Raw Data for the article: How important is the role of iterative liver direct surgery in patients with hepatocellular carcinoma for a transplant center located in an area with a low rate of deceased donation?

<strong>Introduction: </strong>Hepatocellular carcinoma (HCC) accounts for nearly 90% of primary liver cancers, with estimates of over 1 million people affected by 2025. We aimed to explore the impacting role of an iterative surgical treatment approach in a cohort of HCC patients within the Milan criteria, associated with clinical risk factors for tumor recurrence (RHCC) after liver transplant (LT) and loco-regional therapies (LRT), as well as liver resection (LR) and/or microwave thermal ablation (MWTA). <strong>Methods: </strong>We retrospectively analyzed our experience performed during an 8-year period between January 2013 and December 2021 in patients treated for HCC, focusing on describing the impact on preoperative end-stage liver disease severity, oncologic staging, tumor characteristics, and surgical treatments. The Cox model was used to evaluate variables that could predict relapse risks. Relapse risk curves were calculated according to the Kaplan-Meier method, and the log-rank test was used to compare them. <strong>Results: </strong>There were 557 HCC patients treated with a first-line approach of LR and/or LRTs (<em>n</em> = 335) or LT (<em>n</em> = 222). The median age at initial transplantation was 59 versus 68 for those whose first surgical approach was LR and/or LRT. In univariate analysis with the Cox model, nodule size was the single predictor of recurrence of HCC in the posttreatment setting (HR: 1.61, 95% CI: 1.05-2.47, <em>p</em> = 0.030). For the LRT group, we have enlightened the following clinical characteristics as significantly associated with RHCC: hepatitis B virus infection (which has a protective role with HR: 0.34, 95% CI: 0.13-0.94, <em>p</em> = 0.038), number of HCC nodules (HR: 1.54, 95% CI: 1.22-1.94, <em>p</em> &lt; 0.001), size of the largest nodule (HR: 1.06, 95% CI: 1.01-1.12, <em>p</em> = 0.023), serum bilirubin (HR: 1.57, 95% CI: 1.03-2.40, <em>p</em> = 0.038), and international normalized ratio (HR: 16.40, 95% CI: 2.30-118.0, <em>p</em> = 0.006). Among the overall 111 patients with RHCC in the LRT group, 33 were iteratively treated with further curative treatment (12 were treated with LR, two with MWTA, three with a combined LR-MWTA treatment, and 16 underwent LT). Only one of 18 recurrent patients previously treated with LT underwent LR. For these RHCC patients, multivariable analysis showed the protective roles of LT for primary RHCC after IDLS (HR: 0.06, 95% CI: 0.01-0.36, <em>p</em> = 0.002), of the time relapsed between the first and second IDLS treatments (HR: 0.97, 95% CI: 0.94-0.99, <em>p</em> = 0.044), and the impact of previous minimally invasive treatment (HR: 0.28, 95% CI: 0.08-1.00, <em>p</em> = 0.051). <strong>Conclusion: </strong>The coexistence of RHCC with underlying cirrhosis increases the complexity of assessing the net health benefit of ILDS before LT. Minimally invasive surgical therapies and time to HCC relapse should be considered an outcome in randomized clinical trials because they have a relevant impact on tumor-free survival.<strong>引言：</strong>肝细胞癌（Hepatocellular carcinoma, HCC）约占原发性肝癌的90%，据估计到2025年全球患病人数将超过100万。本研究旨在探讨迭代外科治疗策略在符合米兰标准（Milan criteria）的肝细胞癌患者队列中的作用，该队列同时关联了肝移植（liver transplant, LT）、局部区域治疗（loco-regional therapies, LRT）、肝切除术（liver resection, LR）及/或微波热消融（microwave thermal ablation, MWTA）后肿瘤复发（recurrent hepatocellular carcinoma, RHCC）的临床危险因素。 <strong>方法：</strong>我们回顾性分析了2013年1月至2021年12月这8年间，本中心收治的肝细胞癌患者的临床诊疗经验，重点阐述其对术前终末期肝病严重程度、肿瘤分期、肿瘤特征及外科治疗方案的影响。采用Cox模型（Cox model）评估可预测复发风险的变量；通过Kaplan-Meier法（Kaplan-Meier method）绘制复发风险曲线，并使用对数秩检验（log-rank test）进行组间比较。 <strong>结果：</strong>本研究共纳入557例肝细胞癌患者，一线治疗方案为肝切除术及/或局部区域治疗（n=335）或肝移植（n=222）。首次接受肝移植患者的中位年龄为59岁，而首次采用肝切除术及/或局部区域治疗的患者中位年龄为68岁。在Cox模型单因素分析中，结节大小是治疗后肝细胞癌复发的唯一预测因素（风险比（HR）=1.61，95%置信区间（CI）：1.05~2.47，P=0.030）。对于局部区域治疗组，本研究明确了以下与复发性肝细胞癌显著相关的临床特征：乙型肝炎病毒感染（具有保护作用，HR=0.34，95%CI：0.13~0.94，P=0.038）、肝细胞癌结节数量（HR=1.54，95%CI：1.22~1.94，P<0.001）、最大结节直径（HR=1.06，95%CI：1.01~1.12，P=0.023）、血清胆红素水平（HR=1.57，95%CI：1.03~2.40，P=0.038）及国际标准化比值（international normalized ratio, INR）（HR=16.40，95%CI：2.30~118.0，P=0.006）。局部区域治疗组中共计111例复发性肝细胞癌患者，其中33例接受了进一步的治愈性治疗（12例行肝切除术，2例行微波热消融，3例行肝切除术联合微波热消融，16例行肝移植）。此前接受肝移植治疗的复发患者中，仅1例行肝切除术。针对该部分复发性肝细胞癌患者的多因素分析显示，肝移植对首次迭代治疗后复发性肝细胞癌具有保护作用（HR=0.06，95%CI：0.01~0.36，P=0.002），两次迭代治疗间的复发间隔时间（HR=0.97，95%CI：0.94~0.99，P=0.044）以及既往微创治疗（HR=0.28，95%CI：0.08~1.00，P=0.051）也具有显著影响。 <strong>结论：</strong>复发性肝细胞癌合并基础肝硬化会增加肝移植前迭代外科治疗策略净健康获益评估的复杂性。微创外科治疗方案及肝细胞癌复发间隔时间应作为随机对照临床试验的观察终点，因其对无瘤生存具有显著影响。