【作者】 陈洁；

【导师】 黎乐群；

【作者基本信息】 广西医科大学 ， 肿瘤学（专业学位）， 2014， 博士

【摘要】 第一部分肝切除术与经肝动脉化疗栓塞比较治疗中晚期肝细胞癌的疗效分析目的：目前国际上的肝病指南对中晚期肝细胞癌（hepatocellularcarcinoma，HCC）的指导意见并不统一。本文从回顾性分析和循证医学的角度探讨肝切除术治疗巴塞罗那临床肝癌（Barcelona ClinicLiver Cancer，BCLC）分期B期和C期HCC的疗效和安全性。方法：选择2000-2007年首次在广西医科大学附属肿瘤接受治疗的1259例BCLC-B/C期HCC患者，其中908例接受肝切除术治疗，351例接受经肝动脉化疗栓塞（transarterial chemoembolization，TACE）治疗。为校正回顾性分析导致的患者基线资料的不均衡性，我们使用了倾向性分析匹配组间基线资料。首要观察指标为患者总生存率和复发率，次要观察指标为围手术期死亡率和并发症发生率。另外，为提高本单中心研究结论的可信度，我们系统检索了PubMed数据库，分析报道肝切除术治疗BCLC-B/C期HCC患者的疗效和围手术期死亡率的研究。结果：本研究病例中，肝切除术组患者术后30天和90天死亡率分别为1.9%和3.1%。肝切除术组患者的术后并发症发生率（27%）显著高于TACE治疗组（19%，P=0.005）。肝切除术组和TACE治疗组患者的1、3、5年总生存率分别为88%、62%、39%和81%、33%、16%（P<0.001）。肝切除术组患者的1、3、5年肿瘤复发率分别为32%、58%和74%。倾向性分析和基于肿瘤大小、肿瘤数量、大血管侵犯、门脉高压与否的亚组分析同样显示肝切除术治疗组患者的总生存率显著高于接受TACE治疗的患者。系统检索到的36个研究均报道肝切除术治疗的HCC患者远期生存率佳，围手术期死亡率低。多因素分析结果显示，甲胎蛋白≥400ng/mL、糖尿病、大血管侵犯和门脉高压是BCLC-B/C期HCC患者预后不良的独立危险因素。结论：本临床研究和文献分析结果显示，对于肝功能Child-PughA级的HCC患者，孤立性大肿瘤、多结节肿瘤、大血管侵犯或合并门脉高压均非肝切除术治疗的禁忌症。对这部分HCC患者，肝切除术的疗效明显优于TACE治疗。第二部分肝切除术治疗合并门脉高压的肝细胞癌患者的疗效与安全性的探讨背景与目的：我们的前期研究显示，肝细胞癌（Hepatocellularcarcinoma，HCC）患者肝硬化伴有门脉高压的比例很高，门脉高压明显增加肝切除术治疗中出血和术后肝功能衰竭的风险。本文评价肝切除术治疗HCC合并门脉高压患者的疗效、安全性，以及门脉高压患者的手术适应证。方法：回顾性分析我院2008-2010年接受肝切除术治疗的564例肝功能Child-Pugh A级的HCC患者临床资料，其中486例患者无门脉高压，合并门脉高压78例。经倾向性分析校正组间资料平衡后，按1:1比例对患者进行配对。比较两组患者的肝切除术术后并发症、术后30和90天死亡率、总生存率和复发率。根据巴塞罗那临床肝癌分期标准（Barcelona Clinic Liver Cancer，BCLC）和手术范围大小行亚组分析。结果：门脉高压组患者的术后并发症、术后30和90天死亡率均显著高于非门脉高压组（P<0.05）。经（平均32.1个月）随访，门脉高压组和非门脉高压组患者术后1、3、5年总生存率分别为75%、45%、32%和90%、66%、48%（P<0.001）；复发率分别为31%、57%、73%和26%、53%、67%（P=0.53）。倾向性分析匹配后，两组患者总生存率和复发率比较均无统计学差异（P>0.05）。亚组分析结果显示，在BCLC-A期和接受小范围肝切除术的两组患者中，总生存率的比较无统计学差异（P>0.05）。结论：门脉高压并非HCC患者行肝切除术治疗的绝对禁忌证。在合并门脉高压的HCC患者中，BCLC-A期和预计行小范围肝切除术的患者可选择相应肝切除术。更多还原

【Abstract】 Part1The efficacy of hepatic resection compared to transarterialchemoembolization for intermediate and advanced hepatocellularcarcinomaBackground and Objective: Nowadays, different internationalguidelines about the treatment of hepatocellular carcinoma (HCC)recommend different treatment modalities for Barcelona Clinic LiverCancer (BCLC) B and C stage HCC. This study explored the efficacy andsafety of hepatic resection for BCLC-B/C HCC based on our cohort studyand systematic review. Methods: Between2000and2007, a consecutive sample of1259patients with BCLC stage B/C HCC who underwent HR (n=908) ortransarterial chemoembolization (TACE, n=351) were included.Moreover, propensity score-matched patients were analyzed to adjust forany baseline differences. Primary outcomes were overall survival andrecurrence rates. Secondary outcome was adverse event. In parallel withthis retrospective clinical study, the PubMed database was systematicallysearched for studies evaluating the efficacy and safety of HR forBCLC-B/C HCC.Results: Among our patient sample, the30-and90-day mortalityrates in the HR group were1.9%and3.1%. The morbidity rate of HRgroup (27%) was significantly higher than TACE group (19%, P=0.005).However, HR provided a survival benefit over TACE at1,3, and5years(88%vs81%,62%vs33%, and39%vs16%, respectively; P<0.001).Propensity scoring and subgroup analyses based on tumor size, tumornumber, presence or absence of macrovascular invasion, and portalhypertension (PHT) also showed that HR was associated with betterlong-term survival than TACE. The1,3, and5years recurrence rate ofHR group patient was32%,58%and74%. All36studies identified in ourliterature search reported that HR is associated with good long-termsurvival and low mortality. Multivariate analyses revealed thatalpha-fetoprotein≥400ng/mL, diabetes mellitus, macrovascular invasion, and PHT are independent predictors of poor prognosis in patients withBCLC stage B/C HCC.Conclusions: Our clinical and literature analyses suggest that inpatients with HCC with Child-Pugh A liver function, the presence of large,solitary tumors, multinodular tumors, macrovascular invasion, or PHT arenot contraindications for HR. For patients with BCLC-B/C HCC, HRprovides better survival than TACE. Part2Liver resection for patients with hepatocellular carcinoma and portalhypertensionBackground and Aim: The proportion of hepatocellular carcinoma(HCC) patients with cirrhosis and portal hypertension (PHT) is high. PHTmay increase the risk of hemorrhage and liver failure. The aim of thisstudy is to evaluate the safety and efficacy of hepatic resection (HR) forpatients with HCC and PHT.Methods: From2000to2008, a total of564HCC patients withChild-Pugh A liver function and with (78) or without PHT (486) wereretrospective analysis. Morbidity,90-days mortality, overall survival (OS), and recurrence rates were compared between the two groups. Propensityscore analysis was also conducted to reduce confounding bias betweenthe groups. Moreover, subgroup analysis based on tumor stage and therange of resection was carried out.Results: The morbidity and90-days mortality of patients withPHT were significantly higher than those without PHT, before and afterpropensity analysis (P<0.05). After an average follow-up of32.1months,the1-,3-,5-year OS of patients with PHT (75%,45%and32%) wassignificantly worse than those without PHT (90%,66%and48%;P<0.001). However, the1-,3-, and5-year recurrence rates were similarbetween PHT group (31%,57%, and73%) and without PHT group (26%,53%, and67%; P=0.53). Moreover, the OS of the two groups weresimilar after propensity analysis, and for patients with early stage HCCand those who underwent minor hepatectomy (all P>0.05).Conclusion: PHT is not the contraindication of HR for patientswith HCC. Those with early stage HCC and who underwent minorhepatectomy are the best candidates to HR therapy.更多还原