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Surgery Today

, 41:1332 | Cite as

Surgical management of pancreatic neuroendocrine tumors

  • Wataru Kimura
  • Koji Tezuka
  • Ichiro Hirai
Review Article

Abstract

This study outlines the surgical management and clinicopathological findings of pancreatic neuroendocrine tumors (P-NETs). There are various surgical options, such as enucleation of the tumor, spleen-preserving distal pancreatectomy, distal pancreatectomy with splenectomy, pancreatoduodenectomy, and duodenum-preserving pancreas head resection. Lymph node dissection is performed for malignant cases. New guidelines and classifications have been proposed and are now being used in clinical practice. However, there are still no clear indications for organ-preserving pancreatic resection or lymph node dissection. Hepatectomy is the first choice for liver metastases of well-differentiated neuroendocrine carcinoma without extrahepatic metastases. On the other hand, cisplatin-based combination therapy is performed as first-line chemotherapy for metastatic poorly differentiated neuroendocrine carcinoma. Other treatment options are radiofrequency ablation, transarterial chemoembolization/embolization, and liver transplantation. Systematic chemotherapy and biotherapy, such as that with somatostatin analogue and interferon-α, are used for recurrence after surgery. The precise surgical techniques for enucleation of the tumor and spleen-preserving distal pancreatectomy are described.

Key words

Neuroendocrine tumor Enucleation Spleen-preserving pancreatectomy Surveillance 

References

  1. 1.
    Eriksson B, Oberg K. Neuroendocrine tumours of the pancreas. Br J Surg 2000;87:129–131.PubMedCrossRefGoogle Scholar
  2. 2.
    Lam KY, Lo CY. Pancreatic endocrine tumour: a 22-year clinicopathological experience with morphological, immunohistochemi cal observation and a review of the literature. Eur J Surg Oncol 1997;23:36–42.PubMedGoogle Scholar
  3. 3.
    Moldow RE, Connelly RR. Epidemiology of pancreatic cancer in Connecticut. Gastroenterology 1968;55:677–686.PubMedGoogle Scholar
  4. 4.
    Ito T, Sasano H, Tanaka M, Osamura RY, Sasaki I, Kimura W, et al. Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan. J Gastroenterol 2010;45:234–243.PubMedCrossRefGoogle Scholar
  5. 5.
    Halfdanarson TR, Rubin J, Farnell MB, Grant CS, Petersen GM. Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors. Endocr Relat Cancer 2008;15:409–427.PubMedCrossRefGoogle Scholar
  6. 6.
    Frantz VK. Islet cell tumors. In: Frantz VK, editor. Tumor of the pancreas. Washington DC: AFIP; 1959. p. 79–141.Google Scholar
  7. 7.
    Friesen SR, Tomita T. The APUD concept of islet cell tumors. In: Howard JM, editor. Surgical disease of the pancreas. Philadelphia: Lea & Febiger; 1987. p. 803–813.Google Scholar
  8. 8.
    Kimura W, Kuroda A, Morioka Y. Clinical pathology of endocrine tumors of the pancreas. Analysis of autopsy cases. Dig Dis Sci 1991;36:933–942.PubMedCrossRefGoogle Scholar
  9. 9.
    Heitz PU, Komminoth P, Perren A, Klimstra DS, Dayal Y. Tumors of the endocrine pancreas. In: De Lellis RA, Lloyd RV, Heitz PU, Eng C, editors. World Health Organization classification of tumours: pathology and genetics of tumours of endocrine organs. 1st ed. Lyon: IARC Press; 2004. p. 177–182.Google Scholar
  10. 10.
    Rha SE, Jung SE, Lee KH, Ku YM, Byun JY, Lee JM. CT and MR imaging findings of endocrine tumor of the pancreas according to WHO classification. Eur J Radiol 2007;62:371–377.PubMedCrossRefGoogle Scholar
  11. 11.
    Ballarin R, Masetti M, Losi L, Di Benedetto F, Di Sandro S, De Ruvo N, et al. Cystic pancreatic neuroendocrine neoplasms with uncertain malignant potential: report of two cases. Surg Today 2009;39:162–167.PubMedCrossRefGoogle Scholar
  12. 12.
    Klöppel G, Couvelard A, Perren A, Komminoth P, McNicol AM, Nilsson O, et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: towards a standardized approach to the diagnosis of gastroenteropancreatic neuroendocrine tumors and their prognostic stratification. Neuroendocrinology 2009;90:162–166.PubMedCrossRefGoogle Scholar
  13. 13.
    Rindi G, Klöppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2006;449:395–401.PubMedCrossRefGoogle Scholar
  14. 14.
    Sobin LH, Gospodarowicz MK, Wittekind C (editors). International Union Against Cancer (UICC): TNM classification of malignant tumors. 7th ed. Oxford: Wiley-Blackwell; 2009.Google Scholar
  15. 15.
    Bilimoria KY, Bentrem DJ, Merkow RP, Tomlinson JS, Stewart AK, Ko CY, et al. Application of the pancreatic adenocarcinoma staging system to pancreatic neuroendocrine tumors. J Am Coll Surg 2007;205:558–563.PubMedCrossRefGoogle Scholar
  16. 16.
    La Rosa S, Klersy C, Uccella S, Dainese L, Albarello L, Sonzogni A, et al. Improved histologic and clinicopathologic criteria for prognostic evaluation of pancreatic endocrine tumors. Hum Pathol 2009;40:30–40.PubMedCrossRefGoogle Scholar
  17. 17.
    Pape UF, Jann H, Müller-Nordhorn J, Bockelbrink A, Berndt U, Willich SN, et al. Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer 2008;113:256–265.PubMedCrossRefGoogle Scholar
  18. 18.
    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;14:7798–7803.PubMedCrossRefGoogle Scholar
  19. 19.
    Fischer L, Kleeff J, Esposito I, Hinz U, Zimmermann A, Friess H, et al. Clinical outcome and long-term survival in 118 consecutive patients with neuroendocrine tumours of the pancreas. Br J Surg 2008;95:627–635.PubMedCrossRefGoogle Scholar
  20. 20.
    Scarpa A, Mantovani W, Capelli P, Beghelli S, Boninsegna L, Bettini R, et al. Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients. Mod Pathol 2010;23:824–833.PubMedCrossRefGoogle Scholar
  21. 21.
    Ferrone CR, Tang LH, Tomlinson J, Gonen M, Hochwald SN, Brennan MF, et al. Determining prognosis in patients with pancreatic endocrine neoplasms: can the WHO classification system be simplified? J Clin Oncol 2007;25:5609–5615.PubMedCrossRefGoogle Scholar
  22. 22.
    Franko J, Feng W, Yip L, Genovese E, Moser AJ. Non-functional neuroendocrine carcinoma of the pancreas: incidence, tumor biology, and outcomes in 2,158 patients. J Gastrointest Surg 2010;14:541–548.PubMedCrossRefGoogle Scholar
  23. 23.
    Bilimoria KY, Tomlinson JS, Merkow RP, Stewart AK, Ko CY, Talamonti MS, et al. Clinicopathologic features and treatment trends of pancreatic neuroendocrine tumors: analysis of 9,821 patients. J Gastrointest Surg 2007;11:1460–1469.PubMedCrossRefGoogle Scholar
  24. 24.
    Kimura W. Therapeutic surgical strategies for neuroendocrine tumors of pancreas (in Japanese). Suizo (Jpn J Pancr Soc) 2008;23:703–709.CrossRefGoogle Scholar
  25. 25.
    Triponez F, Dosseh D, Goudet P, Cougard P, Bauters C, Murat A, et al. Epidemiology data on 108 MEN1 patients from the GTE with isolated nonfunctioning tumors of the pancreas. Ann Surg 2006;243:265–272.PubMedCrossRefGoogle Scholar
  26. 26.
    Fendrich V, Waldmann J, Bartsch DK, Langer P. Surgical management of pancreatic endocrine tumors. Nat Rev Clin Oncol 2009;6:419–428.PubMedCrossRefGoogle Scholar
  27. 27.
    Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol 2005;19:753–781.PubMedCrossRefGoogle Scholar
  28. 28.
    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;242:757–766.PubMedCrossRefGoogle Scholar
  29. 29.
    Hellman P, Hennings J, Akerström G, Skogseid B. Endoscopic ultrasonography for evaluation of pancreatic tumours in multiple endocrine neoplasia type 1. Br J Surg 2005;92:1508–1512.PubMedCrossRefGoogle Scholar
  30. 30.
    Triponez F, Dosseh D, Goudet P, Cougard P, Bauters C, Murat A, et al. Epidemiology data on 108 MEN1 patients from the GTE with isolated nonfunctioning tumors of the pancreas. Ann Surg 2006;243:265–272.PubMedCrossRefGoogle Scholar
  31. 31.
    Dralle H, Krohn SL, Karges W, Boehm BO, Brauckhoff M, Gimm O. Surgery of resectable nonfunctioning neuroendocrine pancreatic tumors. World J Surg 2004;28:1248–1260.PubMedCrossRefGoogle Scholar
  32. 32.
    Figueiredo FA, Giovannini M, Monges G, Bories E, Pesenti C, Caillol F, et al. EUS-FNA predicts 5-year survival in pancreatic endocrine tumors. Gastrointest Endosc 2009;70:907–914.PubMedCrossRefGoogle Scholar
  33. 33.
    Chatzipantelis P, Konstantinou P, Kaklamanos M, Apostolou G, Salla C. The role of cytomorphology and proliferative activity in predicting biologic behavior of pancreatic neuroendocrine tumors: a study by endoscopic ultrasound-guided fine-needle aspiration cytology. Cancer Cytopathol 2009;117:211–216.CrossRefGoogle Scholar
  34. 34.
    Falconi M, Plockinger U, Kwekkeboom DJ, Manfredi R, Korner M, Kvols L, et al; Frascati Consensus Conference; European Neuroendocrine Tumor Society. Well-differentiated pancreatic nonfunctioning tumors/carcinoma. Neuroendocrinology 2006;84:196–211.PubMedCrossRefGoogle Scholar
  35. 35.
    Kulke MH, Anthony LB, Bushnell DL, de Herder WW, Goldsmith SJ, Klimstra DS, et al. NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas 2010;39:735–752.PubMedCrossRefGoogle Scholar
  36. 36.
    Zerbi A, Falconi M, Rindi G, Delle Fave G, Tomassetti P, Pasquali C, et al; AISP-Network Study Group. Clinicopathological features of pancreatic endocrine tumors: a prospective multicenter study in Italy of 297 sporadic cases. Am J Gastroenterol 2010;105:1421–1429.PubMedCrossRefGoogle Scholar
  37. 37.
    Crippa S, Bassi C, Salvia R, Falconi M, Butturini G, Pederzoli P. Enucleation of pancreatic neoplasms. Br J Surg 2007;94:1254–1259.PubMedCrossRefGoogle Scholar
  38. 38.
    Crippa S, Bassi C, Warshaw AL, Falconi M, Partelli S, Thayer SP, et al. Middle pancreatectomy: indications, short- and long-term operative outcomes. Ann Surg 2007;246:69–76.PubMedCrossRefGoogle Scholar
  39. 39.
    Falconi M, Zerbi A, Crippa S, Balzano G, Boninsegna L, Capitanio V, et al. Parenchyma-preserving resections for small nonfunctioning pancreatic endocrine tumors. Ann Surg Oncol 2010;17:1621–1627.PubMedCrossRefGoogle Scholar
  40. 40.
    Pitt SC, Pitt HA, Baker MS, Christians K, Touzios JG, Kiely JM, et al. Small pancreatic and periampullary neuroendocrine tumors: resect or enucleate? J Gastrointest Surg 2009;13:1692–1698.PubMedCrossRefGoogle Scholar
  41. 41.
    Kimura W, Yano M, Sugawara S, Okazaki S, Sato T, Moriya T, et al. Spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein: techniques and its significance. J Hepatobiliary Pancreat Sci 2010;17:813–823.PubMedCrossRefGoogle Scholar
  42. 42.
    Fernández-Cruz L, Blanco L, Cosa R, Rendón H. Is laparoscopic resection adequate in patients with neuroendocrine pancreatic tumors? World J Surg 2008;32:904–917.PubMedCrossRefGoogle Scholar
  43. 43.
    Schindl M, Kaczirek K, Kaserer K, Niederle B. Is the new classification of neuroendocrine pancreatic tumors of clinical help? World J Surg 2000;24:1312–1318.PubMedCrossRefGoogle Scholar
  44. 44.
    Klöppel G, Perren A, Heitz PU. The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann N Y Acad Sci 2004;1014:13–27.PubMedCrossRefGoogle Scholar
  45. 45.
    Casadei R, Ricci C, Rega D, D’Ambra M, Pezzilli R, Tomassetti P, et al. Pancreatic endocrine tumors less than 4 cm in diameter: resect or enucleate? A single-center experience. Pancreas 2010;39:825–828.PubMedCrossRefGoogle Scholar
  46. 46.
    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;19:903–908.PubMedCrossRefGoogle Scholar
  47. 47.
    Casadei R, Ricci C, Pezzilli R, Campana D, Tomassetti P, Calculli L, et al. Value of both WHO and TNM classification systems for patients with pancreatic endocrine tumors: results of a single-center series. World J Surg 2009;33:2458–2463.PubMedCrossRefGoogle Scholar
  48. 48.
    Schurr PG, Strate T, Rese K, Kaifi JT, Reichelt U, Petri S, et al. Aggressive surgery improves long-term survival in neuroendocrine pancreatic tumors: an institutional experience. Ann Surg 2007;245:273–281.PubMedCrossRefGoogle Scholar
  49. 49.
    Schmitt AM, Anlauf M, Rousson V, Schmid S, Kofler A, Riniker F, et al. WHO 2004 criteria and CK19 are reliable prognostic markers in pancreatic endocrine tumors. Am J Surg Pathol 2007;31:1677–1682.PubMedCrossRefGoogle Scholar
  50. 50.
    Casadei R, Ricci C, Pezzilli R, Campana D, Tomassetti P, Calculli L, et al. Are there prognostic factors related to recurrence in pancreatic endocrine tumors? Pancreatology 2010;10:33–38.PubMedCrossRefGoogle Scholar
  51. 51.
    Gullo L, Migliori M, Falconi M, Pederzoli P, Bettini R, Casadei R, et al. Nonfunctioning pancreatic endocrine tumors: a multicenter clinical study. Am J Gastroenterol 2003;98:2435–2439.PubMedCrossRefGoogle Scholar
  52. 52.
    Deshpande V, Fernandez-del Castillo C, Muzikansky A, Deshpande A, Zukerberg L, Warshaw AL, et al. Cytokeratin 19 is a powerful predictor of survival in pancreatic endocrine tumors. Am J Surg Pathol 2004;28:1145–1153.PubMedCrossRefGoogle Scholar
  53. 53.
    Bilimoria KY, Talamonti MS, Tomlinson JS, Stewart AK, Winchester DP, Ko CY, et al. Prognostic score predicting survival after resection of pancreatic neuroendocrine tumors: analysis of 3851 patients. Ann Surg 2008;247:490–500.PubMedCrossRefGoogle Scholar
  54. 54.
    Nikfarjam M, Warshaw AL, Axelrod L, Deshpande V, Thayer SP, Ferrone CR, et al. Improved contemporary surgical management of insulinomas: a 25-year experience at the Massachusetts General Hospital. Ann Surg 2008;247:165–172.PubMedCrossRefGoogle Scholar
  55. 55.
    Zhang L, Smyrk TC, Oliveira AM, Lohse CM, Zhang S, Johnson MR, et al. KIT is an independent prognostic marker for pancreatic endocrine tumors: a finding derived from analysis of islet cell differentiation markers. Am J Surg Pathol 2009;33:1562–1569.PubMedCrossRefGoogle Scholar
  56. 56.
    Solorzano CC, Lee JE, Pisters PW, Vauthey JN, Ayers GD, Jean ME, et al. Nonfunctioning islet cell carcinoma of the pancreas: survival results in a contemporary series of 163 patients. Surgery 2001;130:1078–1085.PubMedCrossRefGoogle Scholar
  57. 57.
    Hung JS, Chang MC, Lee PH, Tien YW. Is surgery indicated for patients with symptomatic nonfunctioning pancreatic neuroendocrine tumor and unresectable hepatic metastases? World J Surg 2007;31:2392–2397.PubMedCrossRefGoogle Scholar
  58. 58.
    Bettini R, Mantovani W, Boninsegna L, Crippa S, Capelli P, Bassi C, et al. Primary tumour resection in metastatic nonfunctioning pancreatic endocrine carcinomas. Dig Liver Dis 2009;41:49–55.PubMedCrossRefGoogle Scholar
  59. 59.
    Bloomston M, Muscarella P, Shah MH, Frankel WL, Al-Saif O, Martin EW, et al. Cytoreduction results in high perioperative mortality and decreased survival in patients undergoing pancreatectomy for neuroendocrine tumors of the pancreas. J Gastrointest Surg 2006;10:1361–1370.PubMedCrossRefGoogle Scholar
  60. 60.
    Touzios JG, Kiely JM, Pitt SC, Rilling WS, Quebbeman EJ, Wilson SD, et al. Neuroendocrine hepatic metastases: does aggressive management improve survival? Ann Surg 2005;241:776–785.PubMedCrossRefGoogle Scholar
  61. 61.
    Norton JA, Warren RS, Kelly MG, Zuraek MB, Jensen RT. Aggressive surgery for metastatic liver neuroendocrine tumors. Surgery 2003;134:1057–1065.PubMedCrossRefGoogle Scholar
  62. 62.
    Elias D, Lasser P, Ducreux M, Duvillard P, Ouellet JF, Dromain C, et al. Liver resection (and associated extrahepatic resections) for metastatic well-differentiated endocrine tumors: a 15-year single center prospective study. Surgery 2003;133:375–382.PubMedCrossRefGoogle Scholar
  63. 63.
    Steinmüller T, Kianmanesh R, Falconi M, Scarpa A, Taal B, Kwekkeboom DJ, et al. Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 2008;87:47–62.PubMedCrossRefGoogle Scholar
  64. 64.
    Kimura W, Futakawa N, Muto T. The management of pancreatic neuroendocrine tumor (in Japanese). Kurinika (Clinica) 1996;23:483–491.Google Scholar
  65. 65.
    Eriksson B, Arnberg H, Lindgren PG, Lörelius LE, Magnusson A, Lundqvist G, et al. Neuroendocrine pancreatic tumours: clinical presentation, biochemical and histopathological findings in 84 patients. J Intern Med 1990;228:103–113.PubMedCrossRefGoogle Scholar
  66. 66.
    McEntee GP, Nagorney DM, Kvols LK, Moertel CG, Grant CS. Cytoreductive hepatic surgery for neuroendocrine tumors. Surgery 1990;108:1091–1096.PubMedGoogle Scholar
  67. 67.
    Modlin IM, Lewis JJ, Ahlman H, Bilchik AJ, Kumar RR. Management of unresectable malignant endocrine tumors of the pancreas. Surg Gynecol Obstet 1993;176:507–518.PubMedGoogle Scholar
  68. 68.
    Wessels FJ, Schell SR. Radiofrequency ablation treatment of refractory carcinoid hepatic metastases. J Surg Res 2001;95:8–12.PubMedCrossRefGoogle Scholar
  69. 69.
    Ardengh JC, Rosenbaum P, Ganc AJ, Goldenberg A, Lobo EJ, Malheiros CA, et al. Role of EUS in the preoperative localization of insulinomas compared with spiral CT. Gastrointest Endosc 2000;51:552–555.PubMedCrossRefGoogle Scholar
  70. 70.
    Gouya H, Vignaux O, Augui J, Dousset B, Palazzo L, Louvel A, et al. CT, endoscopic sonography, and a combined protocol for preoperative evaluation of pancreatic insulinomas. AJR Am J Roentgenol 2003;181:987–992.PubMedGoogle Scholar
  71. 71.
    McLean AM, Fairclough PD. Endoscopic ultrasound in the localisation of pancreatic islet cell tumours. Best Pract Res Clin Endocrinol Metab 2005;19:177–193.PubMedCrossRefGoogle Scholar
  72. 72.
    Nawata S, Sakurai F, Hirai I, Nawata S, Kimura W. Surgical management of insulinoma. Special reference to the enucleation procedure for insulinoma located in the head of the pancreas (in Japanese). Suizo (Jpn J Pancr Soc) 2002;17:114–119.Google Scholar
  73. 73.
    Kimura W. Surgical anatomy of the pancreas for limited resection. J Hepato-Biliary-Pancreatic Surg 2000;7:473–479.CrossRefGoogle Scholar
  74. 74.
    Pimpl W, Dapunt O, Kaindl H, Thalhamer J. Incidence of septic and thromboembolic-related deaths after splenectomy in adults. Br J Surg 1989;76:517–521.PubMedCrossRefGoogle Scholar
  75. 75.
    Bonderman D, Jakowitsch J, Adlbrecht C, Schemper M, Kyrle PA, Schönauer V, et al. Medical conditions increasing the risk of chronic thromboembolic pulmonary hypertension. Thromb Haemost 2005;93:512–516.PubMedGoogle Scholar
  76. 76.
    Waghorn DJ. Overwhelming infection in asplenic patients: current best practice preventive measures are not being followed. J Clin Pathol 2001;54:214–218.PubMedCrossRefGoogle Scholar
  77. 77.
    Kimura W, Inoue T, Futakawa N, Shinkai H, Han I, Muto T. Spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein. Surgery 1996;120:885–890.PubMedCrossRefGoogle Scholar
  78. 78.
    Fendrich V, Waldmann J, Bartsch DK, Schlosser K, Rothmund M, Gerdes B. Multiple primary malignancies in patients with sporadic pancreatic endocrine tumors. J Surg Oncol 2008;97:592–595.PubMedCrossRefGoogle Scholar
  79. 79.
    Oberg K, Janson ET, Eriksson B. Tumour markers in neuroendocrine tumours. Ital J Gastroenterol Hepatol 1999;31:160–162.Google Scholar
  80. 80.
    Lebtahi R, Cadiot G, Sarda L, Daou D, Faraggi M, Petegnief Y, et al. Clinical impact of somatostatin receptor scintigraphy in the management of patients with neuroendocrine gastroenteropancreatic tumors. J Nucl Med 1997;38:853–858.PubMedGoogle Scholar
  81. 81.
    Chiti A, Fanti S, Savelli G, Romeo A, Bellanova B, Rodari M, et al. Comparison of somatostatin receptor imaging, computed tomography and ultrasound in the clinical management of neuroendocrine gastro-entero-pancreatic tumours. Eur J Nucl Med 1998;25:1396–1403.PubMedCrossRefGoogle Scholar
  82. 82.
    Arnold R, Chen YJ, Costa F, Falconi M, Gross D, Grossman AB, et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: follow-up and documentation. Neuroendocrinology 2009;90:227–233.PubMedCrossRefGoogle Scholar
  83. 83.
    Arnold R, Wilke A, Rinke A, Mayer C, Kann PH, Klose KJ, et al. Plasma chromogranin A as marker for survival in patients with metastatic endocrine gastroenteropancreatic tumors. Clin Gastroenterol Hepatol 2008;6:820–827.PubMedCrossRefGoogle Scholar
  84. 84.
    Nikou GC, Marinou K, Thomakos P, Papageorgiou D, Sanzanidis V, Nikolaou P, et al. Chromogranin A levels in diagnosis, treatment and follow-up of 42 patients with non-functioning pancreatic endocrine tumours. Pancreatology 2008;8:510–519.PubMedCrossRefGoogle Scholar
  85. 85.
    Bajetta E, Ferrari L, Martinetti A, Celio L, Procopio G, Artale S, et al. Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors. Cancer 1999;86:858–865.PubMedCrossRefGoogle Scholar
  86. 86.
    Schillaci O, Spanu A, Scopinaro F, Falchi A, Danieli R, Marongiu P, et al. Somatostatin receptor scintigraphy in liver metastasis detection from gastroenteropancreatic neuroendocrine tumors. J Nucl Med 2003;44:359–368.PubMedGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  • Wataru Kimura
    • 1
  • Koji Tezuka
    • 1
  • Ichiro Hirai
    • 1
  1. 1.First Department of SurgeryYamagata University School of MedicineYamagataJapan

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