. However, a single elevated VIP level should be confirmed by repeat testing.

Evaluation of the patient with secretory diarrhea to exclude other causes is discussed in detail, separately. (See 'Differential diagnosis' below and "Approach to the adult with chronic diarrhea in resource-abundant settings".)

DIFFERENTIAL DIAGNOSIS — Other disorders that can cause secretory diarrhea include surreptitious abuse of saline cathartics, enteritis caused by enterotoxigenic Escherichia coli or Vibrio cholera, microscopic colitis, bile salt malabsorption due to ileal resection, and the carcinoid syndrome (table 2). (See "Approach to the adult with chronic diarrhea in resource-abundant settings".)

TUMOR LOCALIZATION

Approach to imaging — After diagnosis, imaging studies are required to accurately localize the tumor. Cross-sectional imaging with multiphasic computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen can localize the tumor and stage the extent of disease. We begin with helical (spiral) multiphasic contrast-enhanced CT for evaluation of patients with a VIPoma. We perform MRI when CT shows indeterminate lesions that need further characterization. If cross-sectional imaging is inconclusive, endoscopic ultrasound (EUS), somatostatin receptor scintigraphy, or integrated PET/CT using Gallium-68-DOTA-0-Phe1-Tyr3-Octreotate (Gallium Ga-68 DOTATATE) or Ga-68-DOTA-0-Phe¹-Tyr³-Octreotide (Ga-68 DOTATOC), copper 64-Cu DOTATATE PET/CT, should be performed to identify the tumor. Because of its greater sensitivity, 68-Ga DOTATATE or Ga-68 DOTATOC PET/CT is preferred over conventional somatostatin receptor scintigraphy, if available [18,19]. In addition, we perform Ga-68 DOTATATE (or Ga-68 DOTATOC) PET/CT in the evaluation of a patient with VIPoma if the finding of extra-abdominal metastases would change treatment. (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine neoplasms", section on 'Somatostatin-receptor-based imaging'.)

●Computed tomography – CT scan is noninvasive and readily available. Intravenous contrast enhances the detection of smaller lesions, especially when images are obtained during the arterial phase. In addition, arterial phase and portal venous phase sequences can be used to maximize the conspicuity of liver metastases compared with the surrounding normal liver parenchyma. CT scans are highly accurate for detecting primary pancreatic neuroendocrine tumors (NETs), and, using multiphase imaging techniques, sensitivity is >80 percent [20-22]. Since most pancreatic VIPomas are more than 3 cm in size at presentation, a pancreatic mass can usually be identified by CT in the majority of cases [23]. The sensitivity of contrast-enhanced CT for these tumors approaches 100 percent [24,25]. (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine neoplasms", section on 'Computed tomography'.)

●Magnetic resonance imaging – On MRI, pancreatic NETs are typically characterized by low signal intensity on T1-weighted images and high signal intensity on T2-weighted images (image 1 and image 2). MRI may have a higher sensitivity for liver metastases as compared with CT [26]. (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine neoplasms", section on 'Magnetic resonance imaging'.)

●Somatostatin receptor scintigraphy – Somatostatin receptor scintigraphy (OctreoScan) using radiolabeled form of the somatostatin analog octreotide (Indium-111 [111-In]) pentetreotide has the advantage of instantaneous whole body scanning, which also allows detection of metastases outside of the abdominal region [27]. However, somatostatin-receptor scintigraphy (SRS) is less sensitive than PET-CT and has largely been replaced by 68Ga/64Cu-DOTA-PET imaging. Guidelines from the European Neuroendocrine Tumor Society, the European Society for Medical Oncology (ESMO), and the National Comprehensive Cancer Network [28] suggest that DOTA-PET-imaging is preferred over SRS [29-31]. (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine neoplasms", section on 'Somatostatin-receptor-based imaging'.)

●Endoscopic ultrasound – EUS can detect pancreatic tumors as small as 2 to 3 mm, provide accurate information on the local extent of disease, and allow for transmucosal needle biopsy of pancreatic lesions. However, EUS is rarely used in the evaluation of VIPomas as these tumors are diagnosed by hormonal assays and VIPomas are usually detectable on CT/MRI at diagnosis. (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine neoplasms".)

●Functional PET imaging with Ga-68 DOTATATE and Ga-68 DOTATOC – Several positron emission tomography (PET) tracers for functional imaging have emerged (18-F-dihydroxy-phenyl-alanine [18F-DOPA], 11-C-5-hydroxytryptophan [11-C-5-HTP], Ga-68-DOTA-D-Phe¹-Tyr³-Octreotide [gallium Ga-68-DOTATOC], and Ga-68-DOTA-D-Phe¹-Tyr³-Octreotate [galliumGa-68 DOTATATE]) that offer higher spatial resolution than conventional SRS and are associated with improved sensitivity for detection of small lesions [32]. Like SRS, Ga-68 DOTATATE, Ga-68 DOTATOC, and Cu-64 DOTATATE detect somatostatin receptor (SSTR) expression on NETs. These tracers are approved in the United States for use with PET for localization of SSTR positive NETs. Integrated DOTA-PET/CT or DOTA-PET/MRI scanning is the functional imaging modality of choice for staging and localization of most well-differentiated NETs (where available) [29-31]. (See "Metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors: Presentation, prognosis, imaging, and biochemical monitoring" and "Metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors: Presentation, prognosis, imaging, and biochemical monitoring", section on 'Somatostatin receptor-based imaging techniques'.)

STAGING — Pancreatic neuroendocrine tumors, including VIPomas, are staged using the tumor, node, metastasis (TNM) classification from the joint American Joint Committee on Cancer/Union for International Cancer Control adapted from the ENETs staging system [33]. The staging system is highly prognostic for both relapse-free and overall survival [34-36]. The newest release of the TNM staging classification (8^th edition, 2017) has a staging system for neuroendocrine tumors of the pancreas that is separate from that used for exocrine pancreatic tumors [37]. (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine neoplasms", section on 'Staging system'.)

TREATMENT

Symptomatic treatment

Repletion of fluid and electrolytes — Treatment of a patient with a VIPoma begins with replacement of fluid losses and correction of electrolyte abnormalities. Many patients require more than 5 L of fluid and 350 mEq of potassium daily. (See "Maintenance and replacement fluid therapy in adults", section on 'Replacement fluid therapy' and "Clinical manifestations and treatment of hypokalemia in adults", section on 'Treatment' and "Treatment of hypovolemia (dehydration) in children".)

Somatostatin analogs — Somatostatin and its analogs (eg, octreotide, lanreotide) inhibit the secretion of vasoactive intestinal polypeptide (VIP) and are the treatment of choice to control diarrhea in patients with VIPoma [3,38-40]. (See "Metastatic well-differentiated pancreatic neuroendocrine tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion", section on 'Somatostatin analogs'.)

Symptomatic patients may be initiated on short-acting octreotide (50 to 100 micrograms subcutaneously every eight hours) with rapid transition to a long-acting formulation and subsequent titration of dose to optimize symptom control [41,42]. Sandostatin LAR, a depot preparation, is typically initiated at a dose of 20 mg IM monthly with gradual dose escalation as needed for optimal symptom control [43]. Patients may use additional short-acting octreotide for breakthrough symptoms while doses are being titrated; therapeutic levels of octreotide are not reached until 10 to 14 days after the initiation of the LAR injection. Lanreotide, another long-acting somatostatin analog (SSA), can be self-administered once monthly using a deep subcutaneous injection and appears to have similar efficacy to octreotide [44-46].

Somatostatin analogs are usually well tolerated, but there are some side effects, including nausea, abdominal discomfort, bloating, loose stools, and fat malabsorption [47,48]. Side effects are often worst during the first several weeks of therapy, after which the symptoms subside. Mild glucose intolerance rarely occurs, due to transient inhibition of insulin secretion. Somatostatin analogs reduce postprandial gallbladder contractility and delay gallbladder emptying, and up to 25 percent of patients develop asymptomatic cholesterol gallstones or sludge during the first 18 months of therapy [48]. (See "Metastatic well-differentiated pancreatic neuroendocrine tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion", section on 'Side effects'.)

Other agents — The use of glucocorticoids (eg, prednisone 60 mg), clonidine, and loperamide are generally reserved for patients with diarrhea that is refractory to somatostatin analogs [3,39]. Emerging data suggest that cinacalcet may be useful for treating cystic fibrosis transmembrane conductance regulator (CTFR)-mediated secretory diarrhea as seen in VIPoma [49].

Pancreatic resection — Primary tumors can be managed with distal pancreatectomy. However, up to 60 percent have metastasized to lymph nodes, liver, kidneys, or bone at diagnosis [9,50]. Lack of symptomatic improvement after resection of functional neuroendocrine tumors (NETs) is associated with worse relapse-free survival [51]. (See "Surgical resection of lesions of the body and tail of the pancreas" and "Surgical resection of sporadic pancreatic neuroendocrine tumors", section on 'Others'.)

Management of advanced/metastatic disease

Liver-directed therapy for metastatic disease

●Surgery – Hepatic resection is indicated for the treatment of metastatic liver disease in the absence of diffuse bilobar involvement, compromised liver function, or extrahepatic metastases (eg, pulmonary, peritoneal). Although eventual recurrence is the rule, palliation of symptoms stemming from hormone hypersecretion can be achieved, and prolonged survival is often possible given the slow-growing nature of these tumors [52,53].

Note that life-threatening fluid losses and electrolyte abnormalities should be corrected before surgery with somatostatin analog treatment, plus intravenous and electrolyte therapy [54]. Surgical resection for patients with metastases from pancreatic NETs is discussed in detail, separately. (See "Metastatic gastroenteropancreatic neuroendocrine tumors: Local options to control tumor growth and symptoms of hormone hypersecretion", section on 'Surgical resection'.)

●Hepatic artery embolization – Hepatic arterial embolization with or without selective hepatic artery infusion of chemotherapy is a palliative technique in patients with symptomatic hepatic metastases who are not candidates for surgical resection. Embolization can be performed via the infusion of gel foam powder into the hepatic artery through an angiography catheter (bland embolization) or in conjunction with chemotherapy (ie, doxorubicin, cisplatin, or streptozocin, or drug-eluting beads) administered via the hepatic artery (chemoembolization). A third embolization technique uses radioactive isotopes (eg, yttrium-90 [90-Y]) that are tagged to glass or resin microspheres and delivered selectively to the tumor via the hepatic artery. Response rates, as measured by a decrease in hormonal secretion or by radiographic regression, are generally over 50 percent [55-69]. (See "Metastatic gastroenteropancreatic neuroendocrine tumors: Local options to control tumor growth and symptoms of hormone hypersecretion", section on 'Hepatic arterial embolization'.)

●Radiofrequency ablation and cryoablation – Ablation can be used as a primary treatment modality for neuroendocrine liver metastases or as an adjunct to surgical resection [70]. Ablation can be performed percutaneously or laparoscopically and is less invasive than either hepatic resection or hepatic artery embolization. However, ablation is applicable only to smaller lesions (typically <3 cm), and its long-term efficacy is uncertain [71]. (See "Metastatic gastroenteropancreatic neuroendocrine tumors: Local options to control tumor growth and symptoms of hormone hypersecretion", section on 'Ablation'.)

●Liver transplantation – Liver transplantation is considered an investigational approach for metastatic pancreatic NETs, including VIPoma, as the number of patients with liver-isolated metastatic disease in whom orthotopic liver transplantation has been attempted is small, and follow-up data are insufficient to judge whether cure has been achieved [72-75]. (See "Metastatic gastroenteropancreatic neuroendocrine tumors: Local options to control tumor growth and symptoms of hormone hypersecretion", section on 'Liver transplantation'.)

Somatostatin analogs — In addition to decreasing hormone secretion and improving symptom control, somatostatin analogs have cytostatic activity in well-differentiated NETs [76,77]. Given their favorable safety profile, somatostatin analogs are considered the treatment of choice in patients with slow-growing, unresectable, metastatic well-differentiated NETs.

Molecularly targeted therapy and other novel agents — Molecularly targeted agents (eg, everolimus, sunitinib) have a role in the management of patients with progressive, advanced VIPomas and are discussed elsewhere [78,79]. These and other novel therapies, such as peptide receptor radioligand therapy, are discussed in detail elsewhere. (See "Metastatic well-differentiated pancreatic neuroendocrine tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion", section on 'Molecularly targeted therapy' and "Metastatic well-differentiated pancreatic neuroendocrine tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion", section on 'Peptide receptor radioligand therapy'.)

Cytotoxic chemotherapy — For patients who are highly symptomatic due to tumor bulk or who have rapidly enlarging metastases, chemotherapy has been used as initial treatment together with a somatostatin analog. The options for therapy typically include a streptozocin-based combination or a temozolomide-containing regimen [80-82]. However, experience with systemic chemotherapy in patients with VIPomas, specifically, is limited, and few patients have been included in modern clinical series. The use of cytotoxic chemotherapy in patients with pancreatic NETs is discussed in detail elsewhere. (See "Metastatic well-differentiated pancreatic neuroendocrine tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion", section on 'Cytotoxic chemotherapy'.)

Peptide receptor radionuclide therapy — Peptide receptor radionuclide therapy (PRRT) is another option for progressive SSTR positive pancreatic NETs and is discussed elsewhere. Symptomatic and radiological responses have been noted in the setting of treatment of functional pancreatic NETs, including VIPoma, with Lu177-dotatate PRRT [83]. (See "Metastatic well-differentiated pancreatic neuroendocrine tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion", section on 'Peptide receptor radioligand therapy'.)

POST-TREATMENT SURVEILLANCE — There is limited evidence from which to make recommendations for follow-up after resection of a VIPoma, and guidelines are based on expert consensus. Our approach for follow-up after treatment of a VIPoma is consistent with guidelines from the National Comprehensive Cancer Network and consists of the following [84]:

●3 to 12 months post-resection: History and physical examination, serum VIP level, and abdominal multiphasic computed tomography (CT) or magnetic resonance imaging (MRI); and chest CT scan +/- contrast as clinically indicated.

●>1 year post-resection to a maximum of 10 years: History and physical examination with serum VIP level every 6 to 12 months. Consider abdominal multiphasic CT or MRI (and chest CT scan +/- contrast) as clinically indicated.

PROGNOSIS — The median survival of patients with VIPomas is 96 months [85]. Prognosis is largely dependent on VIPoma tumor grade, staging, and surgical resectability. Five- and ten-year survival rates for patients undergoing resection of gastroenteropancreatic neuroendocrine tumors (both pancreatic neuroendocrine and carcinoid tumors) stratified by stage at presentation are presented in the table (table 3) [86].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Well-differentiated gastroenteropancreatic neuroendocrine tumors".)

SUMMARY AND RECOMMENDATIONS

●VIPomas are rare neuroendocrine tumors that secrete vasoactive intestinal polypeptide (VIP). (See 'Introduction' above.)

●VIPomas are usually diagnosed between 30 and 50 years of age in adults and between two and four years of age in children. Pancreatic VIPomas are usually solitary, more than 3 cm in diameter, and occur in the tail of pancreas in 75 percent of patients. Approximately 60 to 80 percent of VIPomas have metastasized by the time of diagnosis.

●VIPomas usually occur as isolated tumors, but in 5 percent of patients they are part of the multiple endocrine neoplasia syndrome type 1 (MEN1).

●VIPoma syndrome is characterized by watery diarrhea that persists even during fasting. The stools are tea-colored, odorless with stool volumes exceeding 700 mL/day. In 70 percent of patients, stool volume can exceed 3000 mL/day. Abdominal pain is mild or absent. Associated symptoms include flushing, lethargy, nausea, vomiting, muscle weakness, and muscle cramps. (See 'Clinical features' above.)

●Patients with VIPoma have secretory diarrhea with a low osmotic gap (<50 mOsm/kg) (calculator 1). Hypochlorhydria occurs in 75 percent of patients. Other common laboratory findings include hyperglycemia and hypercalcemia. (See 'Laboratory findings' above.)

●The diagnosis of a VIPoma is suspected in patients with unexplained high-volume secretory diarrhea. The diagnosis is established by a serum vasoactive intestinal polypeptide (VIP) concentration >75 pg/mL. However, a single elevated VIP level should be confirmed by repeat testing. (See 'Diagnosis' above.)

●Cross-sectional imaging with multiphasic computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen can localize the tumor and stage the extent of disease. If cross-sectional imaging is inconclusive, endoscopic ultrasound, somatostatin receptor scintigraphy, or Gallium Ga-68 DOTATATE (or Gallium Ga-68 DOTATOC) PET/CT (preferred) should be performed to identify the tumor. In addition, we perform somatostatin receptor scintigraphy or Ga-68 DOTATATE (or Ga-68 DOTATOC) PET/CT (preferred) in patients with VIPomas if the finding of extra-abdominal metastases would change treatment. Because of its greater sensitivity, Ga-68 DOTATATE or Ga-68 DOTATOC PET/CT is preferred over conventional somatostatin receptor scintigraphy, where available. (See 'Tumor localization' above.)

●Treatment of hormone-mediated symptoms in a patient with a VIPoma begins with replacement of fluid losses and correction of electrolyte abnormalities. For treatment of the diarrhea, we suggest a somatostatin analog (Grade 2B). Treatment is initiated with short-acting octreotide (50 to 100 micrograms subcutaneously every eight hours) with rapid transition to a long-acting octreotide formulation and subsequent titration of dose to optimize symptom control (lanreotide is also a reasonable consideration) (see 'Somatostatin analogs' above). Furthermore, use of anti-cancer therapy, particularly in the form of debulking surgery, liver-directed therapy, chemotherapy, or another systemic agent, may also lead to improved symptom control.

●Primary tumors arising in the tail of the pancreas can be managed with distal pancreatomy. However, up to 60 percent of VIPomas have metastasized to lymph nodes, liver, kidneys, or bone at diagnosis. (See "Surgical resection of sporadic pancreatic neuroendocrine tumors" and 'Pancreatic resection' above.)

●Hepatic resection and/or ablation can be considered in patients with metastatic disease in the absence of diffuse bilobar involvement, compromised liver function, or extensive extrahepatic metastases. Hepatic arterial embolization with or without selective hepatic artery infusion of chemotherapy may be used for palliation in patients with symptomatic hepatic metastases who are not candidates for surgical resection. Tumor control can also be achieved with somatostatin analogs, cytotoxic chemotherapy, and molecularly targeted agents such as sunitinib and everolimus. Lu-177 dotatate peptide receptor radionuclide therapy is also now approved for well-differentiated pancreatic neuroendocrine tumors. (See 'Management of advanced/metastatic disease' above and "Metastatic well-differentiated pancreatic neuroendocrine tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion" and "Metastatic gastroenteropancreatic neuroendocrine tumors: Local options to control tumor growth and symptoms of hormone hypersecretion".)

●The median survival of patients with VIPomas is 96 months. Our approach for follow-up after treatment of a VIPoma is consistent with guidelines from the National Comprehensive Cancer Network and consists of the following (see 'Post-treatment surveillance' above and 'Prognosis' above):

•3 to 12 months post-resection: History and physical examination, serum VIP level, and abdominal multiphasic CT or MRI (and chest CT scan +/- contrast as clinically indicated).

•>1 year post-resection to a maximum of 10 years: History and physical examination with serum VIP level every 6 to 12 months. Consider abdominal multiphasic CT or MRI (and chest CT scan +/- contrast) as clinically indicated.

ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. Stephen E. Goldfinger, MD, for his past contributions as an author to this topic review.

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Topic 2610 Version 34.0

VIPoma: Clinical manifestations, diagnosis, and management

References