Skip to main content
SpringerLink
Log in

Predictive Value of Chromogranin A and a Pre-Operative Risk Score to Predict Recurrence After Resection of Pancreatic Neuroendocrine Tumors

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

Abstract

Intro

Chromogranin A (CgA) may be prognostic for patients with neuroendocrine tumors; however, the clinical utility of this test is unclear.

Methods

Patients undergoing resection for pancreatic neuroendocrine tumors (pNET) were selected from the eight institutions of the US Neuroendocrine Tumor Study Group database. Cox regression was used to identify pre-operative variables that predicted recurrence-free survival (RFS), and those with p < 0.1 were included in a risk score. The risk score was tested in a unique subset of the overall cohort.

Results

In the entire cohort of 287 patients, median follow-up time was 37 months, and 5-year RFS was 73%. Cox regression analysis identified four variables for inclusion in the risk score: CgA > 5x ULN (HR 4.3, p = 0.01), tumor grade 2/3 (HR 3.7, p = 0.01), resection for recurrent disease (HR 6.2, p < 0.01), and tumor size > 4 cm (HR 4.5, p = 0.1). Each variable was assigned 1 point. Risk-score testing in the unique validation cohort of 63 patients revealed a 95% negative predictive value for recurrence in patients with zero points.

Discussion

This simple pre-operative risk scoring system resulted in a high degree of specificity for identifying patients at low-risk for tumor recurrence. This test can be utilized pre-operatively to aid informed decision-making.

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
Fig. 3

Similar content being viewed by others

References

  1. Bilimoria KY, Talamonti MS, Tomlinson JS, Stewart AK, Winchester DP, Ko CY, Bentrem DJ. Prognostic Score Predicting Survival After Resection of Pancreatic Neuroendocrine Tumors. Ann Surg. 2008;247:490–500.

    Article  PubMed  Google Scholar 

  2. Saxena A, Chua TC, Chu F, Al-Zahrani A, Morris DL. Optimizing the Surgical Effort in Patients With Advanced Neuroendocrine Neoplasm Hepatic Metastases. Am J Clin Oncol. 2012;35:439–445.

    Article  PubMed  Google Scholar 

  3. Kim MJ, Choi DW, Choi SH, Heo JS, Park HJ, Choi KK, Jang K-T, Sung J-Y. Surgical strategies for non-functioning pancreatic neuroendocrine tumours. Br J Surg. 2012;99:1562–1568.

    Article  CAS  PubMed  Google Scholar 

  4. Slagter AE, Ryder D, Chakrabarty B, Lamarca A, Hubner RA, Mansoor W, O’Reilly DA, Fulford PE, Klümpen HJ, Valle JW, McNamara MG. Prognostic factors for disease relapse in patients with neuroendocrine tumours who underwent curative surgery. Surg Oncol. 2016;25:223–228.

    Article  CAS  PubMed  Google Scholar 

  5. Ricci C, Casadei R, Taffurelli G, Campana D, Ambrosini V, Pacilio CA, Santini D, Brighi N, Minni F. Is radical surgery always curative in pancreatic neuroendocrine tumors? A cure model survival analysis. Pancreatology. 2018;18:313–317.

    Article  PubMed  Google Scholar 

  6. Ricci C, Casadei R, Taffurelli G, Buscemi S, D’Ambra M, Monari F, Santini D, Campana D, Tomassetti P, Minni F. The role of lymph node ratio in recurrence after curative surgery for pancreatic endocrine tumours. Pancreatology. 2013;13:589–593.

    Article  PubMed  Google Scholar 

  7. Genç CG, Jilesen AP, Partelli S, Falconi M, Muffatti F, van Kemenade FJ, van Eeden S, Verheij J, van Dieren S, van Eijck CHJ, Nieveen van Dijkum EJM. A New Scoring System to Predict Recurrent Disease in Grade 1 and 2 Nonfunctional Pancreatic Neuroendocrine Tumors. Ann Surg. 2018;267:1148–1154.

    Article  PubMed  Google Scholar 

  8. Strosberg JR, Cheema A, Weber JM, Ghayouri M, Han G, Hodul PJ, Kvols LK. 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.

    Article  PubMed  Google Scholar 

  9. Nobels FR, Kwekkeboom DJ, Coopmans W, Schoenmakers CH, Lindemans J, De Herder WW, Krenning EP, Bouillon R, Lamberts SW. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones. J Clin Endocrinol Metab. 1997;82:2622–2628.

    CAS  PubMed  Google Scholar 

  10. Shanahan MA, Salem A, Fisher A, Cho CS, Leverson G, Winslow ER, Weber SM. Chromogranin A predicts survival for resected pancreatic neuroendocrine tumors. J Surg Res. 2016;201:38–43.

    Article  CAS  PubMed  Google Scholar 

  11. Ekeblad S, Skogseid B, Dunder K, Oberg K, Eriksson B. Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution. Clin Cancer Res. 2008;14:7798–7803.

    Article  CAS  PubMed  Google Scholar 

  12. Mirkin KA, Hollenbeak CS, Wong J. Impact of chromogranin A, differentiation, and mitoses in nonfunctional pancreatic neuroendocrine tumors ≤ 2 cm. J Surg Res. 2017;211:206–214.

    Article  CAS  PubMed  Google Scholar 

  13. Qiu W, Christakis I, Silva A, Bassett RL, Cao L, Meng QH, Gardner Grubbs E, Zhao H, Yao JC, Lee JE, Perrier ND. Utility of chromogranin A, pancreatic polypeptide, glucagon and gastrin in the diagnosis and follow-up of pancreatic neuroendocrine tumours in multiple endocrine neoplasia type 1 patients. Clin Endocrinol. 2016;85:400–407.

    Article  CAS  Google Scholar 

  14. Korse CM, Muller M, Taal BG. Discontinuation of proton pump inhibitors during assessment of chromogranin A levels in patients with neuroendocrine tumours. Br J Cancer. 2011;105:1173–1175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pregun I, Herszényi L, Juhász M, Miheller P, Hritz I, Patócs A, Rácz K, Tulassay Z. Effect of Proton-Pump Inhibitor Therapy on Serum Chromogranin A Level. Digestion. 2011;84:22–28.

    Article  CAS  PubMed  Google Scholar 

  16. Tramonti G, Ferdeghini M, Annichiarico C, Norpoth M, Donadio C, Bianchi R, Bianchi C. Relationship between renal function and blood level of chromogranin A. Ren Fail. 2001;23:449–457.

    Article  CAS  PubMed  Google Scholar 

  17. Nikou GC, Marinou K, Thomakos P, Papageorgiou D, Sanzanidis V, Nikolaou P, Kosmidis C, Moulakakis A, Mallas E. Chromogranin a levels in diagnosis, treatment and follow-up of 42 patients with non-functioning pancreatic endocrine tumours. Pancreatology. 2008;8:510–519.

    Article  CAS  PubMed  Google Scholar 

  18. Landoni L, Marchegiani G, Pollini T, Cingarlini S, D’Onofrio M, Capelli P, De Robertis R, Davì M V., Amodio A, Impellizzeri H, Malpaga A, Miotto M, Boninsegna L, Crepaz L, Nessi C, Zingaretti CC, Paiella S, Esposito A, Casetti L, Malleo G, Tuveri M, Butturini G, Salvia R, Scarpa A, Falconi M, Bassi C. The Evolution of Surgical Strategies for Pancreatic Neuroendocrine Tumors (Pan-NENs). Ann Surg. 2017. [Epub] Available from: http://www.ncbi.nlm.nih.gov/pubmed/29189384

  19. Birnbaum DJ, Turrini O, Vigano L, Russolillo N, Autret A, Moutardier V, Capussotti L, Le Treut Y-P, Delpero J-R, Hardwigsen J. Surgical Management of Advanced Pancreatic Neuroendocrine Tumors: Short-Term and Long-Term Results from an International Multi-institutional Study. Ann Surg Oncol. 2015;22:1000–1007.

    Article  PubMed  Google Scholar 

  20. Tsutsumi K, Ohtsuka T, Fujino M, Nakashima H, Aishima S, Ueda J, Takahata S, Nakamura M, Oda Y, Tanaka M. Analysis of risk factors for recurrence after curative resection of well-differentiated pancreatic neuroendocrine tumors based on the new grading classification. J Hepatobiliary Pancreat Sci. 2014;21:418–425.

    Article  PubMed  Google Scholar 

  21. Postlewait LM, Ethun CG, Baptiste GG, Le N, McInnis MR, Cardona K, Russell MC, Sarmiento JM, Kooby DA, Staley CA, Maithel SK. Pancreatic neuroendocrine tumors: Preoperative factors that predict lymph node metastases to guide operative strategy. J Surg Oncol. 2016;114:440–445.

    Article  PubMed  Google Scholar 

  22. Nanno Y, Toyama H, Matsumoto I, Otani K, Asari S, Goto T, Ajiki T, Zen Y, Fukumoto T, Ku Y. Baseline plasma chromogranin A levels in patients with well-differentiated neuroendocrine tumors of the pancreas: A potential predictor of postoperative recurrence. Pancreatology. 2017;17:291–294.

    Article  CAS  PubMed  Google Scholar 

  23. Wong KK, Waterfield RT, Marzola MC, Scarsbrook AF, Chowdhury FU, Gross MD, Rubello D. Contemporary nuclear medicine imaging of neuroendocrine tumours. Clin Radiol. 2012;67:1035–1050.

    Article  CAS  PubMed  Google Scholar 

  24. Klimstra DS, Modlin IR, Coppola D, Lloyd R V., Suster S. The Pathologic Classification of Neuroendocrine Tumors. Pancreas. 2010;39:707–712.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

SMW and DEA are supported with the resources and use of facilities at the William S. Middleton Memorial Veterans Hospital, Madison, WI.

Funding

AVF’s position as a research fellow is supported by NIH Surgical Oncology Training Grant (T32 CA090217), and an American College of Surgeons Resident Research Scholarship.

Author information

Authors and Affiliations

  1. Department of Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, BX7375 Clinical Science Center, Madison, WI, 53792-3284, USA

    Alexander V. Fisher, Victoria R. Rendell, Courtney Pokrzywa, Emily R. Winslow, Daniel E. Abbott & Sharon M. Weber

  2. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Alexandra G. Lopez-Aguiar & Shishir K. Maithel

  3. Department of Surgery, Virginia Mason Medical Center, Seattle, WA, USA

    Flavio G. Rocha & Zaheer S. Kanji

  4. Department of Surgery, Stanford University Medical Center, Stanford, CA, USA

    George A. Poultsides & Eleftherios A. Makris

  5. Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA

    Mary E. Dillhoff & Eliza W. Beal

  6. Department of Surgery, Washington University School of Medicine, St Louis, MO, USA

    Ryan C. Fields & Roheena Z. Panni

  7. Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

    Kamran Idrees & Paula Marincola Smith

  8. Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA

    Clifford S. Cho & Megan V. Beems

Authors
  1. Alexander V. Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexandra G. Lopez-Aguiar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Victoria R. Rendell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Courtney Pokrzywa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Flavio G. Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zaheer S. Kanji
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. George A. Poultsides
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eleftherios A. Makris
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mary E. Dillhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eliza W. Beal
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ryan C. Fields
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Roheena Z. Panni
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kamran Idrees
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Paula Marincola Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Clifford S. Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Megan V. Beems
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Shishir K. Maithel
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Emily R. Winslow
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Daniel E. Abbott
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Sharon M. Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sharon M. Weber.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This work was accepted for plenary oral presentation on June 3, 2018, at the Society for Surgery of the Alimentary Tract Annual Meeting in Washington, D.C.

Electronic Supplementary Material

ESM 1

(DOCX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fisher, A.V., Lopez-Aguiar, A.G., Rendell, V.R. et al. Predictive Value of Chromogranin A and a Pre-Operative Risk Score to Predict Recurrence After Resection of Pancreatic Neuroendocrine Tumors. J Gastrointest Surg 23, 651–658 (2019). https://doi.org/10.1007/s11605-018-04080-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-018-04080-1

Keywords

Search

Navigation