• 四川大學(xué)華西醫(yī)院腹部腫瘤科（成都，610041）;

胰腺神經(jīng)內(nèi)分泌腫瘤（PNET）是來源自胰腺多能神經(jīng)內(nèi)分泌干細(xì)胞的一種罕見的胰腺腫瘤，臨床表現(xiàn)復(fù)雜多樣，病程緩慢, 最終發(fā)生轉(zhuǎn)移致死。PNET分為功能性和非功能性，目前治療有手術(shù)、化學(xué)療法、放射治療、介入、生物治療以及分子靶向藥物治療，近年生物治療及分子靶向藥物治療在研究中顯示出了良好療效。根據(jù)國內(nèi)外文獻(xiàn)及最新臨床試驗研究進(jìn)展，現(xiàn)就PNET治療進(jìn)展進(jìn)行綜述。

引用本文： 何建萍,易成,李寧,畢鋒,許峰. 胰腺神經(jīng)內(nèi)分泌腫瘤的治療進(jìn)展. 華西醫(yī)學(xué), 2012, 27(11): 1754-1756. doi: 復(fù)制

1. 　Oberg K. Pancreatic endocrine tumors[J]. Semin Oncol, 2010, 37(6): 594-618.
2. 　Halfdanarson TR, Rubin J, Farnell MB, et al. Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors[J]. Endocr Relat Cancer, 2008, 15(2): 409-427 .
3. 　Key C. Cancer of the pancreas[M]// Ries LAG, Young JL, Keel GE, et al. SEER Survival Monograph Bethesda. MD: NIH Publishers, 2007: 59-65.
4. 　Irvin MM, Kjell O, Daniel CC, et al. Gastroenteropancreatic neuroendocrine tumors[J]. Lancet Oncol, 2008, 9(12): 61.
5. 　Ehehalt F, Saeger H, Schmidt C, et al. Neuroendocrine tumors of the pancreas[J]. Oncologist, 2009, 12: 456-467.
6. 　Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35 825 cases in the United States[J]. J Clin Oncol, 2008, 26(18): 3063-3072.
7. 　Halfdanarson TR, Rabe KG, Rubin J, et al. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival[J]. Ann Oncol, 2008, 19(5A): 1727-1733.
8. 　Sarmiento JM, Farnell MB, Que FG, et al. Pancreaticodu-odenectomy for islet cell tumors of head of the pancreas:Long-term survival analysis [J].World J Surg, 2002, 26(10): 1267-71.
9. 　Kouvaraki MA, Ajani JA, Hoff P, et al. Fluorouracil,doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas[J]. J Clin Oncol,2004，22(23): 4762.
10. 　John DH, David R, Litchy S，et al. PhaseⅡtrial of paclitaxel,carboplatin,and etoposide in advanced poorly differentiated neuroendocrine carcinoma: a minnie pearl cancer research network study [J]. J Clin Oncol,2006，24(22): 3548.
11. 　Kulke MH, Anthony LB，Bushnell DL et al. NANETS treatmentguidelines: well-differentiated neuroendocrine tumors of thestomach and pancreas[J]. Pancreas, 2010, 39(6): 735-752.
12. 　Boudreaux JP, Klimstra DS, Hassan MM, et al. The NANETSconsensus guideline for the diagnosis and management ofneuroendocrine tumors: well-differentiated neuroendocrine tumorsof the Jejunum, Ileum, Appendix, and Cecum[J]. Pancreas, 2010, 39(6): 753-766.
13. 　Strosberg JR, Coppola D, Klimstra DS, et al. The NANETS consensus guidelines for the diagnosis and management of poorly differentiated(high-grade）extrapulmonary neuroendocrine carcinomas[J]. Pancreas, 2010, 39(6): 799-800.
14. 　Eriksson B, Annibale B, Bajetta E, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors：chemotherapy in patients with neuroendocrine tumors[J]. Neuroendocrinology, 2009, 90(2): 214-219.
15. 　Chakmvarthy A, Abrams BA. Radiation therapy in the management of patients with malignant careinoid tumors[J]. Cancer, 1995, 75(6): 1386-1390．.
16. 　Kwekkeboom DJ, Teunissen JJ, Bakker WH, et a1. Radiolabeled matoetatin analog[177h-DOTA0, Tyr3]octreotate in patients with endocrine gastrcenterepancreatic tumors[J]. J Clin Oncol, 2005, 23 (12): 2754-2762．.
17. 　Anthony LB, Strosberg JR, Klimstra DS, et al. The NANETS consensus guidelines for the diagnosis and management of gastrointestinal neuroendocrine tumors(nets): well-differentiated nets of the distal colon and rectum[J]. Pancreas, 2010, 39(6): 767-774.
18. 　O’Toole D, Ruszniewski P. Chemoembolization and other ablative therapies for liver metastases of gastrointestinal endocrine tumours [J]. Best Pract Res Clin Gastroenterol,2005, 19(4): 585.
19. 　Kwekkeboom DJ, Krenning EP, Lebtahi R, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors：peptide receptor radionuclide therapy with radiolabeled somatostatin analogs[J]. Neuroendocrinology, 2009, 90(2): 220-226.
20. 　P10ckinger U, Wiedenmann B. Treatment of gastroenteropancreatic neurocndocrine tumors[J]. Virchows Arch, 2007, 451(Suppl 1): 71(10): 80．.
21. 　Fazlo N, de Brand F, Fave GD, et a1. Interferon and somatostatin analog in patients with gastreenteropancreatic neuronndocfine careino-№[J]. Ann Oncol, 2007, 18(1): 13-19．.
22. 　Falss S, Papa UF, Bohmig M, et a1. Prospective，randomized, multicenter trial on the antipmliferative effect of lameotide．interferon 8l·fa, and their combination for therapy of metastatic neureendocfine gastroenteropancreatie tumors-the International Lanreotide and Interferon Alfa Study Greup[J]. J Clin Oncol, 21(3): 2689-2696．.
23. 　Boudreaux JP, Klimstra DS, Hassan MM, et al. The NANETSconsensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumorsof the Jejunum, Ileum, Appendix, and Cecum[J]. Pancreas, 2010, 39(6): 753-766.
24. 　Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors[J]. N Engl J Med，2011, 364(6): 501-513.
25. 　Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors[J]. N Engl J Med，2011, 364(6): 514-523.
26. 　Kulke MH, Siu LL, Tepper JE, et al. Future directions in the treatment of neuroendocrine tumors: consensus report of the National Cancer Institute Neuroendocrine Tumor clinical trials planning meeting[J]. J Clin Oncol, 2011, 29(7): 934-943 .
27. 　Oberg KE. Gastrointestinal neuroendocrine tumors[J]. Ann Oncol，2010， 21 (Suppl 7): 72-80.
  1. 1. 　Oberg K. Pancreatic endocrine tumors[J]. Semin Oncol, 2010, 37(6): 594-618.
  2. 2. 　Halfdanarson TR, Rubin J, Farnell MB, et al. Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors[J]. Endocr Relat Cancer, 2008, 15(2): 409-427 .
  3. 3. 　Key C. Cancer of the pancreas[M]// Ries LAG, Young JL, Keel GE, et al. SEER Survival Monograph Bethesda. MD: NIH Publishers, 2007: 59-65.
  4. 4. 　Irvin MM, Kjell O, Daniel CC, et al. Gastroenteropancreatic neuroendocrine tumors[J]. Lancet Oncol, 2008, 9(12): 61.
  5. 5. 　Ehehalt F, Saeger H, Schmidt C, et al. Neuroendocrine tumors of the pancreas[J]. Oncologist, 2009, 12: 456-467.
  6. 6. 　Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35 825 cases in the United States[J]. J Clin Oncol, 2008, 26(18): 3063-3072.
  7. 7. 　Halfdanarson TR, Rabe KG, Rubin J, et al. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival[J]. Ann Oncol, 2008, 19(5A): 1727-1733.
  8. 8. 　Sarmiento JM, Farnell MB, Que FG, et al. Pancreaticodu-odenectomy for islet cell tumors of head of the pancreas:Long-term survival analysis [J].World J Surg, 2002, 26(10): 1267-71.
  9. 9. 　Kouvaraki MA, Ajani JA, Hoff P, et al. Fluorouracil,doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas[J]. J Clin Oncol,2004，22(23): 4762.
  10. 10. 　John DH, David R, Litchy S，et al. PhaseⅡtrial of paclitaxel,carboplatin,and etoposide in advanced poorly differentiated neuroendocrine carcinoma: a minnie pearl cancer research network study [J]. J Clin Oncol,2006，24(22): 3548.
  11. 11. 　Kulke MH, Anthony LB，Bushnell DL et al. NANETS treatmentguidelines: well-differentiated neuroendocrine tumors of thestomach and pancreas[J]. Pancreas, 2010, 39(6): 735-752.
  12. 12. 　Boudreaux JP, Klimstra DS, Hassan MM, et al. The NANETSconsensus guideline for the diagnosis and management ofneuroendocrine tumors: well-differentiated neuroendocrine tumorsof the Jejunum, Ileum, Appendix, and Cecum[J]. Pancreas, 2010, 39(6): 753-766.
  13. 13. 　Strosberg JR, Coppola D, Klimstra DS, et al. The NANETS consensus guidelines for the diagnosis and management of poorly differentiated(high-grade）extrapulmonary neuroendocrine carcinomas[J]. Pancreas, 2010, 39(6): 799-800.
  14. 14. 　Eriksson B, Annibale B, Bajetta E, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors：chemotherapy in patients with neuroendocrine tumors[J]. Neuroendocrinology, 2009, 90(2): 214-219.
  15. 15. 　Chakmvarthy A, Abrams BA. Radiation therapy in the management of patients with malignant careinoid tumors[J]. Cancer, 1995, 75(6): 1386-1390．.
  16. 16. 　Kwekkeboom DJ, Teunissen JJ, Bakker WH, et a1. Radiolabeled matoetatin analog[177h-DOTA0, Tyr3]octreotate in patients with endocrine gastrcenterepancreatic tumors[J]. J Clin Oncol, 2005, 23 (12): 2754-2762．.
  17. 17. 　Anthony LB, Strosberg JR, Klimstra DS, et al. The NANETS consensus guidelines for the diagnosis and management of gastrointestinal neuroendocrine tumors(nets): well-differentiated nets of the distal colon and rectum[J]. Pancreas, 2010, 39(6): 767-774.
  18. 18. 　O’Toole D, Ruszniewski P. Chemoembolization and other ablative therapies for liver metastases of gastrointestinal endocrine tumours [J]. Best Pract Res Clin Gastroenterol,2005, 19(4): 585.
  19. 19. 　Kwekkeboom DJ, Krenning EP, Lebtahi R, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors：peptide receptor radionuclide therapy with radiolabeled somatostatin analogs[J]. Neuroendocrinology, 2009, 90(2): 220-226.
  20. 20. 　P10ckinger U, Wiedenmann B. Treatment of gastroenteropancreatic neurocndocrine tumors[J]. Virchows Arch, 2007, 451(Suppl 1): 71(10): 80．.
  21. 21. 　Fazlo N, de Brand F, Fave GD, et a1. Interferon and somatostatin analog in patients with gastreenteropancreatic neuronndocfine careino-№[J]. Ann Oncol, 2007, 18(1): 13-19．.
  22. 22. 　Falss S, Papa UF, Bohmig M, et a1. Prospective，randomized, multicenter trial on the antipmliferative effect of lameotide．interferon 8l·fa, and their combination for therapy of metastatic neureendocfine gastroenteropancreatie tumors-the International Lanreotide and Interferon Alfa Study Greup[J]. J Clin Oncol, 21(3): 2689-2696．.
  23. 23. 　Boudreaux JP, Klimstra DS, Hassan MM, et al. The NANETSconsensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumorsof the Jejunum, Ileum, Appendix, and Cecum[J]. Pancreas, 2010, 39(6): 753-766.
  24. 24. 　Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors[J]. N Engl J Med，2011, 364(6): 501-513.
  25. 25. 　Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors[J]. N Engl J Med，2011, 364(6): 514-523.
  26. 26. 　Kulke MH, Siu LL, Tepper JE, et al. Future directions in the treatment of neuroendocrine tumors: consensus report of the National Cancer Institute Neuroendocrine Tumor clinical trials planning meeting[J]. J Clin Oncol, 2011, 29(7): 934-943 .
  27. 27. 　Oberg KE. Gastrointestinal neuroendocrine tumors[J]. Ann Oncol，2010， 21 (Suppl 7): 72-80.