Annals of Surgical Oncology

, Volume 21, Issue 11, pp 3515–3521 | Cite as

Impact of Extent of Surgery on Survival in Patients with Small Nonfunctional Pancreatic Neuroendocrine Tumors in the United States

  • Lauren Gratian
  • John Pura
  • Michaela Dinan
  • Sanziana Roman
  • Shelby Reed
  • Julie Ann Sosa
Endocrine Tumors



Nonfunctional pancreatic neuroendocrine tumors (PNETs) ≤2 cm have uncertain malignant potential, and optimal treatment remains unclear. Objectives of this study were to better understand their malignant potential, determine whether extent of surgery or lymph node dissection is associated with overall survival (OS), and identify other factors associated with OS.


Patients with nonfunctional PNETs ≤2 cm were identified from the National Cancer Data Base (1998 to 2011). Descriptive statistics were used for patient characteristics and surgical resection patterns. Five-year OS was estimated using Kaplan–Meier analyses across extent of surgery and compared using the log-rank test. Cox proportional regression modeling was used to test the association between survival and extent of surgery.


A total of 1854 patients with nonfunctional PNETs ≤2 cm were included. From 1998 to 2011, these tumors increased three-fold as a proportion of all PNETs. Among tumors ≤0.5 cm, 33 % presented with regional lymph node metastases and 11 % with distant metastases. Five-year OS for patients not undergoing surgery was 27.6 % vs. 83.0 % for partial pancreatectomy, 72.3 % for pancreaticoduodenectomy, and 86.0 % for total pancreatectomy (p < 0.01). Multivariate analysis demonstrated no difference in OS based on type of surgery or the addition of regional lymphadenectomy (p = 0.16). Younger age and later year of diagnosis were independently associated with improved survival.


Small nonfunctional PNETs represent an increasing proportion of all PNETs and have a significant risk of malignancy. Survival is improving over time despite older age at diagnosis. Type of surgical resection and the addition of lymph node resection were not associated with OS.


Overall Survival Total Pancreatectomy Regional Lymph Node Metastasis Islet Cell Tumor National Cancer Data Base 
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.



The authors declare no conflict of interest. The data used in the study are derived from a deidentified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology used, or the conclusions drawn from these data by the investigators.


  1. 1.
    Yao JC, Eisner NP, Leary C, et al. Population-based study of islet cell carcinoma. Ann Surg Oncol. 2007;14:3492–3500.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Lawrence B, Gustafsson BI, Chan A, Svejda B, Kidd M, Modlin IM. The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am. 2011;40:1–18.PubMedCrossRefGoogle Scholar
  3. 3.
    Kuo EJ, Salem RR. Population-level analysis of pancreatic neuroendocrine tumors 2 cm or less in size. Ann Surg Oncol. 2013;9:2815–2821.CrossRefGoogle Scholar
  4. 4.
    Lee LC, Grant CS, Salomao DR, et al. Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors (PNETs): role for nonoperative management. Surgery. 2012;152:965–974.PubMedCrossRefGoogle Scholar
  5. 5.
    Cherenfant J, Stocker SJ, Gage MK, et al. Predicting aggressive behavior in nonfunctioning pancreatic neuroendocrine tumors. Surgery. 2013;154:785–793.PubMedCrossRefGoogle Scholar
  6. 6.
    Haynes AB, Deshpande V, Ingkakul T, et al. Implications of incidentally discovered, nonfunctioning pancreatic endocrine tumors: short-term and long-term patient outcomes. Arch Surg. 2011;146:534–538.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    NCCN clinical practice guidelines in oncology. Version 1.2012. Neuroendocrine tumors.Google Scholar
  8. 8.
    Falconi M, Plöckinger U, Kwekkeboom DJ, et al. Well-differentiated pancreatic nonfunctioning tumors/carcinoma. Neuroendocrinology. 2006;84:196–211.PubMedCrossRefGoogle Scholar
  9. 9.
    Kloppel 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
  10. 10.
    Watzka FM, Laumen C, Fottner C, et al. Resection strategies for neuroendocrine pancreatic neoplasms. Langenbecks Arch Surg. 2013;3:431–440.CrossRefGoogle Scholar
  11. 11.
    Bilimoria KY, Bentrem DJ, Merkow RP, et al. Application of the pancreatic adenocarcinoma staging system to pancreatic neuroendocrine tumors. J Am Coll Surg. 2007;205:558–563.PubMedCrossRefGoogle Scholar
  12. 12.
    Rindi G, Klöppel G, Alhman H, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006;449:395.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual. 7th ed. New York, NY: Springer; 2010.Google Scholar
  14. 14.
    Strosberg JR, Cheema A, Weber J, Han G, Coppola D, Kvols LK. Prognostic validity of a novel American Joint Committee on Cancer Staging Classification for pancreatic neuroendocrine tumors. J Clin Oncol. 2011;29:3044–3049.PubMedCrossRefGoogle Scholar
  15. 15.
    Strosberg JR, Cheema A, Weber JM, et al. Relapse-free survival in patients with nonmetastatic, surgically resected pancreatic neuroendocrine tumors: an analysis of the AJCC and ENETS staging classifications. Ann Surg. 2012;256:321–325.PubMedCrossRefGoogle Scholar
  16. 16.
    Ellison TA, Wolfgang CL, Shi C, et al. A single institution’s 26-year experience with nonfunctional pancreatic neuroendocrine tumors: a validation of current staging systems and a new prognostic nomogram. Ann Surg. 2014;259:204–212.PubMedCrossRefGoogle Scholar
  17. 17.
    Bilimoria KY, Tomlinson JS, Merkow RP, 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
  18. 18.
    Winchester DP, Stewart AK, Bura C, Jones RS. The National Cancer Data Base: a clinical surveillance and quality improvement tool. J Surg Oncol. 2004;85:1–3.PubMedCrossRefGoogle Scholar
  19. 19.
    Raghunathan TW, Lepkowksi JM, Van Hoewyk J, Solenbeger P. A multivariate technique for multiply imputing missing values using a sequence of regression models. Survey Method. 2001;27:85–95.Google Scholar
  20. 20.
    Parekh JR, Wang SC, Bergsland EK, et al. Lymph node sampling rates and predictors of nodal metastasis in pancreatic neuroendocrine tumor resections: the UCSF experience with 149 patients. Pancreas. 2012;41:840–844.PubMedCrossRefGoogle Scholar
  21. 21.
    Hill JS, McPhee JT, McDade TP, et al. Pancreatic neuroendocrine tumors: the impact of surgical resection on survival. Cancer. 2009;115:741–751.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Lauren Gratian
    • 1
  • John Pura
    • 2
  • Michaela Dinan
    • 3
  • Sanziana Roman
    • 4
  • Shelby Reed
    • 3
  • Julie Ann Sosa
    • 3
    • 4
  1. 1.Division of Endocrinology Department of MedicineDuke University School of MedicineDurhamUSA
  2. 2.Department of BiostatisticsDuke University School of MedicineDurhamUSA
  3. 3.Duke Clinical Research InstituteDurhamUSA
  4. 4.Section of Endocrine Surgery, Department of SurgeryDuke University School of MedicineDurhamUSA

Personalised recommendations