Medical Oncology

, Volume 24, Issue 3, pp 330–337

Endocrine pancreatic tumors with glucagon hypersecretion: a retrospective study of 23 cases during 20 years

  • Henrik Kindmark
  • Anders Sundin
  • Dan Granberg
  • Kristina Dunder
  • Britt Skogseid
  • Eva Tiensuu Janson
  • Staffan Welin
  • Kjell Öberg
  • Barbro Eriksson
Original Paper

Abstract

Background

Glucagon-secreting endocrine pancreatic tumor is a rare disease, hence controlled studies on clinical management are lacking. In an attempt to assess the efficacy of diagnostic and therapeutic measures in patients with glucagonoma, a retrospective study was performed using the archives of a tertiary care center.

Patients and methods

Records from 340 patients with endocrine pancreatic tumors were reassessed and 23 patients with malignant endocrine pancreatic tumor and elevated plasma glucagon levels were identified.

Results

About 7% of patients with histologically verified tumors fullfilled our criteria for glucagonoma. Only 22% of these patients had developed diabetes prior to the diagnosis of glucagonoma. Seventy eight percent had metastatic disease to the liver at diagnosis. Necrolytic migratory erythema was diagnosed or clinically suspected in 52%. Somatostatin receptor scintigraphy was positive in 95%. Nineteen patients received chemotherapy at some point, in 18 cases streptozotocin and 5 FU. With this treatment, objective radiological responses were seen in 50% of evaluable patients. Other treatment modalities used were interferon, somatostatin analogs, hepatic artery embolization, radio-frequency ablation of liver metastases, and radiolabeled somatostatin analogs. During the study period, 11 patients died at a median of 80 months from diagnosis whereas 11 patients are still alive after a median follow up of 52 months. One patient was lost to follow-up.

Conclusions

Glucagonomas represent 7% of our comprehensive referal material of endocrine pancreatic tumors. Necrolytic migratory erythema was a common finding (52%) and diabetes less frequent at presentation than previously reported. Tumors were positive on somatostatin receptor scintigraphy and objective responses were seen to chemotherapy.

Keywords

Neuroendocrine tumor Somatostatin receptor scintigraphy Chemotherapy Survival CT 

References

  1. 1.
    Becker SW, Kahn D, Rothman S. Cutaneous manifestations of internal malignant tumors. Arch Dermatol Syphilol 1942;45:1069–80Google Scholar
  2. 2.
    McGavran MH, Unger RH, Recant L. A glucagon-secreting alpha-cell carcinoma of the pancreas. New Engl J Med 1966;274:1408–13PubMedCrossRefGoogle Scholar
  3. 3.
    Mallinson CN, Bloom SR, Warin AP, Salmon PR, Cox B. A glucagonoma syndrome. Lancet 1974;2:1–5PubMedCrossRefGoogle Scholar
  4. 4.
    Case CC, Vassilopoulou-Sellin R. Reproduction of features of the glucagonoma syndrome with continous intravenous glucagon infusion as therapy for tumor-induced hypoglycemia. Endocr Pract 2003;9(1):22–5PubMedGoogle Scholar
  5. 5.
    Vinik AI, Moattari AR. Treatment of endocrine tumors of the pancreas. Endocrinol Metab Clin North Am 1989;18:483–518PubMedGoogle Scholar
  6. 6.
    Öberg K, Eriksson B. Endocrine tumors of the panceras Best Prac Res Clin Gastroenterol 2005;19(5):753–81CrossRefGoogle Scholar
  7. 7.
    Eriksson B, Öberg K. An update of the medical treatment of malignant endocrine pancreatic tumors. Acta Oncol 1993;32(2):203–8PubMedGoogle Scholar
  8. 8.
    Arnold R, Rinke A, Schmidt C, Hofbauer L. Chemotherapy. Best Prac Res Clin Gastroenter 2005;19(4):649–56CrossRefGoogle Scholar
  9. 9.
    Eriksson B, et al. Treatment of malignant endocrine pancreatic tumors with human leucocyte interferon. Lancet 1986;2(8519):1307–9PubMedCrossRefGoogle Scholar
  10. 10.
    Rosenbaum A, Flourie B, Chagnon S, Blery M, Modigliani R. Octreotide (SMS 201–995) in the treatment of metastatic glucagonoma: report of a case and review of the literature. Digestion 1989;42:116–20PubMedGoogle Scholar
  11. 11.
    Eriksson B, et al. Liver Embolization of patients with malignant neuroendocrine gastrointestinal tumors. Cancer 1998;83:2293–301PubMedCrossRefGoogle Scholar
  12. 12.
    Therasse P, et al. New guidelindes to evaluate the response to treatment in solid tumors. J Nat Cancer Inst 2000;92:205–16PubMedCrossRefGoogle Scholar
  13. 13.
    Unger RH, Auillar-Parada E, Müller WA, Eisentraut AM. Study of pancreatic alpha cell function in normal and diabetic subjects. J Clin Invest 1970;49:837–48PubMedGoogle Scholar
  14. 14.
    Wermers RA, Fatourechi V, Wynne AG, Kvols LK, Lloyd RV. The glucagonoma syndrome. Clinical and pathologic features in 21 patients. Medicine (Baltimore) 1996;75(2):53–63CrossRefGoogle Scholar
  15. 15.
    Lewis AE. The glucagonoma syndrome. Int J Dermatol 1979;18:17–22PubMedGoogle Scholar
  16. 16.
    Mozell E, Stenzel P, Woltering EA, Rosch J, O’Dorisio TM. Functional endocrine tumors of the pancreas: Clinical presentation, diagnosis and treatment. Curr Prob Surg 1990;27:301–386CrossRefGoogle Scholar
  17. 17.
    Boden G. Insulinoma and glucagonoma. Semin Oncol 1987;14:253–62PubMedGoogle Scholar
  18. 18.
    Stacpoole PW. The glucagonoma syndrome: clinical features, diagnosis and treatment. Endocr Rev 1981;2:347–61PubMedCrossRefGoogle Scholar
  19. 19.
    Vauleon E, et al. Glucagonoma: a recent series of 7 cases. Bull Cancer, 2004;91(7–8):637–40Google Scholar
  20. 20.
    Krennning EP, Kwekkeboom DJ, Pauwels S, Kvols LK, Reubi JC. Somatostatin receptor scintigraphy In: Freeman LM, editor. Nuclear Medicine Annual. New York NY: Raven Press; 1995. p. 1–50Google Scholar
  21. 21.
    Eriksson B, et al. Medical treatment and long term survival in a prospective study of 84 patients with endocrine pancreatic tumors. Cancer 1990;65:1883–90PubMedCrossRefGoogle Scholar
  22. 22.
    Clarke MR, Baker EE, Weyant RJ, Hill L, Carty SE. Proliferative activity in pancreatic endocrine tumors: association with function, metastases and survival. Endocr Pathol 1997;8(3):181–7PubMedGoogle Scholar
  23. 23.
    Kwekkeboom DJ, et al. Radiolabeled somatostatin analog [177Lu-DOTA0, Tyr3] Octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol 2005;23(12):2754–62PubMedCrossRefGoogle Scholar
  24. 24.
    de Jong M, Breeman WA, Valkema R, Bernard BF, Krenning EP. Combination radionuclide therapy using 177Lu- and 90Y-labeled somatostatin analogs. J Nucl Med 2005;46(Suppl1):13S–7SPubMedGoogle Scholar
  25. 25.
    Welin SV, et al. High-dose treatment with a long-acting somatostatin analogue in patients with advanced midgut carcinoid tumours. Eur J Endocrinol 2004;151(1):107–12PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Henrik Kindmark
    • 1
  • Anders Sundin
    • 2
  • Dan Granberg
    • 1
  • Kristina Dunder
    • 1
  • Britt Skogseid
    • 1
  • Eva Tiensuu Janson
    • 1
  • Staffan Welin
    • 1
  • Kjell Öberg
    • 1
  • Barbro Eriksson
    • 1
  1. 1.Department of Medicine/Endocrine OncologyUniversity HospitalUppsalaSweden
  2. 2.Department of RadiologyUniversity HospitalUppsalaSweden

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