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Liver Transplantation for perihilar cholangiocarcinoma. Do we need to move forward? 肝移植治疗肝门周围胆管癌。我们需要继续前进吗?
Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2022.75
C. Dopazo, R. Charco
Perihilar cholangiocarcinoma (pCCA) is a challenging disease with limited options. Surgical resection and adjuvant therapy remain the only established treatment for those with resectable disease. Since the publication of the Mayo protocol in 2000, neoadjuvant chemoradiation and liver transplantation have become the standard of care in selected patients with unresectable de novo pCCA or resectable pCCA arising under primary sclerosing cholangitis. However, its application is diverse worldwide, and the need for donor organs is one of the main limitations. Also, differences in the neoadjuvant regimen used were observed. In this review, we discuss the latest results of this approach, the recommended tools for diagnostic work-up, and advances in systemic therapy to improve patient selection and long-term survival.
肝门周围胆管癌(pCCA)是一种具有挑战性的疾病,选择有限。手术切除和辅助治疗仍然是治疗可切除疾病的唯一方法。自2000年梅奥协议发表以来,新辅助放化疗和肝移植已成为不可切除的新生pCCA或原发性硬化性胆管炎下可切除的pCCA患者的标准治疗方法。然而,它的应用在世界范围内是多种多样的,对供体器官的需求是主要限制之一。此外,还观察了新辅助治疗方案的差异。在这篇综述中,我们讨论了该方法的最新结果,推荐的诊断检查工具,以及改善患者选择和长期生存的全身治疗的进展。
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引用次数: 1
Current landscape and future directions for systemic treatments of hepatocellular carcinoma 肝细胞癌系统治疗的现状和未来方向
Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2023.63
L. G. Fonseca, F. Carrilho
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引用次数: 0
Challenges and barriers in hepatocellular carcinoma (HCC) surveillance for patients with non-alcoholic fatty liver disease (NAFLD) 非酒精性脂肪性肝病(NAFLD)患者肝细胞癌(HCC)监测的挑战和障碍
Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2022.92
Kara Wegermann, A. Diehl, C. Moylan
The proportion of hepatocellular carcinoma (HCC) cases due to NAFLD is expected to increase, paralleling the rise in NAFLD due to the obesity epidemic. Early detection is critical, as it potentially enables curative treatment. Current guidelines recommend ultrasound imaging with or without serum AFP measurement in patients with cirrhosis. Unfortunately, several challenges and barriers impede the effective surveillance of HCC in patients with NAFLD. In this review, we focus on four main challenges and barriers: the scale of the NAFLD epidemic, the lack of accurate risk stratification tools, the limitations of available surveillance tools themselves, and the existing disparities in access to care for chronic liver disease. We describe potential solutions, including public health approaches to obesity, improving clinical risk scores using genomic and metabolomic data, improved imaging techniques and blood-based biomarkers, and focusing on underserved groups with liver disease.
预计NAFLD导致的肝细胞癌(HCC)病例的比例将增加,与肥胖流行导致的NAFLD增加的比例相当。早期发现至关重要,因为它有可能使治疗成为可能。目前的指南推荐对肝硬化患者进行超声显像,包括或不包括血清AFP检测。不幸的是,一些挑战和障碍阻碍了对NAFLD患者HCC的有效监测。在这篇综述中,我们关注四个主要的挑战和障碍:NAFLD流行的规模,缺乏准确的风险分层工具,现有监测工具本身的局限性,以及慢性肝脏疾病获得护理的现有差异。我们描述了潜在的解决方案,包括肥胖的公共卫生方法,使用基因组和代谢组学数据改善临床风险评分,改进成像技术和基于血液的生物标志物,以及关注肝病患者服务不足的群体。
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引用次数: 0
Biomarkers for Living Donor Liver Transplants in Hepatocellular Carcinoma 肝细胞癌活体供肝移植的生物标志物
Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2023.25
Edward Butt, Rupak Kulkarni, A. Moghe
Liver transplantation is one of the more definitive treatments for hepatocellular carcinoma (HCC). In the United States, liver transplantation has historically been focused on deceased donor organs, and tumor burden is used for risk-stratifying patients on the transplant waitlist. Living donor liver transplantation (LDLT) is gaining popularity in the United States and has long been practiced in Asian countries. To improve outcomes of overall survival and disease-free survival post-living donor liver transplantation, surrogates of tumor biology are now being regarded to be as important as tumor burden. This article reviews the different surrogates of tumor biology and discusses their role in the application of LDLT for advanced HCC.
肝移植是肝细胞癌(HCC)较为明确的治疗方法之一。在美国,肝移植在历史上一直关注于已死亡的供体器官,肿瘤负担被用于对移植等待名单上的患者进行风险分层。活体肝移植(LDLT)在美国越来越受欢迎,在亚洲国家也有很长时间的实践。为了改善活体供肝移植后的总生存期和无病生存期,肿瘤生物学的替代物现在被认为与肿瘤负担一样重要。本文综述了不同的肿瘤生物学替代物,并讨论了它们在晚期肝癌LDLT应用中的作用。
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引用次数: 0
Chemoembolization with Degradable Starch Microspheres (DSM-TACE): expanding indications in HCC multidisciplinary tumor board 可降解淀粉微球化疗栓塞(DSM-TACE):扩大HCC多学科肿瘤委员会的适应症
Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2022.66
Umberto Rozzanigo, Francesco Gatti, Giacomo Luppi, Lorenzo Costa, Benedetto Petralia, Cecilia Pravadelli, Ivana Maioli, Michela Frisinghelli, Sergio Fersino, Riccardo Berletti, G. Pretis, Alberto Brolese
The role of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) management has changed over the last twenty years. There has been a trend towards an overall decline in TACE procedures, but with a more aggressive approach, repeating multiple TACE sessions in case of tumor response. The survival of treated patients was prolonged because of better patient selection and advancements in TACE techniques aimed at preserving liver function. At present, TACE is approved by the International Guidelines also outside of the BCLC intermediate stage after evaluation of a multidisciplinary tumor board (MDTB), permitting a customized treatment for every patient. An alternative therapeutic strategy is represented by hepatic chemoembolization with Degradable Starch Microspheres (DSM-TACE), which is based on the chemotherapeutic effect rather than on the ischemic damage to the liver tumor, requiring multiple cycles of treatment. The higher safety profile of DSM-TACE has broadened the indications to patients waiting for liver transplantation (with bridging or downstaging intention), at high risk of liver failure and ineligible for systemic therapies. This review summarises the scientific publications supporting the use of DSM-TACE and illustrates its indications depending on the disease stage from the Interventional Radiologist’s perspective.
在过去的二十年中,经动脉化疗栓塞(TACE)在肝细胞癌(HCC)治疗中的作用发生了变化。TACE手术有总体下降的趋势,但采用更积极的方法,在肿瘤反应的情况下重复多次TACE治疗。由于更好的患者选择和旨在保护肝功能的TACE技术的进步,治疗患者的生存期延长。目前,在多学科肿瘤委员会(MDTB)评估后,TACE也在BCLC中期之外获得了国际指南的批准,允许为每位患者定制治疗。另一种治疗策略是使用可降解淀粉微球(DSM-TACE)进行肝脏化疗栓塞,这是基于化疗效果而不是对肝脏肿瘤的缺血性损伤,需要多个治疗周期。DSM-TACE更高的安全性将适应症扩大到等待肝移植的患者(有桥接或降低分期的意图),肝衰竭风险高,不适合全身治疗。本综述总结了支持使用DSM-TACE的科学出版物,并从介入放射科医生的角度说明了其根据疾病分期的适应症。
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引用次数: 0
Strategy for ERCP stenting in cholangiocarcinoma 胆管癌ERCP支架置入术的策略
Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2023.20
Radovan Prijic, Agata Ladic, Pave Markos
Considering the steadily growing incidence of cholangiocarcinoma (CCA) worldwide, there is a constant need to re-evaluate and re-think its pathophysiology, diagnostic modalities, and mostly important, its treatment. No matter the histopathological appearance, endoscopic procedures - mainly Endoscopic Retrograde Cholangiopancreatography (ERCP) with stenting - are often used in the treatment of CCA complications, such as biliary obstruction when biliary drainage is indicated. Indications for preoperative biliary drainage in surgical cases are adjusted to each patient’s status. On the contrary, palliative drainage is the first option for relieving symptoms and improving the quality of life in the context of locally advanced and unresectable CCA. Further, concern about stenting techniques depends on the stricture location: Bismuth-Corlette types I and II are usually endoscopically drained with one stent placed in biliary tract, while for types III and IV, even bilateral stenting may prove inadequate. Stents used in ERCP are either plastic or self-expandable metallic stents (SEMS). Though plastic stents show some advantages over SEMS in terms of removability and possibility to adapt to a biliary tree which allows potential reinterventions, SEMS are better in terms of patency, lower complications number, and success of drainage. Besides ERCP, echo-endoscopic drainage is also an option, especially when ERCP approach has not yielded a successful drainage. The aim of this study was to show the potential of ERCP stenting in CCA treatment, its possible pitfalls, and the need to consider multiple levels of ERCP-related care.
考虑到世界范围内胆管癌(CCA)的发病率稳步增长,需要不断重新评估和重新思考其病理生理,诊断方式,最重要的是,其治疗。无论组织病理学表现如何,内镜手术-主要是内镜逆行胆管造影术(ERCP)和支架植入术-通常用于治疗CCA并发症,如胆道梗阻时需要胆道引流。手术病例术前胆道引流的指征根据患者的情况调整。相反,姑息引流是缓解局部晚期和不可切除CCA患者症状和改善生活质量的首选。此外,对支架技术的关注取决于狭窄的位置:Bismuth-Corlette I型和II型通常在胆道内放置一个支架进行内窥镜引流,而对于III型和IV型,即使双侧支架置入也可能是不够的。ERCP中使用的支架是塑料或自膨胀金属支架(SEMS)。尽管塑料支架在可移除性和适应胆道树的可能性(允许潜在的再干预)方面比SEMS有一些优势,但SEMS在通畅、并发症数量少和引流成功率方面更好。除ERCP外,超声内镜引流也是一种选择,特别是当ERCP入路引流不成功时。本研究的目的是显示ERCP支架在CCA治疗中的潜力,其可能的缺陷,以及考虑ERCP相关的多层次护理的必要性。
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引用次数: 0
Ethnic disparities in the epidemiology, treatment, and outcome of patients with hepatocellular carcinoma in the United States. 美国肝细胞癌患者在流行病学、治疗和预后方面的种族差异。
Pub Date : 2023-01-01 Epub Date: 2023-05-18 DOI: 10.20517/2394-5079.2023.10
Mohammad Saeid Rezaee-Zavareh, Jeff Liang, Ju Dong Yang

There are significant ethnic disparities in incidence, tumor stage, curative therapy receipt, and survival among patients with hepatocellular carcinoma (HCC) in the US. While previous models had predicted an increasing trend in the incidence rate of HCC until 2030 in the US, recent studies have shown that HCC incidence plateaued in 2013 and then started to decline in 2015. The decreasing trend has been observed in all ethnicities except for American Indians/Alaska Natives, whose incidence rates of HCC continue to rise. Current evidence shows that African-Americans and Hispanics are two groups that are more likely to be diagnosed with late-stage HCC, and this finding has been consistent in different socioeconomic statuses of the patients. These two ethnic minority groups are also among those who are less likely to have curative therapy for early-stage HCC. Finally, advances in early diagnosis and treatment approaches have led to an improvement in HCC survival for all ethnicities; however, African-Americans continue to have the worst survival. More studies to find the causes of these disparities and interventions to eliminate them are urgently needed.

在美国,肝细胞癌(HCC)患者在发病率、肿瘤分期、接受根治性治疗和生存率方面存在明显的种族差异。虽然以前的模型预测美国的 HCC 发病率在 2030 年前将呈上升趋势,但最近的研究表明,HCC 发病率在 2013 年趋于平稳,然后在 2015 年开始下降。除美国印第安人/阿拉斯加原住民外,所有族裔的发病率都呈下降趋势,而美国印第安人/阿拉斯加原住民的HCC发病率则持续上升。目前的证据显示,非裔美国人和西班牙裔美国人是更有可能被诊断为晚期HCC的两个群体,而且这一发现在不同社会经济地位的患者中是一致的。这两个少数族裔群体也是较少接受早期 HCC 治疗的群体。最后,早期诊断和治疗方法的进步提高了所有种族患者的 HCC 存活率,但非裔美国人的存活率仍然最差。我们亟需开展更多研究,找出造成这些差异的原因,并采取干预措施消除这些差异。
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引用次数: 0
Targeting the interactions between lymphocytes and liver cancer stem cells in combination with immunotherapy is a promising therapeutic strategy 靶向淋巴细胞与肝癌干细胞的相互作用,结合免疫治疗是一种很有前景的治疗策略
Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2022.52
Wojun Chen, Xiao-Ping Zhang, Yuan Yan, X. Sun, Lei Li
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with a poor prognosis and high recurrence rate. Liver cancer stem cells (LCSCs), a small subset of HCC cells, have the capacity for self-renewal and the property of treatment resistance, suggesting that LCSCs are key factors in causing poor prognosis for HCC patients. In addition, LCSCs interact with immune cells to participate in the formation of an immunosuppressive microenvironment and escape the immune surveillance in HCC, especially lymphocytes. At present, immunotherapies for HCC are mainly based on reactivating the lymphocyte system, including immune checkpoint inhibitors, multifunctional antibodies, and adoptive cell therapy. Therefore, blocking the interactions between lymphocytes and LCSCs in combination with immunotherapy may be a promising therapeutic strategy. This review summarizes the interaction mechanisms of lymphocytes and LCSCs and the current exploration of combination therapy in HCC.
肝细胞癌(HCC)是世界范围内最常见的恶性肿瘤之一,预后差,复发率高。肝癌干细胞(Liver cancer stem cells, LCSCs)是HCC细胞的一个小亚群,具有自我更新能力和耐药特性,提示LCSCs是导致HCC患者预后不良的关键因素。此外,LCSCs与免疫细胞相互作用,参与形成免疫抑制微环境,在HCC中逃避免疫监视,尤其是淋巴细胞。目前,肝癌的免疫治疗主要基于淋巴细胞系统的再激活,包括免疫检查点抑制剂、多功能抗体和过继细胞治疗。因此,阻断淋巴细胞与LCSCs之间的相互作用,结合免疫治疗可能是一种很有前景的治疗策略。本文就淋巴细胞与LCSCs的相互作用机制及联合治疗HCC的研究进展进行综述。
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引用次数: 1
Surgical management of intrahepatic cholangiocarcinoma 肝内胆管癌的外科治疗
Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2023.18
Ruff Samantha M.
Intrahepatic cholangiocarcinoma (ICCA) is a rare tumor with a poor prognosis that arises from the intrahepatic biliary tract. Patients who present with locally advanced or metastatic ICCA are generally treated with first-line gemcitabine/cisplatin and/or liver-directed therapy with the hope of downstaging/downsizing the disease. Patients who present with resectable ICCA may be treated with upfront surgery and postoperative adjuvant capecitabine. Staging laparoscopy should be considered to evaluate for occult metastatic disease and laparoscopic ultrasound can be used to better evaluate the liver parenchyma. Resection with the goal of achieving an R0 margin, along with lymphadenectomy to adequately stage patients, should be the standard operative approach. Unfortunately, the surgical technique cannot overcome poor tumor biology, and ICCA has a high incidence of recurrence, with many patients developing metastatic disease. Targeted therapy with IDH and FGFR inhibitors has had promising results in early clinical trials. Future endeavors should strive to identify more effective systemic and targeted therapies, which will hopefully improve survival for patients with ICCA.
摘要肝内胆管癌(ICCA)是一种发生于肝内胆道的罕见肿瘤,预后差。出现局部晚期或转移性ICCA的患者通常接受一线吉西他滨/顺铂和/或肝脏定向治疗,以期降低疾病分期/缩小疾病规模。出现可切除ICCA的患者可采用术前手术和术后辅助卡培他滨治疗。分期应考虑腹腔镜检查以评估隐匿性转移性疾病,腹腔镜超声检查可更好地评估肝实质。以达到R0切缘为目标的切除,以及对患者进行适当分期的淋巴结切除术,应该是标准的手术方法。不幸的是,手术技术不能克服肿瘤生物学不良,ICCA复发率高,许多患者发展为转移性疾病。IDH和FGFR抑制剂的靶向治疗在早期临床试验中取得了令人鼓舞的结果。未来的努力应该努力寻找更有效的系统和靶向治疗,这将有望提高ICCA患者的生存率。
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引用次数: 0
Tumor microenvironment highlighting tumor-associated macrophages and immune cells 肿瘤微环境突出肿瘤相关的巨噬细胞和免疫细胞
Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2023.32
Giulio Lodetti Zangrandi, Dilruba Tirpanlar, M. Pastore, C. Soldani, A. Lleo, C. Raggi
Cholangiocarcinoma (CCA) grows within a highly desmoplastic microenvironment, exhibiting a continuous interconnection with the immune infiltrate, which is characterized by an abundance of immune cells, including natural killer cells, T lymphocytes, and macrophages. The presence of inflammatory cells within the tumor microenvironment plays a crucial role in determining the aggressiveness and growth of CCA. The immune cell population engages in diverse and dynamic interactions with cancer cells. The balance of different subpopulations within CCA can generate varying responses, either inhibiting or promoting tumoral progression. The purpose of this review is to offer a comprehensive overview of the role of various immune infiltrate subpopulations within the tumor microenvironment, with a particular focus on the actions of tumor-associated macrophages (TAMs) and their critical regulation in the development and progression of CCA. TAMs play vital roles in maintaining homeostasis, facilitating tissue repair, and contributing to immune responses due to their significant functional diversity. Macrophages are present in numerous types of cancer, and their emerging role has also been observed in CCA. Recognizing and attaining a deeper comprehension of the intricate interplay between infiltrating immune cells and CCA cells is essential to identify new opportunities to advance treatment strategies.
胆管癌(CCA)生长在高度结缔组织增生的微环境中,表现出与免疫浸润的持续相互连接,其特征是大量的免疫细胞,包括自然杀伤细胞、T淋巴细胞和巨噬细胞。肿瘤微环境中炎症细胞的存在在决定CCA的侵袭性和生长方面起着至关重要的作用。免疫细胞群与癌细胞进行多样化和动态的相互作用。CCA内不同亚群的平衡可以产生不同的反应,抑制或促进肿瘤进展。本综述的目的是全面概述肿瘤微环境中各种免疫浸润亚群的作用,特别关注肿瘤相关巨噬细胞(tam)的作用及其在CCA发生和进展中的关键调控。tam由于其显著的功能多样性,在维持体内平衡、促进组织修复和促进免疫反应中起着至关重要的作用。巨噬细胞存在于许多类型的癌症中,它们在CCA中的新兴作用也被观察到。认识并更深入地理解浸润性免疫细胞和CCA细胞之间复杂的相互作用,对于确定推进治疗策略的新机会至关重要。
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引用次数: 1
期刊
Hepatoma Research
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