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Clinicopathological Features and Prognosis of Gastroenteropancreatic Neuroendocrine Tumors: Analysis from a Single-institution

  • Zeng, Yu-Jie (Department of Gastroenteropancreatic Surgery, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Liu, Lu (Department of Gastroenteropancreatic Surgery, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Wu, Heng (Department of Gastroenteropancreatic Surgery, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Lai, Wei (Department of Gastroenteropancreatic Surgery, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Cao, Jie-Zhi (Department of Second Surgery, Baiyun District Hospital of Traditional Chinese Medicine) ;
  • Xu, He-Yang (Department of Gastroenteropancreatic Surgery, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Wang, Jie (Department of Gastroenteropancreatic Surgery, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University) ;
  • Chu, Zhong-Hua (Department of Gastroenteropancreatic Surgery, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University)
  • Published : 2013.10.30

Abstract

Background: The gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine neoplasm. We summarized data in our centre to investigate the clinicopathological features, diagnostic methods, therapeutic approaches and prognosis for this neoplasm to increase knowledge of this disease in Asian populations. Method: A total of 122 patients treated at Sun Yet-san Memorial Hospital of Sun Yat-sen University between January 2000 and December 2011 were analyzed retrospectively. Results: Pancreas was the most common site of involvement (65/122, 53.3%); this disease has no special symptoms; positive rates of chromogranin A (CgA) and synaptophysin (Syn) were 81.1% and 87.7%, respectively. The positive rate of Syn had statistical difference among the three grades, but not CgA. Some 68 patients had G1 tumors, 32 G2 tumors and 22 G3 tumors, and Chi-square test showed that higher grading was correlated with worse prognosis (${\chi}^2=32.825$, P=0.0001). A total of 32 patients presented with distant metastasis, and 8 cases emerged during following up. Cox proportional hazards regression modeling showed that the tumor grade (P=0.01), lymphatic metastasis (P=0.025) and distant metastasis (P=0.031) were predictors of unfavorable prognosis. The overall 5-year survival rate was 39.6%, the 5-year survival rate of G1 was 55.7%, and the G2 and G3 were 34.2% and 0%, respectively. Conclusions: The incidence of gastroenteropancreatic neuroendocrine tumors has risen over the last 12 years. All grades of these diseases metastasize readily, and further research regarding the treatment of patients after radical surgery is needed to prolong disease-free survival.

Keywords

Gastroenteropancreatic neuroendocrine neoplasms;clinical characteristics;prognosis;treatment

References

  1. Bosman FT CFHR. 2010. WHO classification of tumours of the digestive system. 4th edition. Lyon: International Agency for Research on Cancer...
  2. Erickson LA, Lloyd RV (2004). Practical markers used in the diagnosis of endocrine tumors. Adv Anat Pathol, 11, 175-89. https://doi.org/10.1097/01.pap.0000131824.77317.a7
  3. Estrozi, B, Bacchi, CE (2011). Neuroendocrine tumors involving the gastroenteropancreatic tract: a clinicopathological evaluation of 773 cases. Clinics (Sao Paulo), 66, 1671-5.
  4. Faiss S, Rath U, Mansmann U, et al (1999). Ultra-high-dose lanreotide treatment in patients with metastatic neuroendocrine gastroenteropancreatic tumors. Digestion, 60, 469-76. https://doi.org/10.1159/000007693
  5. Fjallskog ML, Granberg DP, Welin SL, et al (2001). Treatment with cisplatin and etoposide in patients with neuroendocrine tumors. Cancer, 92, 1101-7. https://doi.org/10.1002/1097-0142(20010901)92:5<1101::AID-CNCR1426>3.0.CO;2-V
  6. Garcia-Carbonero, R, Capdevila, J, Crespo-Herrero, G, et al (2010). Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the National Cancer Registry of Spain (RGETNE). Ann Oncol, 21, 1794-803. https://doi.org/10.1093/annonc/mdq022
  7. Hainsworth JD, Spigel DR, Litchy S, Greco FA (2006). Phase II trial of paclitaxel, carboplatin, and etoposide in advanced poorly differentiated neuroendocrine carcinoma: a Minnie Pearl Cancer Research Network Study. J Clin Oncol, 24, 3548-54. https://doi.org/10.1200/JCO.2005.05.0575
  8. Konishi T, Watanabe T, Kishimoto J, et al (2007). Prognosis and risk factors of metastasis in colorectal carcinoids: results of a nationwide registry over 15 years. Gut, 56, 863-8. https://doi.org/10.1136/gut.2006.109157
  9. Hauso O, Gustafsson BI, Kidd M, et al (2008). Neuroendocrine tumor epidemiology: contrasting Norway and North America. Cancer, 113, 2655-64. https://doi.org/10.1002/cncr.23883
  10. Klimstra, D S, Modlin, I R, Adsay, N V, et al (2010). Pathology reporting of neuroendocrine tumors: application of the Delphic consensus process to the development of a minimum pathology data set. Am J Surg Pathol, 34, 300-13. https://doi.org/10.1097/PAS.0b013e3181ce1447
  11. Kloppel G, Couvelard A, Perren A, et al (2009). 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, 90, 162-6. https://doi.org/10.1159/000182196
  12. Kouvaraki MA, Ajani JA, Hoff P, et al (2004). Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol, 22, 4762-71. https://doi.org/10.1200/JCO.2004.04.024
  13. Krstic M, Sumarac M, Diklic A, et al (2005). [Endoscopic ultrasonography (EUS) in preoperative localization of neuroendocrine tumors (NET) of the pancreas]. Acta Chir Iugosl, 52, 97-100. https://doi.org/10.2298/ACI0501097K
  14. Kulke MH, Lenz HJ, Meropol NJ, et al (2008). Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol, 26, 3403-10. https://doi.org/10.1200/JCO.2007.15.9020
  15. Lim T, Lee J, Kim JJ, et al (2011). Gastroenteropancreatic neuroendocrine tumors: incidence and treatment outcome in a single institution in Korea. Asian Pac J Clin Oncol, 7, 293-9. https://doi.org/10.1111/j.1743-7563.2011.01423.x
  16. Mitry E, Baudin E, Ducreux M, et al (1999). Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin. Br J Cancer, 81, 1351-5. https://doi.org/10.1038/sj.bjc.6690325
  17. Oberg K, Jelic S (2009). Neuroendocrine gastroenteropancreatic tumors: ESMO clinical recommendation for diagnosis, treatment and follow-up. Ann Oncol, 20, 150-3.
  18. Modlin IM, Latich I, Kidd M, et al (2006). Therapeutic options for gastrointestinal carcinoids. Clin Gastroenterol Hepatol, 4, 526-47. https://doi.org/10.1016/j.cgh.2005.12.008
  19. Modlin IM, Lye KD, Kidd M (2003). A 5-decade analysis of 13, 715 carcinoid tumors. Cancer, 97, 934-59. https://doi.org/10.1002/cncr.11105
  20. Modlin IM, Oberg K, Chung DC, et al (2008). Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol, 9, 61-72. https://doi.org/10.1016/S1470-2045(07)70410-2
  21. Oberg K, Kvols L, Caplin M, et al (2004). Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol, 15, 966-73. https://doi.org/10.1093/annonc/mdh216
  22. Patel KK, Kim MK (2008). Neuroendocrine tumors of the pancreas: endoscopic diagnosis. Curr Opin Gastroenterol, 24, 638-42. https://doi.org/10.1097/MOG.0b013e32830bf7fb
  23. Plockinger U, Rindi G, Arnold R, et al (2004). Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology, 80, 394-424. https://doi.org/10.1159/000085237
  24. Ploeckinger U, Kloeppel G, Wiedenmann B, Lohmann R (2009). The German NET-registry: an audit on the diagnosis and therapy of neuroendocrine tumors. Neuroendocrinology, 90, 349-63. https://doi.org/10.1159/000242109
  25. Raymond E, Dahan L, Raoul JL, et al (2011). Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med, 364, 501-13. https://doi.org/10.1056/NEJMoa1003825
  26. Wang YH, Lin Y, Xue L, et al (2012). Relationship between clinical characteristics and survival of gastroenteropancreatic neuroendocrine neoplasms: A single-institution analysis (1995-2012) in South China. BMC Endocr Disord, 12, 30. https://doi.org/10.1186/1472-6823-12-30
  27. Rinke A, Muller HH, Schade-Brittinger C, et al (2009). Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol, 27, 4656-63. https://doi.org/10.1200/JCO.2009.22.8510
  28. Starkov I, Solodinina EN, Egorov AV, et al (2010). [Endoscopic ultrasonography in the diagnosis of neuroendocrine tumors of the pancreas]. Eksp Klin Gastroenterol, 2010, 37-45.
  29. Sun W, Lipsitz S, Catalano P, et al (2005). Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281. J Clin Oncol, 23, 4897-904. https://doi.org/10.1200/JCO.2005.03.616
  30. Yalcin S (2011). Advances in the systemic treatment of pancreatic neuroendocrine tumors. Cancer Treat Rev, 37, 127-32. https://doi.org/10.1016/j.ctrv.2010.07.003
  31. Yao JC, Hassan M, Phan A, et al (2008). One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35, 825 cases in the United States. J Clin Oncol, 26, 3063-72. https://doi.org/10.1200/JCO.2007.15.4377
  32. Yao JC, Lombard-Bohas C, Baudin E, et al (2010). Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol, 28, 69-76. https://doi.org/10.1200/JCO.2009.24.2669
  33. Yao JC, Phan AT, Chang DZ, et al (2008). Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol, 26, 4311-8. https://doi.org/10.1200/JCO.2008.16.7858
  34. Yao JC, Shah MH, Ito T, et al (2011). Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med, 364, 514-23. https://doi.org/10.1056/NEJMoa1009290
  35. Younes RN (2008). Neuroendocrine tumors: a registry of 1, 000 patients. Rev Assoc Med Bras, 54, 305-7. https://doi.org/10.1590/S0104-42302008000400014

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