Advertisement

Annals of Surgical Oncology

, Volume 23, Issue 5, pp 1721–1728 | Cite as

Surgical Treatment as a Principle for Patients with High-Grade Pancreatic Neuroendocrine Carcinoma: A Nordic Multicenter Comparative Study

  • Sven-Petter HaugvikEmail author
  • Eva Tiensuu Janson
  • Pia Österlund
  • Seppo W. Langer
  • Ragnhild Sørum Falk
  • Knut Jørgen Labori
  • Lene Weber Vestermark
  • Henning Grønbæk
  • Ivar Prydz Gladhaug
  • Halfdan Sorbye
Pancreatic Tumors

Abstract

Background

This study aimed to evaluate the role of surgery for patients with high-grade pancreatic neuroendocrine carcinoma (hgPNEC) in a large Nordic multicenter cohort study. Prior studies evaluating the role of surgery for patients with hgPNEC are limited, and the benefit of the surgery is uncertain.

Methods

Data from patients with a diagnosis of hgPNEC determined between 1998 and 2012 were retrospectively registered at 10 Nordic university hospitals. Kaplan–Meier curves were used to compare the overall survival of different treatment groups, and Cox-regression analysis was used to evaluate factors potentially influencing survival.

Results

The study registered 119 patients. The median survival period from the time of metastasis was 23 months for patients undergoing initial resection of localized nonmetastatic disease and chemotherapy at the time of recurrence (n = 14), 29 months for patients undergoing resection of the primary tumor and resection/radiofrequency ablation of synchronous metastatic liver disease (n = 12), and 13 months for patients with synchronous metastatic disease given systemic chemotherapy alone (n = 78). The 3-year survival rate after surgery of the primary tumor and metastatic disease was 69 %. Resection of the primary tumor was an independent factor for improved survival after occurrence of metastatic disease.

Conclusions

Patients with resected localized nonmetastatic hgPNEC and later metastatic disease seemed to benefit from initial resection of the primary tumor. Patients selected for resection of the primary tumor and synchronous liver metastases had a high 3-year survival rate. Selected patients with both localized hgPNEC and metastatic hgPNEC should be considered for radical surgical treatment.

Keywords

Primary Tumor Liver Metastasis Good Supportive Care Undergo Liver Resection Metastatic Tissue 
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.

Notes

Acknowledgment

The study was initiated by the Nordic Neuroendocrine Tumor Group. We thank Randi Eikeland (Clinical Cancer Research Office, Haukeland University Hospital, Bergen, Norway) for assisting with data management. The study was supported by grants from the Nordic Cancer Union and Eckbo Foundations. Halfdan Sorbye received funding from the Norwegian Cancer Society; Eva Tiensuu Janson received a research grant from the Swedish Cancer Society; and Henning Grønbæk received a clinical research grant from the Novo Nordisk Foundation.

Disclosure

There are no conflicts of interest.

References

  1. 1.
    Sorbye H, Welin S, Langer SW, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol. 2013;24:152–60.CrossRefPubMedGoogle Scholar
  2. 2.
    Cho MY, Kim JM, Sohn JH, et al. Current trends of the incidence and pathological diagnosis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in Korea 2000–2009: multicenter Study. Cancer Res Treat. 2012;44:157–65.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Lepage C, Bouvier AM, Faivre J. Endocrine tumours: epidemiology of malignant digestive neuroendocrine tumours. Eur J Endocrinol. 2013;168:R77–83.CrossRefPubMedGoogle Scholar
  4. 4.
    Bosman FT, Carneiro F, Hruban RH. WHO Classification of Tumours of the Digestive System. Lyon: International Agency for Research on Cancer (IARC), 2010.Google Scholar
  5. 5.
    Sorbye H, Strosberg J, Baudin E, Klimstra DS, Yao JC. Gastroenteropancreatic high-grade neuroendocrine carcinoma. Cancer. 2014;120:2814–23.CrossRefPubMedGoogle Scholar
  6. 6.
    Panzuto F, Boninsegna L, Fazio N, et al. Metastatic and locally advanced pancreatic endocrine carcinomas: analysis of factors associated with disease progression. J Clin Oncol. 2011;29:2372–7.CrossRefPubMedGoogle Scholar
  7. 7.
    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;29:3044–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Basturk O, Tang L, Hruban RH, et al. Poorly differentiated neuroendocrine carcinomas of the pancreas: a clinicopathologic analysis of 44 cases. Am J Surg Pathol. 2014;38:437–47.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Fischer L, Bergmann F, Schimmack S, et al. Outcome of surgery for pancreatic neuroendocrine neoplasms. Br J Surg. 2014;101:1405–12.CrossRefPubMedGoogle Scholar
  10. 10.
    Kinoshita K, Minami T, Ohmori Y, Kanayama S, Yoshikawa K, Tsujimura T. Curative resection of a small cell carcinoma of the pancreas: report of a case of long survival without chemotherapy. J Gastroenterol Hepatol. 2004;19:1087–91.CrossRefPubMedGoogle Scholar
  11. 11.
    Winter JM, Narang AK, Mansfield AS, et al. Resectable pancreatic small cell carcinoma. Rare Tumors. 2011;3:e5.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Berkel S, Hummel F, Gaa J, et al. Poorly differentiated small cell carcinoma of the pancreas: a case report and review of the literature. Pancreatology. 2004;4:521–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Sorbye H, Westre B, Horn A. Curative surgery after neoadjuvant chemotherapy in metastatic poorly differentiated neuroendocrine carcinoma. Eur J Surg Oncol. 2007;33:1209–10.CrossRefPubMedGoogle Scholar
  14. 14.
    Groeschl RT, Christians KK, Turaga KK, Gamblin TC. Management of primary hepatopancreatobiliary small cell carcinoma. J Surg Oncol. 2013;107:692–5.CrossRefPubMedGoogle Scholar
  15. 15.
    Kolby L, Nilsson O, Ahlman H. Gastroduodenal endocrine tumours. Scand J Surg. 2004;93:317–23.PubMedGoogle Scholar
  16. 16.
    Akerstrom G. Management of carcinoid tumors of the stomach, duodenum, and pancreas. World J Surg. 1996;20:173–82.CrossRefPubMedGoogle Scholar
  17. 17.
    Nilsson O, Van CE, Delle FG, et al. Poorly differentiated carcinomas of the foregut (gastric, duodenal, and pancreatic). Neuroendocrinology. 2006;84:212–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Strosberg JR, Coppola D, Klimstra DS, et al. The NANETS consensus guidelines for the diagnosis and management of poorly differentiated (high-grade) extrapulmonary neuroendocrine carcinomas. Pancreas. 2010;39:799–800.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Kunz PL, Reidy-Lagunes D, Anthony LB, et al. Consensus guidelines for the management and treatment of neuroendocrine tumors. Pancreas. 2013;42:557–77.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Oberg K, Knigge U, Kwekkeboom D, Perren A. Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii124–30.PubMedGoogle Scholar
  21. 21.
    Rindi G, Kloppel G, Alhman H, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006;449:395–401.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hadoux J, Malka D, Planchard D, et al. Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma. Endocr Relat Cancer. 2015;22:289–98.CrossRefPubMedGoogle Scholar
  23. 23.
    Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649–55.CrossRefPubMedGoogle Scholar
  24. 24.
    StataCorp. Stata Statistical Software: Release 13. College Station: StataCorp LP, 2013.Google Scholar
  25. 25.
    Winter JM, Brennan MF, Tang LH, et al. Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades. Ann Surg Oncol. 2012;19:169–75.CrossRefPubMedGoogle Scholar
  26. 26.
    Smith JD, Reidy DL, Goodman KA, Shia J, Nash GM. A retrospective review of 126 high-grade neuroendocrine carcinomas of the colon and rectum. Ann Surg Oncol. 2014;21:2956–62.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Korse CM, Taal BG, van Velthuysen ML, Visser O. Incidence and survival of neuroendocrine tumours in the Netherlands according to histological grade: experience of two decades of cancer registry. Eur J Cancer. 2013;49:1975–83.CrossRefPubMedGoogle Scholar
  28. 28.
    Yang Z, Tang LH, Klimstra DS. Gastroenteropancreatic neuroendocrine neoplasms: historical context and current issues. Semin Diagn Pathol. 2013;30:186–96.CrossRefPubMedGoogle Scholar
  29. 29.
    Velayoudom-Cephise FL, Duvillard P, Foucan L, et al. Are G3 ENETS neuroendocrine neoplasms heterogeneous? Endocr Relat Cancer. 2013;20:649–57.CrossRefPubMedGoogle Scholar
  30. 30.
    Basturk O, Yang Z, Tang LH. Increased (>20%) KI67 proliferation index in morphologically well-differentiated pancreatic neuroendocrine tumors (pannets) correlates with decreased overall survival. Lab Invest. 2013;93(Suppl 1):4234.Google Scholar
  31. 31.
    Shi C, Gonzalez RS, Zhao Z, et al. Liver metastases of small intestine neuroendocrine tumors: Ki-67 heterogeneity and World Health Organization grade discordance with primary tumors. Am J Clin Pathol. 2015;143:398–404.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Zen Y, Heaton N. Elevated Ki-67 labeling index in “synchronous liver metastases” of well-differentiated enteropancreatic neuroendocrine tumor. Pathol Int. 2013;63:532–8.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Sven-Petter Haugvik
    • 1
    • 2
    Email author
  • Eva Tiensuu Janson
    • 3
  • Pia Österlund
    • 4
  • Seppo W. Langer
    • 5
  • Ragnhild Sørum Falk
    • 6
  • Knut Jørgen Labori
    • 1
  • Lene Weber Vestermark
    • 7
  • Henning Grønbæk
    • 8
  • Ivar Prydz Gladhaug
    • 1
    • 2
  • Halfdan Sorbye
    • 9
  1. 1.Department of Hepato-Pancreato-Biliary SurgeryRikshospitalet, Oslo University HospitalOsloNorway
  2. 2.Institute of Clinical MedicineUniversity of OsloOsloNorway
  3. 3.Department of Medical SciencesUppsala UniversityUppsalaSweden
  4. 4.Department of OncologyHelsinki University Central HospitalHelsinkiFinland
  5. 5.Department of OncologyRigshospitalet, University of CopenhagenCopenhagenDenmark
  6. 6.Oslo Centre for Biostatistics and EpidemiologyOslo University HospitalOsloNorway
  7. 7.Department of OncologyOdense University HospitalOdense CDenmark
  8. 8.Department of Hepatology and GastroenterologyAarhus University HospitalAarhusDenmark
  9. 9.Department of OncologyHaukeland University HospitalBergenNorway

Personalised recommendations