Clinicopathology of recurrent hepatocellular carcinomas after radiofrequency ablation treated with salvage surgery

Abstract

Aim: Radiofrequency ablation (RFA) is an effective standard local therapy for small hepatocellular carcinoma (HCC). However, local recurrence and/or tumor seeding after RFA remain major problems. For better understanding of underlying factors, we clarified clinicopathological features of recurrent HCC treated with RFA. Methods: This retrospective study included 21 patients who underwent surgical resection for HCC disease recurrence after RFA. Clinicopathological findings, including patterns of recurrence, immunohistochemical expression of proliferation markers (Ki-67 and p27Kip1) and survival outcome were assessed. Results: The median time interval after RFA until the diagnosis of intrahepatic and/or extrahepatic tumor progression was 12months (range, 3-84). Radical surgical resection was attempted for intrahepatic local recurrence in 16 patients (18 lesions), for peritoneal dissemination in four, for lymph node metastases in three and for adrenal metastasis in two. In 14 of the 21 (67%) patients, the recurrent HCC were histologically diagnosed as of poorly differentiated type. Their average Ki-67 and p27Kip1 labeling indices were significantly higher (P=0.020) and lower (P<0.001), respectively, compared with values for the 108 HCC surgically resected at the initial treatment. Portal involvement was significantly higher (P=0.01) in recurrent tumors after RFA (72%) than in HCC surgically resected at the initial treatment (43%). The mortality rate of salvage surgery was 0%, with cumulative survival rates at 1 and 3years of 58.9% and 35.7%, respectively. Conclusion: The recurrent tumors after RFA have characteristics of poor differentiation degree and abnormalities in cell-cycle regulators and are associated with aggressive vascular invasiveness.