Clinical recurrence patterns in hepatocellular carcinoma: greater consistency with the seed-and-soil hypothesis than with the anatomical/mechanical model of dissemination.

BACKGROUND: Recurrences of hepatocellular carcinoma (HCC) characterized by multiple intrahepatic nodules, macrovascular invasion, or extrahepatic metastases are generally considered non-curative and critically determine postoperative prognosis. Although such recurrences are commonly regarded as metastatic events, whether their dissemination primarily follows vascular anatomy or reflects biological compatibility between tumor cells and organ microenvironments remains unclear. We therefore evaluated whether these recurrence patterns are consistent with predictions derived from the anatomical/mechanical hypothesis of tumor dissemination. METHODS: We retrospectively analyzed 266 patients who underwent initial liver resection for HCC. We examined (i) associations between subtypes of vascular invasion and subsequent recurrence patterns, (ii) temporal relationships among recurrence types, (iii) hierarchical co-occurrence of these events, and (iv) differences in malignant potential across recurrence types using serum alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels. RESULTS: Portal and hepatic venous invasions occurred largely independently and showed no anatomical specificity in relation to recurrence patterns. Each subtype of vascular invasion was similarly associated with all forms of non-curative recurrence without anatomical specificity. Intrahepatic recurrence did not consistently precede extrahepatic metastasis, and no hierarchical relationship was observed among recurrence types. In contrast, patients with extrahepatic metastases had significantly higher AFP and DCP levels than those with intrahepatic non-curative recurrence. CONCLUSIONS: The spatial, temporal, hierarchical, and biological patterns of non-curative recurrence in HCC are more consistent with biologically selective dissemination as conceptualized by the seed-and-soil hypothesis than with the anatomical/mechanical model of dissemination.