Neoadjuvant Locoregional Therapy and Recurrent Hepatocellular Carcinoma after Liver Transplantation

Background Neoadjuvant locoregional therapies (LRTs) have been widely used to reduce tumor burden or to downstage hepatocellular carcinoma (HCC) before orthotopic liver transplantation (OLT). We examined the impact of LRT response on HCC recurrence after OLT. Study Design We performed a retrospective study of 384 patients with HCC treated by OLT. Tumor necrosis was determined by pathologic evaluation. The vascular and lymphatic vessels were localized by immunofluorescence staining in formalin-fixed, paraffin-embedded tissue; expressions of vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3 were analyzed by Western blot. Plasma vascular endothelial growth factor (VEGF)-A and VEGF-C levels of a consecutive cohort of 171 HCC patients were detected by ELISA. Results Of the 384 patients with HCC, 268 had undergone pretransplantation neoadjuvant LRTs. Patients with no tumor necrosis (n = 58; 5.2% recurrence) or complete tumor necrosis (n = 70; 6.1% recurrence) had significantly lower 5-year recurrence rates than those with partial tumor necrosis (n = 140; 22.6% recurrence; p Conclusions Locoregional therapy-induced or spontaneous partially necrotic HCC was associated with increased risk of lymphatic metastases compared with tumors with no or complete tumor necrosis. Anti-lymphangiogenic agents with neoadjuvant LRTs can decrease the pattern of lymphatic metastasis after OLT.