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。     

Epithelioid hemangioendothelioma of the liver

Epithelioid hemangioendothelioma (EH) of the liver is a rare tumor and is difficult to differentiate from cholangiocellular carcinoma or metastatic liver tumor on image diagnosis. A case of curatively resected EH of the liver is reported. A 48-year-old woman was admitted because she had a mass in the liver. Cholangiocellular carcinoma was suspected preoperatively. Right trisegmentectomy of the liver, combined with bile duct resection and portal vein resection and reconstruction, was performed. Characteristic macro- and microscopic findings of the resected specimen revealed EH of the liver. The patient has survived for more than 6 years without recurrence. Because of the tendency of EH of the liver to appear in multiple or scattered forms, only 12 cases of resection for EH have been reported.     

Epithelioid hemangioendothelioma of the liver

Epithelioid hemangioendothelioma (EH) is a rare tumor of vascular origin, which occurs at sites such as soft tissues, liver, or lung, and has a highly unpredictable malignant potential. It is an intermediate entity between well-differentiated hemangioma and angiosarcoma. We present two cases of this rare disease in which the tumor was detected fortuitously and the definitive diagnosis was based on histological evidence. Both our cases are highly illustrative of the two ways in which hepatic EH can present (nodular or diffuse) and of its diagnostic and therapeutic management. Neoplastic cells expressed the factor VIII-related antigen, CD31 or CD34. Treatment was surgical resection in one patient and liver transplant in the other. Although EH of the liver has a better prognosis than other hepatic neoplasms, conservative treatment is not recommended. Our cases highlight the importance of a histological diagnosis to avoid it being mistaken for another entity.     

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。     

Epithelioid hemangioendothelioma of the liver. Diagnostic features and role of liver transplantation

Five cases of epithelioid hemangioendothelioma of the liver are reported. This unusual type of vascular tumor is often difficult to diagnose; its angiogenic nature is not overt at the radiologic level and may be overlooked by conventional histologic examination. At imaging procedures, epithelioid hemangioendothelioma of the liver presents as multiple focal hypovascular areas, disseminated in both lobes. The combination of these imaging abnormalities with a peculiar set of demographic and clinical features, including young age, good general condition, and progressive course, is suggestive. However, the final diagnosis can be established only by histologic examination of appropriate material collected by guided liver biopsies and may be helped by immunohistochemistry and ultrastructural examination. The accurate diagnosis of epithelioid hemangioendothelioma of the liver is of clinical and therapeutic relevance. In view of its favorable clinical course, orthotopic liver transplantation may be considered for the treatment of this tumor when intrahepatic dissemination contraindicates partial hepatectomy and extrahepatic extension, excluded by exploratory laparotomy, is absent.     

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。     

Treatment and prognosis of hepatic epithelioid hemangioendothelioma based on SEER data analysis from 1973 to 2014

Background: Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor of vascular origin with an unknown etiology, a low incidence, and a variable natural course. We evaluated the management and prognosis of HEH from the Surveillance, Epidemiology and End Results (SEER) program and changes in treatment modalities of HEH over 30 years. Methods: From 1973 to 2014 in the SEER database, we selected patients diagnosed with HEH. We analyzed the clinical characteristics, patterns of management, and clinical outcomes of patients with HEH. Results: We identi ed 79 patients with HEH (median age: 54.0 years;male to female ratio: 1:2.6). The initial extent of disease was local in 22 (27.8%) patients, regional metastasis in 22 (27.8%), distant metas-tasis in 31 (39.2%) and unknown in 4 (5.1%). The median size of primary tumor was 3.85 cm (interquartile range, 2.50 7.93 cm). Among 74 patients with available management data, the most common manage-ment was no treatment (29/74, 39.2%), followed by chemotherapy only (22/74, 29.7%), liver resection-based (13/74, 17.6%), and transplantation-based therapy (6/74, 8.1%). The 5-year cancer-speci c survival rate was 57.8%. Patients who underwent surgical treatment had signi cantly higher survival than those who underwent non-surgical treatment (5-year survival;88% vs. 49%, P=0.019). Multivariate analysis revealed that surgical therapy was the only independent prognostic factor for survival (hazard ratio: 0.20, P=0.040). Conclusions: Resection or liver transplantation is worth considering for treatment of patients with HEH.     

Liver transplantation for hepatic tumors:a systematic review

Improvements in the medical and pharmacological management of liver transplantation(LT)recipients have led to a better long-term outcome and extension of the indications for this procedure.Liver tumors are relevant to LT;however,the use of LT to treat malignancies remains a debated issue because the high risk of recurrence.In this review we considered LT for hepatocellular carcinoma(HCC),cholangiocarcinoma(CCA),liver metastases(LM)and other rare tumors.We reviewed the literature,focusing on the past 10 years.The highly selected Milan criteria of LT for HCC(single nodule<5 cm or up to 3 nodules<3cm)have been recently extended by a group from the University of S.Francisco(1 lesion<6.5 cm or up to3 lesions<4.5 cm)with satisfying results in terms of recurrence-free survival and the"up-to-seven criteria".Moreover,using these criteria,other transplant groups have recently developed downstaging protocols,including surgical or loco-regional treatments of HCC,which have increased the post-operative survival of recipients.CCA may be treated by LT in patients who cannot undergo liver resection because of underlying liver disease or for anatomical technical challenges.A well-defined protocol of chemoirradiation and staging laparotomy before LT has been developed by the Mayo Clinic,which has resulted in long term diseasefree survival comparable to other indications.LT for LM has also been investigated by multicenter studies.It offers a real benefit for metastases from neuroendocrine tumors that are well differentiated and when a major extrahepatic resection is not required.If LT is an option in these selected cases,liver metastases from colorectal cancer is still a borderline indication because data concerning the disease-free survival are still lacking.Hepatoblastoma and hemangioendothelioma represent rare primary tumors for which LT is often the only possible and effective cure because of the frequent multifocal,intrahepatic nature of the disease.LT is a very promising procedure for both primary and secondary liver malignancies;however,it needs an accurate evaluation of the costs and benefits for each indication to balance the chances of cure with actual organ availability.     

肝上皮样血管内皮瘤1例报告

正1病例资料患者女性,53岁。因间断右上腹疼痛2个月入院。患者于2个月前无明显诱因出现右上腹疼痛,钝痛,呈间断出现,并伴有腹胀,因不影响正常生活,未系统诊治。半个月前出现食欲减退,厌油腻,恶心,无呕吐,就诊于当地医院,行病毒学检查无阳性提示,腹部CT发现肝脏多发异常密度。为进一步诊     

肝上皮样血管内皮瘤1例

1．病例资料：患者男，27岁，教师。10余天前于饮酒后出现上腹部不适，以剑突下和肝区最为明显，无腰背部放射痛，无畏寒发热，无恶心呕吐，在当地医院CT检查提示“肝肚多发占位，性质待查”转入本院进一步检查治疗。查体：体温36．8℃，血压135／80mmHg，皮肤黏膜无黄染，无出血点及蜘蛛痣。心肺正常。腹平软，肝脾肋下未及．肝区叩击痛阴胜。腹部移动性浊音阴性．脯鸣青5次/min。     

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。     

Hepatitis C virus related cirrhosis decreased as indication to liver transplantation since the introduction of direct-acting antivirals: A single-center study

AIM To evaluate waiting list(WL) registration and liver transplantation(LT) rates in patients with hepatitis C virus(HCV)-related cirrhosis since the introduction of direct-acting antivirals(DAAs).METHODS All adult patients with cirrhosis listed for LT at Padua University Hospital between 2006-2017 were retrospectively collected using a prospectivelyupdated database; patients with HCV-related cirrhosis were divided by indication for LT [dec-HCV vs HCV/hepatocellular carcinoma(HCC)] and into two interval times(2006-2013 and 2014-2017) according to the introduction of DAAs. For each patient, indications to LT, severity of liver dysfunction and the outcome in the WL were assessed and compared between the two different time periods. For patients receiving DAA-based regimens, the achievement of viral eradication and the outcome were also evaluated. RESULTS One thousand one hundred and ninty-four [male(M)/female(F): 925/269] patients were included. Considering the whole cohort, HCV-related cirrhosis was the main etiology at the time of WL registration(490/1194 patients, 41%). HCV-related cirrhosis significantly decreased as indication to WL registration after DAA introduction(from 43.3% in 2006-2013 to 37.2% in 2014-2017, P = 0.05), especially amongst decHCV(from 24.2% in 2006-2013 to 15.9% in 2014-2017, P = 0.007). Even HCV remained the most common indication to LT over time(289/666, 43.4%), there was a trend towards a decrease after DAAs introduction(from 46.3% in 2006-2013 to 39% in 2014-2017, P = 0.06). HCV patients(M/F: 43/11, mean age: 57.7 ± 8 years) who achieved viral eradication in the WL had better transplant-free survival(log-rank test P = 0.02) and delisting rate(P = 0.002) than untreated HCV patients. CONCLUSION Introduction of DAAs significantly reduced WL registrations for HCV related cirrhosis, especially in the setting of decompensated cirrhosis.     

终末期酒精性肝病的肝移植

西方国家常见的酒精性肝病（ALD）近年来在我国也有明显的增加.由于没有疗效确切的药物,肝移植成为目前治疗终末期酒精性肝病（EALD）最有效的手段,而与其他良性终末期肝病肝移植比较,EALD肝移植存在诸多特殊的临床问题.我们回顾分析我院11例EALD肝移植的临床资料及随访结果,对受者的选择、术前的评估及围手术期的处理等问题进行探讨.     

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。     

Epithelioid hemangioendothelioma of the liver following contact with vinyl chloride. Recurrence after orthotopic liver transplantation

Malignant epithelioid hemangioendothelioma of the liver is a recently recognized and uncommon neoplasm of vascular origin. Few cases have been reported and the treatment remains therefore difficult to define. A relationship to oral contraceptive use has been suggested but no other toxic agents have been incriminated. We report here the first case occurring after a close contact with vinyl chloride. Because of wide hepatic destruction and serious portal hypertension with bleeding varices, the patient underwent orthotopic liver transplantation. After a disease-free interval of 20 months, he died from variceal hemorrhage and encephalopathy due to local tumor recurrence with portal thrombosis. Nevertheless, orthotopic liver transplantation remains the only hope of salvage when extensive liver destruction and life-threatening complications are present.     

大鼠30%小体积肝移植模型三种切肝方法的比较

目的:探讨不同肝叶选取和切肝方法对小体积肝移植术后生存率的影响,以建立理想的成功率高的大鼠30%小体积肝移植模型.方法:采用以Kamada的"二袖套法"非动脉化大鼠原位肝移植模型为基础,建立大鼠30%小体积肝移植模型.实验分为3组:Ⅰ组:中叶供肝的30%小体积肝移植组(n=28):Ⅱ组:右中叶和右叶供肝的30%小体积肝移植组(n= 15);Ⅲ组:改进切肝方法的30%中叶供肝小肝移植组(n=36).观察3组术后并发症和7d生存率.结果:Ⅱ组切肝时间和术后肝后下腔静脉狭窄的发生率明显低于Ⅰ组(11±3 min vs 13±2 min,P=0.0305;0/15 vs 8/28,P=0.036),但胆漏的发生率高于Ⅰ组(4/15 vs 0/28,P=0.011).Ⅲ组肝后下腔静脉狭窄的发生率明显低于Ⅰ组(1/36 vs 8/28,P=0.008),其他并发症发生率各组间无明显差别.术后7d生存率Ⅰ(33%)、Ⅱ(50%)、Ⅲ(60%)组间无统计学差别.结论:采用中叶供肝、改进切肝技术可以建立具有更稳定的大鼠30%小体积肝移植模型.     

Challenges in transplantation for alcoholic liver disease

Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist’s assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient’s pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key factor determining the outcome of transplantation for alcoholic cirrhosis is intensive lifelong medical and psychological care. Post-transplant surveillance might be much more important than pre-transplant selection.