Chemotherapie-assoziierte Hepatotoxizität in der Behandlung des kolorektalen Karzinoms (KRK)

Zusammenfassung

Die Einführung moderner, effektiver Chemotherapeutika wie Oxaliplatin und Irinotecan hat die Prognose von Patienten mit Lebermetastasen eines kolorektalen Karzinoms (KRK) entscheidend geändert. So können neue Kombinationstherapien die Umwandlung einer primär palliativen Erkrankung in eine resektable, somit potenziell kurative Erkrankung ermöglichen. Die Vorteile der Chemotherapie müssen allerdings gegenüber möglichen Nebenwirkungen abgewogen werden. Insbesondere bei Patienten mit Lebervorschädigung können chemotherapeutische Substanzen zu Leberveränderungen führen, die histologisch über das Maß reversibler Leberzellverfettung hinausgehen und zu Entzündung, Cholestase und Blutungen führen. In Analogie zur „Nicht alkoholischen Steatohepatitis (NASH)” wird im Schrifttum der Begriff der „Chemotherapie-assoziierten Steatohepatitis (CASH)” empfohlen. Insbesondere platinhaltige Substanzen führen zusätzlich zu Veränderungen der intrahepatischen Mikrozirkulation und damit zum sog. sinusoidalen Okklusionssysndrom (SOS). Erste Fallberichte weisen auf eine erhöhte postoperative Morbidität hin. Daten, die das individuelle Risiko eines Patienten vorhersagen helfen, fehlen bisher. Patienten, die eine Leberwerterhöhung aufweisen, die nicht durch die Lebermetastasen allein erklärbar sind, sollten engmaschig kontrolliert werden. Ggf. sollte eine Leberbiopsie erwogen werden, um die aktuelle Schädigung direkt zu erfassen. Wir empfehlen, die histologischen Veränderungen der Patienten einheitlich zu quantifizieren und zu klassifizieren und schlagen hier in Analogie zu den Hepatitis-Aktivitätsscores ein leicht modifiziertes Punkteschema vor.

Abstract

Modern combination chemotherapies, mainly including oxaliplatin or irinotecan, have demonstrated a significant increase in response rates. This led to the concept of down-sizing irresectable liver metastases from colorectal cancer, thereby achieving secondary resectability and possibly cure. However, these benefits of preoperative chemotherapy must be weighed against potential side effects to the surrounding normal liver tissue. In particular, in patients with pre-existing liver disease combination therapy can cause liver damage which may exceed mere steatosis of hepatocytes and lead to inflammation, cholestasis and bleeding. In correspondence to the “non-alcoholic steatohepatitis” (NASH) the term “chemotherapy associatied steatohepatitis” (CASH) has been proposed in the literature. Platinum derivatives, in particular, can lead to damage of the hepatic microcirculation and the so-called sinusoidal obstruction syndrome (SOS). Few reports mention an increase in perioperative morbidity after combination chemotherapy. However, there are no comprehensive data on the individual risk of a patient for postoperative complications. If elevated liver enzymes are detected before chemotherapy and cannot readily be explained through liver involvement by the tumor, then close monitoring of enzymes should be performed and a biopsy may be considered in unclear cases. We recommend that the histological changes observed in the liver be quantified and classified by a unifying scoring system and propose, in correspondence to the hepatitis activity scores, a modified scoring system.

Schlüsselwörter

kolorektales Karzinom - Lebermetastasen - neoadjuvante Therapie - Klassifikationssystem - Grading - Staging

Key words

colorectal cancer - liver metastesis - neoadjuvant therapy - classification system - grading - staging

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