Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation

AIM:To assess the possible effect of two different types of preoperative transcatheter arterial chemoembolization(TACE)on recurrence-free survival after liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and to analyze the effects of TACE on tumor histology.METHODS:We retrospectively analyzed the histological features of 130 HCC nodules in 63 native livers removed at transplantation.Patients who received any other type of treatment such as radiofrequency tumor ablation,percutaneous ethanol ablation or who were not treated at all were excluded.All patients in the present study were within the Milan Criteria at the last imaging findings before transplantation.Doxorubicineluting bead TACE(DEB-TACE)was performed in 22patients(38 nodules),and conventional TACE(c-TACE)in 16(25 nodules).Patients’and tumors’characteristics were retrospectively reviewed.We performed a pernodule analysis of the explanted livers to establish the mean percentage of necrosis of any nodule treated by TACE(conventional or DEB)and a per-patient analysis to establish the percentage of necrosis in the cumulative tumor area,including 21 nodules not reached by TACE.Inflammatory and fibrotic changes in the tissue surrounding the tumor nodule were analyzed and categorized as poor/absent,moderate and enhanced reaction.Uni-and multivariate analysis of risk factors for HCC-recurrence were performed.RESULTS:The number and diameter of the nodules,the time spent on the waiting list and the number of treatments were similar in the two groups.A trend towards higher appropriate response rates(necrosis≥90%)was observed in the DEB-TACE group(44.7%vs32.0%,P=0.2834).The mean percentage of necrosis in the cumulative tumor area was 58.8%±36.6%in the DEB-TACE group and 50.2%±38.1%in the c-TACE group(P=0.4856).Fibrotic and inflammatory reactions surrounding the tumor nodule were markedly more common in the DEB-TACE group(P<0.0001,for both the parameters).The three-year recurrence-free survival was higher in DEB-TACE-treated patients than in conventionally treated patients(87.4%vs 61.5%,P=0.0493).Other factors affecting recurrence-free survival included viable tumor beyond Milan Criteria on histopathological examination,the percentage of necrosis on CTA≤50%and a pre-transplant serum-fetoprotein level greater than 70 ng/mL.On multivariate analysis,the lack of treatment with DEB-TACE,high levels of-fetoprotein and viable tumor beyond Milan Criteria at histology examination were identified as independent predictors of tumor recurrence.CONCLUSION:DEB-TACE can effectively promote tumor necrosis and improves recurrence-free survival after LT in HCC.

Nervous and Neuroendocrine regulation of the pathophysiology of cholestasis and of biliary carcinogenesis

Cholangiocytes，上皮细胞衬里胆管，是在几肝疾病的靶细胞。自从开始， Cholangiopathies 和 cholangiocarcinoma 在许多科学家产生兴趣。发展中的机制，和这些疾病的治疗学的工具仍然是未定义的。几研究证明许多荷尔蒙， neuropeptides 和 neurotransmitters 在长期的胆汁的疾病期间调整恶意、非恶意的 cholangiocyte 病理生理学。这评论的目的是介绍在贡献了澄清与胆汁郁积和 cholangiocarcinoma 开发联系的 pathophysiologic 事件的紧张、神经内分泌的规定的角色的最近的年里出版的几研究的调查结果。这张手稿被组织成二部分。第一部分提供肝的神经分布和影响 cholangiocyte 功能和新陈代谢的神经内分泌荷尔蒙， neurotransmitters 和 neuropeptides 的起源的概述。第一节也考察几神经内分泌荷尔蒙和神经系统在胆汁郁积期间在 cholangiocyte 生长，幸存和机能活动上玩的效果。在第二节，我们总结在恶意的 cholangiocyte 生长的规定描述神经系统和神经内分泌荷尔蒙的角色的一些研究的结果。

Role of autophagy in cholangiocarcinoma:Pathophysiology and implications for therapy

Cholangiocarcinoma(CCA)is a malignant tumour of the biliary system that originates from the neoplastic transformation of cholangiocytes.CCA is characterized by late diagnosis and poor outcome,with surgery considered as the last option for management.Autophagy is a physiological lysosomal degradation process,essential for cellular homeostasis and ubiquitous in all eukaryotic cells.Several studies have reported a potential involvement of autophagy in cancer,but it remains unclear whether activation of this process represents a survival mechanism of cancer cells.In the present review,we examine the autophagic process and summarize the current knowledge about the involvement of autophagy in the progression of cancer.The link between autophagy and chemoresistance and the use of autophagic markers in diagnosis are also considered in detail.Preliminary evidence shows that the combination of autophagy modulators(activators or inhibitors)with conventional chemotherapeutic agents offers a possible treatment option against signalling pathways that are hyperactivated or altered in CCA.In vitro evidence suggests that combination of chemotherapy agents,such as cisplatin,under activation or inhibition of autophagic processes,in two different CCA cell lines,may improve chemosensitivity and reduce cell survival,respectively.A deeper understanding of these pathways,in both cancer and non-cancer cells,could unveil possible therapeutic targets to treat CCA patients.

肝细胞癌的新见解：从实验到临床

肝细胞癌(简称肝癌)是一个多步骤病变过程,其间涉及不同的遗传变异,最终导致肝细胞的恶性转化。肝脏是多种不同肿瘤转移的主要靶向器官之一,也是慢性疾病过程中的一个重要且较易发生恶变的场所。事实上,肝癌是慢性肝脏疾病自然演变的结果,从肝纤维化,到肝硬化最后肝癌的过程。肝癌是全球第6位常见癌症,每年约630 000例新诊断病例。此外,大约80%肝癌患者经历了疾病由肝纤维化发展为肝硬化最后肝癌的临床过程。导致肝癌的3大主因是乙肝病毒感染、丙肝病毒感染和酗酒。另外,代谢性疾病[如非酒精性脂肪肝(NAFLD),非酒精性脂肪性肝炎(NASH)]和一些发病率较低的自身免疫性疾病也可能导致肝癌的发生。另外一个少见的导致肝脏癌变的病因是黄曲霉毒素B1的感染,尤其多见于一些非洲和亚洲国家。这些病因导致肝癌发生涉及了广泛的途径和分子,具体机制还在研究当中。总之,肝脏癌变是成熟肝细胞基因发生改变,并以细胞增殖和死亡失去控制为主要特征的多因素过程主要源于将基础研究和临床科学相结合,相关作用机制的研究进展是寻找新的潜在疗法的基础。该综述从基础和临床两方面分析了当前用于肝癌基础研究的模型。

遗传学在胆管细胞癌发展中的重要性

胆管细胞癌(CCA)是肝脏一种少见的恶性肿瘤,起源于胆管。在过去的30年里,CCA在世界各地的发病率不断的增高,但其预后依然很差,几乎未改变过。尽管已发现几个危险因子与该肿瘤的发生相关,但这些危险因子中没有一个在大多数患者中得以肯定。由于诊断时多已是晚期以及有限的治疗选择,导致CCA生存率很低。近来对CCA遗传学和表观遗传学上变化的研究结果为重新阐明胆管细胞恶性转化的分子学机制带来了希望。沿着这一方向进一步研究将有助于形成新的诊断、预后和治疗方法。该篇全面概述了CCA的最新进展,描述迄今所报道过的发生在CCA中最重要的基因突变和表观遗传学改变。