VIPomas Treatment & Management

Initial treatment for VIPoma is aimed at correcting any volume, electrolyte, and acid-base abnormalities with intravenous normal saline, potassium chloride, and, if acidosis is severe, sodium bicarbonate. In many cases, these abnormalities are pronounced enough to require hospital admission.

Systemic chemotherapy may be needed in cases of unresectable or progressive disease. Streptozocin, doxorubicin, or fluorouracil, or a combination of these, appears to be beneficial, although the number of treated cases has been limited.

The use of radiolabeled octreotide to target radiation treatment to VIPoma is based on the affinity of octreotide to the somatostatin receptors on the VIPoma cells. In one trial, half of the patients achieved stabilization of previously progressive tumors, with minimal bone marrow toxicity. This therapeutic approach may be applied to advanced neuroendocrine tumors in general.^[16]

Occasionally, external radiation therapy may be indicated in locally advanced unresectable tumors; however, experience with this treatment is limited.

Outpatient care

Patients with VIPomas need frequent outpatient follow-up to monitor hydration status and serum electrolyte levels. In patients with continuing fluid loss that is not controlled effectively by medical and surgical treatment options, a Port-a-Cath or other long-term central venous access device may be implanted; the patient may be trained to replace fluid and electrolytes at home or in an ambulatory setting.

Consultations

Consultations with the following specialists may be warranted:

• Endocrinologist - Consultation with an endocrinologist is indicated, particularly in MEN 1 or other polyhormonal secretion states or if long-term hormonal suppression is required
• Gastroenterologist - Consultation with a gastroenterologist may be indicated for evaluation of long-term diarrhea or for colonoscopy evaluation for villous adenoma
• Surgeon - Consultation with a surgeon who is experienced in pancreatic surgery may be indicated if the evaluation suggests a resectable or debulkable tumor or if exploratory surgery is contemplated

In more than 90% of patients, somatostatin is highly effective in reducing serum levels of vasoactive intestinal polypeptide (VIP) and promptly controlling diarrhea.^[11] To circumvent the short serum half-life of somatostatin, the derivative octreotide is used.

An available long-acting formulation of octreotide called Sandostatin LAR allows for once-monthly intragluteal administration. (Patients on Sandostatin LAR may need monthly clinic visits to receive the injections.) Diarrhea recurs when Sandostatin treatment is discontinued. It is currently debated whether somatostatin analogues also diminish tumor size.

Unless a surgical cure has been achieved, octreotide dosing is continued in most patients. Long-term octreotide treatment frequently results in gradual resistance to this therapy. When maximum tolerable doses of octreotide are unable to control symptoms, interferon alpha may be added to control diarrhea, with a possible modest reduction in tumor size.

Glucocorticoids are less effective but also less expensive, reducing symptoms in approximately 50% of patients.

In patients with advanced disease, tumors may respond to treatment with streptozotocin-based chemotherapy. If conventional chemotherapy and somatostatin are not effective, 5-fluorouracil may be combined with interferon alpha.

Preoperative treatment with a proton pump inhibitor is advisable to prevent rebound gastric acid hypersecretion after surgical tumor removal.

After appropriate fluid and electrolyte replacement, all operable patients with apparently resectable disease should receive abdominal exploration with careful staging. Intraoperative ultrasonography of the pancreas may aid in locating an otherwise unidentified tumor. For patients without nodal or distant metastasis, complete surgical resection offers the only chance for a cure.

Local tumor resection is the treatment of choice.^{[11, 17, 18, 19]} Pancreatoduodenectomy is indicated when the tumor is in the pancreatic head or processus uncinatus.

If no tumor is found at surgery, a blind pancreatic tail resection may be performed. A total pancreatectomy no longer is recommended.

In most cases, at the time of diagnosis of VIPoma, metastatic disease is already present. For these patients, tumor debulking may reduce clinical symptoms,^{[11, 19]} but surgical plans ought to include resection of more than 90% of tumor volume for substantial clinical benefit.

Unresectable liver metastases may be treated with bland hepatic artery embolization or transcatheter chemoembolization with doxorubicin or cisplatin.^[20] When embolization is unsuccessful or not feasible for liver metastases, percutaneous or intraoperative radiofrequency tumor ablation may be attempted, although this is not ideal for large metastatic tumors.

All patients having surgery should undergo a cholecystectomy to alleviate concerns of gallstones with somatostatin analogue therapy, in case such therapy is needed in the future.

Orthotopic liver transplantation has been performed in a small number of select patients with pancreatic endocrine tumors; the 5-year survival rate has been approximately 50%.^[21]

In patients with VIPoma, parathyroidectomy does not correct hypercalcemia. (VIP and its parathyroid hormone–like action cause hypercalcemia.)

Postoperative care

Postoperative octreotide therapy will usually be needed indefinitely to control symptoms of VIP hypersecretion from residual tumor.^[18]

Some patients with VIPoma have hypotension due to peripheral vasodilation. Severe hypertension may develop temporarily after tumor removal.