Lebermetastasierung bei neuroendokrinen Karzinomen des gastro-entero-pankreatischen Systems – Therapiestrategien

Zusammenfassung

Neuroendokrine Tumoren (NET) unterscheiden sich bezüglich ihres biologischen Verhaltens erheblich von Tumoren epithelialen Ursprungs, was im Allgemeinen eine bessere 5-Jahres-Überlebensrate bedingt. Die Lebermetastasierung per se ­bedingt auch bei NET eine signifikante Verschlechterung des Überlebens im Vergleich zu nicht metastasierten Tumoren. Bei Diagnosestellung weisen im Gegensatz zu den epithelialen Tumor­patienten etwa ⅔ der NET-Patienten bereits Lebermetastasen auf, sodass trotz der Seltenheit dieser Tumoren der Chirurg mit dieser Tumor­entität konfrontiert wird. Die Prognose ist unter anderem abhängig von der Primärlokalisation des NET (Pankreas-NET schlechter als Nicht-Pankreas-NET) sowie dem Staging und Grading (Proliferationsindex Ki-67) der Tumoren. In dieser Arbeit soll die chirurgische und ablative Therapie von Lebermetastasen von NET des Gastrointestinaltrakts unter kurativen aber auch palliativen Gesichtspunkten anhand einer kürzlich publizierten Leitlinie der ENETS (European Neuroendo­crine Tumour Society) charakterisiert werden; weiterhin sollen die verschiedenen konservativen Therapieoptionen diskutiert und in ihrem Stellenwert dargestellt werden. Die Resektion von Leber­metastasen stellt bei lokalisiertem Tumorbefall auch beider Leberlappen (ein- und mehrzeitige Operation, ggf. in Kombination mit RFA) nach wie vor den Therapiestandard dar. Leber­resektionen auch im Sinne von Debulking-Operationen (Ziel: Resektion von > 90 % Tumorvolumen) können bei guter präoperativer Planung auch ­unter palliativen Kriterien durchgeführt werden. Bei diffuser Lebermetastasierung mit über 50 % Tumorvolumen in der Leber ist in Einzelfällen die orthotope Lebertransplantation ggf. sogar als multiviszerale Transplantation zu erwägen. In ­Abhängigkeit von der Tumorlast der Leber, der Tumorlokalisation (intrahepatisch versus intra- und extrahepatisch), dem Tumorgrading (Proliferationsindex Ki-67), der Dynamik des Tumorwachstums und der Primarius­lokalisation des Tumors sollten bei inoperabler Metastasierung jeweils differenziert Biotherapie mit Somatostatinanaloga, peptidvermittelte Radiorezeptor-Therapie (PRRT), transarterielle Chemoembolisation (TACE) und selektive intraarterielle Radiotherapie (SIRT), Chemotherapie und neue molekular zielgerich­tete Therapieansätze eingesetzt werden. 

Abstract

Neuroendocrine tumours (NET) differ appreciably with regard to their biological behaviour from ­tumours of epithelial origin. In general this leads to a better 5-year survivial rate. Liver metastases per se and also in cases of NET result in a significantly poorer survival in comparison to tumours without metastases. In contrast to those with ­epithelial tumours, about ⅔ of the NET patients ­already have liver metastases at the time of diagnosis. Thus, in spite of the rarity of these tumours, the surgeon is frequently confronted with this ­tumour entity. Among other factors the prognosis depends on the primary localisation of the NET (panceatic NET poorer than non-pancreatic NET) as well as the staging and grading (proliferation index Ki-67) of the tumours. In this article, we characterise the surgical and ablative therapies for liver metastases from NET of the gastrointestinal tract from both curative and palliative points of view on the basis of the recently published guide­lines of the ENETS (European Neuroendo­crine Tumour Society). Furthermore, the various options for conservative therapy are discussed and assessed for their relative values. For loca­lised tumour disease, also of both liver lobes, the resection of liver metastases (single or multi-stage operation, if necessary in combination with RFA) remains the standard therapy. Liver resec­tions as debulking operations (target: resection of > 90 % tumour volume) with good preoperative planning can also be carried out under palliative criteria. For diffuse liver metastases with more than 50 % tumour volume in the liver, orthotopic liver transplantation, if necessary even as a multivisceral transplantation, may be considered in ­individual cases. For inoperable metastases, depending on the tumour load in the liver, the ­tumour localistaion (intrahepatic versus intra- and extrahepatic), the tumour grading (proliferation index Ki-67), the dynamics of tumour growth, and the primary localisation of the tumour, differen­tiat­ed biotherapy with somatostatin analogues, peptide-medi­ated radioreceptor therapy (PRRT), transarterial chemoembolisation (TACE) and selective intraarterial radiotherapy (SIRT), chemo­ther­apy and new molecular target-directed therapy op­tions can be employed. The utilities of these treatment options are pre­sented and discussed. 

Schlüsselwörter

neuroendokrine Tumoren - Lebermetastasen

Key words

neuroendocrine tumours - liver metastases

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