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VIPomas Treatment & Management

  • Author: Sai-Ching Jim Yeung, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
 
Updated: Jun 02, 2014
 

Approach Considerations

Initial treatment of VIPomas is directed toward correcting volume and electrolyte abnormalities. Octreotide acetate controls diarrhea in up to 90% of patients with VIPomas. Glucocorticoids reduce symptoms in 50%.

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

Local tumor resection is the treatment of choice. In advanced disease, tumor debulking may relieve symptoms, but it is not effective in all cases. Embolization of the hepatic artery with doxorubicin HCl and ethiodized oil may provide palliation in patients with extensive hepatic disease. This treatment may be repeated several times, depending on tumor growth and symptoms. External radiation therapy may be indicated in unresectable tumors. Laparoscopic surgical resection has been successful in at least one adult with hepatic metastasis.

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

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Pharmacologic Therapy

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

In more than 90% of patients, somatostatin effectively reduces serum vasoactive intestinal peptide (VIP) levels and promptly controls diarrhea.[14] To circumvent the short serum half-life of somatostatin, the derivative octreotide is used. A long-acting octreotide formulation is available that allows once-monthly intragluteal administration. (Patients may have to make monthly clinic visits to receive the injections.) Diarrhea recurs when treatment is discontinued. It is currently debated whether somatostatin analogues also diminish tumor size.

Unless a surgical cure has been achieved (see Surgical Intervention), octreotide dosing is continued in most patients. Long-term octreotide treatment frequently results in gradually increasing resistance to this therapy. When the highest tolerable dosages of octreotide are unable to control symptoms, interferon alfa may be added to control diarrhea (and, possibly, achieve a modest reduction in tumor size).

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

In patients with advanced disease, tumors may respond to treatment with streptozocin-based chemotherapy (eg, streptozocin combined with 5-fluorouracil [5-FU]). If conventional chemotherapy and somatostatin are not effective, 5-FU may be combined with interferon alfa. Other chemotherapy agents that may be considered include dacarbazine and doxorubicin HCl.

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Radiation Therapy

The use of radiolabeled octreotide to target radiation treatment toward a VIPoma is based on the affinity of octreotide for 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.[20] This therapeutic approach may be applied to advanced neuroendocrine tumors in general.

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

Surgical Intervention

Surgical exploration with tumor resection (see the image below) leads to cure in 50% of patients. 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.

Patient with a large VIPoma. (A) Arteriogram showi Patient with a large VIPoma. (A) Arteriogram showing vascularity of a large VIPoma preoperatively. (B) Large mass seen intraoperatively. (C) Gross pathologic specimen. Patient subsequently developed liver metastases; he was treated with chemoembolization of liver masses multiple times and finally succumbed to disease 20 years after initial surgical treatment.

Local tumor resection is the treatment of choice.[14, 21, 22, 23] 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. Serum VIP levels may normalize within an hour after curative tumor resection. Preoperative treatment with a proton pump inhibitor is advisable to prevent rebound gastric acid hypersecretion after surgical tumor removal.

Severe hypotension may develop temporarily during and after tumor removal as a consequence of the vasodilatory effect of the VIP released during manipulation of the tumor. Severe hypertension may develop temporarily after tumor removal. Postoperatively, octreotide therapy will usually be needed indefinitely to control symptoms of VIP hypersecretion from residual tumor.[22]

In most cases, at the time of diagnosis of VIPoma, metastatic disease is already present. For these patients, tumor debulking may reduce clinical symptoms,[14, 23] but for substantial clinical benefit to be achieved, operative planning ought to include resection of more than 90% of tumor volume.

Unresectable liver metastases may be treated with hepatic artery radioembolization or transcatheter chemoembolization with doxorubicin or cisplatin.[24] When embolization is unsuccessful or not feasible for liver metastases, percutaneous or intraoperative radiofrequency tumor ablation may be attempted, though it is not ideal for large metastatic tumors.

All patients being surgically treated for a VIPoma should undergo a cholecystectomy to alleviate concerns of gallstones with somatostatin analogue therapy, in case such therapy is needed in the future. In patients with VIPomas, a parathyroidectomy does not correct hypercalcemia unless the VIPoma is resected.

Orthotopic liver transplantation has been performed in a small number of adult patients with pancreatic endocrine tumors; the 5-year survival rate has been approximately 50%.[25]

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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 in cases where long-term hormonal suppression is required
  • Gastroenterologist - Consultation with a gastroenterologist may be indicated for evaluation of long-term diarrhea or for colonoscopic evaluation for villous adenoma
  • Surgeon - Consultation with a surgeon experienced in pancreatic surgery may be indicated if the evaluation suggests a resectable or debulkable tumor or if exploratory surgery is contemplated
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Long-Term Monitoring

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 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.

Posttreatment VIP levels may serve as a tumor marker for recurrent disease.

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Contributor Information and Disclosures
Author

Sai-Ching Jim Yeung, MD, PhD, FACP Professor of Medicine, Department of Emergency Medicine, Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center

Sai-Ching Jim Yeung, MD, PhD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Medical Association, American Thyroid Association, Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel S Tung, MD Fellow in Endocrinology, Department of Internal Medicine, Baylor College of Medicine

Daniel S Tung, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Alicia Diaz-Thomas, MD, MPH Assistant Professor of Pediatrics, University of Tennessee Health Science Center

Alicia Diaz-Thomas, MD, MPH is a member of the following medical societies: American Academy of Clinical Endocrinology, Tennessee Medical Association, and The Endocrine Society

Disclosure: Nothing to disclose.

Robert J Ferry Jr, MD Le Bonheur Chair of Excellence in Endocrinology, Professor and Chief, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Eli Lilly & Co Grant/research funds Investigator; MacroGenics, Inc Grant/research funds Investigator; Ipsen, SA (formerly Tercica, Inc) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Grant/research funds Investigator; Bristol-Myers-Squibb Grant/research funds Other; Amylin Other; Pfizer Grant/research funds Other; Takeda Grant/research funds Other

Stephen Kemp, MD, PhD Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research, and The Endocrine Society

Disclosure: Nothing to disclose.

Lynne Lipton Levitsky, MD Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Pediatric Endocrine Society, Society for Pediatric Research, and The Endocrine Society

Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds Other; Eli Lily Grant/research funds PI; NovoNordisk Grant/research funds PI; NovoNordisk Consulting fee Consulting; Onyx Heart Valve Consulting fee Consulting

Klaus Radebold, MD, PhD Former Research Associate, Department of Surgery, Yale University School of Medicine

Disclosure: Nothing to disclose.

Arlan L Rosenbloom, MD Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida College of Medicine; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology

Arlan L Rosenbloom, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Epidemiology, American Pediatric Society, Florida Pediatric Society, Pediatric Endocrine Society, Society for Pediatric Research, and The Endocrine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Frederick H Ziel, MD Associate Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Physician-In-Charge, Endocrinology/Diabetes Center, Director of Medical Education, Kaiser Permanente Woodland Hills; Chair of Endocrinology, Co-Chair of Diabetes Complete Care Program, Southern California Permanente Medical Group

Frederick H Ziel, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society for Bone and Mineral Research, California Medical Association, Endocrine Society, and InternationalSociety for Clinical Densitometry

Disclosure: Nothing to disclose.

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Patient with a large VIPoma. (A) Arteriogram showing vascularity of a large VIPoma preoperatively. (B) Large mass seen intraoperatively. (C) Gross pathologic specimen. Patient subsequently developed liver metastases; he was treated with chemoembolization of liver masses multiple times and finally succumbed to disease 20 years after initial surgical treatment.
 
 
 
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