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


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.


Gastroenteropancreatic neuroendocrine neoplasms;clinical characteristics;prognosis;treatment


  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.
  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.
  5. Fjallskog ML, Granberg DP, Welin SL, et al (2001). Treatment with cisplatin and etoposide in patients with neuroendocrine tumors. Cancer, 92, 1101-7.<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.
  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.
  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.
  9. Hauso O, Gustafsson BI, Kidd M, et al (2008). Neuroendocrine tumor epidemiology: contrasting Norway and North America. Cancer, 113, 2655-64.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  19. Modlin IM, Lye KD, Kidd M (2003). A 5-decade analysis of 13, 715 carcinoid tumors. Cancer, 97, 934-59.
  20. Modlin IM, Oberg K, Chung DC, et al (2008). Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol, 9, 61-72.
  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.
  22. Patel KK, Kim MK (2008). Neuroendocrine tumors of the pancreas: endoscopic diagnosis. Curr Opin Gastroenterol, 24, 638-42.
  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.
  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.
  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.
  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.
  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.
  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.
  30. Yalcin S (2011). Advances in the systemic treatment of pancreatic neuroendocrine tumors. Cancer Treat Rev, 37, 127-32.
  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.
  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.
  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.
  34. Yao JC, Shah MH, Ito T, et al (2011). Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med, 364, 514-23.
  35. Younes RN (2008). Neuroendocrine tumors: a registry of 1, 000 patients. Rev Assoc Med Bras, 54, 305-7.

Cited by

  1. Somatostatin Analogues Do Not Prevent Carcinoid Crisis vol.15, pp.16, 2014,
  2. Neuroendocrine tumors in the Iran Cancer Institute: Predictive Factors of Patient Survival vol.15, pp.18, 2014,
  3. Analysis on the Characteristics and Prognosis of Pulmonary Neuroendocrine Tumors vol.15, pp.5, 2014,
  4. Computer Tomography and Magnetic Resonance Image Manifestations of Primary Hepatic Neuroendocrine Cell Carcinomas vol.15, pp.6, 2014,
  5. Somatostatin Receptor 2 and 5 Expressions in Gastroenteropancreatic Neuroendocrine Tumors in Turkey vol.16, pp.10, 2015,
  6. Advances in the Management of Unresectable or Metastatic Pancreatic Neuroendocrine Tumors: Chemotherapy, Targeted Therapy, Hormonal Treatment, and Future Directions vol.16, pp.6, 2015,
  7. Clinicopathological features and prognosis of gastroenteropancreatic neuroendocrine neoplasms in a Chinese population: a large, retrospective single-centre study vol.17, pp.1, 2017,