Skip to main content
SpringerLink
Log in

Further Classification for Node-Positive Gastric Neuroendocrine Neoplasms

  • 2018 SSAT Quick Shot Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

For gastric neuroendocrine neoplasms (GNEN), the current AJCC lymph node (N) stage classifies patients into N0/N1 disease (with/without locoregional nodal metastases); however, this does not account for the number of involved nodes. The objective of this study was to evaluate the prognostic significance of the number of involved locoregional nodes among resected GNEN.

Methods

The National Cancer Database (2004–2014) was queried for GNEN patients who had undergone partial/total gastrectomy with known nodal status. Nearest-neighborhood grouping was used to identify survival clusters by number of metastatic nodes and to use these groupings to construct a new N classification (pN). External validation was performed using the SEER database. Kaplan-Meier analysis and Cox regression models were used to assess the prognostic strength of the pN classification.

Results

One thousand two hundred seventy-five patients met study inclusion criteria. Patients with 1–6 positive nodes (pN1) demonstrated a distinct survival pattern from patients with > 6 positive nodes (pN2) as well as those with no positive nodes (N0) {5-year OS N0: 80% (95% CI 77–83%) vs. 65% (95% CI 61–69%) vs. 43% (95% CI 33–53%), p < 0.001}. On external validation, the pN classification demonstrated strong discriminatory ability for survival {5-year OS N0: 70% (95% CI 65–75%) vs. pN1:53% (95% CI 46–59%) vs. pN2:18% (95% CI 9–29%), p < 0.001}. On multivariable analysis, the pN classification remained an independent predictor of OS.

Conclusions

The number of metastatic lymph nodes is an independent prognostic factor in GNEN. Current AJCC N1 disease contains two groups of patients with distinctive prognoses, hence needs to be subclassified into pN1 (1–6 positive lymph nodes) and pN2 (> 6 positive nodes).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97(4):934–59. https://doi.org/10.1002/cncr.11105.

    Article  PubMed  Google Scholar 

  2. Tsikitis VL, Wertheim BC, Guerrero MA. Trends of incidence and survival of gastrointestinal neuroendocrine tumors in the United States: a seer analysis. Journal of Cancer. 2012;3:292–302. https://doi.org/10.7150/jca.4502.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. Journal of Clinical oncology: Official Journal of the American Society of Clinical Oncology. 2008;26(18):3063–72. https://doi.org/10.1200/jco.2007.15.4377.

    Article  Google Scholar 

  4. Boyce M, Thomsen L. Gastric neuroendocrine tumors: prevalence in Europe, USA, and Japan, and rationale for treatment with a gastrin/CCK2 receptor antagonist. Scandinavian Journal of Gastroenterology. 2015;50(5):550–9. https://doi.org/10.3109/00365521.2015.1009941.

    Article  CAS  PubMed  Google Scholar 

  5. Oberg K, Jelic S. Neuroendocrine gastroenteropancreatic tumors: ESMO clinical recommendation for diagnosis, treatment and follow-up. Annals of Oncology : Official Journal of the European Society for Medical Oncology / ESMO. 2009;20 Suppl 4:150–3. https://doi.org/10.1093/annonc/mdp158.

    Article  Google Scholar 

  6. Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010;39(6):707–12. https://doi.org/10.1097/MPA.0b013e3181ec124e.

    Article  PubMed  Google Scholar 

  7. Postlewait LM, Baptiste GG, Ethun CG, Le N, Cardona K, Russell MC et al. A 15-year experience with gastric neuroendocrine tumors: does type make a difference? J Surg Oncol. 2016;114(5):576–80. https://doi.org/10.1002/jso.24369.

    Article  PubMed  Google Scholar 

  8. Li TT, Qiu F, Qian ZR, Wan J, Qi XK, Wu BY. Classification, clinicopathologic features and treatment of gastric neuroendocrine tumors. World J Gastroenterol. 2014;20(1):118–25. https://doi.org/10.3748/wjg.v20.i1.118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rindi G, Luinetti O, Cornaggia M, Capella C, Solcia E. Three subtypes of gastric argyrophil carcinoid and the gastric neuroendocrine carcinoma: a clinicopathologic study. Gastroenterology. 1993;104(4):994–1006.

    Article  CAS  PubMed  Google Scholar 

  10. Borch K, Ahren B, Ahlman H, Falkmer S, Granerus G, Grimelius L. Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg. 2005;242(1):64–73.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Norton JA, Melcher ML, Gibril F, Jensen RT. Gastric carcinoid tumors in multiple endocrine neoplasia-1 patients with Zollinger-Ellison syndrome can be symptomatic, demonstrate aggressive growth, and require surgical treatment. Surgery. 2004;136(6):1267–74. https://doi.org/10.1016/j.surg.2004.06.057.

    Article  PubMed  Google Scholar 

  12. Sato Y, Hashimoto S, Mizuno K, Takeuchi M, Terai S. Management of gastric and duodenal neuroendocrine tumors. World J Gastroenterol. 2016;22(30):6817–28. https://doi.org/10.3748/wjg.v22.i30.6817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kulke MH, Shah MH, Benson AB, 3rd, Bergsland E, Berlin JD, Blaszkowsky LS et al. Neuroendocrine tumors, version 1.2015. J Natl Compr Canc Netw. 2015;13(1):78–108.

    Article  CAS  PubMed  Google Scholar 

  14. Delle Fave G, Kwekkeboom DJ, Van Cutsem E, Rindi G, Kos-Kudla B, Knigge U et al. ENETS Consensus Guidelines for the management of patients with gastroduodenal neoplasms. Neuroendocrinology. 2012;95(2):74–87. https://doi.org/10.1159/000335595.

    Article  CAS  PubMed  Google Scholar 

  15. Edge S. B. BDR, Compton C. F., Fritz A. G., Greene F. L., Trotti A. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010.

    Google Scholar 

  16. Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK et al. AJCC Cancer Staging Manual. 8 ed. New York: Springer; 2017.

    Book  Google Scholar 

  17. Flatow V, Warner RR, Overbey J, Divino CM. The prognostic significance of lymph node ratio in carcinoid tumors. Pancreas. 2016;45(3):342–4. https://doi.org/10.1097/mpa.0000000000000476.

    Article  CAS  PubMed  Google Scholar 

  18. Martin JA, Warner RRP, Aronson A, Wisnivesky JP, Kim MK. Lymph node metastasis in the prognosis of gastroenteropancreatic neuroendocrine tumors. Pancreas. 2017;46(9):1214–8. https://doi.org/10.1097/mpa.0000000000000921.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kim MK, Warner RR, Ward SC, Harpaz N, Roayaie S, Schwartz ME et al. Prognostic significance of lymph node metastases in small intestinal neuroendocrine tumors. Neuroendocrinology. 2015;101(1):58–65. https://doi.org/10.1159/000371807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tang X, Chen Y, Guo L, Zhang J, Wang C. Prognostic significance of metastatic lymph node number, ratio and station in gastric neuroendocrine carcinoma. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2015;19(2):234–41. https://doi.org/10.1007/s11605-014-2691-1.

    Article  Google Scholar 

  21. Bilimoria KY, Stewart AK, Winchester DP, Ko CY. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Annals of Surgical Oncology. 2008;15(3):683–90. https://doi.org/10.1245/s10434-007-9747-3.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Liu DJ, Fu XL, Liu W, Zheng LY, Zhang JF, Huo YM et al. Clinicopathological, treatment, and prognosis study of 43 gastric neuroendocrine carcinomas. World Journal of Gastroenterology. 2017;23(3):516–24. https://doi.org/10.3748/wjg.v23.i3.516.

    Article  PubMed  PubMed Central  Google Scholar 

  23. National Comprehensive Cancer Network. NCCN Guidelines Neuroendocrine Tumors Version 3.2017. 2017. https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf. Accessed November 30 2017.

  24. Kim J, Huynh R, Abraham I, Kim E, Kumar RR. Number of lymph nodes examined and its impact on colorectal cancer staging. The American Surgeon. 2006;72(10):902–5.

    PubMed  Google Scholar 

  25. Lee HK, Yang HK, Kim WH, Lee KU, Choe KJ, Kim JP. Influence of the number of lymph nodes examined on staging of gastric cancer. The British Journal of Surgery. 2001;88(10):1408–12. https://doi.org/10.1046/j.0007-1323.2001.01875.x.

    Article  CAS  PubMed  Google Scholar 

  26. Terrone C, Guercio S, De Luca S, Poggio M, Castelli E, Scoffone C et al. The number of lymph nodes examined and staging accuracy in renal cell carcinoma. BJU Int. 2003;91(1):37–40.

    Article  CAS  PubMed  Google Scholar 

  27. 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(6):735–52. https://doi.org/10.1097/MPA.0b013e3181ebb168.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author Contribution

LMP contributed to study conception and design, the data analysis and interpretation, manuscript drafting and revisions. TY contributed to data analysis and interpretation and manuscript revisions. JW contributed to study conception and design, data analysis and interpretation, and manuscript drafting and revisions. All authors gave final approval of this manuscript version to be published and agree to be accountable for all aspects of the work in accuracy and integrity.

Author information

Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, MA, 02115, USA

    Linda M. Pak, Tingsong Yang & Jiping Wang

  2. Center for Surgery and Public Health, Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, 1620 Tremont St, Boston, MA, 02120, USA

    Linda M. Pak & Jiping Wang

Authors
  1. Linda M. Pak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tingsong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiping Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jiping Wang.

Ethics declarations

Disclosures

The National Cancer Data Base (NCDB) is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. The CoC’s NCDB and the hospitals participating in the CoC NCDB are the source of the de-identified data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors.

Additional information

This study was presented as a Society for Surgery of the Alimentary Tract quick shot presentation at Digestive Disease Week 2018 in June 2018 in Washington, D.C.

Electronic supplementary material

Supplemental Figure 1

Nearest neighborhood grouping by number of metastatic lymph nodes was used to identify patient groups with distinct survival outcomes (a-c). Patients with 0, 1–6, and ≥ 7 lymph nodes demonstrate distinct survival outcomes (d). (PPTX 271 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pak, L.M., Yang, T. & Wang, J. Further Classification for Node-Positive Gastric Neuroendocrine Neoplasms. J Gastrointest Surg 23, 720–729 (2019). https://doi.org/10.1007/s11605-018-3845-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-018-3845-3

Keywords

Search

Navigation