儿童肝移植的现状和未来

儿童肝移植已经成为儿童终末期肝病的标准治疗方法。发展儿童肝移植意义重大。本文从适应证、生存率、手术方式、技术性并发症、免疫抑制治疗、远期生存状况和受体危险度分层等方面对目前儿童肝移植的发展水平进行初步概述,并对未来发展作初步展望。     

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。     

肝癌肝移植的临床及基础研究

肝移植是对于肝癌最为有效的治疗方式。因为其可以根除肿瘤主体及镜下微小肿瘤病灶并提供给患者一个具备良好功能的肝脏。如今肝移植治疗小肝癌的5年成活率已经高达80%。但是由于肝移植手术仅能提供给一些本就预期预后良好的肝癌初期患者,所以只有小部分符合条件的肝癌患者能够受惠     

肝移植治疗肝胆系统恶性肿瘤

肝移植治疗肝癌已开始注意选择具有很高治愈可能的早期肿瘤患者作为移植对象。据Ｗｉｌｌｉａｍ报道 ,严格选择合并肝硬化的早期肝细胞癌的病人 ,(主要指单发病灶直径≤ 5ｃｍ ;多发和 3个或几个病灶直径≤ 3ｃｍ ;无血管受侵犯者 ) ,肝移植后5年精确生存率大致可达 75 %。在许多中心 ,辅助化疗和新辅助化疗被列入治疗方案 ,但同时筛选肝癌患者作为移植治疗对象具备了更严格的标准 ,因此 ,很难将疗效的提高完全归功于化疗。然而 ,对于在接受肝移植前可能要长时间等待的患者 ,新辅助化疗栓塞术治疗肝细胞癌是符合逻辑的。纤维板层肝癌发展较…     

小儿肝脏恶性肿瘤的临床与病理分析

目的探讨儿童肝脏恶性肿瘤的临床病理类型、甲胎蛋白(AFP)水平及预后特点。方法经手术或活检确诊的肝脏恶性肿瘤患儿55例,根据病理类型分为肝母细胞瘤(HB)和肝细胞癌(HCC)两组,比较两组年龄、临床表现、AFP阳性率、乙肝病毒感染率、手术完整切除率、1年累计生存率等方面的差异。结果 55例患儿多以腹部肿块起病就诊,病理类型以HB为主。HB组平均发病年龄、乙肝病毒感染率均低于HCC组(P<0.05或<0.01),手术完整切除率及1年累计生存率高于HCC组(P<0.05或<0.01)。结论儿童肝脏恶性肿瘤以HB为多,临床首发症状以腹部肿块为主。HCC患儿乙肝病毒感染率高于HB;HB发病年龄明显小于HCC,且手术完整切除率高,预后相对较好。     

在规范中前进的肝移植

肝移植应用于临床半个世纪以来,技术日趋成熟,从被动消极的无奈选择演进为主动积极的治疗手段.作为一项复杂的"系统工程",肝移植的成功需要精湛的手术技术、完善的围手术期管理及妥善的术后随访治疗,各个环节缺一不可.由于缺乏宏观高效的管理监督体系,近年来我国肝移植数量的迅速上升一度引发一些负面效应,既浪费有限的社会资源,又增加了患者的痛苦.     

活体肝移植的进展与展望

活体肝移植（LDLT）可扩大供肝来源,有效缓解供体紧缺局面,尤其是对儿童、急性肝功能衰竭患者和无,法长期等待的肝癌患者有着十分重要的意义。为尽可能减少LDLT潜在的手术风险,尤其是供者的风险,应由肝病内外科医师共同进行严格的供受体术前评估和准备,选择恰当的手术方案。中闰应稳步开展LDLT,并积极拓展尸体和脑死亡供体肝移植,进一步发展儿童LDLT和劈离式肝移植（SIX）以提高器官利用率。在第六届上海国际胃肠病学会议期间,国内外肝病专家就LDLT的现状作了相关报道,本文就此次会议的有关内容和最新进展作一简要介绍。     

免疫治疗时代下的肝癌肝移植

我国大部分肝癌患者在就诊时不能获得根治性手术治疗,近年来肝癌免疫治疗的突破性进展为这些中晚期肝癌患者带来了曙光。在肝癌肝移植领域,免疫治疗更是因为在肿瘤免疫和移植免疫中扮演的双重角色而备受关注。在术前降期治疗和移植术后肿瘤复发的治疗中均有创新性的应用。在免疫治疗的时代下如何应用移植肿瘤学思维使肝癌肝移植患者获益是一个崭新的课题,这需要在临床实践中进行多学科团队协作,探讨最佳的肝癌肝移植患者治疗策略,最终改善中晚期肝癌患者的预后。     

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。     

移植肿瘤学开创肝移植治疗肝癌新时代

近年来,外科学、肿瘤学、免疫学、药学和影像学等深度交叉融合,逐渐形成了新兴学科——移植肿瘤学。随着移植肿瘤学的发展,肝移植在肝胆胰恶性肿瘤的治疗中发挥了越来越关键的作用。回溯移植肿瘤学的发展并总结其特点,重点阐述移植肿瘤学发展在肝癌精准诊治,尤其是肝癌肝移植受者选择、供肝来源拓展中发挥的重要作用,强调肝癌肝移植术后肿瘤复发防治及其机制的探索仍是移植肿瘤学研究的重点攻关方向。     

儿童急性肝衰竭的肝移植治疗

儿童急性肝衰竭(PALF)是一种罕见的综合征,致死率高。肝移植仍然是目前PALF唯一疗效肯定的治疗方法。近年来,我国儿童肝移植技术日趋成熟,已显著改善PALF预后。但PALF进行肝移植仍存在许多问题,充分讨论PALF患儿行肝移植术术前、术中和术后存在的客观问题,将进一步改善PALF患儿的整体预后。     

Indications for liver transplantation

Patients should be considered for liver transplantation if they have evidence of fulminant hepatic failure, a life-threatening systemic complication of liver disease, or a liver-based metabolic defect or, more commonly, cirrhosis with complications such as hepatic encephalopathy, ascites, hepatocellular carcinoma, hepatorenal syndrome, or bleeding caused by portal hypertension. While the complications of cirrhosis can often be managed relatively effectively, they indicate a change in the natural history of the disease that should lead to consideration of liver transplantation. Referral to a liver transplant center is followed by a detailed medical evaluation to ensure that transplantation is technically feasible, medically appropriate, and in the best interest of both the patient and society. Patients approved for transplantation are placed on a national transplant list, although donor organs are allocated locally and regionally. Since 2002, priority for transplantation has been determined by the Model of End-Stage Liver Disease (MELD) score, which provides donor organs to listed patients with the highest estimated short-term mortality.     

Epithelioid hemangioendothelioma of the liver as a rare indication for liver transplantation

AIM: To investigate the indications and outcomes of liver transplantation for hepatic epithelioid hemangioendothelioma (HEHE).METHODS: Between 1989 and August 2013, in the Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 1306 orthotopic liver transplantations (OLTx) were performed, including 72 retransplantations. Unresectable HEHE was an indication for OLTx in 10 patients (0.8% of primary OLTx), the mean age of the patients was 40.5 ± 13.3 years (range 23-65 years), and the male-to-female ratio was 2:8. Kaplan-Meier survival analysis in HEHE, hepatocellular carcinoma (HCC), and other OLTx recipients groups was performed. The differences in mortality were compared using the χ² test. A P-value < 0.05 indicated statistical significance.RESULTS: No concomitant liver disease was found in any patient. There was no neoadjuvant chemotherapy or radiotherapy. Liver function test results were normal in most of the patients. The levels of alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9 were normal. In immunohistochemical staining, the neoplastic cells were positive for factor VIII-related antigen, CD31, and CD34, which are endothelial cell markers, and negative for cytokeratin 19, cytokeratin 7, and HepPar-1. Nine patients were alive without tumor recurrence. One patient died 2 mo after OLTx due to septic complications. No morbidity was observed. Maximum follow-up was 11.4 years, with a minimum of 1 mo. The cumulative survival rate at the end of follow-up in HEHE patients was 87.5% compared with 54.3% in the HCC group and 76.3% in the other OLTx recipients group (χ² test = 1.784, df = 2, P = 0.409).CONCLUSION: Unresectable HEHE, without extrahepatic metastases is an excellent indication for liver transplantation. Long-term survival is very good and much better than in HCC patients and the entire group of OLTx patients.     

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？     

我国肝脏外科病理学研究回顾与展望

肝脏外科病理学研究的主要对象是经外科治疗的肝脏及肝内胆管系统各类肿瘤或瘤样病变,以及肝脏移植手术后各种并发症的病理学发生机制、病理生物学特性和诊断病理学特征.自20世纪80年代开始,随着我国肝脏肿瘤外科和肝脏移植外科发展的加快,肝脏肿瘤病理标本数量及类型的增多,由此也极大地促进了肝脏外科病理学的发展.本文拟简要回顾我国肝脏外科病理学科取得的主要进展,并对今后应关注的一些研究方向提出扼要讨论.     

自体骨髓干细胞移植治疗慢性肝衰竭研究

目的探索自体骨髓干细胞移植对肝衰竭患者的治疗作用,为干细胞移植的临床应用研究提供基础。方法35例慢性重症肝病患者,20例行自体骨髓干细胞移植治疗,15例作为对照。在无菌条件下,从患者髂后上棘抽取骨髓30～50ml,分离纯化骨髓干细胞。在局部麻醉下行肝动脉介入,将分离的骨髓干细胞移植于肝脏。患者在移植后1、2、4、8周进行肝功能检测。观察患者移植后不同时间症状改善情况及术后不良反应情况。结果在移植8周后,患者丙氨酸转氨酸逐渐降低,由平均181.7μmolL降至72.1μmolL;总胆红素由平均153.8μmolL降至80.2μmolL;直接胆红素由平均74.1μmolL降至40.5μmolL;白蛋白逐渐升高,由平均26.5μmolL升至31.5μmolL;与对照组相比有明显差异,表明移植后患者肝功能明显改善。干细胞移植后凝血酶原活动度逐渐上升,由术前平均28.2%上升至50.1%。进一步观察自体骨髓干细胞移植对肝衰竭患者生存率的影响,发现移植后1周生存率为100%,4周为95%(1920),8周后为90%(1820),12周后为85%(1720),较对照组生存率明显升高。移植后大多数患者有明显症状改善,移植后8周内腹水减轻10例(50%),食欲改善15例(75%),体力好转11例(55%),腹胀减轻9例(45%)。在20例移植患者中未发现严重并发症,术后有轻度恶心1例,发热1例。结论自体骨髓干细胞移植治疗后,患者肝功能和凝血机制明显改善,生存率提高,症状好转,表明骨髓干细胞移植对肝衰竭患者治疗有效,安全,不良反应少。     

Intrahepatic transplantation of hepatic oval cells for fulminant hepatic failure in rats

AIM： To evaluate the effect of intrahepatic transplantation of hepatic oval cells （HOC） on fulminant hepatic failure （FHF） in rats.
METHODS： HOC obtained from rats were labeled with green fluocescent protein （GFP） or 5, 6- carboxyfluorescein diacetate succinmidyl ester （CFDASE）. Cell fluorescence was observed under fluorescent microscope at 6, 24, 48 and 72 h after labeling. CFDA- SE labeled HOC （5 × 10^6 cells each rat） were injected into livers of rats with FHF induced by D-galactosamine. Serum albumin （ALB）, alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and total bilirubin （TBil） levels were measured at different time points. Liver function of rats was examined on days 3, 7, 14 and 21 after HOC transplantation.
RESULTS： The positive rate of GFP and CFDA-SE labeled HOC was 10% and 90%, respectively, with no significant change in cell viabilities. The survival rate was higher in HOC transplantation group than in control group, especially 48 （9/15 vs 6/15） and 72 h （9/15 vs 4/15） after HOC transplantation. The serum ALT, AST and TBil levels were decreased while the serum AIb level was increased after HOC transplantation. Fluorescence became faded and diffused in liver tissues, suggesting that proliferation and differentiation occur in transplanted HOC.
CONCLUSION： CFDA-SE is superior to GFP in labeling HOC, although fluorescence intensity is decreased progressively with cell division. HOC transplantation can improve the liver function and increase the survival rate of recipients.