Neuroendokrine Tumoren des Gastrointestinaltraktes

 

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Zusammenfassung

Zwei Drittel aller neuroendokrinen Tumoren (NET) sind im gastroentero-pankreatischen System lokalisiert. Je nach Lokalisation zeigen sich Unterschiede in Differenzierung, klinischer Symptomatik und Prognose. Die Symptome sind meistens durch lokale Tumormasseneffekte oder tumorassoziierte Fibrose bedingt. Ein „Karzinoidsyndrom” mit Flush und Diarrhoe tritt bei < 10 % der Patienten auf. Diagnostisch sind initial die Bestimmung von Chromogranin A (Serum) oder der 5-Hydroxyindolessigsäure (24h-Sammelurin) angezeigt. Bildgebend steht die Somatostatinrezeptorszintigraphie im Vordergrund, kann aber durch die CT/MRT zur genaueren topographischen Abgrenzung ergänzt werden. Neuere endoskopische Verfahren wie die Kapselendoskopie werden in der Diagnostik von NET des Dünndarms momentan evaluiert. In der Behandlung stellt die chirurgische Resektion nach wie vor das einzig kurative Verfahren dar. Allerdings ist diese nur in etwa 20 % der Fälle möglich, abhängig von der Lokalisation und Ausdehnung des Primarius. Bei hepatischer Beteiligung sollten lokal ablative Verfahren erwogen werden. In der konservativen Therapie sind Somatostatinanaloga der Goldstandard bei vergleichbarem therapeutischem Potential von Interferonen. Traditionelle zytotoxische Chemotherapie ist nur bei schlecht differenzierten, therapierefraktären NET indiziert. Neue Agenzien mit Angriff an unterschiedlichen intra- und interzellulären Signalwegen werden momentan geprüft. Eine symptombezogene supportive Therapie ist sinnvoll.

Summary

Two thirds of all neuroendocrine tumors (NET) are located in the gastroentero-pancreatic system. Depending on its localisation, each tumor presents a different histological pattern as well as different clinical symptoms and prognosis. Symptoms are usually due to the mass effects of the local tumor or tumor-related fibrosis. The classical „carcinoid-syndrome” with flush and diarrhea is seen in fewer than 10 %. Tests like chromogranin A (serum) or 5-hydroxyindolacetic acid (24h urine-collection) are indicators for the initial diagnosis of NET. Somatostatin-receptor scintigraphy is the most valuable imaging modality. In addition CT/MRI can be used for further topographical definition. Endoscopic techniques like the use of capsule endoscopy are being evaluated for the diagnosis of small intestinal NETs. The only curative treatment of NET is still complete surgical resection. However, it can only be done in 20 %, depending on localization and local extension of the primary tumor. If the liver is involved local ablation techniques should be considered. The gold standard for medical treatment is the use of somatostatin analogs, although interferons show a comparable therapeutic potential. Traditional cytotoxic agents should only be used for poorly differentiated tumors refractory to other forms of treatment. New compounds that target different pathways at the intra- and intercellular level are under investigation. Supportive therapy should be considered for the control of symptoms.

Literatur

• 1 Ahlman H, Nilsson O, Olausson M. Interventional treatment of the carcinoid syndrome.  Neuroendocrinology. 2004;  80 Suppl 1 67-73
  Google Scholar
• 2 Arnold R, Rinke A, Schmidt C. et al . Endocrine tumours of the gastrointestinal tract: Chemotherapy.  Best Pract Res Clin Gastroenterol. 2005;  19 649-656
  Google Scholar
• 3 Berber E, Flesher N, Siperstein A E. Laparoscopic radiofrequency ablation of neuroendocrine liver metastases.  World J Surg. 2002;  26 985-990
  Google Scholar
• 4 Berge T, Lundberg S. Cancer in Malmo 1958 – 1969. An autopsy study.  Acta Pathol Microbiol Scand Suppl. 1977;  260 1-235
  Google Scholar
• 5 Bruns C, Lewis I, Briner U. et al . SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile.  Eur J Endocrinol. 2002;  146 707-716
  Google Scholar
• 6 Buchmann I, Henze M, Engelbrecht S. et al . Comparison of (68)Ga-DOTATOC PET and (111)In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours.  Eur J Nucl Med Mol Imaging. 2007;  34 1617-1626
  Google Scholar
• 7 Chung M H, Pisegna J, Spirt M. et al . Hepatic cytoreduction followed by a novel long-acting somatostatin analog: a paradigm for intractable neuroendocrine tumors metastatic to the liver.  Surgery. 2001;  130 954-962
  Google Scholar
• 8 Correale P, Sciandivasci A, Intrivici C. et al . Chemo-hormone therapy of non-well-differentiated endocrine tumours from different anatomic sites with cisplatinum, etoposide and slow release lanreotide formulation.  Br J Cancer. 2007;  7,96 1343-1347
  Google Scholar
• 9 Esser J P, Krenning E P, Teunissen J J. et al . Comparison of [(177)Lu-DOTA(0),Tyr(3)]octreotate and [(177)Lu-DOTA(0),Tyr(3)]octreotide: which peptide is preferable for PRRT?.  Eur J Nucl Med Mol Imaging. 2006;  33 1346-1351
  Google Scholar
• 10 Feldman J M, Lee E M. Serotonin content of foods: effect on urinary excretion of 5-hydroxyindoleacetic acid.  Am J Clin Nutr. 1985;  42 639-643
  Google Scholar
• 11 Forrer F, Uusijarvi H, Storch D. et al . Treatment with 177Lu-DOTATOC of patients with relapse of neuroendocrine tumors after treatment with 90Y-DOTATOC.  J Nucl Med. 2005;  46 1310-1316
  Google Scholar
• 12 Frilling A, Weber F, Saner F. et al . Treatment with (90)Y- and (177)Lu-DOTATOC in patients with metastatic neuroendocrine tumors.  Surgery. 2006;  140 968-976
  Google Scholar
• 13 Gabriel M, Decristoforo C, Kendler D. et al . 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT.  J Nucl Med. 2007;  48 508-518
  Google Scholar
• 14 Gay G, Delvaux M, Rey J F. The role of video capsule endoscopy in the diagnosis of digestive diseases: a review of current possibilities.  Endoscopy. 2004;  36 913-920
  Google Scholar
• 15 Gustafsson B I, Tommeras K, Nordrum I. et al . Long-term serotonin administration induces heart valve disease in rats.  Circulation. 2005;  29,111 1517-1522
  Google Scholar
• 16 Kaltsas G A, Besser G M, Grossman A B. The diagnosis and medical management of advanced neuroendocrine tumors.  Endocr Rev. 2004;  25 458-511
  Google Scholar
• 17 Lewis B S, Eisen G M, Friedman S. A pooled analysis to evaluate results of capsule endoscopy trials.  Endoscopy. 2005;  37 960-965
  Google Scholar
• 18 Modlin I M, Kidd M, Latich I. et al . Current status of gastrointestinal carcinoids.  Gastroenterology. 2005;  128 1717-1751
  Google Scholar
• 19 Modlin I M, Latich I, Kidd M. et al . Therapeutic options for gastrointestinal carcinoids.  Clin Gastroenterol Hepatol. 2006;  4 526-547
  Google Scholar
• 20 Modlin I M, Latich I, Zikusoka M. et al . Gastrointestinal carcinoids: the evolution of diagnostic strategies.  J Clin Gastroenterol. 2006;  40 572-582
  Google Scholar
• 21 Modlin I M, Lye K D, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors.  Cancer. 2003;  15,97 934-959
  Google Scholar
• 22 Modlin I M, Tang L H. Approaches to the diagnosis of gut neuroendocrine tumors: the last word (today).  Gastroenterology. 1997;  112 583-590
  Google Scholar
• 23 Nilsson O, Kolby L, Wangberg B. et al . Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours.  Br J Cancer. 1998;  77 632-637
  Google Scholar
• 24 Oberg K, Kvols L, Caplin M. et al . Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system.  Ann Oncol. 2004;  15 966-973
  Google Scholar
• 25 Okamoto Y, Fujii M, Tateiwa S. et al . Treatment of multiple rectal carcinoids by endoscopic mucosal resection using a device for esophageal variceal ligation.  Endoscopy. 2004;  36 469-470
  Google Scholar
• 26 Osborne D A, Zervos E E, Strosberg J. et al . Improved outcome with cytoreduction versus embolization for symptomatic hepatic metastases of carcinoid and neuroendocrine tumors.  Ann Surg Oncol. 2006;  13 572-581
  Google Scholar
• 27 Plockinger U, Rindi G, Arnold R. et al . Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS).  Neuroendocrinology. 2004;  80 394-424
  Google Scholar
• 28 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
  Google Scholar
• 29 Sarmiento J M, Heywood G, Rubin J. et al . Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival.  J Am Coll Surg. 2003;  197 29-37
  Google Scholar
• 30 Schmid H A. Pasireotide (SOM230): Development, mechanism of action and potential applications.  Mol Cell Endocrinol. 2008;  286 69-74
  Google Scholar
• 31 Solcia E, Kloppel G, Sobin L H. et al .Histological typing of endocrine tumours. WHO international histological classification of tumours. Berlin; Springer 2000
  Google Scholar
• 32 Sutcliffe R, Maguire D, Ramage J. et al . Management of neuroendocrine liver metastases.  Am J Surg. 2004;  187 39-46
  Google Scholar
• 33 Tormey W P, FitzGerald R J. The clinical and laboratory correlates of an increased urinary 5-hydroxyindoleacetic acid.  Postgrad Med J. 1995;  71 542-545
  Google Scholar
• 34 Vilar E, Salazar R, Perez-Garcia J. et al . Chemotherapy and role of the proliferation marker Ki-67 in digestive neuroendocrine tumors.  Endocr Relat Cancer. 2007;  14 221-232
  Google Scholar
• 35 Welsh J S, Kennedy A S, Thomadsen B. Selective Internal Radiation Therapy (SIRT) for liver metastases secondary to colorectal adenocarcinoma.  Int J Radiat Oncol Biol Phys. 2006;  66 62-73
  Google Scholar
• 36 Zuetenhorst J M, Taal B G. Metastatic carcinoid tumors: a clinical review.  Oncologist. 2005;  10 123-131
  Google Scholar

Irvin M. Modlin

Director, GI Surgical Pathobiology Research Group, Yale School of Medicine, Department of Surgery

P.O. Box 208062

New Haven, Connecticut 06520-8062

USA

Phone: 001-203 785 5429

Fax: 001-203 737 4067

Email: imodlin@optonline.net