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Neuroendokrine Neoplasien des gastroenteropankreatischen Systems

Chirurgische Therapie

Gastroenteropancreatic neuroendocrine neoplasms

Surgical treatment

  • Schwerpunkt: Neuroendokrine Tumoren
  • Published:
Der Gastroenterologe Aims and scope

Zusammenfassung

Hintergrund

Gastroenteropankreatische neuroendokrine Neoplasien (GEP-NEN) stellen eine heterogene Tumorgruppe dar, welche sich hinsichtlich ihrer Prognose und Therapie von gewöhnlichen Adenokarzinomen des Gastrointestinaltrakts unterscheidet. Neben der chirurgischen Therapie stehen Biotherapie, Chemotherapie, Radiopeptidtherapie oder lokal ablative Verfahren zur Verfügung.

Ziel der Arbeit

Die Übersichtsarbeit soll aktuelle chirurgische Behandlungsstrategien von GEP-NEN darstellen.

Material und Methoden

Es wurden Publikationen und geltende Leitlinien zur Behandlung neuroendokriner Neoplasien ausgewertet.

Ergebnisse

GEP-NEN stellen aufgrund ihres variablen biologischen Verhaltens, der ggf. bestehenden hormonellen Aktivität und nicht selten assoziierter genetischer Prädispositionen komplexe Erkrankungen dar. Die vollständige Erfassung der klinischen Erscheinungsbilder ist Voraussetzung für ein differenziertes therapeutisches Vorgehen. Das therapeutische Spektrum umfasst neben der chirurgischen Resektion Biotherapie, Chemotherapie, Radiopeptidtherapie und lokal ablative Verfahren. Die chirurgische Therapie ist für die Behandlung neuroendokriner Neoplasien von zentraler Bedeutung. Aufgrund bisher unzureichender Evidenz zu Indikation, Zeitpunkt und notwendigem Resektionsausmaß chirurgischer Therapiestrategien fehlen jedoch in vielen Bereichen detaillierte Angaben in den geltenden Leitlinien.

Diskussion

Das chirurgische Vorgehen wird weiterhin in hohem Maße von zentrumsspezifischen Erfahrungen bestimmt. Die Beurteilung der präoperativen Befunde und die Festlegung des Vorgehens sollten in einem spezialisierten interdisziplinären Tumorboard erfolgen.

Abstract

Background

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) constitute a heterogeneous group of tumors. Prognosis and therapy differ significantly from adenocarcinomas of the gastrointestinal tract. Apart from surgery biotherapy, chemotherapy, radiopeptide therapy, and local ablation are available treatment options.

Objectives

The review describes the current surgical treatment strategies for GEP-NENs.

Materials and methods

Publications and established guidelines for the treatment of neuroendocrine neoplasms were evaluated.

Results

Because of the variable biological behavior, the possible hormone activity, and the frequently associated genetic predisposition, GEP-NENs present complex clinical pictures. The differentiated therapy is based on the comprehensive evaluation of the clinical situation. Apart from surgical resection the therapeutic spectrum encompasses biotherapy, chemotherapy, peptide receptor radionuclide therapy (PRRT), and local ablative methods. Surgical treatment is the only curative option and therefore of central importance. However, owing to the limited evidence referring to indication, optimal time, and the necessary extent of resection, detailed information is not outlined in many areas in the current guidelines.

Conclusions

The surgical strategy is still predominantly guided by center-specific experience. The assessment of preoperative findings and the determination of the optimal strategy should be discussed on specialized interdisciplinary boards.

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Literatur

  1. Salazar R, Wiedenmann B, Rindi G, Ruszniewski PENETS (2011) Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Tumors: an update. Neuroendocrinology 95(2):71–73

    Article  Google Scholar 

  2. Ramage JK, Ahmed A, Ardill J, Bax N, Breen DJ, Caplin ME et al (2012) Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut 61(1):6–32

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Pavel M, Baudin E, Couvelard A, Krenning E, Oberg K, Steinmuller T 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(2):157–176

    Article  CAS  PubMed  Google Scholar 

  4. Pape UF, Perren A, Niederle B, Gross D, Gress T, Costa F et al (2012) ENETS Consensus Guidelines for the management of patients with neuroendocrine neoplasms from the jejuno-ileum and the appendix including goblet cell carcinomas. Neuroendocrinology 95(2):135–156

    Article  CAS  PubMed  Google Scholar 

  5. Jensen RT, Cadiot G, Brandi ML, de Herder WW, Kaltsas G, Komminoth P et al (2012) ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. Neuroendocrinology 95(2):98–119

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Falconi M, Bartsch DK, Eriksson B, Kloppel G, Lopes JM, O’Connor JM et al (2012) ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic non-functioning tumors. Neuroendocrinology 95(2):120–134

    Article  CAS  PubMed  Google Scholar 

  7. Delle Fave G, Kwekkeboom DJ, Van Cutsem E, Rindi G, Kos-Kudla B, Knigge U et al (2012) ENETS consensus guidelines for the management of patients with gastroduodenal neoplasms. Neuroendocrinology 95(2):74–87

    Article  CAS  PubMed  Google Scholar 

  8. Caplin M, Sundin A, Nillson O, Baum RP, Klose KJ, Kelestimur F et al (2012) ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: colorectal neuroendocrine neoplasms. Neuroendocrinology 95(2):96–97

    Article  Google Scholar 

  9. Strosberg JR, Coppola D, Klimstra DS, Phan AT, Kulke MH, Wiseman GA et al (2010) The NANETS consensus guidelines for the diagnosis and management of poorly differentiated (high-grade) extrapulmonary neuroendocrine carcinomas. Pancreas 39(6):799–800

    Article  PubMed Central  PubMed  Google Scholar 

  10. Phan AT, Oberg K, Choi J, Jr Harrison LH, Hassan MM, Strosberg JR et al (2010) NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the thorax (includes lung and thymus). Pancreas 39(6):784–798

    Article  PubMed  Google Scholar 

  11. Kulke MH, Anthony LB, Bushnell DL, de Herder WW, Goldsmith SJ, Klimstra DS et al (2010) NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas 39(6):735–752

    Article  PubMed Central  PubMed  Google Scholar 

  12. Anthony LB, Strosberg JR, Klimstra DS, Maples WJ, O’Dorisio TM, Warner RR et al (2010) The NANETS consensus guidelines for the diagnosis and management of gastrointestinal neuroendocrine tumors (nets): well-differentiated nets of the distal colon and rectum. Pancreas 39(6):767–774

    Article  PubMed  Google Scholar 

  13. Oberg K, Knigge U, Kwekkeboom D, Perren A, Group EGW (2012) Neuroendocrine gastro-entero-pancreatic tumors: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(Suppl 7):vii124–vii130

    PubMed  Google Scholar 

  14. Janson ET, Sorbye H, Welin S, Federspiel B, Gronbaek H, Hellman P et al (2014) Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms. Acta Oncol 53(10):1284–1297

    Article  PubMed  Google Scholar 

  15. Kharazmi E, Pukkala E, Sundquist K, Hemminki K (2013) Familial risk of small intestinal carcinoid and adenocarcinoma. Clin Gastroenterol Hepatol 11(8):944–949

    Article  PubMed  Google Scholar 

  16. Marini F, Giusti F, Brandi ML (2015) Genetic test in multiple endocrine neoplasia type 1 syndrome: An evolving story. World J Exp Med 5(2):124–129

    Article  PubMed Central  PubMed  Google Scholar 

  17. Cunningham JL, Diaz de Stahl T, Sjoblom T, Westin G, Dumanski JP, Janson ET (2011) Common pathogenetic mechanism involving human chromosome 18 in familial and sporadic ileal carcinoid tumors. Genes Chromosom Cancer 50(2):82–94

    Article  CAS  PubMed  Google Scholar 

  18. Ichikawa J, Tanabe S, Koizumi W, Kida Y, Imaizumi H, Kida M et al (2003) Endoscopic mucosal resection in the management of gastric carcinoid tumors. Endoscopy 35(3):203–206

    Article  CAS  PubMed  Google Scholar 

  19. Rappel S, Altendorf-Hofmann A, Stolte M (1995) Prognosis of gastric carcinoid tumours. Digestion 56(6):455–462

    Article  CAS  PubMed  Google Scholar 

  20. Kloppel G, Scherubl H (2010) Neuroendocrine tumors of the stomach. Risk stratification and therapy. Pathologe 31(3):182–187

    Article  CAS  PubMed  Google Scholar 

  21. Campana D, Ravizza D, Ferolla P, Faggiano A, Grimaldi F, Albertelli M et al (2015) Clinical management of patients with gastric neuroendocrine neoplasms associated with chronic atrophic gastritis: a retrospective, multicentre study. Endocrine. DOI 10.1007/s12020-015-0584-z

  22. Delle Fave G, Capurso G, Annibale B, Panzuto F (2004) Gastric neuroendocrine tumors. Neuroendocrinology 80(Suppl 1):16–19

    Article  CAS  PubMed  Google Scholar 

  23. Akerstrom G, Hellman P (2007) Surgery on neuroendocrine tumours. Best practice research. Clin Endocrinol Metab 21(1):87–109

    Google Scholar 

  24. Rindi G, Bordi C, Rappel S, La Rosa S, Stolte M, Solcia E (1996) Gastric carcinoids and neuroendocrine carcinomas: pathogenesis, pathology, and behavior. World J Surg 20(2):168–172

    Article  CAS  PubMed  Google Scholar 

  25. Makridis C, Rastad J, Oberg K, Akerstrom G (1996) Progression of metastases and symptom improvement from laparotomy in midgut carcinoid tumors. World J Surg 20(7):900–906 (discussion 7)

    Article  CAS  PubMed  Google Scholar 

  26. Paul TV, Jacob JJ, Vasan SK, Thomas N, Rajarathnam S, Selvan B et al (2008) Management of insulinomas: analysis from a tertiary care referral center in India. World J Surg 32(4):576–582

    Article  PubMed  Google Scholar 

  27. Goretzki P, Starke A, Lammers B, Schwarz K, Roher HD (2010) Pancreatic hyperinsulinism-changes of the clinical picture and importance of differences in sporadic disease course (experience with 144 patients operated in the period 1986–2009. Zentralbl Chir 135(3):218–225

    Article  CAS  PubMed  Google Scholar 

  28. Anlauf M, Bauersfeld J, Raffel A, Koch CA, Henopp T, Alkatout I et al (2009) Insulinomatosis: a multicentric insulinoma disease that frequently causes early recurrent hyperinsulinemic hypoglycemia. Am J Surg Pathol 33(3):339–346

    Article  PubMed  Google Scholar 

  29. Mignon M, Ruszniewski P, Podevin P, Sabbagh L, Cadiot G, Rigaud D et al (1993) Current approach to the management of gastrinoma and insulinoma in adults with multiple endocrine neoplasia type I. World J Surg 17(4):489–497

    Article  CAS  PubMed  Google Scholar 

  30. Deutsch GB, Lee JH, Bilchik AJ (2015) Long-term survival with long-acting Somatostatin analogues plus aggressive Cytoreductive surgery in patients with metastatic Neuroendocrine carcinoma. J Am Coll Surg 221(1):26–36

    Article  PubMed  Google Scholar 

  31. Brunner SM, Weber F, Werner JM, Agha A, Farkas SA, Schlitt HJ et al (2015) Neuroendocrine tumors of the pancreas: a retrospective single-center analysis using the ENETS TNM-classification and immunohistochemical markers for risk stratification. Bmc Surg 15:49

    Article  PubMed Central  PubMed  Google Scholar 

  32. Watzka FM, Fottner C, Miederer M, Schad A, Weber MM, Otto G et al (2015) Surgical therapy of neuroendocrine neoplasm with hepatic metastasis: patient selection and prognosis. Langenbeck’s Arch Surg 400(3):349–358

    Article  CAS  Google Scholar 

  33. Franko J, Feng W, Yip L, Genovese E, Moser AJ (2010) Non-functional neuroendocrine carcinoma of the pancreas: incidence, tumor biology, and outcomes in 2,158 patients. J Gastrointest Surg 14(3):541–548

    Article  PubMed  Google Scholar 

  34. Furukori M, Imai K, Karasaki H, Watanabe K, Oikawa K, Miyokawa N et al (2014) Clinicopathological features of small nonfunctioning pancreatic neuroendocrine tumors. World J Gastroenterol Wjg 20(47):17949–17954

    PubMed  Google Scholar 

  35. Hashim YM, Trinkaus KM, Linehan DC, Strasberg SS, Fields RC, Cao D et al (2014) Regional lymphadenectomy is indicated in the surgical treatment of pancreatic neuroendocrine tumors (PNETs). Ann Surgery 259(2):197–203

    Article  Google Scholar 

  36. Rindi G, Kloppel G, Alhman H, Caplin M, Couvelard A, de Herder WW et al (2006) TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch Int J Pathol 449(4):395–401

    Article  CAS  Google Scholar 

  37. Fendrich V, Bartsch DK (2011) Surgical treatment of gastrointestinal neuroendocrine tumors. Langenbeck’s Arch Surg 396(3):299–311

    Article  Google Scholar 

  38. Musholt TJ (2011) Extent of resection for neuroendocrine tumors of the small intestine. Chirurg 82(7):591–597

    Article  CAS  PubMed  Google Scholar 

  39. Öhrvall U, Eriksson B, Juhlin C, Karacagil S, Rastad J, Hellman P et al (2000) Method for dissection of mesenteric metastases in mid-gut carcinoid tumors. World J Surgery 24(11):1402–1408

    Article  Google Scholar 

  40. Norlen O, Stalberg P, Oberg K, Eriksson J, Hedberg J, Hessman O et al (2012) Long-term results of surgery for small intestinal neuroendocrine tumors at a tertiary referral center. World J Surg 36(6):1419–1431

    Article  PubMed  Google Scholar 

  41. Bertani E, Falconi M, Grana C, Botteri E, Chiappa A, Misitano P et al (2015) Small intestinal neuroendocrine tumors with liver metastases and resection of the primary: Prognostic factors for decision making. Int J Surg 20:58–64

    Article  PubMed  Google Scholar 

  42. Henderson L, Fehily C, Folaranmi S, Kelsey A, McPartland J, Jawaid WB et al (2014) Management and outcome of neuroendocrine tumours of the appendix-a two centre UK experience. J Pediatr Surgery 49(10):1513–1517

    Article  Google Scholar 

  43. Dralle H (2011) Surgical strategies for accidental detection of appendix carcinoids. Chirurg 82(7):598–606

    Article  CAS  PubMed  Google Scholar 

  44. Musholt TJ (2010) Therapiehandbuch. Urban & Fischer, München

    Google Scholar 

  45. Ahmed A, Turner G, King B, Jones L, Culliford D, McCance D et al (2009) Midgut neuroendocrine tumours with liver metastases: results of the UKINETS study. Endocrine-related Cancer 16(3):885–894

    Article  CAS  PubMed  Google Scholar 

  46. Miller HC, Drymousis P, Flora R, Goldin R, Spalding D, Frilling A (2014) Role of Ki-67 proliferation index in the assessment of patients with neuroendocrine neoplasias regarding the stage of disease. World J Surg 38(6):135

    Article  Google Scholar 

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Authors and Affiliations

  1. Sektion Endokrine Chirurgie der Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsmedizin der Johannes Gutenberg Universität Mainz, Langenbeckstr. 1, 55101, Mainz, Deutschland

    T. J. Musholt & F. M. Watzka

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Correspondence to T. J. Musholt.

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T. J. Musholt und F. M. Watzka geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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R. Schmid, München

B. Wiedenmann, Berlin

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Musholt, T.J., Watzka, F.M. Neuroendokrine Neoplasien des gastroenteropankreatischen Systems. Gastroenterologe 10, 410–417 (2015). https://doi.org/10.1007/s11377-015-0003-2

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