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Development of shellfish allergy after exposure to dual immune checkpoint blockade. 暴露于双重免疫检查点阻断后贝类过敏的发展。
IF 5 Q4 ONCOLOGY Pub Date : 2018-02-09 eCollection Date: 2018-01-01 DOI: 10.2217/hep-2017-0021
Zachary J Brown, Bernd Heinrich, Tim F Greten

Hepatocellular carcinoma (HCC) is a major health problem worldwide with limited systemic therapies available. Immunotherapy is a fast-moving field that is quickly evolving as a treatment for HCC with three recent clinical trials published treating HCC with immune checkpoint inhibitors with promising results. Checkpoint inhibition may lead to a unique adverse event profile with the potential to cause immune-related adverse events by unbalancing the immune system. Here, we report a case of a 61-year-old male with advanced HCC who developed a shellfish allergy after completing three cycles of combination of tremelimumab and durvalumab therapy.

肝细胞癌(HCC)是世界范围内的一个主要健康问题,可用的全身治疗方法有限。免疫治疗是一个快速发展的领域,作为HCC的治疗方法正在迅速发展,最近发表了三个用免疫检查点抑制剂治疗HCC的临床试验,结果很有希望。检查点抑制可能导致独特的不良事件概况,有可能引起免疫系统失衡的免疫相关不良事件。在这里,我们报告了一例61岁晚期HCC男性患者,在完成tremelimumab和durvalumab联合治疗三个周期后发生贝类过敏。
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引用次数: 3
Systemic treatments for hepatocellular carcinoma: challenges and future perspectives. 肝细胞癌的系统治疗:挑战和未来展望。
IF 5 Q4 ONCOLOGY Pub Date : 2018-02-08 DOI: 10.2217/hep-2017-0020
Francesco Tovoli, Giulia Negrini, Francesca Benevento, Chiara Faggiano, Elisabetta Goio, Alessandro Granito

Sorafenib has been the only approved systemic treatment of hepatocellular carcinoma (HCC) for almost a decade. Recently, two new drugs showed positive results in two Phase III studies. The RESORCE trial identified regorafenib as a valid second-line treatment for patients progressing to sorafenib, the REFLECT trial showed that lenvatinib is noninferior to sorafenib as front-line treatment. Following these trials, the therapeutic scenario will be dominated by anti-VEGFR drugs, with three different molecules showing a proven anticancer activity. Some open problems still remain and different immunotherapy trials are underway, following promising preliminary results. In this review we analyze: the most recent advancements about patients treated with sorafenib; the results of RESORCE and REFLECT trials; and the ongoing Phase III clinical trials. Finally, we discuss how they could address the current problems and possibly reshape the future of the systemic treatments for HCC.

索拉非尼是近十年来唯一被批准的肝细胞癌(HCC)的系统性治疗方法。最近,两种新药在两项III期研究中显示出阳性结果。RESOURCE试验确定雷戈非尼是治疗索拉非尼进展期患者的有效二线治疗方法,REFLECT试验表明,乐伐替尼与索拉非尼作为一线治疗方法并无差异。在这些试验之后,治疗方案将以抗VEGFR药物为主,三种不同的分子显示出已证实的抗癌活性。一些悬而未决的问题仍然存在,在取得有希望的初步结果后,不同的免疫疗法试验正在进行中。在这篇综述中,我们分析了:索拉非尼治疗患者的最新进展;RESRCE和REFLECT试验的结果;以及正在进行的III期临床试验。最后,我们讨论了他们如何解决当前的问题,并可能重塑HCC系统治疗的未来。
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引用次数: 34
Cellular senescence associated immune responses in liver cancer. 肝癌细胞衰老相关的免疫反应。
IF 5 Q4 ONCOLOGY Pub Date : 2017-10-01 Epub Date: 2017-11-17 DOI: 10.2217/hep-2017-0011
Tim F Greten, Tobias Eggert

Cellular senescence is a stress-induced cell-cycle arrest program that prevents malignant transformation of senescent cells following oncogenic pathway activation and DNA damage. Senescent cells are metabolically active and secrete cytokines and chemokines that shape the function and composition of their microenvironment. These cytokines can recruit immune cells such as lymphocytes and myeloid cells that depending on the context can either promote or inhibit liver tumor development and progression. Accordingly, pharmacologically targeting of secreted cytokines or reprogramming the expression of these cytokines in senescent cells represents a promising approach to skew senescence-associated immune responses toward cancer cell killing.

细胞衰老是一种应激诱导的细胞周期阻滞程序,可防止衰老细胞在致癌途径激活和DNA损伤后发生恶性转化。衰老细胞代谢活跃,分泌细胞因子和趋化因子,形成其微环境的功能和组成。这些细胞因子可以招募免疫细胞,如淋巴细胞和骨髓细胞,根据不同的情况,它们可以促进或抑制肝脏肿瘤的发生和进展。因此,在衰老细胞中以分泌的细胞因子为药理学目标或重新编程这些细胞因子的表达是一种很有希望的方法,可以使衰老相关的免疫反应偏向于杀死癌细胞。
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引用次数: 14
Locoregional therapies in cholangiocarcinoma. 胆管癌的局部疗法。
IF 5 Q4 ONCOLOGY Pub Date : 2017-10-01 Epub Date: 2017-11-17 DOI: 10.2217/hep-2017-0014
Peter L Labib, Brian R Davidson, Ricky A Sharma, Stephen P Pereira

Cholangiocarcinoma is a rare and aggressive malignancy of the biliary tract. Complete surgical resection can be curative, but the majority of patients are diagnosed with advanced disease and usually die within a year of diagnosis. Most deaths are attributable to local disease progression rather than distant metastases, supporting the use of locoregional therapies. There is evidence that locoregional therapies can provide local tumor control resulting in increased survival while avoiding some of the side effects of systemic treatments, increasing potential treatment options for patients who may be unsuitable for systemic palliative treatments. This review considers the evidence for locoregional therapies in cholangiocarcinoma, which can be classified into endoscopic, vascular, percutaneous and radiation oncological therapies. Current guidelines do not recommend the routine use of locoregional therapies due to a lack of prospective data, but the results of ongoing trials are likely to increase the evidence base and impact on clinical practice.

胆管癌是胆道中一种罕见的侵袭性恶性肿瘤。完全手术切除可以治愈,但大多数患者确诊时已是晚期,通常在确诊后一年内死亡。大多数死亡归因于局部疾病进展而非远处转移,这支持了局部治疗的使用。有证据表明,局部治疗可以控制局部肿瘤,从而提高生存率,同时避免全身治疗的一些副作用,为不适合全身姑息治疗的患者增加了潜在的治疗选择。本综述考虑了胆管癌局部治疗的证据,可分为内镜、血管、经皮和放射肿瘤治疗。由于缺乏前瞻性数据,目前的指南并不建议常规使用局部疗法,但正在进行的试验结果可能会增加证据基础并对临床实践产生影响。
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引用次数: 0
Biomarker development for hepatocellular carcinoma early detection: current and future perspectives. 肝细胞癌早期检测的生物标志物发展:当前和未来的观点。
IF 5 Q4 ONCOLOGY Pub Date : 2017-10-01 Epub Date: 2017-11-17 DOI: 10.2217/hep-2017-0019
Shreya Sengupta, Neehar D Parikh

Early detection of hepatocellular carcinoma (HCC) leads to improved survival; however, current early detection strategies for HCC surveillance are ineffective. Thus, there has been interest in developing biomarkers to aid in the early detection HCC. In this review, we discuss the five phases of biomarker discovery that are necessary for clinical implementation. We also describe the most promising investigational biomarkers and their phase of discovery. We review several promising technologies for the early detection of HCC, including miRNA, metabolomics and proteomics. Promisingly, there are samples from multiple longitudinal cohorts of patients with cirrhosis in the USA that are being collected in order to validate candidate biomarkers for HCC. A biomarker-based strategy has the potential to become the primary surveillance method for HCC detection.

早期发现肝细胞癌(HCC)可提高生存率;然而,目前用于HCC监测的早期检测策略是无效的。因此,人们对开发生物标志物来帮助早期发现HCC很感兴趣。在这篇综述中,我们讨论了临床实施所必需的生物标志物发现的五个阶段。我们还描述了最有希望的研究性生物标志物及其发现阶段。我们回顾了几种有前途的HCC早期检测技术,包括miRNA、代谢组学和蛋白质组学。有希望的是,美国正在收集来自多个肝硬化患者纵向队列的样本,以验证HCC的候选生物标志物。基于生物标志物的策略有可能成为HCC检测的主要监测方法。
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引用次数: 53
Radiologic criteria of response to systemic treatments for hepatocellular carcinoma. 肝细胞癌全身治疗反应的放射学标准。
IF 5 Q4 ONCOLOGY Pub Date : 2017-10-01 Epub Date: 2017-11-17 DOI: 10.2217/hep-2017-0018
Francesco Tovoli, Matteo Renzulli, Alessandro Granito, Rita Golfieri, Luigi Bolondi

Sorafenib has been the only approved systemic therapy for hepatocellular carcinoma until very recently. However, the radiologic assessment of its biological activity is a disputed matter as at least five different criteria have been proposed. In this review, we describe the characteristic of the Response Evaluation Criteria In Solid Tumors (RECIST), European Association for the Study of The Liver (EASL), modified RECIST (mRECIST), Response Evaluation Criteria In the Cancer of the Liver (RECICL) and Choi criteria. The existing comparative studies are reported together with recent pieces of evidence, analyzing the reasons behind the split between recommendations of the scientific societies and regulatory agencies. Future perspectives in the wake of the impending results of the immunotherapy trials are also discussed.

直到最近,索拉非尼一直是唯一被批准用于肝细胞癌的全身疗法。然而,其生物活性的放射学评估是一个有争议的问题,因为至少有五种不同的标准被提出。在这篇综述中,我们描述了实体肿瘤反应评价标准(RECIST)、欧洲肝脏研究协会(EASL)、修订后的RECIST (mRECIST)、肝癌反应评价标准(RECICL)和Choi标准的特点。现有的比较研究与最近的证据一起报告,分析了科学协会和监管机构的建议之间分歧的原因。在即将到来的免疫治疗试验的结果之后,未来的观点也进行了讨论。
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引用次数: 17
Surgical salvage of recurrence after resection of colorectal liver metastases: incidence and outcomes. 结直肠肝转移灶切除术后复发的手术挽救:发生率和结果。
IF 5 Q4 ONCOLOGY Pub Date : 2017-08-03 DOI: 10.2217/hep-2017-0002
Nuh N Rahbari, Michael I D'Angelica

Surgical resection remains the primary curative treatment option for patients with colorectal liver metastases. While the majority of patients will develop tumor relapse within or outside of the liver after hepatic metastasectomy, a subset of these patients may be amenable to salvage surgical resection. However, outcomes for this approach are not well defined. In this article, we summarize the current evidence for the incidence, feasibility and outcomes of salvage resection for recurrence after initial resection of colorectal liver metastases.

手术切除仍是结直肠肝转移患者的主要根治性治疗方案。虽然大多数患者在肝转移切除术后会在肝内或肝外出现肿瘤复发,但其中一部分患者可能适合进行挽救性手术切除。然而,这种方法的疗效尚不明确。在这篇文章中,我们总结了目前有关结直肠肝转移瘤初次切除术后复发的挽救性切除术的发生率、可行性和疗效的证据。
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引用次数: 0
Chemoembolization versus radioembolization for the treatment of unresectable intrahepatic cholangiocarcinoma in a single institution image-based efficacy and comparative toxicity. 化疗栓塞与放射栓塞治疗不可切除肝内胆管癌在单一机构基于图像的疗效和比较毒性。
IF 5 Q4 ONCOLOGY Pub Date : 2017-07-01 Epub Date: 2017-10-30 DOI: 10.2217/hep-2017-0005
Olaguoke Akinwande, Veer Shah, Abigail Mills, Christopher Noda, Eric Weiner, Gretchen Foltz, Nael Saad

Aim: Compare radioembolization (Y90) and chemoembolization (CE) for the treatment of unresectable intrahepatic cholangiocarcinoma (UICC).

Materials & methods: Institutional Review Board-approved, retrospective search was performed. Forty patients with UICC were treated with either Y90 (n = 25, 39 treatments) or CE (n = 15, 35 treatments). Comparative analysis was performed using Student's t and fisher-exact tests. Multivariable-logistic regression was also performed.

Results: Median ages were 60 and 64 years for CE and Y90 groups, respectively (p = 0.798). Patient variables including age, Eastern Cooperative Oncology Group score, tumor burden, extra-hepatic disease, prior chemotherapy and prior surgery were similar between groups. Adverse events were similar in both groups (CE 20%, Y90 26%; p > 0.9). Overall response rate (CE 6%, Y90 4%; p > 0.9) and disease control rate (CE 46%, Y90 48%; p > 0.9) were statistically similar. Multilogistic regression did not identify any variables that correlated with disease control rate, including Eastern Cooperative Oncology Group score and tumor burden.

Conclusion: Our observation shows that CE and Y90 display similar toxicity and disease control in the treatment of UICC.

目的:比较放射栓塞(Y90)与化疗栓塞(CE)治疗不可切除肝内胆管癌(UICC)的疗效。材料和方法:经机构审查委员会批准,进行回顾性检索。40例UICC患者分别接受Y90 (n = 25, 39例)或CE (n = 15, 35例)治疗。采用Student’st检验和fisher精确检验进行比较分析。还进行了多变量逻辑回归。结果:CE组和Y90组的中位年龄分别为60岁和64岁(p = 0.798)。年龄、东部肿瘤合作组评分、肿瘤负担、肝外疾病、既往化疗和既往手术等患者变量组间相似。两组不良事件相似(CE为20%,Y90为26%;p > 0.9)。总体反应率(CE 6%, Y90 4%;p > 0.9)和疾病控制率(CE 46%, Y90 48%;P > 0.9),差异有统计学意义。多元logistic回归未发现任何与疾病控制率相关的变量,包括东部肿瘤合作组评分和肿瘤负担。结论:我们的观察表明,CE和Y90在治疗UICC方面具有相似的毒性和疾病控制作用。
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引用次数: 11
'Hug sign': a new radiological sign of intraprocedural success after combined treatment for hepatocellular carcinoma. “拥抱征”:肝细胞癌联合治疗后术中成功的新影像学征象。
IF 5 Q4 ONCOLOGY Pub Date : 2017-07-01 Epub Date: 2017-10-30 DOI: 10.2217/hep-2017-0017
Roberto Iezzi, Maurizio Pompili, Eleonora Brigida Annicchiarico, Matteo Garcovich, Massimo Siciliano, Antonio Gasbarrini, Riccardo Manfredi

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. A careful multidisciplinary assessment of tumor characteristics, liver function and physical status is required for proper therapeutic management. In recent years, several studies have supported the feasibility and benefit of combined therapy in the treatment of single large HCC, defined as those exceeding 3 cm in size. We present a case of combined treatment using radiofrequency ablation followed by trans-arterial chemoembolization with radiopaque embolic beads. The aim of this technical report was to describe the radiologic findings during combined radiofrequency ablation and radiopaque bead embolization, pointing out the differences and the potential advantages of using radiopaque beads compared with non-radiopaque beads. Furthermore, it is also the first report on using radiopaque beads in combined treatment for HCC.

肝细胞癌是世界上最常见的癌症之一。需要对肿瘤特征、肝功能和身体状况进行仔细的多学科评估,以进行适当的治疗管理。近年来,几项研究支持联合治疗单个大型HCC(定义为体积超过3cm的HCC)的可行性和益处。我们提出一个联合治疗的情况下,射频消融后经动脉化疗栓塞与不透射线的栓塞珠。本技术报告的目的是描述联合射频消融和不透射线珠栓塞的放射学表现,指出与不透射线珠相比,使用不透射线珠的差异和潜在优势。此外,这也是首个使用不透射线珠治疗HCC的报道。
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引用次数: 4
Prognostic signatures from hepatocellular carcinoma biopsy. 肝细胞癌活检的预后特征。
IF 5 Q4 ONCOLOGY Pub Date : 2017-07-01 Epub Date: 2017-10-30 DOI: 10.2217/hep-2017-0016
Luca Marzi, Erica Villa
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引用次数: 0
期刊
Hepatic Oncology
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