Determination of Clonal Origin of Recurrent Hepatocellular Carcinoma for Personalized Therapy and Outcomes Evaluation: A New Strategy for Hepatic Surgery
Determination of Clonal Origin of Recurrent Hepatocellular Carcinoma for Personalized Therapy and Outcomes Evaluation: A New Strategy for Hepatic Surgery
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DOI：
10.1016/j.jamcollsurg.2013.07.402
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发表时间：
2013-12-01
影响因子：
5.2
通讯作者：
Wu, Meng-Chao
中科院分区：
文献类型：
--
作者：
Wang, Bin;Xia, Chun-Yan;Wu, Meng-Chao
背景：肝细胞癌根治性切除术后复发是肝脏外科医生面临的主要挑战。更好地了解RHCC的克隆起源将有助于临床医生设计个性化治疗和评估术后结局。目前的研究进行，以确定克隆起源的RHCC及其临床significant.Study设计：15个高频率的DNA微卫星杂合性丢失的100个肿瘤结节在60对RHCC从40例患者进行肝切除术确定。结果：60对RHCC中有2种克隆型和6种亚克隆型，其中1种克隆型的起源与临床病理特征及预后有关。多中心型14例（23.3%），肝内转移型46例（76.7%）。MO型与IM型RHCC的临床病理特征，包括复发时间、肿瘤大小、血管浸润、组织学分级和相关慢性肝病，均存在显著差异（p < 0.05 ~ 0.001）。与IM组患者相比，MO组患者的总体生存率明显更好（130.8 ± 8.5个月vs 80.8 ± 8.5个月; p < 0.05）和无复发生存期（33.8 +/- 4.5个月vs 14.2 +/- 2.5个月; p < 0.001）。结论：与IM型RHCC相比，MO型RHCC与更好的术后结局密切相关。一般情况下，我们建议MO型RHCC行再次肝切除，IM型RHCC行介入治疗。基于微切割技术的微卫星杂合性缺失方案在评估RHCC的克隆起源、个体化治疗模式和临床结局方面具有优势。((C)2013年美国外科医生学会）
BACKGROUND: Recurrent hepatocellular carcinoma (RHCC) after curative resection is a major challenge for hepatic surgeons. A better understanding of the clonal origin of RHCC will help clinicians design personalized therapy and assess postoperative outcomes. The current study was performed to determine the clonal origin of RHCC and its clinical significance.STUDY DESIGN: Fifteen high-frequency of loss of heterozygosity of DNA microsatellites were determined on 100 tumor nodules in 60 matched pairs of RHCC from 40 patients who underwent liver reresections. The relationships among the origin of clonal patterns of RHCC and the surgicopathologic features and clinical outcomes were analyzed.RESULTS: Of 60 pairs of RHCC, there were 2 clonal patterns with 6 subclonal types. Pattern I was multicentric occurrence (MO type) in 14 pairs (23.3%) and pattern II was intrahepatic metastasis (IM type) in 46 pairs (76.7%). The clinicopathologic features, including recurrence time, tumor size, vascular invasion, histological grading, and associated chronic liver diseases in patients with the MO type of RHCC were significantly different from those with the IM type of RHCC (p < 0.05 to 0.001). Compared with patients in the IM group, patients in the MO group had significantly better overall survival (130.8 +/- 8.5 months vs 80.8 +/- 8.5 months; p < 0.05) and recurrence-free survival (33.8 +/- 4.5 months vs 14.2 +/- 2.5 months; p < 0.001).CONCLUSIONS: The MO-type RHCC was closely associated with better postoperative outcomes when compared with the IM-type RHCC. Generally, we recommend liver re-resection for MO-type RHCC, and interventional therapy for IM-type RHCC. Microdissection-based microsatellite loss of heterozygosity protocol has advantages in assessing the clonal origin, modes of personalized treatment, and clinical outcomes of RHCC. ((C) 2013 by the American College of Surgeons)