Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.
Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.
Clin Transl Gastroenterol. 2019 Feb;10(2):e00006. doi: 10.14309/ctg.0000000000000006.
Hepatocellular carcinoma (HCC) is characterized by high prevalence of multifocality. Multifocal HCC can arise synchronously or metachronously either from intrahepatic metastasis (IM) or multicentric occurrence (MO). To date, there have been no established criteria to accurately distinguish whether multifocal HCC originates from IM or MO. Histopathological features remain the most convenient strategy but with subjectivity and limited accuracy. Various molecular biological techniques involving assessment of TP53 mutation status, hepatitis B virus integration sites, and chromosomal alterations have been applied to determine the clonal origin. The introduction of next-generation sequencing facilitates a more comprehensive annotation of intertumor heterogeneity, resulting in more sensitive and accurate clonal discrimination. Generally, MO-HCC has better overall survival than IM-HCC after curative resection. Adjuvant antiviral treatment has been proved to decrease post-treatment recurrence probably by reducing MO-HCC recurrence, whereas adjuvant sorafenib treatment targeting prior micrometastasis failed to reduce IM-HCC recurrence. Recent studies recommended transcatheter arterial chemoembolization (TACE) and traditional Chinese medicine Huaier granule as effective adjuvant treatments probably by preventing IM and both types of recurrences respectively. Immunotherapy that inhibits immune checkpoint interaction may be an optimal choice for both MO- and IM-HCC. In the future, effective personalized therapy against multifocal HCC may be achieved.
肝细胞癌（HCC）的特点是多灶性发生率高。多灶性 HCC 可以同步或异时发生，源于肝内转移（IM）或多中心发生（MO）。迄今为止，尚无明确标准来准确区分多灶性 HCC 是源于 IM 还是 MO。组织病理学特征仍然是最方便的策略，但具有主观性和有限的准确性。各种分子生物学技术，包括评估 TP53 突变状态、乙型肝炎病毒整合位点和染色体改变，已被用于确定克隆起源。下一代测序的引入促进了肿瘤间异质性的更全面注释，从而实现了更敏感和准确的克隆区分。一般来说，根治性切除后，MO-HCC 的总生存率优于 IM-HCC。辅助抗病毒治疗已被证明可以通过降低 MO-HCC 的复发率来减少治疗后复发，而针对先前微转移的辅助索拉非尼治疗未能降低 IM-HCC 的复发率。最近的研究建议经导管动脉化疗栓塞（TACE）和中药槐耳颗粒作为有效的辅助治疗方法，可能分别通过预防 IM 和两种类型的复发来实现。抑制免疫检查点相互作用的免疫疗法可能是 MO 和 IM-HCC 的最佳选择。未来，可能会实现针对多灶性 HCC 的有效个体化治疗。
