索拉非尼联合TACE治疗肝癌复发生存期影响因素预测模型建立

<正>原发性肝癌是消化系统常见恶性肿瘤,手术治疗效果欠佳,而肝移植术是目前最有效的治疗方式,但肝移植术后肝癌复发的发生率较高,严重影响患者生存率。射频消融、肝动脉灌注化疗栓塞术(TACE)、索拉非尼等均是肝移植术后肝癌复发的常见干预手段,但干预效果大多不理想^[1,2]。有文献报道索拉非尼联合TACE治疗对于肝移植术后肝癌复发的干预效果优于手术切除、射频消融等,在一定程度上提高生存率,明确影响肝移植术后肝癌复发患者生存期的影响因素,     

肝癌肝移植

肝移植和肝切除是目前肝癌的2种主要治疗方法。早期肝癌合并晚期肝病患者肝移植后疗效评估最佳;但是对于肝功能代偿尚可、不伴门静脉高压的早期肝癌患者来说,最佳的治疗方案仍存在争议。大量的研究证明肝移植后无病生存率更高,但是尚不清楚长期生存率如何。通过改进手术技术和实行补救性肝移植的方法可明显改善肝切除后患者生存率,且避免了可因切除治愈的患者因等待移植时间过长而失去机会。     

应对肝源短缺问题的策略探讨

世界卫生组织发布的数据显示,中国有1.4亿乙型和丙型肝炎病毒携带者,约占全球乙、丙两型肝炎病毒携带者的28％;其中有3200万慢性活动性肝病患者;年发病人数3000万,每年有40万人死于病毒性肝病[1].由于社会生活方式和饮食习惯的改变,过去西方国家较多发的脂肪肝、药物性和酒精性肝炎、肝硬化等肝病也在我国逐渐增多[2].另外我国现有29.7万肝癌患者,占全球肝癌患者总和的一半以上[3].所以,肝病是影响我国生产力和社会安定的重大疾病.目前对急重型肝炎和肝癌等晚期肝病治疗的临床疗效不佳.原位肝移植是目前国际公认的有效方法[4-5].然而,由于肝脏供体的稀缺及高昂的治疗费用,使众多的重型肝病和肝衰竭患者得不到及时救治而死亡.寻求一种新的治疗措施和解决肝源的严重稀缺成为当务之急,也引起世界卫生组织和我国政府的高度重视[6].本文分析和回顾了目前世界范围内科学技术研究应对肝源短缺的前沿领域和方法,并提出了开源节流的相关策略,期望对我国肝源短缺、病患难以得到治疗的情况有所缓解,以探讨临床治疗的新希望.     

肝癌肝移植的研究进展与挑战

［摘要］　　肝移植是根治终末期肝病的有效手段之一,为肝癌患者提供了新的选择。然而,术后肿瘤复发、转移已成为影响肝移植疗效的最主要因素,是肝癌肝移植必须面临的挑战。该文就肝癌肝移植的适应证标准、候肝期治疗、免疫治疗、肿瘤监测、复发治疗进行述评,为肝癌肝移植的临床应用提供临床参考。     

肝癌肝移植转化治疗策略进展

肝移植能够在彻底去除肿瘤的同时完整移除病肝,对于合并肝硬化的肝癌患者是最佳选择。近年来,随着肝癌综合治疗研究的进展,转化治疗理念被引入肝癌外科治疗领域以及肝移植领域,成功的转化治疗有望将超出标准肝癌患者转变为符合标准而接受肝移植手术,从而极大改善其预后。就肝癌肝移植转化治疗的进展进行简要介绍。     

介入治疗活体肝移植术后急性流出道阻塞2例

活体肝移植具有供肝来源广、质量高、排异轻和预后较好等优点,是治疗肝脏终末期疾病及缓解供肝来源匮乏的有效方法.由于肝移植技术复杂,仍具有较高的并发症发生率和病死率,其中血管并发症是最严重的并发症之一[1-3].我们用血管内介入技术治疗活体肝移植术后发生急性流出道阻塞患者2例,获得良好效果,现报道如下.     

钇90微球治疗原发性肝癌

本文讨论钇90微球治疗原发性肝细胞癌在临床上的应用。在适当选择和计划内放射剂量的情况下,钇90微球可以达到疗效高而副作用少的治疗目的。已发表的医学研究显示钇90微球可有效作为姑息性治疗T晚期肝癌,亦可作为肝移植前的肝癌过渡治疗,延长患者等候肝源的时间。钇90微球能把不能切除的肝癌降期到可切除,亦可把不能进行肝移植的肝癌变成为可以肝移植。使用钇90微球作为内放射肝段/肝叶切除的新方法的疗效非常理想。部分肝切除后肝癌复发的患者,钇90微球亦有理想的疗效。     

肝癌患者肝移植的选择标准

我国是世界肝癌发病率最高的国家，而肝癌患者能够接受手术切除的不到10％，20世纪60年代肝移植的出现为肝癌治疗提供了新的选择。选择合适的适应证是提高肝癌肝移植疗效，保证极为宝贵的供肝资源得到公平有效利用的关键。那么，什么样的肝癌患者适合做肝移植呢？     

壳聚糖支架上猪肝细胞的内源性逆转录病毒分泌

由于肝移植受供体短缺的限制,基于功能肝细胞的生物人工肝(BAL)有望成为等待肝移植患者的过渡性治疗手段,但已有的BAL临床试验结果并不理想.如何通过合适的支架材料提高肝细胞体外功能一直是该领域的研究热点[1].     

成人肝移植术后新生未分化性肝肉瘤1例

未分化性肝肉瘤(undifferentiated sarcomaoftheliver,UESL)多发生于6～10岁的儿童,误诊率高,成人少见,肝移植术后发生更为罕见[1].我院收治了1例肝移植术后新生UESL成年患者,现报道如下.     

急性胰腺炎合并肝损害临床分析

目的分析急性胰腺炎合并肝损害的临床特点。方法回顾性分析2009年2月至2012年8月西安市中心医院收治的116例急性胰腺炎患者的临床资料。结果67％（78／116）的急性胰腺炎患者合并肝损害。按病因分类,胆源性胰腺炎合并肝损害者的发病率为79％（38／48）,胰胆手术后（含胆囊切除术后及经内镜逆行性胰胆管造影术后）所致的急性胰腺炎合并肝损害的发病率为68％（15／22）,暴饮暴食所致的急性胰腺炎合并肝损害的发病率为67％（20／30）,其他因素所致的急性胰腺炎合并肝损害的发生率低。胆源性胰腺炎较非胆源性胰腺炎肝功能损害更明显,总胆红素、直接胆红素、谷丙转氨酶、谷草转氨酶、γ-谷氨酰转肽酶、碱性磷酸酶浓度差异均有统计学意义（t值分别为3．16、3．72、4．12、3．26、3．64、3．25,P均〈0．01）。结论胆源性胰腺炎患者大多合并肝损害。     

Antiviral therapy in patients with HCV-cirrhosis

The main cause of liver cirrhosis and liver cancer in the western world is Hepatitis C virus (HCV) infection. Liver transplantation is the only effective treatment once the disease is decompensated. In viremic patients who undergo transplantation, disease recurrence is universal resulting in the development of a new cirrhosis in about one third of the patients after 5 to 10 years of follow-up. Initiation of the antiviral treatment with Peg-IFN and ribavirin prior to transplantation may prevent HCV recurrence if a sustained viral response (SVR) is achieved. Moreover, it might even be possible to achieve an improvement of the liver function degree so that transplantation may be differed.There are few studies that assess the efficacy and safety of the antiviral treatment in the cirrhotic setting. Available information shows SVR rates between 20 and 40%, lower with decompensated disease. The need for treatment withdrawal and dose reductions is significant in this setting. Cytopenias are one of the most frequent adverse effects; hematopoietic growth factors have shown to increase patient compliance, but it is still unclear whether they result in greater SVR. In addition, an increased risk of bacterial infections has been recently described, with a recommendation to use prophylactic therapy during antiviral treatment. In conclusion, antiviral therapy is an option for cirrhotic patients who have a good liver function but should not be recommended in patients with Child-Pugh-Turcotte class C, due to a high risk of severe complications.     

Liver regeneration after liver resection: Clinical aspects and correlation with infective complications

AIM:To investigate whether early liver regeneration after resection in patients with hepatic tumors might be influenced by post-operative infective complications.METHODS:A retrospective analysis of 27 liver resections for tumors performed in a single referral center from November 2004 to January 2010.Regeneration was evaluated by multidetector computed tomographyat a mean follow-up of 43.85 d.The Clavien-Dindo classification was used to evaluate postoperative events in the first 6 mo after transplantation,and Centers for Disease Control and Prevention definitions were used for healthcare associated infections data.Generalized linear regression models with Gaussian family distribution and log link function were used to reveal the principal promoters of early liver regeneration.RESULTS:Ten of the 27 patients(37%)underwent chemotherapy prior to surgery,with a statistically significant prevalence of patients with metastasis(P=0.007).Eight patients(30%)underwent embolization,3 with primary tumors,and 5 with secondary tumors.Twenty patients(74%)experienced complications,with 12(60%)experiencing Clavien-Dindo Grade 3a to 5 complications.Regeneration≥100%occurred in 10(37%)patients.The predictors were smaller future remnant liver volume(-0.002;P<0.001),and a greater spleen volume/future remnant liver volume ratio(0.499;P=0.01).Patients with a resection of≥5 Couinaud segments experienced greater early regeneration(P=0.04).Nine patients experienced surgical site infections,and in 7 cases Clavien-Dindo Grade 3a to 4 complications were detected(P=0.016).There were no significant differences between patients with primary or secondary tumors,and either onset or infections or severity of surgical complications.CONCLUSION:Regardless of the onset of infective complications,future remnant liver and spleen volumes may be reliable predictors of early liver regeneration after hepatic resection on an otherwise healthy liver.     

慢性乙型肝炎患者肝组织病理研究

目的:探讨慢性乙型肝炎(CHB)患者临床表现和病理诊断的相关性.方法:收集30例CHB患者的临床资料,分析临床表现与病理诊断的相关性.结果:肝组织的炎症和纤维化程度的相关性显著(r=0.659,P＜0.01),白蛋白/球蛋白比值(A/G)与肝脏炎症和纤维化分级显著负相关(r=-0.368,P＜0.05;r=-0.401,P＜0.05).年龄、性别及其他化验指标如ALT、AST、TP、ALB、GLO、TBil、PLT、PT、PTA、门静脉宽度、脾脏厚度等与肝组织炎症和纤维化分级无显著相关性(P＞0.05).结论:慢性乙型肝炎肝脏炎症和纤维化的严重程度密切相关,仅根据肝功能判断轻中度的CHB患者的肝脏炎症及纤维化程度有相当的局限性.     

Non-alcoholic steatohepatitis with normal aminotransferase values

AIM： To investigate the aspects of liver histology in patients with non-alcoholic steatohepatitis （NASH） who had normal aminotransferase levels. METHODS： Thirty-four patients diagnosed with liver steatosis by ultrasonographic examination participated in the study. We compared all non- alcoholic fatty liver disease and NASH cases, according to aminotransferase level, aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio and presence of metabolic syndrome. RESULTS： Sixteen of 25 patients with high aminotransferase levels were diagnosed with NASH and nine with simple fatty liver according to liver histology. Among the nine patients with normal aminotransferase levels, seven had NASH and two had simple fatty liver. The patients with normal and high liver enzyme levels had almost the same prevalence of NASH and metabolic syndrome. Liver histology did not reveal any difference according to aminotransferase levels and AST/ALT ratio. CONCLUSION： Aminotransferase levels and AST/AIT ratio do not seem to be reliable predictors for NASH. Despite numerous non-invasive biomarkers, all patients with fatty liver should undergo liver biopsy.     

儿童肝脏恶性肿瘤的肝移植适应证

儿童肝脏恶性瘤与成人肝脏恶性肿瘤的起源和发展存在明显差别,即使是同一种肝脏恶性肿瘤,在儿童体内的发生、发展、治疗方法和治疗效果方面,也与成人存在较大的差别。肝脏恶性肿瘤的组织学表现和解剖定位可以反映出这些肿瘤侵袭转移的特性、外科手术根治的难度和药物治疗的敏感性。因此在治疗方式选择上,需要依据这些特点进行判断。儿童的肝脏恶性肿瘤对化疗等辅助治疗的敏感性更高。肝移植术前或术后,配合使用化疗等辅助治疗可以获得更为满意的疗效,肝移植的适应证范围也因此得到了一定的扩展。儿童肝脏恶性肿瘤中,肝母细胞瘤、肝细胞癌和未分化胚胎肉瘤较为常见,均可以通过肝移植进行治疗,且多数患者预后满意。儿童肝脏恶性肿瘤如果肝切除治疗预期效果不佳,而肿瘤局限于肝内,均可考虑肝移植。     

肝硬化终末期患者的治疗和管理

肝硬化终末期通常指肝硬化失代偿期所致的慢性肝衰竭,为人类健康带来沉重负担。肝移植是最为有效的治疗,但受肝源缺乏、费用高昂等因素的严重限制。人工肝往往作为桥接治疗。细胞治疗的发展为其带来新的希望。探讨了肝硬化终末期病因治疗及并发症的管理,介绍了肝硬化终末期进行人工肝、细胞治疗、肝移植的适应证和时机。     

生物人工肝在肝衰竭治疗中的应用

重型肝炎及其引起的肝衰竭病死率极高,迄今仍缺乏特效的治疗方法.目前公认的最有效的治疗方法是肝移植,但由于供肝短缺,远远不能满足临床需求.例如在美国,14%需要紧急肝移植的患者在等待供肝过程中死亡.如果在肝衰竭的严重阶段通过人工的或者辅助的手段代替肝脏的主要功能,则患者将有更多机会获得供肝或者避免肝移植.各种非生物型人工肝,如血液灌流、血浆置换等由于其不能代替肝脏的合成和代谢功能而疗效有限.     

Pancreatic neuroendocrine tumor accompanied with multiple liver metastases

Pancreatic neuroendocrine tumor(P-NET) is rare and slow-growing. Current classifications predict its progno-sis and postoperative recurrence. Curative resection is ideal, although often difficult, because over 80% of pa-tients have unresectable multiple liver metastases and extrahepatic metastasis. Aggressive surgery for liver metastases is important to improve survival. Aggressive or cytoreductive surgery for liver metastases is indi-cated to reduce hormone levels and improve symptoms and prognosis. Liver transplantation was originally con-ceived as an ideal therapy for unresectable liver metas-tases. Unfortunately, there is no clear consensus on the role and timing of surgery for primary tumor and liver metastases. Surgeons still face questions in deciding the best surgical scenario in patients with P-NET with unresectable liver metastases.     

血清高尔基体蛋白73在慢性肝病患者中的临床应用

高尔基体蛋白73（GP73）是细胞高尔基体上的一种跨膜蛋白,可被切割释放入血。近年来,越来越多的临床研究表明,血清GP73的升高与肝脏疾病密切相关,有望作为评估慢性肝脏疾病进展的新型血清学标志物。现围绕血清GP73对不同病因引起的慢性肝炎、肝纤维化、肝硬化和肝细胞癌中的临床应用进行综述,并对未来研究进行展望。