Hepatoma Research最新文献

英文中文

Role of diagnostic radiology in the management of intrahepatic cholangiocarcinoma 诊断放射学在肝内胆管癌治疗中的作用

Hepatoma Research

Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2023.29

Shadi Afyouni, A. Borhani, Alireza Mohseni, M. Mirza-Aghazadeh-Attari, Seyedeh Panid Madani, Haneyeh Shahbazian, Ghazal Zandieh, T. Pawlik, I. Kamel

Intrahepatic cholangiocarcinoma (ICC) is a rare and aggressive form of primary liver cancer that presents significant diagnostic and treatment challenges. In this review, we discuss the role of diagnostic radiology in the management of ICC, and future directions for research and clinical practice in the management of ICC.

肝内胆管癌(ICC)是一种罕见的侵袭性原发性肝癌，对诊断和治疗提出了重大挑战。在这篇综述中，我们讨论了诊断放射学在ICC管理中的作用，以及未来在ICC管理中的研究和临床实践方向。

引用次数: 0

Barriers to surveillance for hepatocellular cancer among patients with chronic liver disease -providers' perspectives 慢性肝病患者肝细胞癌监测的障碍——提供者的观点

Hepatoma Research

Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2023.75

Eliza W. Beal, Leva Gorji, Jaclyn Volney, Lindsey Sova, Ann Scheck McAlearney, Allan Tsung

Aims: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. While patients who are known to be at high risk for HCC should be under surveillance, only 20% of eligible patients in the United States are surveilled. The aim of this study was to identify providers’ perspectives about patient-, provider- and system-level barriers to surveillance for HCC among high-risk patients and to examine provider knowledge and attitudes related to HCC surveillance. We also explored interventions providers suggested as ways to improve HCC surveillance. Methods: Purposive sampling was used to recruit physicians and nurse practitioners in hepatology, gastroenterology, and primary care (internal and family medicine) from one academic medical center to participate in semi-structured interviews. Interviews were transcribed verbatim, and analyzed deductively and inductively to reveal emergent themes. Results: 22 informants were interviewed. During these interviews, several important themes emerged, including: (1) Provider comfort with managing chronic liver disease and the relationships between hepatology, gastroenterology, infectious disease, and primary care providers; (2) Provider knowledge of guidelines for HCC surveillance in high-risk patients and their knowledge about the impact that HCC surveillance can have; (3) How providers discuss HCC surveillance with their high-risk patients; (4) Provider-Level barriers to surveillance; (5) System-level barriers to surveillance; (6) COVID-19; (7) Patient-level barriers to surveillance, and (8) Suggested interventions to improve HCC surveillance rates. Conclusions: In designing interventions to improve HCC surveillance rates of high-risk patients in the United States, there are important targets at the patient, provider and system levels.

目的:肝细胞癌(HCC)是最常见的原发性肝癌类型。虽然已知HCC高危患者应该接受监测，但在美国，只有20%的符合条件的患者接受了监测。本研究的目的是确定提供者对高危患者中HCC监测的患者、提供者和系统层面障碍的看法，并检查提供者对HCC监测的知识和态度。我们还探讨了提供者建议的改善HCC监测的干预措施。方法:采用有目的抽样的方法，从一家学术医疗中心招募肝病学、胃肠病学和初级保健(内科和家庭医学)的医生和护士参加半结构化访谈。采访被逐字记录下来，并进行演绎和归纳分析，以揭示紧急主题。结果:共访谈22名举报人。在这些访谈中，出现了几个重要的主题，包括:(1)提供者管理慢性肝病的舒适度以及肝病学、胃肠病学、传染病学和初级保健提供者之间的关系;(2)提供者对高危患者肝细胞癌监测指南的了解以及对肝细胞癌监测可能产生的影响的了解;(3)提供者如何与高危患者讨论HCC监测;(4)提供商级别的监视障碍;(5)系统层面的监控障碍;(6) COVID-19;(7)患者层面的监测障碍;(8)提高HCC监测率的建议干预措施。结论:在设计干预措施以提高美国高危患者的HCC监测率时，在患者、提供者和系统层面都有重要的目标。

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引用次数: 0

Hepatocellular carcinoma in Pacific Islanders: comparison of Pacific Island-born vs. US-born. 太平洋岛民的肝细胞癌：太平洋岛民与美国出生岛民的比较。

Hepatoma Research

Pub Date : 2023-01-01 Epub Date: 2023-03-17 DOI: 10.20517/2394-5079.2022.85

Shelby K Yee, Brenda Y Hernandez, Sandi Kwee, Linda L Wong

Aim: To describe demographic, clinical, and outcome differences in Pacific Island-born (PI-born) compared to US-born hepatocellular carcinoma (HCC) patients of Pacific Island ancestry within a clinical cohort in Hawaii.

Methods: A prospectively collected database of 1608 patients diagnosed with HCC over a 30-year period (1993-2022) identified 252 patients of Pacific Islander ethnicity. Data collected: demographics, medical history, laboratory data, tumor characteristics, treatment, and survival. Patients were divided into two groups: PI-born and US-born. Categorical variables were analyzed using ANOVA and chi-square analysis. Odds ratios with 95% confidence intervals were calculated using univariate and multivariate logistic regression. Overall survival was evaluated using Kaplan-Meier analysis.

Results: PI-born patients were younger (57.3 vs. 61.8 years, P = 0.002) and more likely to have hepatitis B (OR 14.10, 7.50-26.50) and underlying cirrhosis (OR 2.28, 1.17-4.45). In comparison, US-born patients had a significantly higher likelihood of Hepatitis C, nonalcoholic steatohepatitis/nonalcoholic fatty liver disease, history of non-HCC cancer, and positive smoking history compared to PI-born patients. PI-born patients were more likely to forego treatment (OR 3.22, 1.77-5.87) and be lost to follow-up (OR 9.21, 1.97-43.03). Both groups were equally likely to have the opportunity for curative surgical treatment (liver resection or transplant). US-born status was associated with higher mortality risk, while transplantation was associated with lower mortality risk. The PI-born cohort demonstrated higher overall survival at 3 and 5 years compared to US-born.

Conclusion: HBV remains the primary risk factor for HCC in PI-born patients, whereas HCC in US-born patients is more associated with the adoption of a Westernized lifestyle.

目的：在夏威夷的一个临床队列中，描述太平洋岛国出生的肝细胞癌（HCC）患者与美国出生的太平洋岛国血统的肝细胞癌（HCC）患者在人口统计学、临床和预后方面的差异：方法：在一个前瞻性数据库中收集了 30 年间（1993-2022 年）1608 名确诊为 HCC 的患者，其中发现 252 名太平洋岛民患者。收集的数据包括：人口统计学、病史、实验室数据、肿瘤特征、治疗和存活率。患者分为两组：太平洋岛民出生组和美国出生组。采用方差分析和卡方分析对分类变量进行分析。使用单变量和多变量逻辑回归法计算了带有 95% 置信区间的比值比。采用 Kaplan-Meier 分析法评估了总生存率：美国出生的患者更年轻（57.3 岁对 61.8 岁，P = 0.002），更有可能患有乙型肝炎（OR 14.10，7.50-26.50）和潜在肝硬化（OR 2.28，1.17-4.45）。相比之下，在美国出生的患者患丙型肝炎、非酒精性脂肪性肝炎/非酒精性脂肪肝、非肝癌癌症史和阳性吸烟史的可能性明显高于在郫县出生的患者。郫县出生的患者更有可能放弃治疗（OR 3.22，1.77-5.87）和失去随访（OR 9.21，1.97-43.03）。两组患者接受根治性手术治疗（肝切除或移植）的可能性相同。在美国出生的患者死亡率较高，而接受移植手术的患者死亡率较低。与在美国出生的患者相比，在巴基斯坦出生的患者组群的3年和5年总生存率更高：结论：HBV仍然是郫县出生患者患HCC的主要风险因素，而美国出生患者患HCC则更多地与采用西方化生活方式有关。

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引用次数: 0

Genomic alterations and targeted therapies in extrahepatic cholangiocarcinoma 肝外胆管癌的基因组改变和靶向治疗

Hepatoma Research

Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2023.04

Arnau Oronich, O. Pallisé, A. Salud, R. Montal

The global morbimortality of biliary tract cancer (BTC) is steadily increasing and accounts for ~10% of all primary liver cancer. Distinct anatomical locations of BTC have singularities in their etiopathogenesis, which are translated into differences in their molecular fingerprints and the associated therapeutic approaches. Extrahepatic cholangiocarcinoma (eCCA), arising in the large and distal bile ducts, presents recurrent activating mutations of KRAS and loss-of-function alterations in TP53, SMAD4, and CDKN2A/B. Despite being highly prevalent, no targeted therapies are yet available for these oncogenic drivers. ERBB2 mutations and amplifications, on the other hand, are the most recurrent actionable alterations for eCCA, with several clinical trials aiming to provide benefits in biomarker-enriched populations. In addition, integrative multi-omics analysis of eCCA has allowed the identification of novel molecular classes of this disease that could be therapeutically exploited. Beyond that, the highly immunosuppressive tumor microenvironment of eCCA has prevented until now the success of immune checkpoint inhibitors, recently approved in combination with cytotoxic chemotherapy. Further characterization of eCCA at the molecular level would potentially foster treating patients based on a precision oncology approach in order to increase the clinical outcomes for this challenging disease.

胆道癌(BTC)的全球死亡率稳步上升，约占所有原发性肝癌的10%。不同解剖位置的BTC在其发病机制上具有独特性，这转化为其分子指纹和相关治疗方法的差异。肝外胆管癌(eCCA)发生于大胆管和远端胆管，表现为KRAS的反复激活突变和TP53、SMAD4和CDKN2A/B的功能丧失改变。尽管非常普遍，但目前还没有针对这些致癌驱动因素的靶向治疗方法。另一方面，ERBB2突变和扩增是eCCA最常见的可操作改变，一些临床试验旨在为生物标志物丰富的人群提供益处。此外，eCCA的综合多组学分析已经允许识别这种疾病的新分子类别，可以用于治疗开发。除此之外，eCCA的高度免疫抑制肿瘤微环境一直阻碍着免疫检查点抑制剂的成功，最近被批准与细胞毒性化疗联合使用。在分子水平上进一步表征eCCA可能会促进基于精确肿瘤学方法的患者治疗，从而提高这种具有挑战性疾病的临床结果。

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引用次数: 0

Assessment of response to liver directed radiation-based therapies: Current guidelines, challenges, and future directions 肝定向放射治疗反应评估:当前指南、挑战和未来方向

Hepatoma Research

Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2022.60

Amra Banda, G. Johnson, G. Cunha

Radiation-based local-regional therapies for hepatocellular carcinoma (HCC) have gained wide acceptance due to promising rates of tumor response, survival, and safety profiles. After treatment, it is important to assess tumor response to determine further management, patient prognosis, and endpoint outcomes for clinical trials. To standardize imaging interpretation and reporting of HCC response to local-regional treatment, a few imaging-based response assessment systems were developed. Two of them have emerged as the most used: the Liver Imaging Reporting and Data System (LI-RADS) Treatment Response Algorithm (LR-TRA) and the modified Response Evaluation Criteria in Solid Tumors (mRECIST). While these systems have been validated for the assessment of response to ablative locoregional therapies, assessment of response to radiation-based therapies can be challenged by persistent or evolving imaging features and is still an area of active research. Following the advances in technology and a better understanding of tumor biology that allowed for the increased application of radiation-based local-regional therapies for the treatment of HCC, research is still needed to address the limitations of current imaging criteria for assessing tumor response to these novel techniques. In this review, we describe radiation-based liver-directed treatment options, examine imaging criteria for assessing treatment response, discuss practical limitations and gaps in knowledge when applying these response criteria, and address future directions that may help to improve accuracy and outcomes when assessing response to radiation-based HCC treatment.

基于放射的局部区域治疗肝细胞癌(HCC)因其有希望的肿瘤反应率、生存率和安全性而获得广泛接受。治疗后，重要的是评估肿瘤反应，以确定进一步的管理，患者预后和临床试验的终点结果。为了规范HCC对局部-区域治疗反应的影像学解释和报告，开发了一些基于影像学的反应评估系统。其中最常用的两种方法是:肝脏成像报告和数据系统(LI-RADS)治疗反应算法(LR-TRA)和实体肿瘤反应评价标准(mRECIST)。虽然这些系统已被验证用于评估对局部区域消融治疗的反应，但对基于放射治疗的反应评估可能会受到持续或不断变化的影像学特征的挑战，这仍然是一个积极研究的领域。随着技术的进步和对肿瘤生物学的更好理解，基于放射的局部区域疗法在HCC治疗中的应用越来越多，目前评估肿瘤对这些新技术反应的成像标准的局限性仍然需要研究。在这篇综述中，我们描述了基于放射的肝脏定向治疗方案，检查了评估治疗反应的影像学标准，讨论了应用这些反应标准时的实际局限性和知识空白，并指出了未来可能有助于提高评估基于放射的HCC治疗反应的准确性和结果的方向。

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引用次数: 0

Improve the precise pathological diagnosis of intrahepatic cholangiocarcinoma: introduction to 2022 expert consensus on pathological diagnosis of intrahepatic cholangiocarcinoma in China 提高肝内胆管癌病理诊断精准度:介绍2022年中国肝内胆管癌病理诊断专家共识

Hepatoma Research

Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2023.11

Xin Zhang

引用次数: 0

Hepatocellular carcinoma after treatment of hepatitis C with direct-acting antivirals: a critical re-appraisal 直接作用抗病毒药物治疗丙型肝炎后的肝细胞癌:一个关键的重新评估

Hepatoma Research

Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2022.35

E. Kouroumalis, Ioannis Tsomidis, A. Voumvouraki

Soon after introducing direct-acting antiviral agents (DAAs) for chronic hepatitis C treatment, there began a debate over the possibility of hepatocellular carcinoma (HCC) after viral clearance. Although several reports suggested that the question has been answered negatively, other reports suggested the opposite. The present review presents data in favor and against the null hypothesis and analyzes the scientific background of the possible participation of DAAs in HCC development. The reasons for the discrepancy among studies are presented. These include heterogeneity of patient selection, the nature of the studies, and the tumors themselves are responsible for varying results. Exogenous factors like alcohol consumption or metabolic syndrome confound these findings and suggest the need for statistical adjustments. The need for careful attention to the statistical details is exemplified, and the significant points of almost universal agreements are identified. The conclusion is that the definitive study is impossible for ethical and scientific reasons, and the physician should not ignore even simple personal observations and screening of all patients with extensive fibrosis in HCC, irrespective of sustained virologic response, until a robust, reliable prognostic model can be invented.

在引入直接作用抗病毒药物(DAAs)治疗慢性丙型肝炎后不久，就开始了关于病毒清除后肝细胞癌(HCC)可能性的争论。虽然有几份报告认为对这个问题的回答是否定的，但另一些报告则认为情况正好相反。本综述提供了支持和反对原假设的数据，并分析了DAAs可能参与HCC发展的科学背景。提出了各研究之间存在差异的原因。这些因素包括患者选择的异质性、研究的性质以及导致不同结果的肿瘤本身。饮酒或代谢综合征等外源性因素混淆了这些发现，表明需要进行统计调整。它举例说明了仔细注意统计细节的必要性，并指出了几乎普遍的协定的要点。结论是，由于伦理和科学原因，不可能进行明确的研究，医生不应忽视即使是简单的个人观察和对所有HCC广泛纤维化患者的筛查，而不考虑持续的病毒学反应，直到可以发明一个强大，可靠的预后模型。

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引用次数: 1

Combined hepatocellular-cholangiocarcinoma: morpho-molecular updates and considerations 合并肝细胞-胆管癌:形态学-分子的更新和考虑

Hepatoma Research

Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2022.81

N. Ahmed, Francesca Falcinelli, M. Rimini, V. Burgio, A. Casadei‐Gardini, L. Aldrighetti, F. Ratti, F. Pedica

Combined Hepatocellular-Cholangiocarcinoma is a heterogenous primary malignant epithelial tumor of the liver with variable morphological and immunophenotypical features. Although the biology of this tumor has been described in the literature, changes in classification and its heterogeneity imply difficulties in collecting reliable homogenous groups to compare. The article aims to review available data on morphology and immunohistochemistry for practicing pathologists integrated with original data from our referral Center.

肝细胞胆管合并癌是肝脏的一种异质性原发性恶性上皮性肿瘤，具有不同的形态学和免疫表型特征。尽管该肿瘤的生物学已在文献中有所描述，但分类的变化及其异质性意味着难以收集可靠的同质组进行比较。本文的目的是回顾现有的形态学和免疫组织化学数据为执业病理学家整合原始数据从我们的转诊中心。

引用次数: 0

Mitochondrial calcium signaling in cholangiocarcinoma 胆管癌中的线粒体钙信号传导

Hepatoma Research

Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2023.28

Ana Carolina Loyola-Machado, Mateus T. Guerra, M. Nathanson

Cholangiocarcinoma (CCA) is a primary liver cancer whose diagnosis and treatment remain challenging. Although recent developments derived from molecular characterization of CCAs have led to the availability of new pharmacological agents, a better understanding of the genetic and molecular alterations in CCA is still required for the development of more effective or broader targeting treatments. One emerging signaling pathway of interest in the pathogenesis of CCA is ER to mitochondrial Ca2+ signaling. This pathway is of particular importance because it regulates both cell death through apoptosis and necrosis, and metabolic reprograming of cancer cells through regulation of energy metabolism in mitochondria. Here we discuss the latest findings regarding the dysregulation of mitochondrial Ca2+ signals and its key regulatory molecules with a special focus on the intracellular Ca2+ channels of the inositol 1,4,5-trisphosphate receptor (ITPR) family. We also discuss the role of ER-mitochondrial contact sites in determining mitochondrial health and how these points of contact between organelles might represent a druggable target in CCA.

胆管癌(CCA)是原发性肝癌，其诊断和治疗仍然具有挑战性。尽管CCA分子特征的最新进展导致了新的药理学药物的可用性，但为了开发更有效或更广泛的靶向治疗，仍然需要更好地了解CCA的遗传和分子改变。在CCA的发病机制中，一个新兴的信号通路是ER到线粒体Ca2+信号。这一途径特别重要，因为它既通过细胞凋亡和坏死调节细胞死亡，又通过调节线粒体的能量代谢调节癌细胞的代谢重编程。在这里，我们讨论了线粒体Ca2+信号失调及其关键调控分子的最新发现，特别关注肌醇1,4,5-三磷酸受体(ITPR)家族的细胞内Ca2+通道。我们还讨论了er -线粒体接触位点在确定线粒体健康中的作用，以及这些细胞器之间的接触点如何代表CCA中的可药物靶点。

引用次数: 0

Risk of hepatocellular carcinoma development in long-term nucles(t)ide analog suppressed patients with chronic hepatitis B 长期核(t)ide类似物抑制的慢性乙型肝炎患者肝细胞癌发展的风险

Hepatoma Research

Pub Date : 2023-01-01 DOI: 10.20517/2394-5079.2022.51

M. Fasano, Mariacristina Poliseno, M. Milella, Francesco Rosario Paolo Ieva, M. Ciarallo, B. Caccianotti, T. Santantonio

Aim: In long-term nucleos(t)ide analog (NA) suppressed patients with chronic hepatitis B (CHB), hepatocellular carcinoma (HCC) can still develop. Few data exist on the incidence and the predictors of HCC development beyond the first five years in long-term treated patients. To assess the prevalence, incidence, and risk factors for HCC development in a real-life cohort of successfully NA-treated CHB patients for more than five years. Methods: All CHB patients under NAs for ≥ 60 months with stable virologic response were enrolled. HCC surveillance was carried out using liver ultrasound and dosing of serum alpha-fetoprotein every year in patients with CHB and every six months in cirrhotic patients. The baseline PAGE-B score was calculated for each patient. Results: 343 patients (76% male, 86% HBeAg-negative, 30% cirrhotic) were enrolled. During a median (IQR) follow-up of 144 (105-182) months, 21 patients (6%) developed HCC despite virologic suppression (incidence rate 40 cases/1000 person-years follow-up). In multivariate analysis, higher PAGE B score [adjusted Hazard Ratio, aHR 1.26 (95%CI: 1.13-1.54), P = .022] and cirrhosis [aHR 9.71 (95%CI: 2.02-46.48), P = .005] were predictors of HCC development. PAGE B score showed a significant association with HCC (R2 0.225, P < .001) and good prognostic capacity (AUC 0.863) of HCC. Conclusions: Our results confirm that in successfully NA-treated CHB patients, sustained viral replication suppression does not abolish the risk of HCC. The PAGE-B score could be a useful tool for identifying high-risk subjects.

目的:长期NA抑制的慢性乙型肝炎(CHB)患者仍可发生肝细胞癌(HCC)。在长期治疗的患者中，很少有关于5年后HCC发病率和发展预测因素的数据。评估5年以上接受na治疗的CHB患者的流行率、发病率和HCC发展的危险因素。方法:纳入所有接受NAs治疗≥60个月且病毒学反应稳定的CHB患者。对CHB患者每年和肝硬化患者每6个月分别使用肝脏超声和血清甲胎蛋白给药进行HCC监测。计算每位患者的基线PAGE-B评分。结果:共纳入343例患者(76%为男性，86%为hbeag阴性，30%为肝硬化)。在144(105-182)个月的中位(IQR)随访期间，尽管有病毒学抑制，仍有21例(6%)患者发生HCC(发病率为40例/1000人年随访)。在多因素分析中，较高的PAGE B评分[校正危险比，aHR 1.26 (95%CI: 1.13-1.54)， P = 0.022]和肝硬化[aHR 9.71 (95%CI: 2.02-46.48)， P = 0.005]是HCC发展的预测因子。PAGE B评分与HCC (R2 0.225, P < 0.001)及预后良好(AUC 0.863)呈正相关。结论:我们的研究结果证实，在na治疗成功的CHB患者中，持续的病毒复制抑制并不能消除HCC的风险。PAGE-B分数可能是识别高风险受试者的有用工具。

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引用次数: 0

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