Zusammenfassung
Hochdosierte regionale Chemotherapie, Chemoembolisation und andere Verfahren lokaler Tumorablation werden bei Malignomen der Leber abgesehen von hochmalignen Lebertumoren des Kindesalters meist palliativ eingesetzt. Sie führen zu charakteristischen Regressionsbefunden: Narbig abgekapselte Nekrosen resultieren aus einer Zerstörung des Tumorgewebes einschließlich seines fibrovaskulären Stromas. Zellarme Ödemfibrosen sind Folge einer elektiven Tumorzelleradikation unter Erhalt des Gefäßbettes. Vollständig eradizierte und rasch resorbierte hochmaligne Tumorinfiltrate werden durch knotig regenerierendes Lebergewebe ersetzt. Obliterierende Gefäßwandhyalinosen und perivaskuläre Tumornekrosen zeigen eine über das Gefäßnetz vermittelte therapeutische Schädigung an. Degenerative Tumorzellpleomorphie, z. B. Zellhydrops und Verfettung in HCC sind Folge zelltoxischer Schädigung.
Bei HCC beeinflusst der Makrotyp das Ansprechen auf die zytoreduktive Therapie. In multinodulären HCC bleiben nicht selten unbeeinträchtigte Knoten neben zerstörten Knoten bestehen. Gekapselte uninoduläre Tumoren sind leichter vollständig zu zerstören. Tumorgröße und Kapselstrukturen begrenzen die Wirkung einer Injektionsbehandlung von HCC durch Ethanol. Bei Karzinomen mit infiltrierendem Randsaum, insbesondere bei Metastasen von Adenokarzinomen und Cholangiokarzinomen der Leber reduziert die Zytostase am stärksten die Tumorperipherie. Dennoch sind Invasionsfront, Tumorgewebe in Portalvenen und Gallengängen sowie Residuen im Winkel zwischen subkapsulärem Tumor, Leberkapsel und benachbartem Parenchym selbst durch hochdosierte regionale Zytostase nur schwer vollständig zu treffen. Diese Residuen sind Ausgangsgewebe für den lokalen Tumorprogress und weitere metastatische Aussaat. Die wesentlich von Vaskularisation und Perfusion bestimmte topische Resistenz limitiert neben tumorzellgebundenen Resistenzmechanismen den Effekt selbst einer intensiven zytoreduktiven Tumortherapie.
Abstract
High dosage regional chemotherapy, chemoembolization and other methods of regional treatment are commonly used to treat unresectable primary liver malignancies and liver metastases. In liver malignancies of childhood neoadjuvant chemotherapy is successfully combined with surgical treatment. Chemotherapy and local tumor ablation lead to characteristic histomorphologic changes: Complete destruction of the tumor tissue and its vascular bed is followed by encapsulated necroses. After selective eradication of the tumor cells under preservation of the fibrovasular bed the tumor is replaced by hypocellular edematous and fibrotic tissue. If completely damaged tumor tissue is absorbed quickly, the tumor area is replaced by regenerating liver tissue. Obliterating fibrohyalinosis of tumor vessels, and perivascular edema or necrosis indicate tissue damage along the vascular bed. Degenerative pleomorphism of tumor cells, steatosis, hydropic swelling and Malloryhyalin in HCC can represent cytologic findings of cytotoxic cellular damage.
Macroscopic type of HCC influences significantly the response to treatment. Multinodular HCC often contain viable tumor nodules close to destroyed nodules after treatment. Encapsulated uninodular tumors undergo complete necrosis much easier. Large size and a tumor capsule limitate the effect of percutaneous injection of ethanol into HCC. In carcinomas with an infiltrating border, especially in metastases of adenocarcinomas and hepatic cholangiocarcinoma cytostatic treatment damages the tumor tissue mainly in the periphery. Nevertheless the infiltrating rim, portal veins, lymphatic spaces and bile ducts as well as the angle between liver capsule, tumor nodule and bordering parenchyma are the main refugees of viable tumor tissue even after high dosage regional chemotherapy. This local resistance is caused by special local conditions of vascularization and perfusion. These residues are the source of local tumor progression and distant metastases. Besides intrinsic cellular mechanisms architectural, and microenvironmental factors relevantly limitate the effect of intensive locoregional therapy.
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Für die Hilfe bei der Bildbearbeitung danke ich Herrn Gerrit Klemm und Herrn Sven Padberg.
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Fischer, HP. Leberkarzinome und Lebermetastasen. Pathologe 26, 191–200 (2005). https://doi.org/10.1007/s00292-005-0749-2
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DOI: https://doi.org/10.1007/s00292-005-0749-2