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The evolving landscape of precision medicine in primary liver cancer. 原发性肝癌精准医学的发展前景。
IF 5 Q4 ONCOLOGY Pub Date : 2019-06-04 DOI: 10.2217/hep-2019-0004
Sean P Martin, Xin Wei Wang
The incidence of primary liver cancer (PLC) is rising faster than any other malignancy in the USA and is estimated to result in over 31,000 deaths in 2019 [1]. PLC poses a unique challenge in that the majority of patients suffer from both their malignancy and underlying liver damage which is the inciting factor for their hepatocarcinogenesis. Viral infections such as Hepatitis B and C, lifestyle choices such as heavy alcohol use and inherited genetic disorders such as primary biliary cirrhosis can all lead to underlying liver cirrhosis leaving the patient vulnerable to malignancy and without aggressive treatment options. There are multiple histologic subtypes which comprise PLC but by far the two most common are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Interestingly, while historically treated as two distinct malignancies, there is a growing body of evidence that they may be more alike than previously thought. Classically it was believed that iCCA arose from cholangiocytes, and while the origins of HCC remained more elusive it was hypothesized that hepatic stem cells in addition to hepatocytes were implicated. More recent work reveals that both malignancies could originate from hepatocytes and more strikingly, in certain subsets of patients, share a common molecular subtype [2–4]. These commonalities shed light on the potential drivers of hepatocarcinogenesis and are the first steps of novel targeted therapies. With a more thorough understanding of these tumors, directed personalized care is possible.
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引用次数: 7
Current options and future possibilities for the systemic treatment of hepatocellular carcinoma. 肝细胞癌系统治疗的当前选择和未来可能性。
IF 5 Q4 ONCOLOGY Pub Date : 2019-06-04 DOI: 10.2217/hep-2019-0001
Jean-Luc Raoul, Jean-Sébastien Frenel, Judith Raimbourg, Marine Gilabert

Most hepatocellular carcinoma patients could not benefit from or experience disease recurrence after curative treatments. In 2007 sorafenib demonstrated efficacy in first line treatment of advanced hepatocellular carcinoma. After a decade of negative trials, in early 2019 we now have another tyrosine kinase inhibitor available in first line, lenvatinib, three other targeted therapies in second line post-sorafenib (regorafenib, cabozantinib and ramucirumab) and promising data from two immunotherapies (nivolumab and pembrolizumab). Unfortunately, no biomarkers have been identified to help guide our choice. In this short review we summarize the results of these different therapies and propose a therapeutic algorithm based on subgroup analysis. It is most likely that we will not have head-to-head comparisons in second line trials.

大多数肝细胞癌患者在治疗后不能从疾病复发中获益或经历疾病复发。2007年,索拉非尼在晚期肝细胞癌的一线治疗中显示出疗效。经过十年的阴性试验,2019年初,我们在一线有了另一种酪氨酸激酶抑制剂乐伐替尼,在索拉非尼后的二线有了其他三种靶向疗法(瑞戈非尼、卡博扎替尼和拉穆丘单抗),以及两种免疫疗法(尼沃单抗和pembrolizumab)的有希望的数据。不幸的是,目前还没有发现有助于指导我们选择的生物标志物。在这篇简短的综述中,我们总结了这些不同疗法的结果,并提出了一种基于亚组分析的治疗算法。我们很可能不会在二线试验中进行正面比较。
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引用次数: 28
Journal Watch: Dr Tu looks back at the most important research articles released in 2018 relating to models and biomarkers of hepatocellular carcinoma. 期刊观察:屠博士回顾了2018年发表的与肝细胞癌模型和生物标志物相关的最重要的研究文章。
IF 5 Q4 ONCOLOGY Pub Date : 2019-02-12 eCollection Date: 2019-03-01 DOI: 10.2217/hep-2019-0002
Thomas Tu
Wang G, Chow RD, Ye L et al. Mapping a functional cancer genome atlas of tumor suppressors in mouse liver using AAV-CRISPR-mediated direct in vivo screening. Sci. Adv. 4(2), eaao5508 (2018). Multiple putative hepatocellular carcinoma (HCC) driver mutations have been identified using next-generation sequencing, but the majority have not been confirmed in in vivo settings or in combination with each other. Wang et al. describe a high-throughput solution by transducing transgenic mice containing a Cre-dependent Cas9 with hepatocyte-specific adeno-associated virus vectors that encode for Cre recombinase, EGFP and a sgRNA from a library, targeting HCC candidate genes (49 genes drawn from online databases). Indels at target loci were then confirmed and quantified using multiplexed molecular inversion probe sequencing. Within 3 months of transduction, mice developed multifocal GFP-positive HCC, in which significant enrichment of Trp53, Setd2, Cic and Pik3R1 mutations were observed. Several pairs of mutations were significantly enriched, including Cdkn2a and Pten, B2m and Kansl1, and Arid2 and Cdkn2a. This exciting novel HCC model has the potential to confirm thousands of gene candidates identified by sequencing projects.
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引用次数: 0
Corrigendum. 勘误表。
IF 5 Q4 ONCOLOGY Pub Date : 2018-12-21 DOI: 10.2217/hep-2017-0017c1

[This corrects the article DOI: 10.2217/hep-2017-0017.].

[这更正了文章DOI: 10.2217/hep-2017-0017.]。
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引用次数: 0
Hepatocellular carcinoma treatment: hurdles, advances and prospects. 肝细胞癌治疗:障碍、进展和前景。
IF 1.2 Q4 ONCOLOGY Pub Date : 2018-09-28 eCollection Date: 2018-04-01 DOI: 10.2217/hep-2018-0002
Ratna Kumari, Manoj Kumar Sahu, Anindita Tripathy, Kanishka Uthansingh, Manas Behera

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related mortality and is particularly refractory to the available chemotherapeutic drugs. Among various etiologies of HCC, viral etiology is the most common, and, along with alcoholic liver disease and nonalcoholic steatohepatitis, accounts for almost 90% of all HCC cases. HCC is a heterogeneous tumor associated with multiple signaling pathway alterations and its complex patho-physiology has made the treatment decision challenging. The potential curative treatment options are effective only in small group of patients, while palliative treatments are associated with improved survival and quality of life for intermediate/advanced stage HCC patients. This review article focuses on the currently available treatment strategies and hurdles encountered for HCC therapy. The curative treatment options discussed are surgical resection, liver transplantation, and local ablative therapies which are effective for early stage HCC patients. The palliative treatment options discussed are embolizing therapies, systemic therapies, and molecular targeted therapies. Besides, the review also focuses on hurdles to be conquered for successful treatment of HCC and specifies the future prospects for HCC treatment. It also discusses the multi-modal approach for HCC management which maximizes the chances of better clinical outcome after treatment and identifies that selection of a particular treatment regimen based on patients' disease stage, patients' ages, and other underlying factors will certainly lead to a better prognosis.

肝细胞癌(HCC)是导致癌症相关死亡的主要原因之一,对现有的化疗药物尤其难治。在 HCC 的各种病因中,病毒病因最为常见,与酒精性肝病和非酒精性脂肪性肝炎一起,几乎占所有 HCC 病例的 90%。HCC 是一种与多种信号通路改变相关的异质性肿瘤,其复杂的病理生理学使治疗决策充满挑战。潜在的根治性治疗方案仅对一小部分患者有效,而姑息治疗则能提高中晚期 HCC 患者的生存率和生活质量。这篇综述文章重点介绍了目前可用的治疗策略以及治疗 HCC 所遇到的障碍。讨论的根治性治疗方案包括手术切除、肝移植和局部消融疗法,这些方案对早期 HCC 患者有效。讨论的姑息治疗方案包括栓塞疗法、全身疗法和分子靶向疗法。此外,这篇综述还重点讨论了成功治疗 HCC 需要克服的障碍,并明确了 HCC 治疗的未来前景。它还讨论了治疗 HCC 的多模式方法,这种方法能最大限度地提高治疗后临床疗效,并指出根据患者的疾病分期、年龄和其他潜在因素选择特定的治疗方案必将带来更好的预后。
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引用次数: 0
Transcatheter arterial chemoembolization combined with radiofrequency or microwave ablation for hepatocellular carcinoma: a review. 经导管动脉化疗栓塞联合射频或微波消融治疗肝细胞癌:综述。
IF 5 Q4 ONCOLOGY Pub Date : 2018-09-28 eCollection Date: 2018-04-01 DOI: 10.2217/hep-2018-0001
Nikolaos Galanakis, Elias Kehagias, Nikolas Matthaiou, Dimitrios Samonakis, Dimitrios Tsetis

Hepatocellular carcinoma (HCC) is the sixth most common type of malignancy. Several therapies are available for HCC and are determined by stage of presentation, patient clinical status and liver function. Local-regional treatment options, including transcatheter arterial chemoembolization, radiofrequency ablation or microwave ablation, are safe and effective for HCC but are accompanied by limitations. The synergistic effects of combined transcatheter arterial chemoembolization and radiofrequency ablation/microwave ablation may overcome these limitations and improve the therapeutic outcome. The purpose of this article is to review the current literature on these combined therapies and examine their efficacy, safety and influence on the overall and recurrence-free survival in patients with HCC.

肝细胞癌(HCC)是第六大最常见的恶性肿瘤。肝细胞癌有几种治疗方法,根据表现阶段、患者临床状态和肝功能而定。局部区域治疗方案,包括经导管动脉化疗栓塞、射频消融或微波消融,对HCC是安全有效的,但也有局限性。经导管动脉化疗栓塞联合射频消融/微波消融的协同作用可能克服这些局限性,改善治疗效果。本文的目的是回顾目前关于这些联合治疗的文献,并检查它们的有效性、安全性以及对HCC患者总生存率和无复发生存率的影响。
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引用次数: 23
Selective internal radiation therapy: an effective treatment for hormonal syndromes in pancreatic neuroendocrine tumors. 选择性内放射治疗:胰腺神经内分泌肿瘤激素综合征的有效治疗方法。
IF 5 Q4 ONCOLOGY Pub Date : 2018-09-28 eCollection Date: 2018-04-01 DOI: 10.2217/hep-2017-0025
Leyre Zubiri, José I Bilbao, Javier Rodríguez, Bruno Sangro

The hormone secretion in pancreatic neuroendocrine tumors (pNET) causes an important interference in patients' quality of life. We present two cases of pNET metastatic to the liver (a pancreatic endocrine carcinoma with a severe hormonal syndrome and an insulinoma with severe crisis of hypoglycemia and coma) refractory to conventional treatments, which were finally solved with selective internal radiation therapy (SIRT), a nonstandard level 1 therapy. We show two examples of an excellent control of symptoms together with a long survival after treatment with SIRT. The evidence supporting the use of this therapy is level 2. Our case reports strongly support the use of SIRT for the severe clinical syndrome in pNET metastatic to the liver and refractory to somatostatin analogs.

胰腺神经内分泌肿瘤(pNET)的激素分泌是影响患者生活质量的重要因素。我们报告了2例pNET转移到肝脏的病例(1例胰腺内分泌癌伴严重激素综合征,1例胰岛素瘤伴严重低血糖和昏迷危像),常规治疗难治性,最终通过选择性内放射治疗(SIRT)解决,这是一种非标准的1级治疗。我们展示了两个在SIRT治疗后症状得到良好控制和长期生存的例子。支持使用这种疗法的证据是2级。我们的病例报告强烈支持使用SIRT治疗pNET转移到肝脏和对生长抑素类似物难治的严重临床综合征。
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引用次数: 3
Molecular heterogeneity in hepatocellular carcinoma. 肝细胞癌的分子异质性。
IF 1.2 Q4 ONCOLOGY Pub Date : 2018-09-11 eCollection Date: 2018-01-01 DOI: 10.2217/hep-2018-0005
Shijia Zhu, Yujin Hoshida
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引用次数: 0
De novo hepatocellular carcinoma occurrence in hepatitis C cirrhotics treated with direct-acting antiviral agents. 直接作用抗病毒药物治疗丙型肝炎肝硬化中新发肝细胞癌的发生率。
IF 5 Q4 ONCOLOGY Pub Date : 2018-07-25 eCollection Date: 2018-01-01 DOI: 10.2217/hep-2018-0003
Gabriela Kuftinec, Thomas Loehfelm, Michael Corwin, Blythe Durbin-Johnson, MarieChristi Candido, Rebecca Hluhanich, Souvik Sarkar

Aim: Recent studies raise concerns for higher incidence of hepatocellular carcinoma (HCC) after direct-acting antiviral therapy for hepatitis C virus (HCV).

Methods: In this study, using analysis of liver imaging pre- and post-DAA treatment, we queried new occurrence or 'de novo' of HCC in patients with HCV-cirrhosis treated with DAAs. Of 150 patients who met study criteria, 7 (4.7%; 95% CI: 2.1-9.5%) patients developed de novo HCC which did not differ from historical rates of 3% (p = 0.22).

Results: Notably, patients with decompensated cirrhosis had significantly higher rate of de novo HCC (9.3%; 95% CI: 3.12-22.2%; p = 0.04).

Conclusion: Our data support the need for continued surveillance for HCC in HCV cirrhotics even after successful therapy.

目的:最近的研究引起了对丙型肝炎病毒(HCV)直接抗病毒治疗后肝细胞癌(HCC)发生率增高的关注。方法:在本研究中,通过分析daa治疗前后的肝脏影像学,我们询问肝细胞癌新发或“新生”的hcv -肝硬化患者接受daa治疗。在150例符合研究标准的患者中,7例(4.7%;95% CI: 2.1-9.5%),与历史发生率3% (p = 0.22)无差异。结果:值得注意的是,失代偿期肝硬化患者的新发HCC发生率明显较高(9.3%;95% ci: 3.12-22.2%;p = 0.04)。结论:我们的数据支持HCV肝硬化患者即使在治疗成功后仍需要继续监测HCC。
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引用次数: 6
The impact of antiviral therapy on hepatocellular carcinoma epidemiology. 抗病毒治疗对肝细胞癌流行病学的影响。
IF 5 Q4 ONCOLOGY Pub Date : 2018-05-10 eCollection Date: 2018-01-01 DOI: 10.2217/hep-2017-0024
Massimo Colombo, Ana Lleo

The development of nucleos(t)ide analogs and direct antiviral agents has revolutionized the management of chronic infection with HBV and HCV, respectively. These regimens allow to expand treatment to virtually all infected, including those with poor hepatic reserve and those with severe comorbidities. As a result, permanent suppression of HBV and eradication of HCV has been achieved in almost all treated patients, resulting in substantial clinical benefits. In several cohorts, these successes have translated into a reduction of the incidence of hepatocellular carcinoma that was more frequently observed in patients with less advanced hepatitis, whereas liver cancer was more often associated with male gender, cirrhosis, alcohol abuse and diabetes.

核苷(t)类似物和直接抗病毒药物的发展分别彻底改变了HBV和HCV慢性感染的管理。这些方案可以将治疗范围扩大到几乎所有感染者,包括肝储备不良者和有严重合并症者。因此,几乎所有接受治疗的患者都实现了HBV的永久抑制和HCV的根除,从而产生了可观的临床效益。在一些队列中,这些成功转化为肝细胞癌发病率的降低,肝细胞癌在较不严重的肝炎患者中更为常见,而肝癌通常与男性、肝硬化、酗酒和糖尿病有关。
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引用次数: 17
期刊
Hepatic Oncology
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