Advertisement

World Journal of Surgery

, Volume 16, Issue 4, pp 611–618 | Cite as

Pancreatic tumors in multiple endocrine neoplasia type 1: Clinical presentation and surgical treatment

  • D. Grama
  • B. Skogseid
  • E. Wilander
  • B. Eriksson
  • H. Mårtensson
  • B. Cedermark
  • B. Ahrén
  • A. Kristofferson
  • K. Öberg
  • J. Rastad
  • G. Åkerström
Article

Abstract

Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-erm outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors. This strategy should be applied especially in patients with aggressive family histories to possibly reduce the risk of malignant tumor progression.

Keywords

Pancreatic Polypeptide Endocrine Pancreatic Tumor Hyperinsulinism Patient Atteints Tumor Enucleation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Résumé

Parmi 33 patients ayant une tumeur pancréatique endocrine due à une néoplasie endocrine multiple de type 1 (MEN-1), 19 (58%) avaient une hypergastrinémie, 7 (21%) un hyperinsulinisme et 7 (21%) une lésion cliniquement muette. On a mis en évidence au minimum une grosse tumeur chez tous les patients, y compris chez ceux dont les examens préopératoires de dépistage tumoral étaient négatifs. Les patients étaient également porteurs de tumeurs macroscopiques et de nombreux microadénomes. Les lésions montraient souvent un immunomarquage positif pour de multiples hormones, principalement le polypeptide pancréatique, l'insuline, le glucagon et la somatostatine. Des lésions endocrines duodénales furent retrouvées chez 4 des 5 patients explorés; elles montraient un immunomarquage avec les anticorps angigastrine et anti-somatostatine. Une résection pancréatique distale, le plus souvent subtotale, a été réalisée chez 18 patients. Elle était éventuellement complétée par une énucléation tmorale de la tête ou par une duodénotomie. Peu de patients ont bénéficié d'une simple énucléation ou d'une intervention de Whipple. L'évolution postopératoire à long terme a été plus favorable en cas d'insulinome puisque seul un patient a eu une récidive clinique. Les patients atteints de gastrinome n'ont présenté que transitoirement une diminution des taux sériques de gastrine après la chirurgie pancréatique. Quarante sept pour cent de ces patients avaient ou ont développé des métastases contre 57% des patients porteurs de lésions sans traduction clinique. Neuf patients sont décédés en raison de l'extension tumorale au cours du suivi. Conformément à des suggestions antérieures, la chirurgie semble indiquée chez les patients atteints de MEN-1 avec hyperinsulinisme même si la radiologie ne visualise pas de lésion. Mais cette indication peut être élargie aux patients dont seuls les paramètres biologiques sont en faveur d'une grosse tumeur (dont l'hypergastrinémie). Cette stratégie pourrait convenir particulièrement aux patients ayant des antécédents familiaux importants; elle permettrait peut-être de réduire le risque d'extension tumorale.

Resumen

Entre 33 individuos con tumores pancréaticos endocrinos como componente del síndrome de neoplasia endocrina múltiple tipo 1 (NEM-1), 19 pacientes (58%) tenían hipergastrinemia, 7 (21%) hiperinsulinismo y 7 (21%) lesiones clínicas “no funcionantes”. En la totalidad de los pacientes sometidos a cirugía pancreática fue hallado por lo menos un tumor, incluso en aquellos con examenes de localización negativos anteriores a la operación. Estos pacientes también albergaban tumores macroscópicos, así como numerosos microadenomas; con frecuencia las lesiones demostraron inmunocoloración con diferentes hormonas, principalmente polipéptido, insulina, glucagón y somatostatina. Se encontraron lesiones endocrinas duodenales en 4 de cada 5 pacientes investigados, las cuales colorearon con gastrina y anticuerpos a la somatostatina. Se practicó resección pancreática distal (principalmente resección subtotal) en 18 pacientes, eventualmente combinada con enucleación del tumor (cuando éste se hallaba ubicado en la cabeza del páncreas) o duodenectomía; solamente unos pocos pacientes fueron sometidos a simple enucleación del tumor o al procedimiento de Whipple. El resultado a largo plazo fue más favorable en los pacientes con hiperinsulinismo, puesto que sólo uno presentó recurrencia clínica. Los pacientes con hipergastrinemia exhibieron apenas una disminución transitoria de los valores de gastrina sérica luego de la cirugía pancreática. Cuarenta y siete por ciento del conjunto tuvo o desarrolló metástasis, en tanto que la extensión local del tumor se presentó en 57% de los casos con lesiones no funcionantes. Nueve pacientes murieron por progresión de la neoplasia en el curso del seguimiento. En acuerdo con sugerencias previas, se considero quo la cirugía está indicada en pacientes con NEM-1 e hiperinsulinismo, aún en los casos en que no se visualiza radiológicamente la lesión, pero que la indicación puede ser ampliada para incluir también pacientes con sólo marcadores bioquímicos, tales como niveles elevados de gastrina, indicativos de la presencia de tumores macroscópicos. Esta estrategia debe ser aplicada principalmente en aquellos pacientes con historia familiar agresiva, con lo cual tal vez se reduce el riesgo de progesión maligna del tumor.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ballard, H.S., Frame, B., Hartsock, R.J.: Familial multiple endocrine adenoma-peptic ulcer complex. Medicine (Baltimore)43:481, 1964Google Scholar
  2. 2.
    Marx, S.J., Spiegel, A.M., Brown, E.M., Aurbach, G.D.: Family studies in patients with primary parathyroid hyperplasia. Am. J. Med.62:698, 1977PubMedGoogle Scholar
  3. 3.
    Friesen, S.R., Kimmel, J.R., Tomita, T.: Pancreatic polypeptide as screening marker for pancreatic polypeptide apudomas in multiple endocrinopathies. Am. J. Surg.139:61, 1980PubMedGoogle Scholar
  4. 4.
    Skogseid, B., Öberg, K., Benson, L., Lindgren, P.G., Lörelius, L.-E., Lundqvist, G., Wide, L., Wilander, E.: A standardized meal stimulation test of the endocrine pancreas for early detection of pancreatic endocrine neoplasia type 1 syndrome: Five years' experience. J. Clin. Endocrinol. Metab.64:1233, 1987PubMedGoogle Scholar
  5. 5.
    Thompson, N.W., Lloyd, R.V., Nishiyama, R.H., Vinik, A.I., Strodel, W.E., Allo, M.D., Bekhauser, F.E., Talpos, G., Mervak, T.: MEN 1 pancreas: A histological and immunohistochemical study. World J. Surg.8:561, 1984PubMedGoogle Scholar
  6. 6.
    Klöppel, G., Willemer, S., Stamm, B., Häcki, W.H., Heitz, P.U.: Pancreatic lesions and hormonal profile of pancreatic tumors in multiple endocrine neoplasia type 1: An immunocytochemical study in nine patients. Cancer57:1824, 1986PubMedGoogle Scholar
  7. 7.
    Pipelleers-Marichal, M., Somers, G., Willems, G., Foulis, A., Imrie, C., Bishop, A.E., Polak, J.M., Häcki, W.H., Stamm, B., Heitz, P.U., Path, F.R.C., Klöppel, G.: Gastrinomas in the duodenum of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome. N. Engl. J. Med.322:723, 1990PubMedGoogle Scholar
  8. 8.
    van Heerden, J.A., Smith, S.L., Miller, L.J.: Management of the Zollinger-Ellison syndrome in patients with multiple endocrine neoplasia type 1. Surgery100:971, 1986PubMedGoogle Scholar
  9. 9.
    Fraker, D.L., Norton, J.A.: The role of surgery in the management of islet cell tumors. Gastroenterol. Clin. North Am.18:805, 1989PubMedGoogle Scholar
  10. 10.
    Friesen, S.R.: Treatment of the Zollinger-Ellison syndrome: A 25-year assessment. Am. J. Surg.142:331, 1982Google Scholar
  11. 11.
    Gogel, H.K., Buchman, M.T., Cadieux, D., McCarthy, D.M.: Gastric secretion and hormonal interactions in multiple endocrine neoplasia type 1. Arch. Intern. Med.145:855, 1985PubMedGoogle Scholar
  12. 12.
    Eriksson, B.: Recent advances in the diagnosis and management of endocrine pancreatic tumors (Dissertation, Comprehensive summaries). Acta Univ. Upsalla160:7, 1988Google Scholar
  13. 13.
    Skogseid, B., Eriksson, B., Lundqvist, G., Lörelius, L.-E., Rastad, J., Wide, L., Wilander, E., Åkerström, G., Öberg, K.: Multiple endocrine neoplasia type 1: A ten-year prospective screening study in four kindreds. J. Clin. Endocrinol. Metab.73:281, 1991PubMedGoogle Scholar
  14. 14.
    Grama, D., Eriksson, B., Mårtensson, H., Cedermark, B., Ahrén, B., Kristoffersson, A., Rastad, J., Öberg, K., Åkerström, G.: Clinical characteristics, treatment and survival of patients with pancreatic tumors causing hormonal syndromes. World J. Surg.16:632, 1992PubMedGoogle Scholar
  15. 15.
    Puchtler, H., Sweat, F., Levine, M.: On the binding of Congo red by amyloid. J. Histochem. Cytochem.10:355, 1982Google Scholar
  16. 16.
    Singh, I.: A modification of the Masson-Hamperi method for staining of argentaffin cells. Anat. Anz.115:81, 1964PubMedGoogle Scholar
  17. 17.
    Grimelius, L., Wilander, E.: Silver stains in the study of endocrine cell of the gut and pancreas. Invest. Cell Pathol.3:3, 1980PubMedGoogle Scholar
  18. 18.
    Eriksson, B., Arnberg, H., Öberg, K., Hellman, V., Lundquist, G., Wernstedt, C., Wilander, E.: A polyclonal antiserum against chromogranin A and B: A new sensitive marker for neuroendocrine tumours. Acta Endocrinol. (Copenh.)122:145, 1990Google Scholar
  19. 19.
    Knudson, A.G.: Mutation and cancer: Statistical study of retinoblastoma. Proc. Natl. Acad. Sci. U.S.A.68:820, 1971PubMedGoogle Scholar
  20. 20.
    Larsson, C., Skogseid, B., Öberg, K., Nakamura, Y., Nordensköld, M.: Multiple endocrine neoplasia gene maps to chromosome 11 and is lost in insulinoma. Nature332:85, 1988PubMedGoogle Scholar
  21. 21.
    Ellison, E.C., Carey, L.C., Sparks, J., O'Dorisio, T.M., Mekhjian, H.S., Fromkes, J.J., Caldwell, J.H., Thomas, F.B.: Early surgical treatment of gastrinomas. Am. J. Med.82:17 (Suppl. 5B), 1987Google Scholar
  22. 22.
    Sheppard, B.C., Norton, J.A., Doppman, J.L., Maton, P.N., Gardner, J.D., Jensen, R.T.: Management of islet cell tumors in patients with multiple endocrine neoplasia: A prospective study. Surgery106:1108, 1989PubMedGoogle Scholar
  23. 23.
    Vogelstein, B., Fearon, E.R., Hamilton, S.R., Kern, S.E., Preisinger, A.C., Leppert, M., Nakamura, Y., White, R., Smith, A.M.M., Bos, J.: Genetic alteration during colorectal tumor development. N. Engl. J. Med.319:525, 1988PubMedGoogle Scholar
  24. 24.
    Rutter, W.A.: The development of the endocrine and exocrine pancreas. In The Pancreas, P.J. Fitzgerald, A.B. editors, Baltimore, Williams and Wilkins, 1980, pp. 30–38Google Scholar
  25. 25.
    Rasbach, D.A., van Heerden, J.A., Telander, R.L., Grant, C.S., Carney, J.A.: Surgical management of hyperinsulinism in the multiple endocrine neoplasia, type 1 syndrome. Arch. Surg.120:584, 1985PubMedGoogle Scholar
  26. 26.
    Thompson, N.W., Bondeson, A.-G., Bondeson, L., Vinik, A.: The surgical treatment of gastrinoma in MEN I syndrome patients. Surgery106:1081, 1986Google Scholar
  27. 27.
    Gigot, J.F., Gianello, P., Dardanne, A.N., Pringot, J., Detry, R., Otte, J.B., Kestens, P.J.: Intraoperative ultrasonography in endocrine pancreatic surgery: Preliminary results in 6 cases of insulinoma. J. Belge Radiol.69:57, 1986PubMedGoogle Scholar
  28. 28.
    Grant, C.S., van Heerden, J.A., Charboneau, J.W., James, E.M., Reading, C.C.: Insulinoma: The value of intraoperative ultrasonography. Arch. Surg.123:843, 1988PubMedGoogle Scholar
  29. 29.
    Norton, J.A., Cromack, D.T., Shawker, T.H., Doppman, J.L., Comi, R., Gorden, P., Maton, P.N., Gardner, J.D., Jensen, R.T.: Intraoperative ultrasonographic localization of islet cell tumors: A prospective comparison to palpation. Ann. Surg.207:160, 1988PubMedGoogle Scholar
  30. 30.
    Skogseid, B., Grama, D., Ahlström, H., Andersson, T., Eriksson, B., Lindgren, P.-G., Rastad, J., Wilander, E., Åkerström, G., Öberg, K.: Pre- and intra-operative localization of pancreatic tumors in multiple endocrine neoplasia type 1. (Submitted)Google Scholar
  31. 31.
    Tisell, L.E., Ahlman, H., Jansson, S.: Total pancreatectomy in the MEN I syndrome. Br. J. Surg.75:154, 1988PubMedGoogle Scholar

Copyright information

© the Société Internationale de Chirurgie 1992

Authors and Affiliations

  • D. Grama
    • 1
    • 2
    • 3
  • B. Skogseid
    • 1
    • 2
    • 3
  • E. Wilander
    • 1
    • 2
    • 3
  • B. Eriksson
    • 1
    • 2
    • 3
  • H. Mårtensson
    • 1
    • 2
    • 3
  • B. Cedermark
    • 1
    • 2
    • 3
  • B. Ahrén
    • 1
    • 2
    • 3
  • A. Kristofferson
    • 1
    • 2
    • 3
  • K. Öberg
    • 1
    • 2
    • 3
  • J. Rastad
    • 1
    • 2
    • 3
  • G. Åkerström
    • 1
    • 2
    • 3
  1. 1.Departments of Surgery, Medicine, and PathologyUniversity HospitalUppsalaSweden
  2. 2.Department of Surgery at Helsingborg HospitalKarolinska HospitalStockholmSweden
  3. 3.University HospitalsLund, and UmeåSweden

Personalised recommendations