VIPoma: Mechanisms, clinical presentation, diagnosis and treatment (Review)

Abdullayeva,Leila

doi:10.3892/wasj.2019.22

VIPoma: Mechanisms, clinical presentation, diagnosis and treatment (Review)

Authors:
- Leila Abdullayeva
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Affiliations: Department of Clinical Anatomy and Operative Surgery, Joint Stock Company ‘National Medical University’, A05H2A0 Almaty, Kazakhstan
Published online on: September 10, 2019 https://doi.org/10.3892/wasj.2019.22
Pages: 229-235
Copyright: © Abdullayeva . This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Vasoactive intestinal peptide (VIP) secreting tumour (VIPoma) is a rare neuroendocrine tumour that most often originates from pancreatic islet cells and affects one in ten million individuals per year. In adults, it develops most commonly in the fortieth year of life with a sparse female predominance. Excessive VIP secretion induces refractory watery diarrhoea, hypokalemia and achlorhydria. Other symptoms include hyperglycemia (20‑50%), hypercalcaemia (25‑50%), hypochlorhydria (20‑50%) and flushing (15‑30%). VIP plasma levels are increased in almost all patients with VIPoma, and, together with profusing secretory diarrhoea, it is sufficient to establish the diagnosis. Moreover, the majority of VIPomas are malignant or have already metastasised at the time of diagnosis. The treatment of the neoplasm comprises medical management and surgery. While surgery remains the gold standard of treatment, peptide receptor radionuclide therapy represents one of the most effective and well‑tolerated treatment options. The average survival rate of patients with VIPoma is 96 months. The objective of this review was to summarise all features of pancreatic VIPoma, as well as present novel treatment approaches for this rare neoplasm.

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1	Verner JV and Morrison AB: Islet cell tumor and a syndrome of refractory watery diarrhea and hypokalemia. Am J Med. 25:374–380. 1958.PubMed/NCBI View Article : Google Scholar
2	Jensen RT, Cadiot G, Brandi ML, de Herder WW, Kaltsas G, Komminoth P, Scoazec JY, Salazar R, Sauvanet A and Kianmanesh R: Barcelona Consensus Conference participants: ENETS consensus guidelines for the management of patients with digestive neuroendocrine neoplasms: Functional pancreatic endocrine tumor syndromes. Neuroendocrinology. 95:98–119. 2012.PubMed/NCBI View Article : Google Scholar
3	Yao JC, Eisner MP, Leary C, Dagohoy C, Phan A, Rashid A, Hassan M and Evans DB: Population-based study of islet cell carcinoma. Ann Surg Oncol. 14:3492–3500. 2007.PubMed/NCBI View Article : Google Scholar
4	Parbhu SK and Adler DG: Pancreatic neuroendocrine tumors: Contemporary diagnosis and management. Hosp Pract 1995. 44:109–119. 2016.PubMed/NCBI View Article : Google Scholar
5	Long RG, Bryant MG, Mitchell SJ, Adrian TE, Polak JM and Bloom SR: Clinicopathological study of pancreatic and ganglioneuroblastoma tumours secreting vasoactive intestinal polypeptide (vipomas). Br Med J (Clin Res Ed). 282:1767–1771. 1981.PubMed/NCBI View Article : Google Scholar
6	Belei OA, Heredea ER, Boeriu E, Marcovici TM, Cerbu S, Mărginean O, Iacob ER, Iacob D, Motoc AGM and Boia ES: Verner-Morrison syndrome. Literature review. Rom J Morphol Embryol. 58:371–376. 2017.PubMed/NCBI
7	Chen Y, Shi D, Dong F, Han SG, Qian ZH, Yang LI, Wang Y, Yu RS, Li QH and Fu YB: Multiple-phase spiral CT findings of pancreatic vasoactive intestinal peptide-secreting tumor: A case report. Oncol Lett. 10:2351–2354. 2015.PubMed/NCBI View Article : Google Scholar
8	Krejs GJ: VIPoma syndrome. Am J Med. 82:37–48. 1987.PubMed/NCBI View Article : Google Scholar
9	Ghaferi AA, Chojnacki KA, Long WD, Cameron JL and Yeo CJ: Pancreatic VIPomas: Subject review and one institutional experience. J Gastrointest Surg. 12:382–393. 2008.PubMed/NCBI View Article : Google Scholar
10	Said SI and Mutt V: Polypeptide with broad biological activity: Isolation from small intestine. Science. 169:1217–1218. 1970.PubMed/NCBI View Article : Google Scholar
11	Friesen SR: Update on the diagnosis and treatment of rare neuroendocrine tumors. Surg Clin North Am. 67:379–393. 1987.PubMed/NCBI View Article : Google Scholar
12	Schizas D, Mastoraki A, Bagias G, Patras R, Moris D, Lazaridis II, Arkadopoulos N and Felekouras E: Clinicopathological data and treatment modalities for pancreatic vipomas: A systematic review. J BUON. 24:415–423. 2019.PubMed/NCBI
13	Murphy MS, Sibal A and Mann JR: Persistent diarrhoea and occult vipomas in children. BMJ. 320:1524–1526. 2000.PubMed/NCBI View Article : Google Scholar
14	Brentjens R and Saltz L: Islet cell tumors of the pancreas: The medical oncologist's perspective. Surg Clin North Am. 81:527–542. 2001.PubMed/NCBI View Article : Google Scholar
15	Mekhjian HS and O'Dorisio TM: VIPoma syndrome. Semin Oncol. 14:282–291. 1987.PubMed/NCBI
16	Remme CA, de Groot GH and Schrijver G: Diagnosis and treatment of VIPoma in a female patient. Eur J Gastroenterol Hepatol. 18:93–99. 2006.PubMed/NCBI View Article : Google Scholar
17	Metz DC and Jensen RT: Gastrointestinal neuroendocrine tumors: Pancreatic endocrine tumors. Gastroenterology. 135:1469–1492. 2008.PubMed/NCBI View Article : Google Scholar
18	Piet R, Dunckley H, Lee K and Herbison AE: Vasoactive intestinal peptide excites GnRH neurons in male and female mice. Endocrinology. 157:3621–3630. 2016.PubMed/NCBI View Article : Google Scholar
19	Abu-Zaid A, Azzam A, Abudan Z, Algouhi A, Almana H and Amin T: Sporadic pancreatic vasoactive intestinal peptide-producing tumor (VIPoma) in a 47-year-old male. Hematol Oncol Stem Cell Ther. 7:109–115. 2014.PubMed/NCBI View Article : Google Scholar
20	Chen C, Zheng Z, Li B, Zhou L, Pang J, Wu W, Zheng C and Zhao Y: Pancreatic VIPomas from China: Case reports and literature review. Pancreatology. 19:44–49. 2019.PubMed/NCBI View Article : Google Scholar
21	Anderson CW and Bennett JJ: Clinical presentation and diagnosis of pancreatic neuroendocrine tumors. Surg Oncol Clin N Am. 25:363–374. 2016.PubMed/NCBI View Article : Google Scholar
22	Grozinsky-Glasberg S, Mazeh H and Gross DJ: Clinical features of pancreatic neuroendocrine tumors. J Hepatobiliary Pancreat Sci. 22:578–585. 2015.PubMed/NCBI View Article : Google Scholar
23	Smith SL, Branton SA, Avino AJ, Martin JK, Klingler PJ, Thompson GB, Grant CS and van Heerden JA: Vasoactive intestinal polypeptide secreting islet cell tumors: A 15-year experience and review of the literature. Surgery. 124:1050–1055. 1998.PubMed/NCBI View Article : Google Scholar
24	Nilubol N, Freedman EM, Quezado MM, Patel D and Kebebew E: Pancreatic neuroendocrine tumor secreting vasoactive intestinal peptide and dopamine with pulmonary emboli: A case report. J Clin Endocrinol Metab. 101:3564–3567. 2016.PubMed/NCBI View Article : Google Scholar
25	Pasricha G, Padhi P, Daboul N and Monga DK: Management of well-differentiated gastroenteropancreatic neuroendocrine tumors (GEPNETs): A review. Clin Ther. 39:2146–2157. 2017.PubMed/NCBI View Article : Google Scholar
26	Debray MP, Geoffroy O, Laissy JP, Lebtahi R, Silbermann-Hoffman O, Henry-Feugeas MC, Cadiot G, Mignon M and Schouman-Claeys E: Imaging appearances of metastases from neuroendocrine tumours of the pancreas. Br J Radiol. 74:1065–1070. 2001.PubMed/NCBI View Article : Google Scholar
27	Semelka RC, Custodio CM, Cem Balci N and Woosley JT: Neuroendocrine tumors of the pancreas: Spectrum of appearances on MRI. J Magn Reson Imaging. 11:141–148. 2000.PubMed/NCBI View Article : Google Scholar
28	Lam S, Liew H, Khor HT, Dalan R, Kon YC, Jong M, Chew DE and Leow MK: VIPoma in a 37-year-old man. Lancet. 382(832)2013.PubMed/NCBI View Article : Google Scholar
29	Ram R, Natanzi N, Saadat P, Eliav D and Vadmal MS: Skin metastasis of pancreatic vasoactive intestinal polypeptide tumor: Case report and review of the literature. Arch Dermatol. 142:946–947. 2006.PubMed/NCBI View Article : Google Scholar
30	O'Dorisio TM, Mekhjian HS and Gaginella TS: Medical therapy of VIPomas. Endocrinol Metab Clin North Am. 18:545–556. 1989.PubMed/NCBI
31	Ito T, Igarashi H, Uehara H and Jensen RT: Pharmacotherapy of Zollinger-Ellison syndrome. Expert Opin Pharmacother. 14:307–321. 2013.PubMed/NCBI View Article : Google Scholar
32	Jensen RT, Niederle B, Mitry E, Ramage JK, Steinmuller T, Lewington V, Scarpa A, Sundin A, Perren A, Gross D, et al: Frascati Consensus Conference; European neuroendocrine tumor society: Gastrinoma (duodenal and pancreatic). Neuroendocrinology. 84:173–182. 2006.PubMed/NCBI View Article : Google Scholar
33	Zhang X, Zhou L, Liu Y, Li W, Gao H, Wang Y, Yao B, Jiang D and Hu P: Surgical resection of vasoactive intestinal peptideoma with hepatic metastasis aids symptom palliation: A case report. Exp Ther Med. 11:783–787. 2016.PubMed/NCBI View Article : Google Scholar
34	Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, et al: Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 371:224–233. 2014.PubMed/NCBI View Article : Google Scholar
35	Plouin PF, Bertherat J, Chatellier G, Billaud E, Azizi M, Grouzmann E and Epelbaum J: Short-term effects of octreotide on blood pressure and plasma catecholamines and neuropeptide Y levels in patients with phaeochromocytoma: A placebo-controlled trial. Clin Endocrinol (Oxf). 42:289–294. 1995.PubMed/NCBI View Article : Google Scholar
36	Nguyen HN, Backes B, Lammert F, Wildberger J, Winograd R, Busch N, Rieband H and Matern S: Long-term survival after diagnosis of hepatic metastatic VIPoma: Report of two cases with disparate courses and review of therapeutic options. Dig Dis Sci. 44:1148–1155. 1999. View Article : Google Scholar
37	Lamberts SW, Pieters GF, Metselaar HJ, Ong GL, Tan HS and Reubi JC: Development of resistance to a long-acting somatostatin analogue during treatment of two patients with metastatic endocrine pancreatic tumours. Acta Endocrinol (Copenh). 119:561–566. 1988.PubMed/NCBI View Article : Google Scholar
38	Faiss S, Pape UF, Böhmig M, Dörffel Y, Mansmann U, Golder W, Riecken EO and Wiedenmann B: International Lanreotide and Interferon Alfa Study Group: Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors-the International Lanreotide and Interferon Alfa Study Group. J Clin Oncol. 21:2689–2696. 2003.PubMed/NCBI View Article : Google Scholar
39	Lapeña Rodríguez M, Cholvi Calduch R, Muñoz Forner E, Garcés Albir M and Sabater Ortí L: Life-threating diarrhea and acute renal failure secondary to pancreatic VIPoma treated by surgery. Rev Esp Enferm Dig. 111:641–643. 2019.PubMed/NCBI View Article : Google Scholar
40	Dréanic J, Lepère C, El Hajjam M, Gouya H, Rougier P and Coriat R: Emergency therapy for liver metastases from advanced VIPoma: Surgery or transarterial chemoembolization? Ther Adv Med Oncol. 8:383–387. 2016.PubMed/NCBI View Article : Google Scholar
41	Kos-Kudła B, Ćwikła J, Ruchała M, Hubalewska-Dydejczyk A, Jarzab B, Krajewska J and Kamiński G: Current treatment options for gastroenteropancreatic neuroendocrine tumors with a focus on the role of lanreotide. Contemp Oncol (Pozn). 21:115–122. 2017.PubMed/NCBI View Article : Google Scholar
42	Shah M, Goldner W, Halfdanarson T, Bergsland E, Berlin J, Halperin D, Chan J, Kulke M, Benson A, Blaszkowsky L, et al: NCCN clinical practice guidelines in oncology: Neuroendocrine and adrenal tumors. J Natl Compr Canc Netw. 16:693–702. 2018.PubMed/NCBI View Article : Google Scholar
43	Partelli S, Bartsch DK, Capdevila J, Chen J, Knigge U, Niederle B, Nieveen van Dijkum EJM, Pape UF, Pascher A, Ramage J, et al: Antibes consensus conference participants: ENETS consensus guidelines for standard of care in neuroendocrine tumours: Surgery for small intestinal and pancreatic neuroendocrine tumours. Neuroendocrinology. 105:255–265. 2017.PubMed/NCBI View Article : Google Scholar
44	Norton JA, Kivlen M, Li M, Schneider D, Chuter T and Jensen RT: Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors. Arch Surg. 138:859–866. 2003.PubMed/NCBI View Article : Google Scholar
45	Fernández-Cruz L, Blanco L, Cosa R and Rendón H: Is laparoscopic resection adequate in patients with neuroendocrine pancreatic tumors? World J Surg. 32:904–917. 2008.PubMed/NCBI View Article : Google Scholar
46	Pavel M, O'Toole D, Costa F, Capdevila J, Gross D, Kianmanesh R, Krenning E, Knigge U, Salazar R, Pape UF, et al: Vienna Consensus Conference participants: ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology. 103:172–185. 2016.PubMed/NCBI View Article : Google Scholar
47	Moug SJ, Leen E, Horgan PG and Imrie CW: Radiofrequency ablation has a valuable therapeutic role in metastatic VIPoma. Pancreatology. 6:155–159. 2006.PubMed/NCBI View Article : Google Scholar
48	Kennedy A, Bester L, Salem R, Sharma RA, Parks RW and Ruszniewski P: NET-Liver-Metastases Consensus Conference: Role of hepatic intra-arterial therapies in metastatic neuroendocrine tumours (NET): Guidelines from the NET-liver-metastases consensus conference. HPB (Oxford). 17:29–37. 2015.PubMed/NCBI View Article : Google Scholar
49	Mazzaferro V, Pulvirenti A and Coppa J: Neuroendocrine tumors metastatic to the liver: How to select patients for liver transplantation? J Hepatol. 47:460–466. 2007.PubMed/NCBI View Article : Google Scholar
50	Gedaly R, Daily MF, Davenport D, McHugh PP, Koch A, Angulo P and Hundley JC: Liver transplantation for the treatment of liver metastases from neuroendocrine tumours: An analysis of the UNOS database. Arch Surg. 146:953–958. 2011.PubMed/NCBI View Article : Google Scholar
51	Máthé Z, Tagkalos E, Paul A, Molmenti EP, Kóbori L, Fouzas I, Beckebaum S and Sotiropoulos GC: Liver transplantation for hepatic metastases of neuroendocrine pancreatic tumors: A survival-based analysis. Transplantation. 91:575–582. 2011. View Article : Google Scholar
52	Moris D, Tsilimigras DI, Ntanasis-Stathopoulos I, Beal EW, Felekouras E, Vernadakis S, Fung JJ and Pawlik TM: Liver transplantation in patients with liver metastases from neuroendocrine tumors: A systematic review. Surgery. 162:525–536. 2017.PubMed/NCBI View Article : Google Scholar
53	Tsilimigras DI, Ntanasis-Stathopoulos I, Kostakis ID, Moris D, Schizas D, Cloyd JM and Pawlik TM: Is resection of primary midgut neuroendocrine tumors in patients with unresectable metastatic liver disease justified? A systematic review and meta-analysis. J Gastrointest Surg. 23:1044–1054. 2019.PubMed/NCBI View Article : Google Scholar
54	Guo J, Zhang Q, Bi X, Zhou J, Li Z, Huang Z, Zhang Y, Li M, Chen X, Hu X, et al: Systematic review of resecting primary tumor in MNETs patients with unresectable liver metastases. Oncotarget. 8:17396–17405. 2017.PubMed/NCBI View Article : Google Scholar
55	Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, et al: Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 364:514–523. 2011.PubMed/NCBI View Article : Google Scholar
56	Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, et al: Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 364:501–513. 2011.PubMed/NCBI View Article : Google Scholar
57	De Mestier L, Walter T, Brixi H, Lombard-Bohas C and Cadiot G: Sunitinib achieved fast and sustained control of VIPoma symptoms. Eur J Endocrinol. 172:K1–K3. 2015.PubMed/NCBI View Article : Google Scholar
58	Phan AT, Halperin DM, Chan JA, Fogelman DR, Hess KR, Malinowski P, Regan E, Ng CS, Yao JC and Kulke MH: Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine tumours: A multicentre, single-group, phase 2 study. Lancet Oncol. 16:695–703. 2015.PubMed/NCBI View Article : Google Scholar
59	Hobday TJ, Qin R, Reidy-Lagunes D, Moore MJ, Strosberg J, Kaubisch A, Shah M, Kindler HL, Lenz HJ, Chen H and Erlichman C: Multicenter phase II trial of temsirolimus and bevacizumab in pancreatic neuroendocrine tumors. J Clin Oncol. 33:1551–1556. 2015.PubMed/NCBI View Article : Google Scholar
60	Akirov A, Larouche V, Alshehri S, Asa SL and Ezzat S: Treatment options for pancreatic neuroendocrine tumors. Cancers (Basel). 11(E828)2019.PubMed/NCBI View Article : Google Scholar
61	Auernhammer CJ, Spitzweg C, Angele MK, Boeck S, Grossman A, Nölting S, Ilhan H, Knösel T, Mayerle J, Reincke M and Bartenstein P: Advanced neuroendocrine tumours of the small intestine and pancreas: Clinical developments, controversies, and future strategies. Lancet Diabetes Endocrinol. 6:404–415. 2018.PubMed/NCBI View Article : Google Scholar
62	Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, et al: NETTER-1 trial investigators. Phase 3 trial of 177lu-dotatate for midgut neuroendocrine tumours. N Engl J Med. 376:125–135. 2017.PubMed/NCBI View Article : Google Scholar
63	Hicks RJ, Kwekkeboom DJ, Krenning E, Bodei L, Grozinsky-Glasberg S, Arnold R, Borbath I, Cwikla J, Toumpanakis C, Kaltsas G, et al: ENETS consensus guidelines for the standards of care in neuroendocrine neoplasia: Peptide receptor radionuclide therapy with radiolabeled somatostatin analogues. Neuroendocrinology. 105:295–309. 2017.PubMed/NCBI View Article : Google Scholar
64	Brabander T, van der Zwan WA, Teunissen JJM, Kam BLR, Feelders RA, de Herder WW, van Eijck CHJ, Franssen GJH, Krenning EP and Kwekkeboom DJ: Long-term efficacy, survival, and safety of [177Lu-DOTA0, Tyr3]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumours. Clin Cancer Res. 23:4617–4624. 2017.PubMed/NCBI View Article : Google Scholar
65	Zandee WT, Brabander T, Blažević A, Kam BLR, Teunissen JJM, Feelders RA, Hofland J and de Herder WW: Symptomatic and radiological response to 177Lu-DOTATATE for the treatment of functioning pancreatic neuroendocrine tumors. J Clin Endocrinol Metab. 104:1336–1344. 2019.PubMed/NCBI View Article : Google Scholar
66	Adnan A and Basu S: Rare site primary soft tissue neuroendocrine tumour with metastases and near-complete resolution with ¹⁷⁷Lu-DOTATATE: Documenting a promising clinical application of peptide receptor radionuclide therapy. J Nucl Med Technol. 119(227058): Aug 10, 2019 (Epub ahead of print). View Article : Google Scholar
67	Jin XF, Spampatti MP, Spitzweg C and Auernhammer CJ: Supportive therapy in gastroenteropancreatic neuroendocrine tumors: Often forgotten but important. Rev Endocr Metab Disord. 19:145–158. 2018.PubMed/NCBI View Article : Google Scholar
68	Ataeinia B, Loberg C, Kravets H, Beheshti M, von Mallek D, Mottaghy FM and Heinzel A: Successful palliative peptide receptor radionuclide therapy for impending compression of vena cava due to unresectable liver metastasis of neuroendocrine tumor. EXCLI J. 18:273–276. 2019.PubMed/NCBI View Article : Google Scholar
69	Hennrich U and Kopka K: Lutathera^®: The first FDA- and EMA-approved radiopharmaceutical for peptide receptor radionuclide therapy. Pharmaceuticals (Basel). 12(E114)2019.PubMed/NCBI View Article : Google Scholar
70	Roland CL, Bian A, Mansour JC, Yopp AC, Balch GC, Sharma R, Xie XJ and Schwarz RE: Survival impact of malignant pancreatic neuroendocrine and islet cell neoplasm phenotypes. J Surg Oncol. 105:595–600. 2012.PubMed/NCBI View Article : Google Scholar
71	Loh HH and Tan F: Pancreatic vasoactive intestinal peptide producing tumor (VIPoma): A case report and literature review. Endokrinolojide Diyalog. 10:32–37. 2013.
72	Karim N, Zarzour A, Daw HA, Palaparty P, Taftaf R, Shehata M and Taylor HC: Prolonged survival in a patient with metastatic vasoactive intestinal peptide producing pancreatic neuroendocrine tumors. J Clin Case Rep. 2(210)2012. View Article : Google Scholar
73	Soga J and Yakuwa Y: Vipoma/diarrheogenic syndrome: A statistical evaluation of 241 reported cases. J Exp Clin Cancer Res. 17:389–400. 1998.PubMed/NCBI