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WDHA Syndrome

  • Author: Richard K Gilroy, MBBS, FRACP; Chief Editor: Julian Katz, MD  more...
 
Updated: Feb 14, 2014
 

Background

The syndrome of watery diarrhea, hypokalemia, and achlorhydria (ie, WDHA syndrome) is a rare condition characterized by severe, watery diarrhea resulting from the oversecretion of vasoactive intestinal peptide (VIP) from non–beta pancreatic islet cells.[1, 2] Patients usually have elevated VIP levels and have a history of frequent hospitalizations for dehydration and/or hypokalemia. Because this condition resembles cholera, Matsumoto and colleagues (1966) suggested the alternative term pancreatic cholera. (See Etiology, Presentation, Treatment, and Medication.)[3]

A small percentage of patients with WDHA syndrome also have hypercalcemia, hyperglycemia, hypochlorhydria, and flushing. Multiple endocrine neoplasia type 1 (MEN-1) syndrome (ie, Wermer syndrome) is present in a very small subset of patients with hypercalcemia and WDHA syndrome. (See Etiology.)

VIP-secreting tumors are rare, affecting 0.05-0.2 per million adults, and these tumors most often originate in the pancreas (approximately 80%). With these pancreatic primaries, around 50% have metastasized at the time of diagnosis of the tumor. Other ectopic primary sites of VIP production include the liver and jejunum in about 10% of patients with WDHA syndrome, and, on occasion, other tumors can deteriorate into VIP-producing tumors (eg, phaeochromocytomas[4, 5] ). In children, the VIPoma syndrome is caused by either a ganglioneuroma or ganglioneuroblastoma.

The goals of therapy are prolongation of life, control of symptoms, and correction of the electrolyte abnormalities. Surgical resection offers the only chance for cure, but the tumor not uncommonly has spread to regional lymph nodes and/or to the liver at the time of diagnosis. Palliative treatment consists of surgical resection of the primary tumor with regional lymph node dissection and, if possible, resection of hepatic metastases. Liver transplantation has been performed in and uncontrolled manner, and results appear to demonstrate a potential role, although the scarcity of the resource limits this modality’s availability.[6, 7]

When managed medically, the use of somatostatin analogs has become the mainstay of therapy for symptom control. Other palliative measures include systemic chemotherapy, hepatic arterial embolization with or without chemotherapy, and the use of interferon alfa. (See Treatment, and Medication.)

In contrast to pancreatic carcinoma treatment, an aggressive surgical approach in WDHA syndrome appears warranted in light of improved 5-year survival rates with palliative debulking of tumors. Selected patients with extensive hepatic metastases have been treated with orthotopic liver transplantation with excellent results, although experience remains limited.[6, 7]

Complications

Complications of WDHA syndrome may include the following:

  • Acute renal failure associated with hypokalemia - This is the most common cause of death in WDHA syndrome; the typical renal lesion observed in these patients is a vacuolar tubular nephropathy
  • Dehydration
  • Non–anion gap metabolic acidosis
  • Perianal skin irritation from severe diarrhea
  • Poor quality of life from severe diarrhea

Patient education

Patients should be advised to seek treatment at a center with expertise in this field. Patients need to be aware that dehydration and acute renal failure are significant complications and that they must seek hospitalization if they are not doing well at home.

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Etiology

The pathophysiology of WDHA syndrome is best understood by reviewing the properties of VIP. VIP is a 28–amino acid regulatory peptide that is widely distributed throughout the gastrointestinal tract and brain; it has a half-life of 1-2 minutes. The peptide is secreted, usually from non–beta islet pancreatic cells in response to food containing fat, proteins, and alcohol. It enters the portal circulation and is metabolized by the liver. VIP relaxes smooth muscles, resulting in a decrease in lower esophageal sphincter pressure, relaxation of the gastric antrum and body, and inhibition of the gallbladder and intestinal circular muscle contraction.

Exogenous administration of VIP has many pharmacologic actions, including positive inotropic action on the heart, vasodilatation, increase in intestinal water and electrolyte secretion, inhibition of gastrin and gastric acid secretion, and stimulation of pancreatic secretion, lipolysis, and glycolysis.

Occasionally, patients with WDHA syndrome may have elevated levels of the peptide histidine methionine (PHM), a 27–amino acid peptide originally derived from porcine intestine (ie, peptide histidine isoleucine [PHI]). The distinctive features of PHI are the presence of histidine and isoleucine at the N and C terminals, in contrast to most gastrointestinal peptides, which have amidated C terminal amino acids.

Although PHI/PHM acts via a different receptor on target cells, it has numerous similarities to VIP. For example, both are derived from a common precursor polypeptide and are encoded from the same messenger ribonucleic acid (mRNA). Furthermore, both peptides are co-localized in enteric neurons and VIPomas, with an identical tissue distribution and similar pharmacologic activities.

Although PHI infusions cause intestinal secretion and may cause WDHA syndrome, PHI is 32 times less potent than VIP. In the small percentage of patients with secretory diarrhea who have VIP levels within the reference range, other agents that have been implicated as the diarrhea’s cause include calcitonin, gastric inhibitory peptide, pancreatic polypeptide, prostaglandins, neurotensin, and secretin.

Genetics

WDHA syndrome occurs in 6% of patients with MEN-1 syndrome. Significant advances have been made in elucidating the molecular pathogenesis of WDHA syndrome and other pancreatic endocrine tumors. Studies provide evidence for the importance of several genes, including the following:

  • MEN1 gene
  • p16/MTS1 tumor suppressor gene
  • DPC4/Smad 4 gene - A tumor suppressor gene located on chromosome arm 18q24
  • Amplification of the HER2/neu proto-oncogene
  • Deletions in chromosome 1
  • A possible tumor suppressor gene on chromosome arm 3p

Alterations in the MEN1 gene and the p16/MTS1 1 tumor suppressor gene are particularly important in tumor pathogenesis. The inherited MEN-1 syndrome is caused by mutations in a 10-exon gene that is located on chromosome arm 11q13, which encodes for a protein that interacts with AP1 transcription factor Jun D. The loss of heterozygosity at the MEN1 locus occurs in nearly 93% of sporadic pancreatic endocrine tumors, with mutations in the MEN1 gene locus reported in 27-39% of sporadic tumors.

Mutations in MEN1

Unlike mutations in the MEN-2 gene (ie, MEN2), MEN1 gene mutations in sporadic tumors appear to be distributed throughout the 9 coding exons and are believed to be an early event in tumorigenesis. The frequency and allelic mutations of the MEN1 gene in pancreatic endocrine tumors associated with MEN 1 were analyzed in a study. Allelic deletions of the MEN1 locus were described in 43% of these tumors, and mutations of the MEN1 gene were noted in 13% of these tumors. In most tumor groups, the frequency of allelic deletions at band 11q13 was 2-3 times higher than the frequency of gene mutations. Other factors, such as tumor suppressor genes on band 11q13, may be involved in tumorigenesis of these neoplasms.

Mutations in p16/MTS1

Studies provide evidence that p16/MTS1 alterations located on chromosome arm 9p21 occur in a significant percentage of pancreatic endocrine tumors. These inactivating mutations result in loss of cell cycle inhibition and reportedly occur in nearly 92% of these tumors.

RAF/mitogen-activated protein kinase pathway

A report by Tannapfel et al studied the frequency of the BRAF and k-ras-2 mutations in primary neuroendocrine gastroenteropancreatic tumors.[8] (The BRAF gene, one of the human isoforms of RAF, is activated by ras, leading to cooperative effects in cells responsive to growth factor signals). Although their results suggested BRAF mutations do not have a role in tumorigenesis of neuroendocrine tumors, the authors hypothesized that activation of the RAF/mitogen-activated protein kinase pathway may have a causative role in the development of neuroendocrine tumors, independent of BRAF or k-ras-2 mutation.

Malignant degeneration

A significant proportion of VIPomas develop malignant degeneration, although predicting which tumors will follow such a course is currently not possible. The hope is that in the future, the molecular aberrations in this subset of patients may be identified, allowing earlier and more aggressive treatment.

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Epidemiology

Occurrence in the United States

Pancreatic endocrine tumors are uncommon, with a prevalence of less than 10 cases per million population. VIPomas are a rare subtype of pancreatic islet cell tumors, with an estimated incidence of 0.05-0.2 per million population.

International occurrence

Pancreatic endocrine tumors are uncommon, with a prevalence of less than 10 cases per million population. For example, data from a referral center in Ireland on the relative frequency of these tumors demonstrated an average incidence of 3.6 cases per million population per year. Insulinomas were the most common pancreatic endocrine tumor, occurring 8 times more frequently than VIPomas.

Sex- and age-related demographics

A slight female preponderance in WDHA syndrome appears to exist. The age at diagnosis for individuals with the syndrome has a bimodal distribution, ranging from 10 months to 9 years in children and 32-81 years in adults.

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Prognosis

There are no prognostic models for WDHA syndrome. In general, the extent of disease, presence of metastases, and whether the disease is able to be resected are the more powerful prognostic factors. A proper assessment of the prognosis for WDHA syndrome is limited because of the rarity of the condition. Patients with resectable disease have a 5-year survival rate as high as 79%, while patients with incompletely resected or unresectable disease have a 5-year survival rate of only 28%. Note that these patients represent only a very small proportion (5-9%) of patients with metastatic disease.

Most patients with WDHA syndrome have hepatic metastases at the time of diagnosis, but these tumors usually grow slowly. Therefore, despite advanced disease, patients can have extended survival. A report from Florida on 18 patients noted a mean survival of 3.5 years, with the longest disease-free survival being 15 years and the longest overall survival being 15 years.

A paper from the Mayo Clinic, Jacksonville, reported 5- and 10-year survival rates for malignant tumors of 88% and 25%, respectively.

Soga and Yakuwa (1998) also observed encouraging long-term outcomes in an evaluation of 241 patients with WDHA syndrome.[9] The 5-year survival rate was 94.4% in 46 patients without metastases and 59.6% in 43 patients with metastatic disease.[9]

If treatment for WDHA syndrome is unsuccessful, patients often have a poor quality of life from diarrhea and its complications.

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Contributor Information and Disclosures
Author

Richard K Gilroy, MBBS, FRACP Associate Professor, Medical Director of Liver Transplantation and Hepatology, Department of Internal Medicine, Kansas University Medical Center

Disclosure: Received salary from gilead, NPS pharmaceuticals, salix pharmaceuticals, AbbVie for speaking and teaching.

Coauthor(s)

Randall E Brand, MD Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center

Randall E Brand, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Pancreatic Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Acknowledgements

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Manoop S Bhutani, MD Professor, Co-Director, Center for Endoscopic Research, Training and Innovation (CERTAIN), Director, Center for Endoscopic Ultrasound, Department of Medicine, Division of Gastroenterology, University of Texas Medical Branch; Director, Endoscopic Research and Development, The University of Texas MD Anderson Cancer Center

Manoop S Bhutani, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Institute of Ultrasound in Medicine, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

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

References
  1. Priest WM, Alexander MK. Isletcell tumour of the pancreas with peptic ulceration, diarrhoea, and hypokalaemia. Lancet. 1957 Dec 7. 273(7006):1145-7. [Medline].

  2. Verner JV, Morrison AB. Islet cell tumor and a syndrome of refractory watery diarrhea and hypokalemia. Am J Med. 1958 Sep. 25(3):374-80. [Medline].

  3. Matsumoto KK, Peter JB, Raymond G. Watery diarrhea and hypokalemia associated with pancreatic islet cell adenoma. Gastroenterology. 1966. 50:231-42.

  4. Adam N, Lim SS, Ananda V, Chan SP. VIPoma syndrome: challenges in management. Singapore Med J. 2010 Jul. 51(7):e129-32. [Medline].

  5. Kikuchi Y, Wada R, Sakihara S, Suda T, Yagihashi S. Pheochromocytoma with Histological Transformation to Composite Type Presenting Watery Diarrhea, Hypokalemia, Achlorhydria Syndrome. Endocr Pract. 2012 Mar 22. 1-10. [Medline].

  6. Nguyen NT, Harring TR, Goss JA, O'Mahony CA. Neuroendocrine Liver Metastases and Orthotopic Liver Transplantation: The US Experience. Int J Hepatol. 2011. 2011:742890. [Medline]. [Full Text].

  7. Le Treut YP, Grégoire E, Belghiti J, et al. Predictors of long-term survival after liver transplantation for metastatic endocrine tumors: an 85-case French multicentric report. Am J Transplant. 2008 Jun. 8(6):1205-13. [Medline].

  8. Tannapfel A, Vomschloss S, Karhoff D, Markwarth A, Hengge UR, Wittekind C, et al. BRAF gene mutations are rare events in gastroenteropancreatic neuroendocrine tumors. Am J Clin Pathol. 2005 Feb. 123(2):256-60. [Medline].

  9. Soga J, Yakuwa Y. Vipoma/diarrheogenic syndrome: a statistical evaluation of 241 reported cases. J Exp Clin Cancer Res. 1998 Dec. 17(4):389-400. [Medline].

  10. Kibria R, Ahmed S, Ali SA, Barde CJ. Hypokalemic rhabdomyolysis due to watery diarrhea, hypokalemia, achlorhydria (WDHA) syndrome caused by vipoma. South Med J. 2009 Jul. 102(7):761-4. [Medline].

  11. Virgolini I, Kurtaran A, Leimer M, Kaserer K, Peck-Radosavljevic M, Angelberger P, et al. Location of a VIPoma by iodine-123-vasoactive intestinal peptide scintigraphy. J Nucl Med. 1998 Sep. 39(9):1575-9. [Medline].

  12. Virgolini I, Traub-Weidinger T, Decristoforo C. Nuclear medicine in the detection and management of pancreatic islet-cell tumours. Best Pract Res Clin Endocrinol Metab. 2005 Jun. 19(2):213-27. [Medline].

  13. Onozawa M, Fukuhara T, Minoguchi M, Takahata M, Yamamoto Y, Miyake T. Hypokalemic rhabdomyolysis due to WDHA syndrome caused by VIP-producing composite pheochromocytoma: a case in neurofibromatosis type 1. Jpn J Clin Oncol. 2005 Sep. 35(9):559-63. [Medline].

  14. Moug SJ, Leen E, Horgan PG, Imrie CW. Radiofrequency ablation has a valuable therapeutic role in metastatic VIPoma. Pancreatology. 2006. 6(1-2):155-9. [Medline].

  15. Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10. 364(6):501-13. [Medline].

  16. Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10. 364(6):514-23. [Medline].

  17. Case CC, Wirfel K, Vassilopoulou-Sellin R. Vasoactive intestinal polypeptide-secreting tumor (VIPoma) with liver metastases: dramatic and durable symptomatic benefit from hepatic artery embolization, a case report. Med Oncol. 2002. 19(3):181-7. [Medline].

  18. Akerström G, Hellman P. Surgery on neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. 2007 Mar. 21(1):87-109. [Medline].

  19. Alexakis N, Neoptolemos JP. Pancreatic neuroendocrine tumours. Best Pract Res Clin Gastroenterol. 2008. 22(1):183-205. [Medline].

  20. Ayub A, Zafar M, Abdulkareem A, Ali MA, Lingawi T, Harbi A. Primary hepatic vipoma. Am J Gastroenterol. 1993 Jun. 88(6):958-61. [Medline].

  21. Bartsch D, Hahn SA, Danichevski KD, Ramaswamy A, Bastian D, Galehdari H, et al. Mutations of the DPC4/Smad4 gene in neuroendocrine pancreatic tumors. Oncogene. 1999 Apr 8. 18(14):2367-71. [Medline].

  22. Bartsch DK, Fendrich V, Langer P, Celik I, Kann PH, Rothmund M. Outcome of duodenopancreatic resections in patients with multiple endocrine neoplasia type 1. Ann Surg. 2005 Dec. 242(6):757-64, discussion 764-6. [Medline].

  23. Berkovic MC, Altabas V, Herman D, Hrabar D, Goldoni V, Vizner B, et al. A single-centre experience with octreotide in the treatment of different hypersecretory syndromes in patients with functional gastroenteropancreatic neuroendocrine tumors. Coll Antropol. 2007 Jun. 31(2):531-4. [Medline].

  24. Bettini R, Boninsegna L, Mantovani W, Capelli P, Bassi C, Pederzoli P, et al. Prognostic factors at diagnosis and value of WHO classification in a mono-institutional series of 180 non-functioning pancreatic endocrine tumours. Ann Oncol. 2008 May. 19(5):903-8. [Medline].

  25. Bramley PN, Lodge JP, Losowsky MS, Giles GR. Treatment of metastatic Vipoma by liver transplantation. Clin Transplant. 1990 Oct. 4(5 part 1):276-8; discussion 279. [Medline].

  26. Brunt LM, Mazoujian G, O'Dorisio TM, Wells SA Jr. Stimulation of vasoactive intestinal peptide and neurotensin secretion by pentagastrin in a patient with VIPoma syndrome. Surgery. 1994 Mar. 115(3):362-9. [Medline].

  27. Buchanan KD, Johnston CF, O'Hare MM, Ardill JE, Shaw C, Collins JS, et al. Neuroendocrine tumors. A European view. Am J Med. 1986 Dec 22. 81(6B):14-22. [Medline].

  28. Crowley PF, Slavin JL, Rode J. Massive amyloid deposition in pancreatic vipoma: a case report. Pathology. 1996 Nov. 28(4):377-9. [Medline].

  29. Doherty GM. Multiple endocrine neoplasia type 1. J Surg Oncol. 2005 Mar 1. 89(3):143-50. [Medline].

  30. Doherty GM. Rare endocrine tumours of the GI tract. Best Pract Res Clin Gastroenterol. 2005 Oct. 19(5):807-17. [Medline].

  31. Eriksson B, Oberg K. Interferon therapy of malignant endocrine pancreatic tumors. Mignon M, Jensen RT, eds. Endocrine Tumors of the Pancreas: Recent Advances in Research and Management. Series: Frontiers in Gastrointestinal Research. Basel, Switzerland: S. Karger; 1995. Vol 23: 451-60.

  32. Fendrich V, Habbe N, Celik I, Langer P, Zielke A, Bartsch DK, et al. [Operative management and long-term survival in patients with neuroendocrine tumors of the pancreas--experience with 144 patients]. Dtsch Med Wochenschr. 2007 Feb 2. 132(5):195-200. [Medline].

  33. Frank M, Klose KJ, Wied M, Ishaque N, Schade-Brittinger C, Arnold R. Combination therapy with octreotide and alpha-interferon: effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors. Am J Gastroenterol. 1999 May. 94(5):1381-7. [Medline].

  34. Ghaferi AA, Chojnacki KA, Long WD, Cameron JL, Yeo CJ. Pancreatic VIPomas: subject review and one institutional experience. J Gastrointest Surg. 2008 Feb. 12(2):382-93. [Medline].

  35. Gibril F, Reynolds JC, Chen CC, Yu F, Goebel SU, Serrano J, et al. Specificity of somatostatin receptor scintigraphy: a prospective study and effects of false-positive localizations on management in patients with gastrinomas. J Nucl Med. 1999 Apr. 40(4):539-53. [Medline].

  36. Goh BK, Ooi LL, Tan YM, Cheow PC, Chung YF, Chow PK. Clinico-pathological features of cystic pancreatic endocrine neoplasms and a comparison with their solid counterparts. Eur J Surg Oncol. 2006 Jun. 32(5):553-6. [Medline].

  37. Gumbs AA, Grès P, Madureira F, Gayet B. Laparoscopic vs open resection of pancreatic endocrine neoplasms: single institution's experience over 14 years. Langenbecks Arch Surg. 2008 May. 393(3):391-5. [Medline].

  38. Görtz B, Roth J, Krahenmann A, de Krijger RR, Muletta-Feurer S, Rütimann K, et al. Mutations and allelic deletions of the MEN1 gene are associated with a subset of sporadic endocrine pancreatic and neuroendocrine tumors and not restricted to foregut neoplasms. Am J Pathol. 1999 Feb. 154(2):429-36. [Medline].

  39. Harris AG, O'Dorisio TM, Woltering EA, Anthony LB, Burton FR, Geller RB, et al. Consensus statement: octreotide dose titration in secretory diarrhea. Diarrhea Management Consensus Development Panel. Dig Dis Sci. 1995 Jul. 40(7):1464-73. [Medline].

  40. Ichimura T, Kondo S, Okushiba S, Morikawa T, Katoh H. A calcitonin and vasoactive intestinal peptide-producing pancreatic endocrine tumor associated with the WDHA syndrome. Int J Gastrointest Cancer. 2003. 33(2-3):99-102. [Medline].

  41. Ikuta S, Yasui C, Kawanaka M, Aihara T, Yoshie H, Yanagi H, et al. Watery diarrhea, hypokalemia and achlorhydria syndrome due to an adrenal pheochromocytoma. World J Gastroenterol. 2007 Sep 14. 13(34):4649-52. [Medline].

  42. Jackson C, Buchman AL. Calcitonin-secreting VIPoma. Dig Dis Sci. 2005 Dec. 50(12):2203-6. [Medline].

  43. Kazanjian KK, Reber HA, Hines OJ. Resection of pancreatic neuroendocrine tumors: results of 70 cases. Arch Surg. 2006 Aug. 141(8):765-9; discussion 769-70. [Medline].

  44. Keller J, Mueller-Wolf JC, Ahmadi-Simab K, Fibbe C, Rosien U, Layer P. Do elevated plasma vasoactive intestinal polypeptide (VIP) levels cause small intestinal motor disturbances in humans?. Dig Dis Sci. 2005 Feb. 50(2):276-82. [Medline].

  45. Krejs GJ. Comparison of the effect of VIP and PHI on water and ion movement in the canine jejunum in vivo. Gastroenterol Clin Biol. 1984. 8:868.

  46. Levy-Bohbot N, Merle C, Goudet P, Delemer B, Calender A, Jolly D, et al. Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs Endocrines) registry. Gastroenterol Clin Biol. 2004 Nov. 28(11):1075-81. [Medline].

  47. Lubinski SM, Hendrix T. Images in clinical medicine. VIPoma. N Engl J Med. 2004 Aug 19. 351(8):808. [Medline].

  48. Lévy-Bohbot N, Merle C, Goudet P, Delemer B, Calender A, Jolly D, et al. Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs Endocrines) registry. Gastroenterol Clin Biol. 2004 Nov. 28(11):1075-81. [Medline].

  49. Mansour JC, Chen H. Pancreatic endocrine tumors. J Surg Res. 2004 Jul. 120(1):139-61. [Medline].

  50. Mao C, Carter P, Schaefer P, Zhu L, Dominguez JM, Hanson DJ, et al. Malignant islet cell tumor associated with hypercalcemia. Surgery. 1995 Jan. 117(1):37-40. [Medline].

  51. Maton PN, Gardner JD, Jensen RT. Use of long-acting somatostatin analog SMS 201-995 in patients with pancreatic islet cell tumors. Dig Dis Sci. 1989 Mar. 34(3 Suppl):28S-39S. [Medline].

  52. Moertel CG, Lefkopoulo M, Lipsitz S, Hahn RG, Klaassen D. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992 Feb 20. 326(8):519-23. [Medline].

  53. Murphy MS, Sibal A, Mann JR. Persistent diarrhoea and occult vipomas in children. BMJ. 2000 Jun 3. 320(7248):1524-6. [Medline].

  54. Nguyen HN, Backes B, Lammert F, Wildberger J, Winograd R, Busch N, et al. Long-term survival after diagnosis of hepatic metastatic VIPoma: report of two cases with disparate courses and review of therapeutic options. Dig Dis Sci. 1999 Jun. 44(6):1148-55. [Medline].

  55. Nikou GC, Toubanakis C, Nikolaou P, Giannatou E, Safioleas M, Mallas E. VIPomas: an update in diagnosis and management in a series of 11 patients. Hepatogastroenterology. 2005 Jul-Aug. 52(64):1259-65. [Medline].

  56. Nobels FR, Kwekkeboom DJ, Bouillon R, Lamberts SW. Chromogranin A: its clinical value as marker of neuroendocrine tumours. Eur J Clin Invest. 1998 Jun. 28(6):431-40. [Medline].

  57. Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. 2005 Oct. 19(5):753-81. [Medline].

  58. Orlefors H, Sundin A, Ahlstrom H, Bjurling P, Bergstrom M, Lilja A, et al. Positron emission tomography with 5-hydroxytryprophan in neuroendocrine tumors. J Clin Oncol. 1998 Jul. 16(7):2534-41. [Medline].

  59. Park SK, O'Dorisio MS, O'Dorisio TM. Vasoactive intestinal polypeptide-secreting tumours: biology and therapy. Baillieres Clin Gastroenterol. 1996 Dec. 10(4):673-96. [Medline].

  60. Pederzoli P, Bassi C, Falconi M, Camboni MG. Efficacy of octreotide in the prevention of complications of elective pancreatic surgery. Italian Study Group. Br J Surg. 1994 Feb. 81(2):265-9. [Medline].

  61. Phan GQ, Yeo CJ, Hruban RH, Lillemoe KD, Pitt HA, Cameron JL. Surgical experience with pancreatic and peripancreatic neuroendocrine tumors: review of 125 patients. J Gastrointest Surg. 1998 Sep-Oct. 2(5):472-82. [Medline].

  62. Pratz KW, Ma C, Aubry MC, Vrtiska TJ, Erlichman C. Large cell carcinoma with calcitonin and vasoactive intestinal polypeptide-associated Verner-Morrison syndrome. Mayo Clin Proc. 2005 Jan. 80(1):116-20. [Medline].

  63. Ram R, Natanzi N, Saadat P, Eliav D, Vadmal MS. Skin metastasis of pancreatic vasoactive intestinal polypeptide tumor: case report and review of the literature. Arch Dermatol. 2006 Jul. 142(7):946-7. [Medline].

  64. Remme CA, de Groot GH, Schrijver G. Diagnosis and treatment of VIPoma in a female patient. Eur J Gastroenterol Hepatol. 2006 Jan. 18(1):93-9. [Medline].

  65. Rigabert J, De Clermont H. [Diagnostic procedures and more particularly, place of scintigraphy in neuroendocrine tumors, example of vipoma in MEN 1]. Ann Endocrinol (Paris). 2007 Jun. 68(2-3):199-203. [Medline].

  66. Rindi G, Candusso ME, Solcia E. Molecular aspects of the endocrine tumours of the pancreas and the gastrointestinal tract. Ital J Gastroenterol Hepatol. 1999 Oct. 31 Suppl 2:S135-8. [Medline].

  67. Schonfeld WH, Eikin EP, Woltering EA, Modlin IM, Anthony L, Villa KF, et al. The cost-effectiveness of octreotide acetate in the treatment of carcinoid syndrome and VIPoma. Int J Technol Assess Health Care. 1998 Summer. 14(3):514-25. [Medline].

  68. Smith SL, Branton SA, Avino AJ, Martin JK, Klingler PJ, Thompson GB, et al. Vasoactive intestinal polypeptide secreting islet cell tumors: a 15-year experience and review of the literature. Surgery. 1998 Dec. 124(6):1050-5. [Medline].

  69. Stephen AE, Hodin RA. Neuroendocrine tumors of the pancreas, excluding gastrinoma. Surg Oncol Clin N Am. 2006 Jul. 15(3):497-510. [Medline].

  70. Tauber MT, Harris AG, Rochiccioli P. Clinical use of the long acting somatostatin analogue octreotide in pediatrics. Eur J Pediatr. 1994 May. 153(5):304-10. [Medline].

  71. Tomassetti P, Migliori M, Gullo L. Slow-release lanreotide treatment in endocrine gastrointestinal tumors. Am J Gastroenterol. 1998 Sep. 93(9):1468-71. [Medline].

  72. Warner RR. Enteroendocrine tumors other than carcinoid: a review of clinically significant advances. Gastroenterology. 2005 May. 128(6):1668-84. [Medline].

 
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