Skip to main content
SpringerLink
Log in

Stellenwert der Chirurgie bei fernmetastasierten neuroendokrinen Neoplasien des Pankreas

Importance of surgery in distant metastatic pancreatic neuroendocrine neoplasms

  • Leitthema
  • Published:
Die Chirurgie Aims and scope Submit manuscript

Zusammenfassung

Die Mehrzahl der Patienten mit pankreatischer neuroendokriner Neoplasie (pNEN) weist bereits bei Diagnosestellung eine Fernmetastasierung auf. Die Heterogenität der pNEN und das breite Spektrum der Therapiemöglichkeiten machen eine adäquate Patientenselektion und eine evidenzbasierte Strategie unerlässlich. Beim metastasierten pNEN konnte belegt werden, dass sowohl die Primariusresektion als auch die Resektion der Lebermetastasen zu einer Verbesserung des Gesamtüberlebens führen. Die chirurgische Behandlung der Lebermetastasen kann – insbesondere bei symptomatischen pNEN – auch in palliativer Absicht erfolgen und mit einem positiven Einfluss auf krankheitsfreies Überleben und Gesamtüberleben verbunden sein. Es stehen dem Chirurgen die klassischen Leberresektionstechniken sowie innovative Techniken (2-zeitige Resektionen, Lebertransplantation) zur Verfügung. Bei komplexem Befall gibt es zunehmende Evidenz für eine Kombination der Chirurgie mit ablativen Methoden. Eine Einbindung der Patienten in multimodale Konzepte ist aufgrund eines insgesamt hohen Rezidivrisikos nach Leberresektion immer erforderlich. Aktuelle Spannungsfelder in der Behandlung der metastasierten pNEN sind der Einsatz adjuvanter/neoadjuvanter Chemotherapie und der Chirurgie bei G3-NEN- und G3-NEC(neuroendokrines Karzinom)-Patienten. Ziel dieser Übersichtsarbeit ist es, den Stellenwert der Chirurgie bei fernmetastasierten NEN des Pankreas darzulegen.

Abstract

The majority of patients with pancreatic neuroendocrine neoplasms (pNEN) already present with distant metastases at diagnosis. The heterogeneity of pNEN and the broad spectrum of treatment options make adequate patient selection and an evidence-based strategy essential. In metastatic pNEN both primary resection and resection of liver metastases have been shown to improve overall survival. Surgical treatment of liver metastases can also be carried out with palliative intent, especially for symptomatic pNEN and can have a positive effect on disease-free survival and overall survival. Classical hepatectomy techniques and innovative techniques (two-stage resections, liver transplantation) are available to the surgeon. In complex growth types of liver metastases, there is increasing evidence for a combination of surgery and ablative methods. Due to a relevant risk of recurrence following liver resection, pNEN patients need to be included in multimodal treatment concepts. Current areas of interest in the treatment of metastatic pNEN are the use of adjuvant/neoadjuvant chemotherapy and surgery in G3-NEN and G3-NEC patients. The aim of this review is to give an overview on the impact of surgery in the situation of distant metastatic NEN of the pancreas.

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

Abb. 1

Abbreviations

ALPPS:

Associating liver partition and portal vein ligation for staged hepatectomy

DFS :

Disease free survival (krankheitsfreies Überleben)

ENETS:

European NeuroEndocrine Tumor Society

G1, G2, G3:

Tumorgrading 1, 2, 3

GEP-NEN:

Gastroenteropankreatische neuroendokrine Neoplasie(n)

HIPEC:

Hypertherme intraperitoneale Chemoperfusion

IFN:

Interferon

LiTT:

Laserinduzierte Thermotherapie

NANETS:

North American NeuroEndocrine Tumor Society

NEC:

Neuroendokrines Karzinom

NELM:

Neuroendokrine Lebermetastase(n)

NEN:

Neuroendokrine Neoplasie(n)

NF-pNEN:

Nichtfunktionelle pankreatische neuroendokrine Neoplasie(n)

OS :

Overall survival (Gesamtüberleben)

PC:

Peritonealkarzinose

PFS :

Progression free survival (progressionsfreies Überleben)

PNELM:

Neuroendokrine Lebermetastase(n) eines pNEN

pNEN:

Pankreatische neuroendokrine Neoplasie(n)

PRRT:

Peptidvermittelte Radiorezeptorentherapie

PTR:

Primärtumorresektion

RPVE:

Embolisation der rechten Pfortader

RPVL:

Ligatur der rechten Pfortader

SIRT:

Selektive interne Radiotherapie

SSA:

Somatostatinanaloga

TACE:

Transarterielle Chemoembolisation

TAE:

Transarterielle Embolisation

ZVD:

Zentralvenöser Druck

Literatur

  1. Birnbaum DJ, Turrini O, Vigano L et al (2015) Surgical management of advanced pancreatic neuroendocrine tumors: short-term and long-term results from an international multi-institutional study. Ann Surg Oncol 22:1000–1007

    Article  Google Scholar 

  2. Bösch F, Werner J, Angele MK et al (2018) Oligometastasierung beim neuroendokrinen Tumoren – Ausmaß der Chirurgie. Chirurg 89:516–522

    Article  Google Scholar 

  3. Capurso G, Rinzivillo M, Bettini R et al (2012) Systematic review of resection of primary midgut carcinoid tumour in patients with unresectable liver metastases. Br J Surg 99:1480–1486

    Article  CAS  Google Scholar 

  4. Chan DL, Dixon M, Law CHL et al (2018) Outcomes of Cytoreductive surgery for metastatic low-grade neuroendocrine tumors in the setting of extrahepatic metastases. Ann Surg Oncol 25:1768–1774

    Article  Google Scholar 

  5. Clift AK, Kidd M, Bodei L et al (2020) Neuroendocrine neoplasms of the small bowel and pancreas. Neuroendocrinology 110:444–476

    Article  CAS  Google Scholar 

  6. Cloyd JM, Omichi K, Mizuno T et al (2018) Preoperative fluorouracil, doxorubicin, and streptozocin for the treatment of pancreatic neuroendocrine liver metastases. Ann Surg Oncol 25:1709–1715

    Article  Google Scholar 

  7. Cloyd JM, Mizuno T, Kawaguchi Y et al (2020) Comprehensive complication index validates improved outcomes over time despite increased complexity in 3707 consecutive hepatectomies. Ann Surg 271:724–731

    Article  Google Scholar 

  8. Elias D, David A, Sourrouille I et al (2014) Neuroendocrine carcinomas: optimal surgery of peritoneal metastases (and associated intra-abdominal metastases). Surgery 155:5–12

    Article  Google Scholar 

  9. El Lakis M, Gianakou A, Nockel P et al (2019) Radioguided surgery with gallium 68 Dotatate for patients with neuroendocrine tumors. JAMA Surg 154:40–45

    Article  Google Scholar 

  10. Fairweather M, Swanson R, Wang J et al (2017) Management of neuroendocrine tumor liver metastases: long-term outcomes and prognostic factors from a large prospective database. Ann Surg Oncol 24:2319–2325

    Article  Google Scholar 

  11. Fan ST, Le Treut YP, Mazzaferro V et al (2015) Liver transplantation for neuroendocrine tumour liver metastases. HPB 17:23–28

    Article  Google Scholar 

  12. Feng T, Lu W, Yuan M et al (2019) Surgical resection of the primary tumor leads to prolonged survival in metastatic pancreatic neuroendocrine carcinoma. World J Surg Oncol 17:54

    Article  Google Scholar 

  13. Frilling A, Li J, Malamutmann E et al (2009) Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease. Br J Surg 96:175–184

    Article  CAS  Google Scholar 

  14. Frilling A, Clift AK (2015) Therapeutic strategies for neuroendocrine liver metastases. Cancer 121:1172–1186

    Article  CAS  Google Scholar 

  15. Galleberg RB, Knigge U, Tiensuu Janson E et al (2017) Results after surgical treatment of liver metastases in patients with high-grade gastroenteropancreatic neuroendocrine carcinomas. Eur J Surg Oncol 43:1682–1689

    Article  CAS  Google Scholar 

  16. Haugvik SP, Janson ET, Osterlund P et al (2016) Surgical treatment as a principle for patients with high-grade pancreatic neuroendocrine carcinoma: a nordic multicenter comparative study. Ann Surg Oncol 23:1721–1728

    Article  Google Scholar 

  17. Howe JR, Merchant NB, Conrad C et al (2020) The north American neuroendocrine tumor society consensus paper on the surgical management of pancreatic neuroendocrine tumors. Pancreas 49:1–33

    Article  Google Scholar 

  18. Jiang J, Park J, Kim S et al (2021) Surgical resection of high-grade nonfunctional pancreatic neuroendocrine carcinoma is associated with improved survival. J Surg Oncol 124:1373–1380

    Article  Google Scholar 

  19. Jilesen AP, van Eijck CH, in’t Hof KH et al (2016) Postoperative complications, in-hospital mortality and 5‑year survival after surgical resection for patients with a pancreatic neuroendocrine tumor: a systematic review. World J Surg 40:729–748

    Article  Google Scholar 

  20. Kandil E, Noureldine SI, Koffron A et al (2012) Outcomes of laparoscopic and open resection for neuroendocrine liver metastases. Surgery 152:1225–1231

    Article  Google Scholar 

  21. Keutgen XM, Nilubol N, Glanville J et al (2016) Resection of primary tumor site is associated with prolonged survival in metastatic nonfunctioning pancreatic neuroendocrine tumors. Surgery 159:311–318

    Article  Google Scholar 

  22. Kishi Y, Abdalla EK, Chun YS et al (2009) Three hundred and one consecutive extended right hepatectomies: evaluation of outcome based on systematic liver volumetry. Ann Surg 250:540–548

    Article  Google Scholar 

  23. Klimstra DS, Modlin IR, Coppola D et al (2010) The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas 39:707–712

    Article  Google Scholar 

  24. Linecker M, Kambakamba P, Raptis DA et al (2020) ALPPS in neuroendocrine liver metastases not amenable for conventional resection—lessons learned from an interim analysis of the International ALPPS Registry. HPB 22:537–544

    Article  Google Scholar 

  25. Mazzaferro V, Sposito C, Coppa J et al (2016) The long-term benefit of liver transplantation for hepatic metastases from neuroendocrine tumors. Am J Transplant 16:2892–2902

    Article  CAS  Google Scholar 

  26. Morgan RE, Pommier SJ, Pommier RF (2018) Expanded criteria for debulking of liver metastasis also apply to pancreatic neuroendocrine tumors. Surgery 163:218–225

    Article  Google Scholar 

  27. Moris D, Tsilimigras DI, Ntanasis-Stathopoulos I et al (2017) Liver transplantation in patients with liver metastases from neuroendocrine tumors: a systematic review. Surgery 162:525–536

    Article  Google Scholar 

  28. NCCN Clinical Practice Guidelines in Oncology (2019) Neuroendocrine and Adrenal Tumors. https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf. Zugegriffen: 28. Febr. 2022

  29. Pavel M, Baudin E, Couvelard A et al (2012) ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 95:157–176

    Article  CAS  Google Scholar 

  30. Pavel M, O’Toole D, Costa F et al (2016) ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology 103:172–185

    Article  CAS  Google Scholar 

  31. Perysinakis I, Aggeli C, Kaltsas G et al (2016) Neoadjuvant therapy for advanced pancreatic neuroendocrine tumors: an emerging treatment modality? Hormones 15:15–22

    Article  Google Scholar 

  32. Squires M, Worth P, Konda B et al (2019) Neoadjuvant capecitabine/temozolomide for locally advanced or metastatic pancreatic neuroendocrine tumors. NANETS Annual Meeting, Boston

    Google Scholar 

  33. Shoup M, Gonen M, D’Angelica M et al (2003) Volumetric analysis predicts hepatic dysfunction in patients undergoing major liver resection. J Gastrointest Surg 7:325–330

    Article  Google Scholar 

  34. Taner T, Atwell TD, Zhang L et al (2013) Adjunctive radiofrequency ablation of metastatic neuroendocrine cancer to the liver complements surgical resection. HPB 15:190–195

    Article  Google Scholar 

  35. Yao JC, Fazio N, Singh S et al (2016) Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet 387:968–977

    Article  CAS  Google Scholar 

  36. Yuan CH, Wang J, Xiu DR et al (2016) Meta-analysis of liver resection versus non-surgical treatments for pancreatic neuroendocrine tumors with liver metastases. Ann Surg Oncol 23:244–249

    Article  Google Scholar 

  37. Zheng M, Li Y, Li T et al (2019) Resection of the primary tumor improves survival in patients with gastro-entero-pancreatic neuroendocrine neoplasms with liver metastases: a SEER-based analysis. Cancer Med 8:5128–5136

    Article  CAS  Google Scholar 

  38. Zhou B, Zhan C, Ding Y et al (2018) Role of palliative resection of the primary pancreatic neuroendocrine tumor in patients with unresectable metastatic liver disease: a systematic review and meta-analysis. Onco Targets Ther 11:975–982

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 420, 69120, Heidelberg, Deutschland

    F. Billmann, A. Nießen & T. Hackert

Authors
  1. F. Billmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Nießen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Hackert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. Billmann.

Ethics declarations

Interessenkonflikt

F. Billmann, A. Nießen und T. Hackert geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information

Redaktion

T. Hackert

M.W. Büchler, Heidelberg

figure qr

QR-Code scannen & Beitrag online lesen

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Billmann, F., Nießen, A. & Hackert, T. Stellenwert der Chirurgie bei fernmetastasierten neuroendokrinen Neoplasien des Pankreas. Chirurgie 93, 758–764 (2022). https://doi.org/10.1007/s00104-022-01630-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00104-022-01630-x

Schlüsselwörter

Keywords

Search

Navigation