Neoplasms of the Endocrine Pancreas

Neoplasms of the Endocrine Pancreas

No Results

No Results

processing….

Neoplasms of the endocrine pancreas can be divided into functional and nonfunctional varieties. Most pancreatic endocrine neoplasms discovered clinically are functional—that is, they secrete one or more hormonal products into the blood, which leads to a recognizable clinical syndrome. [1] In 1927, Wilder et al described the first hormone-producing pancreatic tumor syndrome in a patient with hypoglycemia and a metastatic islet cell tumor, extracts of which caused hypoglycemia. [2]

Subsequent to this initial description of insulinoma syndrome, four other classic pancreatic endocrine tumor syndromes have been described. The first is Zollinger-Ellison syndrome (also termed gastrinoma syndrome), described by Zollinger and Ellison in 1955. [3]

The second types comprise a group of three tumor syndromes, termed Verner-Morrison syndrome, WDHA (watery diarrhea, hypokalemia, and achlorhydria) syndrome, and pancreatic cholera (also termed vasoactive intestinal peptide [VIP]–releasing tumor or VIPoma); these were described by Verner and Morrison in 1958. [4]

The third is glucagonoma syndrome, described by Mallinson et al in 1974. The fourth is somatostatinoma syndrome, described by Ganda et al and Larsson et al in 1977. [5, 6]

Several other rare clinical syndromes have been proposed as possible functional endocrine syndromes associated with pancreatic neoplasms. These include the following:

Patients with pancreatic neoplasms that have the histologic characteristics of a pancreatic endocrine tumor but no associated elevation in plasma hormone levels, excluding the pancreatic polypeptide level, and those without a recognizable clinical syndrome are considered to have nonfunctional pancreatic endocrine tumors. A subset of these patients have nonfunctional pancreatic endocrine neoplasms that secrete pancreatic polypeptide (ie, PPomas). Pancreatic polypeptide (PP) is a product that appears to be a marker for pancreatic endocrine tumors, but it is not a mediator of any specific PP-related clinical syndrome. [11]  Other nonfunctional pancreatic endocrine tumors likely secrete unknown products that are of little or no clinical significance.

Each of the classic pancreatic endocrine tumor syndromes is discussed in detail in the following articles:

For discussion of other conditions with which pancreatic endocrine tumors are associated, see the following:

 

 

The cells in pancreatic endocrine neoplasms are termed amine precursor uptake and decarboxylation (APUD) cells because they have a high amine content, are capable of amine precursor uptake, and contain an amino acid decarboxylase. [12] Pearse first used the term APUD in 1968 to unify a group of functionally and structurally similar neuroendocrine cells that are present throughout the body. [13] APUD cells were once believed to originate from the embryologic neural crest, but current evidence suggests that these cells—and thus endocrine tumors of the pancreas and other endocrine tumors of the upper gastrointestinal tract (eg, carcinoid tumors)—actually develop from the embryologic endoderm. [14]

Although the term islet cell tumor is often used to identify neoplasms of the endocrine pancreas, this is a misnomer because many pancreatic neuroendocrine tumors do not develop directly from islet cells. [15] Instead, the tumors arise from APUD stem cells, which are pluripotential neuroendocrine cells located within the ductular epithelium of the exocrine pancreas and elsewhere in the distal foregut. [16] The fact that many gastrinomas and somatostatinomas are found close to, but not within, the pancreatic parenchyma supports the notion of the possible extrapancreatic development of these neoplasms. [17]

Patients with functional pancreatic endocrine neoplasms have physiologic derangements related to the normal action of the hormonal product that the tumors overproduce. Thus, patients with an insulin-secreting tumor (ie, insulinoma) have the pathophysiologic manifestations of hypoglycemia; patients with a gastrin-secreting tumor (ie, gastrinoma) have hypersecretion of gastric acid, which often leads to the development of peptic ulcers (ie, Zollinger-Ellison syndrome); and so on. In contrast, patients with nonfunctional pancreatic endocrine neoplasms typically present later in the course of their disease, when their tumors begin to cause symptoms related to a mass effect.

Neoplasms of the endocrine pancreas occur in two distinct epidemiologic groups. Solitary tumors that develop in patients without a significant personal or family history of endocrine disorders are characterized as the sporadic form. The second form affects kindreds with the multiple endocrine neoplasia type 1 (MEN 1) syndrome in a pattern of autosomal dominant inheritance. [18] Approximately 80% of individuals with MEN 1 syndrome have one or more pancreatic neoplasms in their lifetime; gastrinoma and insulinoma are the most commonly identified lesions. [19]

Clinically recognized neoplasms of the endocrine pancreas are rare, with an overall annual incidence in the United States of 3-10 cases per million persons. [20, 21] However, the much higher prevalence of these tumors in unselected autopsy specimens, 0.5-1.5%, reflects the indolent nature of many of these tumors. [22, 23]

Insulinomas and gastrinomas occur with roughly equal annual incidences; together they account for more than half of all clinically apparent pancreatic endocrine tumors. [23] VIPomas are one-eighth and glucagonomas are one-seventeenth as common, whereas somatostatinomas are even more rare. [20] Nonfunctional tumors account for 14-48% of all recognized neoplasms of the endocrine pancreas. [24, 25]

Because of the relative rarity of pancreatic endocrine tumors in the general population, accurate rates of morbidity and mortality for persons with these lesions are difficult to determine. However, both the survival and the quality of life of patients with neoplasms of the endocrine pancreas are generally improving secondary to improvements in the modalities used to diagnose and treat these lesions (also see Complications and Prognosis).

Sporadic and inherited forms of pancreatic endocrine tumors appear to occur with equal frequency among the different racial groups in the United States.

Neoplasms of the endocrine pancreas seem to have a slightly higher incidence in women than in men. [26, 18, 27] As would be expected in patients with a genetic disorder of autosomal dominant inheritance, no significant sex predilection is observed among patients with pancreatic endocrine tumors as part of MEN 1 syndrome. [17]

Patients with sporadic pancreatic endocrine tumors present most commonly at the age of 30-50 years. [28] In contrast, patients with pancreatic endocrine tumors that develop as part of MEN 1 syndrome tend to present when younger, commonly at age 10-30 years. [18]

Aluri V, Dillon JS. Biochemical Testing in Neuroendocrine Tumors. Endocrinol Metab Clin North Am. 2017 Sep. 46 (3):669-677. [Medline].

Wilder RM, Allan FN, Power WH. Carcinoma of the islands of the pancreas: Hyperinsulinism and hypoglycemia. JAMA. 1927. 89:348.

Zollinger RM, Ellison EH. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg. 1955. 142:709.

Verner JV, Morrison AB. Islet cell tumor and a syndrome of refractory watery diarrhea and hypokalemia. Am J Med. 1958. 25:374.

Ganda OP, Weir GC, Soeldner JS, et al. “Somatostatinoma”: a somatostatin-containing tumor of the endocrine pancreas. N Engl J Med. 1977 Apr 28. 296(17):963-7. [Medline].

Larsson LI, Hirsch MA, Holst JJ, et al. Pancreatic somatostatinoma. Clinical features and physiological implications. Lancet. 1977 Mar 26. 1(8013):666-8. [Medline].

Howard JM, Gohara AF, Cardwell RJ. Malignant islet cell tumor of the pancreas associated with high plasma calcitonin and somatostatin levels. Surgery. 1989 Feb. 105(2 Pt 1):227-9. [Medline].

McLeod MK, Vinik AI. Calcitonin immunoreactivity and hypercalcitoninemia in two patients with sporadic, nonfamilial, gastroenteropancreatic neuroendocrine tumors. Surgery. 1992 May. 111(5):484-8. [Medline].

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

Meko JB, Norton JA. Endocrine tumors of the pancreas. Curr Opin Gen Surg. 1994. 186-94. [Medline].

Langstein HN, Norton JA, Chiang V, et al. The utility of circulating levels of human pancreatic polypeptide as a marker for islet cell tumors. Surgery. 1990 Dec. 108(6):1109-15; discussion 1115-6. [Medline].

Yeo CJ. Neoplasms of the endocrine pancreas. In: Greenfield LJ, Mulholland MW, Oldham KT, eds. Surgery: Scientific Principles and Practice, 3rd ed. Philadelphia, Pa: Lippincott. 2001: 899-913.

Pearse AG. Common cytochemical and ultrastructural characteristics of cells producing polypeptide hormones (the APUD series) and their relevance to thyroid and ultimobranchial C cells and calcitonin. Proc R Soc Lond B Biol Sci. 1968 May 14. 170(18):71-80. [Medline].

Andrew A, Kramer B, Rawdon BB. The origin of gut and pancreatic neuroendocrine (APUD) cells–the last word?. J Pathol. 1998 Oct. 186(2):117-8. [Medline].

Kloppel G, Heitz PU. Pancreatic endocrine tumors. Pathol Res Pract. 1988 Apr. 183(2):155-68. [Medline].

Heitz PU, Kasper M, Polak JM, Kloppel G. Pancreatic endocrine tumors. Hum Pathol. 1982 Mar. 13(3):263-71. [Medline].

Metz DC. Diagnosis and treatment of pancreatic neuroendocrine tumors. Semin Gastrointest Dis. 1995 Apr. 6(2):67-78. [Medline].

Norton JA, Levin B, Jensen RT. Cancer of the endocrine system. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 4th ed. Philadelphia, Pa:. Lippincott-Raven. 1993:1333-435.

Helmrath MA. Miscellaneous endocrine disorders. In: Berry SM, Bass RC, Heaton KM, eds. The Mont Reid Surgical Handbook. 4th ed. St Louis, Mo:. Mosby. 1997: 355-67.

Buchanan KD, Johnston CF, O”Hare MM, et al. Neuroendocrine tumors. A European view. Am J Med. 1986 Dec 22. 81(6B):14-22. [Medline].

Eriksson B, Oberg K, Skogseid B. Neuroendocrine pancreatic tumors. Clinical findings in a prospective study of 84 patients. Acta Oncol. 1989. 28(3):373-7. [Medline].

Weil C. Gastroenteropancreatic endocrine tumors. Klin Wochenschr. 1985 May 15. 63(10):433-59. [Medline].

Jensen RT, Norton JA. Endocrine tumors of the pancreas. In: Feldman M, Scharschmidt BF, Sleisenger M, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 6th ed. Philadelphia, Pa:. WB Saunders. 1998: 871-94.

Eriksson B, Oberg K. PPomas and nonfunctioning endocrine pancreatic tumors: clinical presentation, diagnosis, and advances in management. In: Mignon M, Jensen RT, eds. Endocrine Tumors of the Pancreas. Frontiers of Gastrointestinal Research. Vol 23. Basel, Switzerland:. Karger. 1995: 208.

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

Menegaux F, Schmitt G, Mercadier M, Chigot JP. Pancreatic insulinomas. Am J Surg. 1993 Feb. 165(2):243-8. [Medline].

Thompson GB, Service FJ, van Heerden JA, et al. Reoperative insulinomas, 1927 to 1992: an institutional experience. Surgery. 1993 Dec. 114(6):1196-204; discussion 1205-6. [Medline].

Metz DC, Jensen RT. Endocrine tumors of the pancreas. In: Haubrich WB, Berk F, Schaffner JE, eds. Bockus Gastroenterology. 5th ed. Philadelphia, Pa:. WB Saunders. 1994: 3002-34.

Whipple AO, Frantz VK. Adenoma of islet cells with hyperinsulinism: a review. Ann Surg. 1935. 101:1299.

Fajans SS, Vinik AI. Insulin-producing islet cell tumors. Endocrinol Metab Clin North Am. 1989 Mar. 18(1):45-74. [Medline].

Service FJ. Hypoglycemic disorders. N Engl J Med. 1995 Apr 27. 332(17):1144-52. [Medline].

Wolfe MM, Jensen RT. Zollinger-Ellison syndrome. Current concepts in diagnosis and management. N Engl J Med. 1987 Nov 5. 317(19):1200-9. [Medline].

Way L, Goldman L, Dunphy JE. Zollinger-Ellison syndrome. An analysis of twenty-five cases. Am J Surg. 1968 Aug. 116(2):293-304. [Medline].

Orloff SL, Debas HT. Advances in the management of patients with Zollinger-Ellison syndrome. Surg Clin North Am. 1995 Jun. 75(3):511-24. [Medline].

Miller LS, Vinayek R, Frucht H, et al. Reflux esophagitis in patients with Zollinger-Ellison syndrome. Gastroenterology. 1990 Feb. 98(2):341-6. [Medline].

Bieligk S, Jaffe BM. Islet cell tumors of the pancreas. Surg Clin North Am. 1995 Oct. 75(5):1025-40. [Medline].

Stabile BE, Passaro E Jr. Recurrent peptic ulcer. Gastroenterology. 1976 Jan. 70(1):124-35. [Medline].

Vinik AI, Thompson NW, Averbuch SD. Neoplasms of the gastroenteropancreatic endocrine system. In: Holland JF, Frei E, Bast RC, eds. Cancer Medicine. Philadelphia, Pa: Lea & Febiger. 1993: 1180-209.

Shimoda SS, Saunders DR, Rubin CE. The Zollinger-Ellison syndrome with steatorrhea. II. The mechanism of fat and vitamin B 12 malabsorption. Gastroenterology. 1968 Dec. 55(6):705-23. [Medline].

Wynick D, Williams SJ, Bloom SR. Symptomatic secondary hormone syndromes in patients with established malignant pancreatic endocrine tumors. N Engl J Med. 1988 Sep 8. 319(10):605-7. [Medline].

Chiang HC, O”Dorisio TM, Huang SC, et al. Multiple hormone elevations in Zollinger-Ellison syndrome. Prospective study of clinical significance and of the development of a second symptomatic pancreatic endocrine tumor syndrome. Gastroenterology. 1990 Dec. 99(6):1565-75. [Medline].

O”Dorisio TM, Mekhjian HS, Gaginella TS. Medical therapy of VIPomas. Endocrinol Metab Clin North Am. 1989 Jun. 18(2):545-56. [Medline].

Higgins GA, Recant L, Fischman AB. The glucagonoma syndrome: surgically curable diabetes. Am J Surg. 1979 Jan. 137(1):142-8. [Medline].

Wilkinson DS. Necrolytic migratory erythema with carcinoma of the pancreas. Trans St Johns Hosp Dermatol Soc. 1973. 59(2):244-50. [Medline].

Stacpoole PW. The glucagonoma syndrome: clinical features, diagnosis, and treatment. Endocr Rev. 1981 Summer. 2(3):347-61. [Medline].

Leichter SB. Clinical and metabolic aspects of glucagonoma. Medicine (Baltimore). 1980 Mar. 59(2):100-13. [Medline].

Guillausseau PJ, Guillausseau C, Villet R, et al. [Glucagonomas. Clinical, biological, anatomopathological and therapeutic aspects (general review of 130 cases]. Gastroenterol Clin Biol. 1982 Dec. 6(12):1029-41. [Medline].

Vinik AI, Strodel WE, Eckhauser FE, et al. Somatostatinomas, PPomas, neurotensinomas. Semin Oncol. 1987 Sep. 14(3):263-81. [Medline].

Brodish RJ, Kuvshinoff BW, McFadden DW, Fink AS. Somatostatin inhibits cholecystokinin-induced pancreatic protein secretion via cholinergic pathways. Pancreas. 1995 May. 10(4):401-6. [Medline].

Boden G, Shimoyama R. Somatostatinoma. In: Cohen S, Soloway RD, eds. Hormone-Producing Tumors of the Gastrointestinal Tract. New York, NY: Churchill Livingstone. 1985: 85.

Long PP, Hruban RH, Lo R, et al. Chromosome analysis of nine endocrine neoplasms of the pancreas. Cancer Genet Cytogenet. 1994 Oct. 77(1):55-9. [Medline].

Zeiger MA, Norton JA. Gs alpha–identification of a gene highly expressed by insulinoma and other endocrine tumors. Surgery. 1993 Aug. 114(2):458-62; discussion 462-3. [Medline].

Eubanks PJ, Sawicki MP, Samara GJ, et al. Pancreatic endocrine tumors with loss of heterozygosity at the multiple endocrine neoplasia type I locus. Am J Surg. 1997 Jun. 173(6):518-20. [Medline].

Miller JA, Norton JA. Multiple endocrine neoplasia. Cancer Treat Res. 1997. 90:213-25. [Medline].

Nakeeb A, Lillemoe KD, Yeo CJ. Neoplasms of the exocrine pancreas. In: Greenfield LJ, Mulholland MW, Oldham KT, eds. Surgery: Scientific Principles and Practice. 3rd ed. Philadelphia, Pa:. Lippincott-Raven. 2001:885-99.

[Guideline] NCCN Clinical Practice Guidelines in Oncology. Neuroendocrine Tumors Version 2.2016. National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf. May 25, 2016; Accessed: February 4, 2017.

Ekeblad S, Skogseid B, Dunder K, Oberg K, Eriksson B. Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution. Clin Cancer Res. 2008 Dec 1. 14(23):7798-803. [Medline]. [Full Text].

Warner RR, Curran T, Shafir MK, et al. Serum and ascites chromogranin-A in patients with metastatic neuroendocrine tumors. Pancreas. 2011 May. 40(4):622-6. [Medline].

Mekhjian HS, O”Dorisio TM. VIPoma syndrome. Semin Oncol. 1987 Sep. 14(3):282-91. [Medline].

Krejs GJ. VIPoma syndrome. Am J Med. 1987 May 29. 82(5B):37-48. [Medline].

Krejs GJ, Orci L, Conlon JM, et al. Somatostatinoma syndrome. Biochemical, morphologic and clinical features. N Engl J Med. 1979 Aug 9. 301(6):285-92. [Medline].

Naswa N, Sharma P, Kumar A, et al. Gallium-68-DOTA-NOC PET/CT of patients with gastroenteropancreatic neuroendocrine tumors: a prospective single-center study. AJR Am J Roentgenol. 2011 Nov. 197(5):1221-8. [Medline].

Pelley RJ, Bukowski RM. Recent advances in diagnosis and therapy of neuroendocrine tumors of the gastrointestinal tract. Curr Opin Oncol. 1997 Jan. 9(1):68-74. [Medline].

Moore NR, Rogers CE, Britton BJ. Magnetic resonance imaging of endocrine tumours of the pancreas. Br J Radiol. 1995 Apr. 68(808):341-7. [Medline].

Berger JF, Laissy JP, Limot O, et al. Differentiation between multiple liver hemangiomas and liver metastases of gastrinomas: value of enhanced MRI. J Comput Assist Tomogr. 1996 May-Jun. 20(3):349-55. [Medline].

Gibril F, Reynolds JC, Doppman JL, et al. Somatostatin receptor scintigraphy: its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. A prospective study. Ann Intern Med. 1996 Jul 1. 125(1):26-34. [Medline].

Mitchell DG. Diagnosis and staging of pancreatic tumors by magnetic resonance imaging. Neoplasms of the Digestive System. 1998. Lippincott Raven:

Krausz Y, Bar-Ziv J, de Jong RB, et al. Somatostatin-receptor scintigraphy in the management of gastroenteropancreatic tumors. Am J Gastroenterol. 1998 Jan. 93(1):66-70. [Medline].

Frilling A, Malago M, Martin H, Broelsch CE. Use of somatostatin receptor scintigraphy to image extrahepatic metastases of neuroendocrine tumors. Surgery. 1998 Dec. 124(6):1000-4. [Medline].

Glover JR, Shorvon PJ, Lees WR. Endoscopic ultrasound for localisation of islet cell tumours. Gut. 1992 Jan. 33(1):108-10. [Medline].

Rosch T, Lightdale CJ, Botet JF, et al. Localization of pancreatic endocrine tumors by endoscopic ultrasonography. N Engl J Med. 1992 Jun 25. 326(26):1721-6. [Medline].

Imamura M, Takahashi K, Adachi H, et al. Usefulness of selective arterial secretin injection test for localization of gastrinoma in the Zollinger-Ellison syndrome. Ann Surg. 1987 Mar. 205(3):230-9. [Medline].

Thom AK, Norton JA, Doppman JL, et al. Prospective study of the use of intraarterial secretin injection and portal venous sampling to localize duodenal gastrinomas. Surgery. 1992 Dec. 112(6):1002-8; discussion 1008-9. [Medline].

Pereira PL, Roche AJ, Maier GW, et al. Insulinoma and islet cell hyperplasia: value of the calcium intraarterial stimulation test when findings of other preoperative studies are negative. Radiology. 1998 Mar. 206(3):703-9. [Medline].

Vinik AI, Delbridge L, Moattari R, et al. Transhepatic portal vein catheterization for localization of insulinomas: a ten-year experience. Surgery. 1991 Jan. 109(1):1-11; discussion 111. [Medline].

Fraker DL, Alexander HR. The surgical approach to endocrine tumors of the pancreas. Semin Gastrointest Dis. 1995 Apr. 6(2):102-13. [Medline].

Gooding GA. Adrenal, pancreatic, and scrotal ultrasound in endocrine disease. Radiol Clin North Am. 1993 Sep. 31(5):1069-83. [Medline].

Norton JA, Sigel B, Baker AR, et al. Localization of an occult insulinoma by intraoperative ultrasonography. Surgery. 1985 Mar. 97(3):381-4. [Medline].

Grant CS, van Heerden J, Charboneau JW, et al. Insulinoma. The value of intraoperative ultrasonography. Arch Surg. 1988 Jul. 123(7):843-8. [Medline].

Nasir A, Helm J, Turner L, et al. RUNX1T1: a novel predictor of liver metastasis in primary pancreatic endocrine neoplasms. Pancreas. 2011 May. 40(4):627-33. [Medline].

Somogyi L, Mishra G. Diagnosis and staging of islet cell tumors of the pancreas. Curr Gastroenterol Rep. 2000 Apr. 2(2):159-64. [Medline].

Macdonald JS, Haller D, McDougall IR. Endocrine system: pancreatic islet cell tumors. In: Abeloff MD, Armitage JO, Lichter AS, eds. Clinical Oncology. 2nd ed. New York, NY:. Churchill-Livingstone. 2000: 1384-97.

Modlin IM, Kidd M, Drozdov I, Siddique ZL, Gustafsson BI. Pharmacotherapy of neuroendocrine cancers. Expert Opin Pharmacother. 2008 Oct. 9(15):2617-26. [Medline].

Broder MS, Beenhouwer D, Strosberg JR, Neary MP, Cherepanov D. Gastrointestinal neuroendocrine tumors treated with high dose octreotide-LAR: a systematic literature review. World J Gastroenterol. 2015 Feb 14. 21 (6):1945-55. [Medline]. [Full Text].

Al-Efraij K, Aljama MA, Kennecke HF. Association of dose escalation of octreotide long-acting release on clinical symptoms and tumor markers and response among patients with neuroendocrine tumors. Cancer Med. 2015 Jun. 4 (6):864-70. [Medline]. [Full Text].

Vinik AI, Moattari AR. Treatment of endocrine tumors of the pancreas. Endocrinol Metab Clin North Am. 1989 Jun. 18(2):483-518. [Medline].

Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, et al. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med. 2017 Jan 12. 376 (2):125-135. [Medline]. [Full Text].

Cherk MH, Kong G, Hicks RJ, Hofman MS. Changes in biodistribution on 68Ga-DOTA-Octreotate PET/CT after long acting somatostatin analogue therapy in neuroendocrine tumour patients may result in pseudoprogression. Cancer Imaging. 2018 Jan 24. 18 (1):3. [Medline]. [Full Text].

Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10. 364(6):514-23. [Medline].

Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10. 364(6):501-13. [Medline].

Anthony L, Vinik AI. Evaluating the characteristics and the management of patients with neuroendocrine tumors receiving octreotide LAR during a 6-year period. Pancreas. 2011 Oct. 40(7):987-94. [Medline].

Hobday TJ, Qin R, Reidy-Lagunes D, Moore MJ, Strosberg J, Kaubisch A, et al. Multicenter Phase II Trial of Temsirolimus and Bevacizumab in Pancreatic Neuroendocrine Tumors. J Clin Oncol. 2014 Dec 8. [Medline].

Ducreux M, Dahan L, Smith D, O’Toole D, Lepère C, Dromain C, et al. Bevacizumab combined with 5-FU/streptozocin in patients with progressive metastatic well-differentiated pancreatic endocrine tumours (BETTER trial) – A phase II non-randomised trial. Eur J Cancer. 2014 Dec. 50(18):3098-106. [Medline].

Boden G. Glucagonomas and insulinomas. Gastroenterol Clin North Am. 1989 Dec. 18(4):831-45. [Medline].

Moertel CG, Johnson CM, McKusick MA, et al. The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med. 1994 Feb 15. 120(4):302-9. [Medline].

Bilchik AJ, Sarantou T, Foshag LJ, et al. Cryosurgical palliation of metastatic neuroendocrine tumors resistant to conventional therapy. Surgery. 1997 Dec. 122(6):1040-7; discussion 1047-8. [Medline].

Mazzaglia PJ, Berber E, Milas M, Siperstein AE. Laparoscopic radiofrequency ablation of neuroendocrine liver metastases: a 10-year experience evaluating predictors of survival. Surgery. 2007 Jul. 142(1):10-9. [Medline].

Lillemoe KD, Kaushal S, Cameron JL, et al. Distal pancreatectomy: indications and outcomes in 235 patients. Ann Surg. 1999 May. 229(5):693-8; discussion 698-700. [Medline].

Phan GQ, Yeo CJ, Cameron JL, et al. Pancreaticoduodenectomy for selected periampullary neuroendocrine tumors: fifty patients. Surgery. 1997 Dec. 122(6):989-96; discussion, 996-7. [Medline].

Udelsman R, Yeo CJ, Hruban RH, et al. Pancreaticoduodenectomy for selected pancreatic endocrine tumors. Surg Gynecol Obstet. 1993 Sep. 177(3):269-78. [Medline].

Sugg SL, Norton JA, Fraker DL, et al. A prospective study of intraoperative methods to diagnose and resect duodenal gastrinomas. Ann Surg. 1993 Aug. 218(2):138-44. [Medline].

Farley DR, van Heerden JA, Grant CS, Thompson GB. Extrapancreatic gastrinomas. Surgical experience. Arch Surg. 1994 May. 129(5):506-11; discussion 511-2. [Medline].

Abood GJ, Go A, Malhotra D, Shoup M. The surgical and systemic management of neuroendocrine tumors of the pancreas. Surg Clin North Am. 2009 Feb. 89(1):249-66, x. [Medline].

Mazzaglia PJ, Berber E, Milas M, Siperstein AE. Laparoscopic radiofrequency ablation of neuroendocrine liver metastases: a 10-year experience evaluating predictors of survival. Surgery. 2007 Jul. 142(1):10-9. [Medline].

Gibril F, Doppman JL, Jensen RT. Recent advances in the treatment of metastatic pancreatic endocrine tumors. Semin Gastrointest Dis. 1995 Apr. 6(2):114-21. [Medline].

Keutgen XM, Nilubol N, Glanville J, Sadowski SM, Liewehr DJ, Venzon DJ, et al. Resection of primary tumor site is associated with prolonged survival in metastatic nonfunctioning pancreatic neuroendocrine tumors. Surgery. 2016 Jan. 159 (1):311-8. [Medline]. [Full Text].

Stefanini P, Carboni M, Patrassi N, Basoli A. Beta-islet cell tumors of the pancreas: results of a study on 1,067 cases. Surgery. 1974 Apr. 75(4):597-609. [Medline].

Moertel CG, Hanley JA, Johnson LA. Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1980 Nov 20. 303(21):1189-94. [Medline].

Moertel CG, Lefkopoulo M, Lipsitz S, et al. 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].

Fjallskog ML, Janson ET, Falkmer UG, Vatn MH, Oberg KE, Eriksson BK. Treatment with combined streptozotocin and liposomal doxorubicin in metastatic endocrine pancreatic tumors. Neuroendocrinology. 2008. 88(1):53-8. [Medline].

Rivera E, Ajani JA. Doxorubicin, streptozocin, and 5-fluorouracil chemotherapy for patients with metastatic islet-cell carcinoma. Am J Clin Oncol. 1998 Feb. 21(1):36-8. [Medline].

Arvold ND, Willett CG, Fernandez-Del Castillo C, Ryan DP, Ferrone CR, Clark JW, et al. Pancreatic Neuroendocrine Tumors With Involved Surgical Margins: Prognostic Factors and the Role of Adjuvant Radiotherapy. Int J Radiat Oncol Biol Phys. 2012 Mar 11. [Medline].

Welbourne RB, Wood SM, Polak JM. Pancreatic endocrine tumors. In: Bloom SR, Polak JM, eds. Gut Hormones. 2nd ed. New York, NY: Churchill-Livingstone. 1981: 547-54.

Rothmund M, Angelini L, Brunt LM, et al. Surgery for benign insulinoma: an international review. World J Surg. 1990 May-Jun. 14(3):393-8; discussion 398-9. [Medline].

McGuigan JE. Zollinger-Ellison syndrome and other hypersecretory states. In: Feldman M, Scharschmidt BF, Sleisenger M, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 6th ed. Philadelphia, Pa:. WB Saunders. 1998:679-95.

Stabile BE, Passaro E Jr. Benign and malignant gastrinoma. Am J Surg. 1985 Jan. 149(1):144-50. [Medline].

Fraker DL, Norton JA, Alexander HR, et al. Surgery in Zollinger-Ellison syndrome alters the natural history of gastrinoma. Ann Surg. 1994 Sep. 220(3):320-8; discussion 328-30. [Medline].

Weber HC, Venzon DJ, Lin JT, et al. Determinants of metastatic rate and survival in patients with Zollinger- Ellison syndrome: a prospective long-term study. Gastroenterology. 1995 Jun. 108(6):1637-49. [Medline].

Jensen RT, Fraker DL. Zollinger-Ellison syndrome. Advances in treatment of gastric hypersecretion and the gastrinoma. JAMA. 1994 May 11. 271(18):1429-35. [Medline].

Holst JJ. Glucagon-producing tumors. In: Cohen S, Soloway RD, eds. Hormone-Producing Tumors of the Gastrointestinal Tract. New York, NY: Churchill-Livingstone. 1985: 57.

Verner JV, Morrison AB. Endocrine pancreatic islet disease with diarrhea. Report of a case due to diffuse hyperplasia of nonbeta islet tissue with a review of 54 additional cases. Arch Intern Med. 1974 Mar. 133(3):492-9. [Medline].

Long RG, Bryant MG, Mitchell SJ, et al. Clinicopathological study of pancreatic and ganglioneuroblastoma tumours secreting vasoactive intestinal polypeptide (vipomas). Br Med J (Clin Res Ed). 1981 May 30. 282(6278):1767-71. [Medline].

Kent RB 3rd, van Heerden JA, Weiland LH. Nonfunctioning islet cell tumors. Ann Surg. 1981 Feb. 193(2):185-90. [Medline].

Tomassetti P, Campana D, Piscitelli L. Endocrine pancreatic tumors: factors correlated with survival. Ann Oncol. 2005 Nov. 16(11):1806-10.

Fjallskog ML, Sundin A, Westlin JE. Treatment of malignant endocrine pancreatic tumors with a combination of alpha-interferon and somatostatin analogs. Med Oncol. 2002. 19(1):35-42.

Evan S Ong, MD, MS Assistant Professor of Surgery, Section of Surgical Oncology, University of Arizona College of Medicine

Evan S Ong, MD, MS is a member of the following medical societies: Society of Surgical Oncology, Americas Hepato-Pancreato-Biliary Association, American Society of Clinical Oncology

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: Received salary from Medscape for employment. for: Medscape.

Neetu Radhakrishnan, MD Associate Professor (Adjunct) of Medicine, Division of Hematology/Oncology, University of Cincinnati Medical Center; Hematology/Oncology Medical Director, West Chester Outpatient Clinics

Neetu Radhakrishnan, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Eric J Hanly, MD, Ozanan R Meireles, MD, Michael R Marohn, DO, Charles J Yeo, MD, Keith D Lillemoe, MD, and Lisa H McGrail, MD, are gratefully acknowledged for their contributions to this topic.

Neoplasms of the Endocrine Pancreas

Research & References of Neoplasms of the Endocrine Pancreas|A&C Accounting And Tax Services
Source