Skip to main content
SpringerLink
Log in

Serum Elastase 1 Level as a Risk Factor for Postoperative Recurrence in Patients with Well-Differentiated Pancreatic Neuroendocrine Neoplasms

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

This study was designed to assess the potential role of the preoperative serum level of elastase 1 as a risk factor for recurrence in patients with resectable well-differentiated pancreatic neuroendocrine neoplasms (PanNETs).

Methods

Preoperative serum elastase 1 levels were measured in 53 patients with PanNETs who underwent complete tumor resection in two tertiary referral centers between January 2004 and June 2017. The preoperative elastase 1 levels were correlated with clinicopathological characteristics, including tumor recurrence and recurrence-free survival.

Results

The median elastase 1 level was 96 ng/dL (range: 21–990 ng/dL). Preoperative serum elastase 1 levels were significantly higher in those with tumors ≥ 20 mm in diameter (vs. < 20 mm, P = 0.018), WHO grade 2 (vs. grade 1, P = 0.035), and microscopic venous invasion (vs. without venous invasion, P = 0.039). The median preoperative serum level of elastase 1 was higher in patients with recurrence than in those without recurrence (251 vs. 80 ng/dL, P = 0.004). Receiver operating characteristic analysis of elastase 1 levels showed that a cutoff level of 250 ng/dL was associated with postoperative recurrence, with 63% sensitivity, 100% specificity, and 94% overall accuracy. Patients with higher elastase 1 levels showed significantly worse recurrence-free survival than that of those with lower levels (2-year recurrence-free survival rate: 25% and 92%, respectively, P < 0.001).

Conclusions

Our data provide the first evidence that high preoperative elastase 1 levels may be a risk factor for postoperative recurrence in patients with resectable PanNETs.

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. Modlin IM, Oberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9:61–72.

    Article  CAS  Google Scholar 

  2. Oberg K. Pancreatic endocrine tumors. Semin Oncol. 2010;37:594–618.

    Article  Google Scholar 

  3. Yao JC, Hassan M, Phan A, et al. One hundred years after ‘‘carcinoid’’: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26:3063–72.

    Article  Google Scholar 

  4. Lloyd RV, Osamura RY, Kloppel G, Rosai J. WHO classification of tumours of endocrine organs, 4th edn. Lyon: IARC, 2017.

    Google Scholar 

  5. Hijioka S, Hara K, Mizuno N, et al. Diagnostic performance and factors influencing the accuracy of EUS-FNA of pancreatic neuroendocrine neoplasms. J Gastroenterol. 2016;51:923–30.

    Article  CAS  Google Scholar 

  6. Birnbaum DJ, Turrini O, Ewald J, et al. Pancreatic neuroendocrine tumor: a multivariate analysis of factors influencing survival. Eur J Surg Oncol. 2014;40:1564–71.

    Article  CAS  Google Scholar 

  7. Nanno Y, Toyama H, Otani K, et al. Microscopic venous invasion in patients with pancreatic neuroendocrine tumor as a potential predictor of postoperative recurrence. Pancreatology. 2016;16:882–7.

    Article  Google Scholar 

  8. Demir R, Pohl J, Agaimy A, et al. Necrosis and angioinvasion predict adverse outcome in pancreatic neuroendocrine tumors after curative surgical resection: results of a single-center series. World J Surg. 2011;35:2764–72.

    Article  Google Scholar 

  9. Tsutsumi K, Ohtsuka T, Fujino M, et al. 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;21:418–25.

    Article  Google Scholar 

  10. Nanno Y, Matsumoto I, Zen Y, et al. Pancreatic duct involvement in well-differentiated neuroendocrine tumors is an independent poor prognostic factor. Ann Surg Oncol. 2017;24:1127–33.

    Article  Google Scholar 

  11. Largman C, Brodrick JW, Geokas MC. Purification and characterization of two human pancreatic elastases. Biochemistry. 1976;15:2491–500.

    Article  CAS  Google Scholar 

  12. Tatsuta M, Yamamura H, Noguchi S, Ichii M, Iishi H, Okuda S. Values of serum carcinoembryonic antigen and elastase 1 in diagnosis of pancreatic carcinoma. Gut. 1984;25:1347–51.

    Article  CAS  Google Scholar 

  13. Satake K, Chung YS, Umeyama K. Serum elastase I levels in pancreatic disease. Am J Surg. 1982;144:239–42.

    Article  CAS  Google Scholar 

  14. Gullo L, Pezzilli R, Ventrucci M, Lesi C, Zoni L, D’Ambrosi A, Alvisi V. Serum immunoreactive elastase: is it useful for the diagnosis of pancreatic cancer? Pancreas. 1989;4:335–8.

    Article  CAS  Google Scholar 

  15. Hayakawa T, Kondo T, Shibata T, Kitagawa M, Katada N, Kato K, Takeichi M. Prospective trial for early detection of pancreatic cancer by elevated serum immunoreactive elastase. Gastroenterol Jpn. 1990;25:727–31.

    Article  CAS  Google Scholar 

  16. 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  Google Scholar 

  17. Nanno Y, Toyama H, Matsumoto I, et al. Baseline plasma chromogranin A levels in patients with well-differentiated neuroendocrine tumors of the pancreas: a potential predictor of postoperative recurrence. Pancreatology. 2017;17:291–4.

    Article  CAS  Google Scholar 

  18. Mosli HH, Dennis A, Kocha W, Asher LJ, Van Uum SH. Effect of short-term proton pump inhibitor treatment and its discontinuation on chromogranin A in healthy subjects. J Clin Endocrinol Metab. 2012;97:1731–5.

    Article  Google Scholar 

  19. Bech PR, Ramachandran R, Dhillo WS, Martin NM, Bloom SR. Quantifying the effects of renal impairment on plasma concentrations of the neuroendocrine neoplasia biomarkers chromogranin A, chromogranin B, and cocaine- and amphetamine-regulated transcript. Clin Chem. 2012;58:941–3.

    Article  CAS  Google Scholar 

  20. Seno T, Harada H, Ochi K, et al. Serum levels of six pancreatic enzymes as related to the degree of renal dysfunction. Am J Gastroenterol. 1995;90:2002–5.

    CAS  PubMed  Google Scholar 

  21. Schmid K, Birner P, Gravenhorst V, End A, Geleff S. Prognostic value of lymphatic and blood vessel invasion in neuroendocrine tumors of the lung. Am J Surg Pathol. 2005;29:324–8.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan

    Yoshihide Nanno MD, PhD, Hirochika Toyama MD, PhD, Takuya Mizumoto MD, Yuki Ueda MD, Tetsuo Ajiki MD, PhD & Takumi Fukumoto MD, PhD

  2. Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan

    Yoh Zen MD, PhD, FRCPath & Masayuki Akita MD

  3. Department of Gastroenterological Surgery, Kagawa University Faculty of Medicine, Kagawa, Japan

    Yasuhisa Ando MD, Keiichi Okano MD, PhD & Yasuyuki Suzuki MD, PhD

Authors
  1. Yoshihide Nanno MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hirochika Toyama MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoh Zen MD, PhD, FRCPath
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masayuki Akita MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasuhisa Ando MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takuya Mizumoto MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuki Ueda MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tetsuo Ajiki MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Keiichi Okano MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yasuyuki Suzuki MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Takumi Fukumoto MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hirochika Toyama MD, PhD.

Ethics declarations

Disclosure

All authors have no conflicts of interest and nothing to disclose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nanno, Y., Toyama, H., Zen, Y. et al. Serum Elastase 1 Level as a Risk Factor for Postoperative Recurrence in Patients with Well-Differentiated Pancreatic Neuroendocrine Neoplasms. Ann Surg Oncol 25, 3358–3364 (2018). https://doi.org/10.1245/s10434-018-6675-3

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-018-6675-3

Keywords

Search

Navigation