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Gastroenterologie up2date 2015; 11(02): 119-133
DOI: 10.1055/s-0034-1392312
Ösophagus/ Magen/ Duodenum
© Georg Thieme Verlag KG Stuttgart · New York

Gastrointestinaler Stromatumor (GIST)

Silke Cameron
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Publication History

Publication Date:
15 June 2015 (online)

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Epidemiologie

  • GIST entstehen aus den Schrittmacherzellen des Gastrointestinaltraktes (Cajal-Zellen) oder deren Vorläuferzellen. Externe Risikofaktoren sind nicht bekannt.

  • GIST sind insgesamt seltene Tumoren des Gastrointestinaltraktes mit einer Inzidenz von 1 – 2/100 000 pro Jahr. Der Altersmedian sporadischer GIST liegt bei 55 – 65 Jahren.

  • Pädiatrische GIST, familiäre GIST und syndromale GIST sind beschrieben.

  • Die häufigste Lokalisation ist der Magen (mit 60 %), gefolgt von Dünndarm (25 – 35 %) und Dickdarm (5 %). Ösophagus-GIST sind selten (2 – 3 %).

Diagnostik

  • Die klinische Diagnostik richtet sich nach dem Beschwerdebild des Patienten.

  • Bei Magen-, Duodenal- und Rektum-GIST wird die endoskopische Diagnostik ergänzt durch Ultraschall (endosonografisch gut als submuköser Tumor einzuordnen) und CT.

  • Eine histologische Sicherung mittels Knopflochbiopsie oder endosonografischer Punktion wird empfohlen.

  • Zur Vereinheitlichung der Tumorklassifikationen wurden GIST in die UICC/TNM-Klassifikation maligner Tumoren integriert. In diese gehen Lokalisation, Tumorgröße und Mitoserate ein. Die Angabe der Mitoserate pro 5 mm2 ist der Angabe pro 50 Gesichtsfelder vorzuziehen.

  • Die Einschätzung des Rezidivrisikos orientiert sich an der AFIP-Klassifikation von Miettinen et al. Es werden Hochrisiko-GIST, GIST vom intermediären Typ, Niedrigrisiko-GIST und GIST mit sehr niedrigem Risiko unterschieden.

  • Die Mutationsanalyse hat eine prognostische Bedeutung, vor allem jedoch einen prädiktiven Vorhersagewert für die Wahl der Therapie.

Therapie

  • Die Therapie der Wahl ist die R0-Resektion.

  • Die Tumorresektion erfolgt in der Regel organerhaltend, wenn möglich minimalinvasiv. Eine Lymphknotendissektion ist nicht erforderlich. Eine Tumorruptur ist in jedem Fall zu vermeiden. Bei Ruptur gilt der Tumor als „virtuell“ metastasiert.

  • Der Zeitpunkt der Operation richtet sich nach Tumorgröße und Symptomatik. Magen-GIST sollten ab einer Größe von 2 cm reseziert werden. Für größere GIST kann eine neoadjuvante Therapie nach histologischer Sicherung mit Mutationsanalyse erwogen werden. Dünndarm-GIST werden meist durch ihre klinische Symptomatik apparent, sodass eine zeitnahe Operation notwendig wird.

  • Die medikamentöse Therapie orientiert sich an der Risikoklassifikation.

  • Bei Hochrisiko-GIST erfolgt eine adjuvante Therapie mit Imatinib (400 mg) über 3 Jahre postoperativ. Bei KIT-Exon-9-Mutation kann die Dosis auf 800 mg erhöht werden. Bei Imatinib-resistenten Mutationen wie der PDGFRA-Exon-18-D842V-Mutation wird eine adjuvante Therapie nicht empfohlen.

  • In der palliativen Therapie lokal fortgeschrittener oder metastasierter GIST stellt Imatinib (auch nach adjuvanter Therapie) die erste Behandlungslinie dar.

  • In der Zweitlinie kann Imatinib zunächst auf 800 mg erhöht werden oder eine Umstellung auf Sunitinib (37,5 mg) erfolgen.

  • Die zugelassene Drittlinientherapie ist Regorafenib. Mit einem ausgeprägten Hand-Fuß-Syndrom mit Therapiereduktion ist zu rechnen. Alternativ kann Sorafenib eingesetzt werden. Weitere Multikinase-Inhibitoren werden getestet.

  • Nebenwirkungen betreffen insbesondere Haut und Gastrointestinaltrakt. Substanzen, die über Cytochrom-P450-Isoenzyme (CYP3A4) verstoffwechselt werden, können den Medikamentenspiegel von Tyrosinkinase-Inhibitoren beeinflussen und in ihrem Spiegel beeinflusst werden.

  • Richtlinien zur Nachsorge sind bisher nicht etabliert. Eine regelmäßige und für Patienten mit Hochrisiko-GIST und intermediärem GIST engmaschige (alle 3 – 6 Monate) Nachsorge bis 5 Jahre nach Therapieende wird empfohlen. Spätrezidive und Zweittumoren sind möglich, sodass die Nachsorge in der Regel fortgesetzt wird.

 

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