术前血小板与淋巴细胞比值对肝癌切除术后患者预后价值的Meta分析

背景与目的:肝癌是最常见的恶性肿瘤之一,一直以来影响着人类健康.肝切除术是肝癌首选的治疗方式,但术后复发率高、生存期短严重影响手术疗效.随着肿瘤相关炎症的研究不断深入,包括血小板与淋巴细胞比值(PLR)在内的一系列全身炎症指标被逐步提出,并被认为是可用于预测恶性肿瘤患者预后的标志物.近年来,研究发现术前PLR可作为预测...     

分子标记物在肝癌新辅助治疗中的应用展望

肝切除术是根治原发性肝癌(主要为肝细胞癌的最主要手段,而术后高复发率是制约病人手术预后的首要因素。新辅助治疗能够通过术前干预降低术后肝癌复发的风险,是近几年来兴起的综合治疗手段之一,主要包括新辅助局部治疗(经肝动脉化疗栓塞术、肝动脉灌注化疗和放疗等)和新辅助系统治疗(靶向治疗、免疫治疗及靶免治疗等)。尽管缺乏高级别证据,但是越来越多的前瞻性研究结果显示,接受新辅助治疗的病人在病理缓解率、根治性切除率、术后无瘤生存等方面均能获益。然而,同样也存在部分病人响应率低下、药物耐药等问题,以至于出现新辅助治疗过程中肿瘤进展、术后肿瘤复发等预后较差的情况。因此,如何个体化地通过肝癌分子标记物选择新辅助治疗的受益人群、动态监测术前治疗效果以及预测手术预后成为肝癌新辅助治疗未来的研究热点。     

肝癌干细胞标志物研究的进展

肝癌是常见的恶性肿瘤,其目前的治疗手段是以手术为主的综合治疗,但是术后易复发、转移,预后较差。肿瘤干细胞学说认为只有杀灭肝癌干细胞才能从根本上治愈肝癌,因此分离和鉴定肝癌干细胞成为研究的热点。笔者就目前的肝癌干细胞表面标志物研究进展进行综述。     

预测肝癌患者术后预后的新型评分系统

目的建立一个基于临床病理特征的预测肝癌术后预后的评分系统。方法回顾性的观察2003年至2009年于东方肝胆外科医院肝外四科行肝癌根治性切除术的793例病例,以死亡及复发作为终点,以Kaplan-meier和COX回归确定肝癌术后预后的独立危险因素。以最小加权法建立肝癌术后预后预测的评分系统,并用一致性指数(C-index)来评价该评分系统的准确性。之后我们根据这一评分系统将患者分为高危、中危和低危三个组,比较这三组人群的生存和复发情况。结果单、多因素分析表明,肝癌术后预后的独立危险因素为肿瘤直径,肿瘤数目,微血管侵犯以及手术切缘情况。用上述4个因素依据各自权重建立新的术后预测评分系统:微血管侵犯(有=2,无=0)+直径(5cm=4,≤5cm=0)+肿瘤数目(多发=2,单发=0)+手术切缘(≤1cm=1,1cm=0)。该评分系统的C-index为0.747(95%CI,0.720~0.774)。应用该评分系统将患者分成三个不同风险组,三组之间生存和复发情况的差异均有统计学意义(P0.001)。结论这一评分系统能够准确预测肝癌患者术后的预后,可进一步为肝癌术后预防复发提供重要参考。     

肝细胞癌根治性切除术后复发转移的预防

肝癌根治性切除术后的复发与转移制约了肝癌疗效的进一步提高。预防性TACE能够改善大小超过5 cm、多结节、血管侵犯肝癌的预后;小样本的临床试验表明,口服新一代5-FU前体药物卡培他滨能够推迟肝癌术后的复发时间,大规模的临床试验正在进行中;多中心、前瞻性临床试验证明,辅助应用干扰素能够改善肝癌根治性切除患者的预后,作用机理可能与干扰素抑制肿瘤血管生成及抗肝炎病毒有关,肿瘤组织内microR-NA-26表达水平可以作为干扰素敏感性的预测指标;以应用CIK细胞为代表的过继免疫也可显著提高肝癌患者的无瘤生存率;探索靶向治疗药物索拉非尼以及抗乙肝病毒的核苷类药物预防肝癌根治性切除术后复发转移的临床试验也在全球进行中。随着多中心、大规模、高质量的临床试验开展,将为个体化预防肝癌根治性切除术后复发转移提供更多的选择。     

瞬时弹力测定预测肝脏手术预后的研究进展

目的了解瞬时弹力测定技术预测肝脏手术患者预后的价值。方法对相关文献进行综述分析。结果瞬时弹力测定技术能够定量评价肝脏硬度，随着肝脏硬度增加，肝脏切除术后并发症发生率及肝癌复发率呈升高趋势。在肝移植患者中，急性排斥反应和丙肝复发常伴随肝脏硬度升高。结论瞬时弹力测定技术有助于评价肝脏储备功能，改善患者预后。     

肝癌预后相关影响因素

原发性肝癌是全球最常见的恶性肿瘤之一,影响原发性肝癌预后的因素很多,大致可分为患者因素、肿瘤本身因素、治疗相关因素3大类。笔者就以上影响原发性肝癌预后因素做一综述。     

肝癌切除术预后影响因素的研究近况

肝细胞癌 (简称肝癌 )是我国常见的恶性肿瘤 ,手术切除是治疗肝癌最为有效的手段 ,亦是其获得治愈的最重要途径。然而肝癌肝切除是一风险性很高的手术 ,仍有一定的并发症发生率与手术死亡率。此外 ,肝癌切除后的复发率仍较高 ,使得肝癌病人的总体预后尚不够理想。本文就近年部分学者对影响肝癌切除术预后因素的研究作一综述。1　病人一般情况、肝脏储备功能及肝病背景对预后的影响1.1　年龄、性别及并存疾病　一般认为 ,年龄、性别不影响肝癌手术的预后。Ｔａｋｅｎａｋａ[1] 对高龄肝癌病人的研究表明 ,年龄≥ 70岁和 <70岁的病人相比 ,术…     

白蛋白-胆红素评分在肝癌治疗中的研究进展

目的探讨白蛋白-胆红素(ALBI)评分在肝癌治疗及预后中的应用价值。方法对近年来发表的有关ALBI评分与肝癌相关研究的文献,如ALBI评分来源及其在预测肝癌手术治疗、肝移植及非手术治疗后患者的生存情况等方面进行综述。结果 ALBI评分是肝癌肝切除患者术后的独立预后因素,ALBI评分作为肝癌根治性肝切除后早期复发的危险因素可能有助于复发时根据患者肝功能确定适当的治疗方法;ALBI评分分级3级作为肝移植术后死亡率的独立预测因子,可能对优化肝移植的个体风险评估有帮助;ALBI评分可作为临床医生对肝癌患者在肝切除和非手术治疗之间进行选择的参考工具。结论 ALBI评分评估肝功能的作用不亚于当前广泛应用的Child-Pugh分级,它在评估肝癌患者预后及复发方面有着重要作用,有利于为肝癌患者选择个体化的治疗方式,制定使患者最大获益的治疗方案。     

肝癌肝移植的适应证及应用前景

肝细胞癌是最常见的肝脏原发性恶性肿瘤，全世界每年大约有新发病例54．1万，其中31．8万发生在我国，占全球肝癌的58．8％。由于肝细胞癌早期诊断困难，且常常伴有肝硬变，所以预后较差，未经治疗的肝癌患者的自然生存时间仅为6个月。肝癌常规的治疗方法主要包括手术切除、放疗、化疗、介入治疗等，虽然手术切除是肝癌患者的首选治疗方法，但由于85％～90％的肝癌患者伴有肝硬变、较差的肝功能和肿瘤的多中心性生长，患者往往不能耐受较大范围的肝脏切除术，而接受手术治疗的50％病例在3年中肿瘤复发，手术切除率低及治疗后较高的复发率是肝癌治疗效果差的主要原因。     

肝癌手术治疗进展

The incidence of hepatocellular carcinoma (HCC) has increased worldwide over the past two decades. Surgical resection and liver transplantation have been demonstrated as potentially curative treatment options, which could be considered in 30% -40% of HCC patients. Recent advancements of surgical treatment have focused not only on the surgical techpiques, but also the hepatic functional reserve evaluation, resectability assessment and the effects of biological characteristics of tumor on prognosis. There is no single variable to evaluate the hepatic functional reserve accurately. Combined Child-Pugh classification, ICGI5, portal vein pressure detection and remanent liver volume measurement are required prior to liver resection. The 5-year survival rate after liver resection for HCC is about 50%. The results are acceptable for some selected patients that underwent tumor resection with thrombectomy, including HCC with portal vein tumor thrombus or bile duct thrombosis. The choice of local resection or regular hepatectomy is still controversial although the former is commonly performed to treat HCC with cirrhosis, and the latter is applied to HCC patients without liver cirrhosis. The results of liver transplanta-tion for HCC are better than liver resection, and the Milan criteria is generally accepted. Any attempts to expand the selection criteria should be cautious because of organ shortage. Salvage transplantation for intrabepatic recurrence after liver resection may be a good choice in some resectable HCC. The recurrence and metastasis after surgical treatment are the main obstacles to achieve better results. Identification of predictive factors could be helpful to develop prevention strategies. Due to the importance of biological characteristics in tumor recurrence and metastasis, a molecular classification to predict prognosis of HCC patients will lead to a more personalized medicine. Targeting key molecules of biological pathways could optimize the therapeutic modality in HCC.     

Resection of lung metastases from hepatocellular carcinoma after living donor liver transplantation: report of two cases

Hepatocellular carcinoma (HCC) recurrence after liver transplantation is associated with a poor prognosis; nonetheless, we report two cases of long-term survival after resection of pulmonary metastatic lesions following living donor liver transplantation (LDLT). The intervals between LDLT and pulmonary resection for the metastatic lesion were 24 months and 30 months, respectively. Regular checking of tumor markers and prompt workup for early detection may contribute to the resectability of such metastatic lesions. These cases suggest that resection of a solitary metastatic lesion in the lung from HCC after liver transplantation may be a feasible treatment for selected patients.     

Surgical treatment of hepatocellular carcinoma

Local tumor control is still the most important consideration in the treatment of hepatocellular carcinoma (HCC). Surgical treatments, including liver resection and liver transplantation are, and will remain, the first-line therapeutic strategies for local control in patients with primary HCC. Although aggressive liver resection is often performed for advanced HCC in patients with a large tumor, multiple tumors, or tumors with vascular invasion, liver transplantation is the preferred option, after taking into consideration age and tumor-related factors, when there is poor liver functional reserve. Preventing deterioration in liver function is the second priority in the treatment of HCC. When performing liver resection, extensive removal of noncancerous liver parenchyma during lobectomy or hemihepatectomy, should be avoided as much as possible. Anatomic resection, which refers to systematic elimination of the main tumor with its minute metastases, preserves liver function and is highly recommended. A treatment algorithm based on published evidence is now available, which helps us decide on the most suitable therapeutic option for individual patients, depending on the tumor characteristics and liver functional reserve.     

16 肝细胞癌合并脉管系统癌栓的外科治疗

目的:探讨肝细胞癌（HCC）合并脉管系统癌栓的外科治疗效果。方法:回顾性分析1993年1月—2002年1月采用肝切除和癌栓取出术治疗HCC合并脉管系统癌栓68例的临床资料，其中门静脉癌栓63例，肝左静脉癌栓1例，肝中静脉癌栓合并门静脉左支癌栓1例，肝右静脉、下腔静脉合并门静脉右支癌栓1例，下腔静脉癌栓2例。HCC合并门静脉癌栓患者中6例术后行门静脉化疗。结果:6例术后3个月内死于肝肾功能衰竭， HCC合并脉管系统癌栓患者术后1，3，5年生存率分别为41.7%，20.8%，4.1%。结论:肝切除并癌栓取出术是HCC合并脉管系统癌栓有效的治疗方法，术后辅助治疗能提高治疗的效果。     

肝细胞癌肝切除术后预后影响因素分析

目的探讨影响肝细胞癌肝切除术后预后因素，为进一步治疗及判断预后提供依据。方法回顾性分析1994年10月至1998年10月中国医学科学院肿瘤医院手术切除的230例HCC病人资料。对可能影响预后的各种因素进行单因素分析，采用逐步回归法将可能对预后有影响的指标，依次引入Cox模型进行多因素分析。结果全组1、3、5年复发率分别为35．2％、52．1％、62．4％；总的1、3、5年生存率分别为79．1％、53．7％、40．2％。单因素分析显示肿瘤最大直径是否≥5cm、有无脉管瘤栓、术前AST、肝被膜受侵、肿瘤切缘为影响对肿瘤复发和无瘤生存率有影响（P〈0．05）。多因素分析显示脉管瘤栓、术前AST升高、肿瘤切缘、肝被膜受侵及肿瘤最大直径依次为影响预后的主要因素。结论肝细胞癌的预后是由多种因素决定的，脉管瘤栓、术前AST升高、肿瘤最大直径及肝被膜受侵是影响预后的最主要因素。早期发现、早期治疗是提高肝癌病人生存率的重要途径，对存在预后不良因素的病人，应加强术后随诊，及时发现术后复发和转移。     

Portal vein tumor thrombus from colorectal cancer with no definite metastatic nodules in liver parenchyma

Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) is a common entity. In colorectal liver metastasis, microscopic tumor invasion into the intrahepatic portal vein is also usually observed, but the incidence of macroscopic tumor thrombus in the first branch and trunk of the portal vein is rare. Most reported cases of PVTT from colorectal cancer had concomitant metastatic nodules in liver parenchyma, and the PVTT was continuous with the liver nodule, like PVTT in HCC. We present a case of PVTT from colorectal cancer with no definite metastatic nodules in liver parenchyma. A 58-year old man underwent laparoscopic high anterior resection for rectosigmoid carcinoma accompanied by bulky tumor thrombus in the branch of the inferior mesenteric vein. Six months later, he received left lobectomy and left caudate resection for liver metastasis. The resected specimen demonstrated there was no metastatic nodule in liver parenchyma and that the left portal system was filled with the tumor thrombus. The patient is alive with no sign of recurrence 66 months after hepatectomy. Even if there is a macroscopic PVTT from colorectal cancer, a better prognosis may be expected when the tumor can be completely resected en-bloc by anatomic hepatectomy including PVTT.     

Surgical results for hepatocellular carcinoma with macroscopic portal vein tumor thrombosis

Background: The longterm results after liver resection for hepatocellular carcinoma with macroscopic tumor thrombus of the portal vein are unclear.

Study Design: The records of 47 HCC patients with tumor thrombus in the segmental portal branch (n = 33) and the first portal branch or portal vein trunk (n = 14) were reviewed in this study. Survival rates of the patients were calculated with regard to 14 clinicopathologic variables. A log-rank analysis was performed to identify which variables predicted the prognosis.

Results: Overall 1-, 3-, and 5-year survival rates were 53.9%, 33.2%, and 23.9%, respectively. The indicators of a favorable prognosis included curative liver resection, tumor size less than 10 cm in diameter, and absence of intrahepatic metastases.

Conclusions: Liver resection should be considered a therapeutic option for hepatocellular carcinoma with macroscopic portal vein tumor thrombus when the tumor is small and curative liver resection can be expected.     

Repeat liver resection for hepatocellular carcinoma

BACKGROUND: Although hepatectomy has been accepted as a therapeutic option for the primary tumor of hepatocellular carcinoma (HCC), what role the second liver resection will play in the clinical care of patients with intrahepatic recurrence of HCC after the initial resection has not been well evaluated. STUDY DESIGN: In a retrospective review of the 6-year period between January 1991 and December 1996, records were examined of 94 patients who underwent curative liver resection for HCC. Of these, 57 patients had isolated recurrent disease to the liver; 12 of the 57 patients underwent repeat surgical resection and 45 patients received nonsurgical ablative therapy. Clinical data for these patients were reviewed for operative morbidity and mortality, survival, disease-free survival, and pattern of failure. RESULTS: There were no perioperative deaths during repeat liver resections for recurrent HCC. Operative morbidity in the second resection was comparable to the initial resection. The disease-free survival rate after the second hepatectomy was 31% at 2 years, significantly lower than that after initial hepatectomy (62%) (p = 0.009). The overall survival rate after the second hepatectomy was 90% at 2 years, in contrast to 70% after nonsurgical ablative treatment for recurrent HCC (p = 0.253). CONCLUSIONS: Although the second liver resection for recurrent HCC can be performed safely and may improve survival, the disease-free survival rate after such resection therapy is low. This likelihood of further recurrences encourages studies for the selection of patients who may benefit from repeat liver resection.     

不同治疗模式对不能切除的肝癌二期手术预后的影响

目的探讨不能切除的肝细胞癌(HCC)经皮穿刺肝动脉化疗栓塞(TACE)及经手术肝动脉结扎、置管化疗栓塞(HALCE)缩小后二期切除的疗效,并比较不同治疗模式对预后的影响.方法204例HCC二期切除患者,分成TACE组及HALCE组.TACE组112例,行TACE1～7次(中位2.4).HALCE组92例,其中49例行HALCE,7例行HALCE+肝脏外放射治疗,36例行HALCE+导向内放射治疗.肿瘤缩小后予以切除.选择7个可能对HCC二期切除术后预后产生影响的临床因素通过单因素、多因素Cox模型对预后进行分析.结果随访至1999年6月,首次TACE及HALCE后1、3、5、7年生存率分别为95.7%、69.3%、56.5%及44.5%,切除肿瘤后1、3、5、7年生存率分别为88.5%、64.9%、51.9%及38.3%.TACE组及HALCE组1、3、5、7年生存率分别为94.1%、64.7%、51.2%、40.8%和96.3%、73.9%、61.6%、45.2%,2组差异无显著性意义(P＞0.05).影响预后的主要因素是肝硬化程度和肿瘤坏死程度(P＜0.05).TACE组中肝硬化程度、缩小后肿瘤有无包膜及肿瘤坏死程度是影响预后的主要因素(P＜0.05),而HALCE组各因素对预后影响差异无显著性意义(P＞0.05).结论不能一期切除的HCC缩小后应进行二期切除,且可获得满意疗效.而肝硬化程度、肿瘤坏死程度是影响肝癌二期切除预后的主要因素.     

10年间3种病理学类型肝癌手术预后变化及其与肿瘤直径和淋巴结转移关系：基于SEER数据库10 672例病人长期预后分析

目的 分析比较肝细胞癌（HCC）、肝内胆管癌（ICC）和混合型肝癌（CHC）病人术后的预后差异。方法 回顾性分析SEER数据库2004—2015年间接受手术治疗的原发性肝癌10 672例,其中包括HCC病人 9044例,ICC 病人1421例,CHC病人 207例。所有病人包括完整的TNM分期、手术、生存时间及生存状态等信息。比较3种肿瘤术后总体生存（OS）情况及长期预后差异。同时观察N分期亚组（N0组、N1组）及肿瘤直径亚组（0~＜2 cm组,2~5 cm组,>5 cm组）中3种肿瘤病人的预后差异,绘制生存曲线并进行多因素cox回归分析校正,进一步行交叉生存曲线Landmark分析。结果 自2004—2015年3种病理学类型肝癌病人的3年存活率均有不同程度提高。其中,HCC病人术后总体生存明显优于ICC与CHC。ICC与CHC病人术后的早期预后（<40个月）虽差异无统计学意义,但CHC病人的长期预后（>40个月）显著优于ICC病人（P=0.014）。对影响肿瘤分期的肿瘤直径及淋巴结分期行进一步亚组分析显示,在所有亚组中,HCC病人的预后均优于ICC与CHC,而在N0期亚组以及肿瘤直径<5 cm的亚组中,ICC预后最差;而N1期亚组及肿瘤直径>5 cm的亚组中,CHC预后最差。结论 3种病理学类型肝癌病人中,HCC预后最佳,而CHC与ICC在早期（40个月内）虽无预后差异,但CHC的长期预后（40个月以后）明显优于ICC。此外,肿瘤直径>5 cm及N1分期的CHC病人预后差于其他两类肝癌,可能与其具有较强的肿瘤干细胞特性有关。