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World Journal of Gastrointestinal Oncology 2021年第12期13卷 2038-2049页

作者： Saleh A Alqahtani massimo G colombo Division of Gastroenterology and Hepatology Johns Hopkins UniversityBaltimoreMD 21287United States Liver Transplant Center and BiostatisticsEpidemiologyand Scientific Computing DepartmentKing Faisal Specialist Hospital&Research CenterRiyadh 11564Saudi Arabia Liver Center IRCCS San Raffaele HospitalMilan 20132Italy

Globally,hepatocellular carcinoma(HCC)is a frequently diagnosed malignancy with rapidly increasing incidence and mortality ***,many of these patients are diagnosed in the advanced stages when locoregional treatments are not *** 2008,no effective drug treatments existed to prolong survival,until the breakthrough multi-tyrosine kinase inhibitor(TKI)sorafenib was *** remained the standard treatment option for advanced HCC for 10 years,with a battery of other candidate drugs in clinical trials failing to produce similar efficacy *** 2018,the REFLECT trial introduced another multi-TKI,lenvatinib,which has non-inferior overall survival compared with ***,offering patients and their treating physicians two effective treatment ***,immunotherapy-based drugs,such as atezolizumab and bevacizumab,have shown promising results in patients with unresectable *** review summarizes clinical trial and real-world data studies of sorafenib and lenvatinib in patients with unresectable *** offer guidance on the optimal choice between the two treatments and discuss the potential of immunotherapy-based combination;when more data become available,this will likely make the choice between sorafenib and lenvatinib somewhat obsolete.

关键词： Hepatocellular carcinoma Immune checkpoint inhibitor Lenvatinib Multityrosine kinase inhibitor Sorafenib

Is there a real survival benefit of surveillance for hepatocellular carcinoma in cirrhotic patients?

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Hepatobiliary Surgery and Nutrition 2019年第2期8卷 148-150页

作者： massimo colombo Ana Lleo Humanitas Clinical and Research Center-IRCCS Rozzano(MI)Italy Department of Biomedical Sciences Humanitas UniversityPieve Emanuele(MI)Italy

Surveillance with abdominal ultrasound(US)of patients with chronic liver disease who are at risk of developing a hepatocellular carcinoma(HCC),has progressively emerged as a consolidated practice for achieving early diagnosis and improving treatment of liver cancer,despite the lack of robust evidence-based *** is recommended by the international societies from both hemispheres(1-3),where however recommendations from Far East voice some nuances with respect to the need for adding serum alfa fetoprotein(AFP)to US and of adopting accelerated intervals of screening for patients at very high risk of HCC,like those with viral hepatitis and multiple co-morbidities.A recent meta-analysis form the US confirms indeed a benefit in adding serum AFP to US(4).In the western world,a 6-month interval is considered more than adequate for screening patients with compensated cirrhosis of any aetiology,as several meta-analyses have reported appreciable survival benefits in those patients who had a small tumor detected with US surveillance that ultimately could access curative treatment with liver transplantation,hepatic resection or local ablation(5,6).

关键词： patients adding benefit

Bridging to liver transplantation patients with a hepatocellular carcinoma within Milan criteria: how worth is it?

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Hepatobiliary Surgery and Nutrition 2018年第3期7卷 202-205页

作者： Angelo Sangiovanni massimo colombo Division of Gastroenterology and Hepatology CRC“AM e A Migliavacca”Center for Liver DiseaseFondazione IRCCS CàGranda Ospedale Maggiore PoliclinicoUniversitàdegli Studi di MilanoMilanoItaly Department of Medicine Humanitas Clinical and Research CenterHumanitas HospitalRozzanoItaly

The American Association for the Study of the Liver has recently provided conditional recommendations for locoregional ablative therapy to consolidate listing to liver transplantation of patients with a hepatocellular carcinoma (HCC) fulfilling the Milan criteria (MC, OPTN T2), an approach aiming at preventing tumor progression and patients to be delisted accordingly (1).

关键词： patients hepatocellular liver

Individualized hepatocellular carcinoma risk: The challenges for designing successful chemoprevention strategies

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World Journal of Gastroenterology 2013年第9期19卷 1359-1371页

作者： Cristina Della Corte Alessio Aghemo massimo colombo AM Migliavacca Center for Liver Diseases First Division of Gastroenterology Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Università degli Studi di Milano 20122 Milan Italy

Hepatocellular carcinoma (HCC) develops in the context of environmental risk factors like chronic viral hepatitis, diabetes and alcohol exposure, often associated to an increased risk of cirrhosis. Antiviral treatments that are effective to counteract hepatitis B and C may also attenuate the risk of tumor development. However, since hepatitis B-related carcinogenesis is promoted independently of the onset of cirrhosis, such antiviral treatments as nucleo(t)side analogs can promote regression of cirrhosis, prevent clinical decompensation and variceal bleeding but not HCC. This means that in successfully treated patients with cirrhosis, HCC is often the consequence of their extended survival. In hepatitis C patients, a sustained virological response to interferon-based therapies can reduce the rate of HCC development, even in patients with cirrhosis who experience histological regression of their liver disease. Future therapies aimed at this endpoint in at risk populations should take into consideration pretreatment patient stratification for host, viral and environmental risk factors. In this context the recent discovery of single nucleotide polymorphisms involved in the immune system function and tumorigenesis, might permit enrollment of populations of patients enriched with HCC risk factors for targeted chemopreventive therapies. This could finally pave the way to personalized algorithms, as already seen in the diagnosis and treatment schemes for chemoprevention.

关键词： Hepatocellular carcinoma Hepatitis C virus Peginterferon Hepatitis B virus Human immunodeficiency virus Nucleoside analogues Sustained virological response Single nucleotide polymorphisms

Viral hepatitis as a risk factor for the development of hepatocellular carcinoma

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Hepatoma Research 2020年第9期6卷 21-38页

作者： Saleh A.Alqahtani massimo colombo Liver Transplantation Unit King Faisal Specialist Hospital&Research CentreRiyadh 12713Saudi Arabia Division of Gastroenterology and Hepatology John Hopkins UniversityBaltimoreMD 21287USA Center of Translational Research in Hepatology Humanitas HospitalRozzano 20089Italy.

Hepatocellular carcinoma(HCC)is the fourth leading global cause of tumor-related *** has a high prevalence in patients with chronic liver diseases,and it mostly results from cirrhosis caused by infection with blood-borne *** the implementation of various diagnostic and prevention strategies,the rates of new HCC cases and mortality are increasing globally due to the aging and growth of the world population as well as their increased exposure to dominant risk factors like alcohol,hepatitis B and C,and clinical correlates of metabolic *** studies indicate that sanitation practices,implementation of vaccination programs against hepatitis B,and expanded recognition and treatment of patients with chronic hepatitis B and C could greatly contribute to the eradication of viral hepatitis B and *** the availability of generic antiviral drugs could partially overcome the bottleneck represented by the lack of resources in low and middle-income countries,where viral hepatitis is the leading cause of liver cancer,the enthusiasm for the prevention of liver cancer through antiviral therapy is mitigated by the risk of cancer in many patients who are treated late in the hepatitis *** present work aimed to review in detail the various types,epidemiology,and carcinogenesis mechanisms of viral infections that are associated with a significantly increased risk for the development of HCC.

关键词： Antiviral agents hepatitis viruses hepatocellular carcinoma blood-borne hepatitis cirrhosis hepatitis B vaccine

Systemic therapy for advanced cholangiocarcinoma:new options on the horizon

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Hepatoma Research 2020年第10期6卷 45-59页

作者： Saleh A.Alqahtani massimo colombo Liver Transplant Center King Faisal Specialist Hospital&Research CenterRiyadh 12713Saudi Arabia Division of Gastroenterology and Hepatology Johns Hopkins UniversityBaltimoreMD 21287USA Liver Center San Raffaele HospitalMilan 20132Italy

Patients with unresectable cholangiocarcinoma(CCA)face a poor prognosis,and there are few effective treatment options for the *** standard of care for patients with locally advanced or metastatic CCA is chemotherapy with a gemcitabine-based ***,the clinical benefit obtained with these regimens is modest,with a median overall survival of about one *** CCA that is chemotherapy-refractory or recurs after first-line chemotherapy,the treatment options are even more limited,and no relevant randomized controlled data are *** recent years,molecular profiling has shed light on the molecular basis of CCA and identified subgroups of patients that might benefit from a personalized treatment *** efforts resulted in the recent FDA approval of the fibroblast growth factor receptor(FGFR)inhibitor,pemigatinib,as a second-line treatment for patients with advanced CCA harboring an FGFR2-fusion or *** other targeted agents also are under evaluation in patients with CCA,of which the isocitrate dehydrogenase inhibitor has had the most promising ***,immunotherapy is being explored as a new treatment approach for advanced CCA patients;indeed,the immune checkpoint inhibitor pembrolizumab can already be used to treat CCAs that are mismatch repair *** review is a comprehensive overview of the treatment options for CCA and offers a glimpse into what the future could hold for these patients.

关键词： Cholangiocarcinoma fibroblast growth factor receptor inhibitor isocitrate dehydrogenase inhibitor immune checkpoint inhibitor

Accelerating the elimination of hepatitis C in Kuwait: An expert opinion

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World Journal of Gastroenterology 2020年第30期26卷 4415-4427页

作者： Fuad Hasan Ahmad Alfadhli Abeer Al-Gharabally Mahmoud Alkhaldi massimo colombo Jeffrey V Lazarus Department of Internal Medicine Faculty of MedicineKuwait UniversityKuwait 12037Kuwait Department of Gastroenterology Amiri HospitalKuwait 13041Kuwait Public Health Department Ministry of HealthKuwait 13110Kuwait Head Center of Translational Research in Hepatology Humanitas Clinical and Research CenterRozzano 20089Italy Barcelona Institute for Global Health Barcelona Institute for Global Health(ISGlobal)University of BarcelonaBarcelona 08036Spain

The hepatitis C virus(HCV)is estimated to affect 71 million people *** 2016,the World Health Organization adopted the first global health sector strategy to eliminate viral hepatitis as a public health threat by *** December 2018,the European Association for the Study of the Liver,International Liver Foundation convened an expert panel to address the elimination of HCV in *** steps have already been taken to eliminate HCV in Kuwait,including free HCV treatment for Kuwait’s citizens,high blood safety standards,and the implementation of screening and awareness *** expert panel made several recommendations aimed at accelerating the elimination of HCV in Kuwait:The development of a national strategy and action plan to guide all HCV elimination activities;the formation of a coordination mechanism to support collaboration between hepatitis working committees;the prioritization of microelimination at primary,secondary or tertiary facilities,in prisons and rehabilitation centers;and ensuring the involvement of multiple stakeholders–including relevant civil society groups–in all *** screening and linkage to care should be prioritized in Kuwait,with the expansion of the prescriber base to primary healthcare providers and nurse practitioners to be *** awareness and educating people about HCV infection also remain essential to achieve the goal of HCV ***,a national HCV registry should be developed to help monitor the implementation of viral hepatitis plans and progress towards achieving national and international targets.

关键词： Awareness Hepatitis C virus Kuwait Micro-elimination Registries Prescribers

Consensus on management of hepatitis C virus infection in resource-limited Ukraine and Commonwealth of Independent States regions

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World Journal of Gastroenterology 2019年第29期25卷 3897-3919页

作者： massimo Giuseppe colombo Erkin Isakovich Musabaev Umed Yusupovich Ismailov Igor A Zaytsev Alexander V Nersesov Igor Anatoliyevich Anastasiy Igor Alexandrovich Karpov Olga A Golubovska Kulpash S Kaliaskarova Ravishankar AC Sanjay Hadigal Research and Clinical Center Department of Medicine Humanitas Hospital Rozzano 20089 MI Italy Research Institute of Virology Scientific Research Institute of Virology Tashkent 100194 Uzbekistan Hepatoсenter Research Institute of Virology Scientific Research Institute of Virology Tashkent 100194 Uzbekistan Department of Therapy Infectious Diseases and Dermatology Bogomolets National Medical University Kyiv 01601 Ukraine Department of Gastroenterology and Hepatology National Research Institute of Cardiology and Internal Diseases Almaty 050000 Kazakhstan Department Infectious Diseases Bogomolets National Medical University Kyiv 01601 Ukraine Department Infectious Diseases Belarus State Medical University Minsk 220116 Belarus Hepatology Ministry of Health Astana 010000 Kazakhstan Medical Affairs Mylan Pharmaceuticals Private Limited Kadubeesanahalli Bengaluru 560103 India

Globally, 69.6 million individuals were infected with hepatitis C virus (HCV) infection in 2016. Of the six major HCV genotypes (GT), the most predominant one is GT1, worldwide. The prevalence of HCV in Central Asia, which includes most of the Commonwealth of Independent States (CIS), has been estimated to be 5.8% of the total global burden. The predominant genotype in the CIS and Ukraine regions has been reported to be GT1, followed by GT3. Inadequate HCV epidemiological data, multiple socio-economic barriers, and the lack of regionspecific guidelines have impeded the optimal management of HCV infection in this region. In this regard, a panel of regional experts in the field of hepatology convened to discuss and provide recommendations on the diagnosis, treatment, and pre-, on-, and posttreatment assessment of chronic HCV infection and to ensure the optimal use of cost-effective antiviral regimens in the region. A comprehensive evaluation of the literature along with expert recommendations for the management of GT1-GT6 HCV infection with the antiviral agents available in the region has been provided in this review. This consensus document will help guide clinical decision-making during the management of HCV infection, further optimizing treatment outcomes in these regions.

关键词： Antiviral agents Commonwealth of Independent States Genotype Hepatitis C virus Sustained virologic response Ukraine

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地壳岩浆氧化性和斑岩型铜矿床成矿潜力

中国科学:地球科学 2025年第1期 227-238页

作者：艾宇民 massimo CHIARADIA 吴超陈华勇中国科学院广州地球化学研究所矿物学与成矿学重点实验室中国科学院大学 Department of Earth Sciences University of Geneva 广东省矿物物理与材料研究开发重点实验室

斑岩型铜矿床是全球铜(Cu)、钼(Mo)和金(Au)资源的主要供应源,其形成过程受到多种地质因素的控制,尤其是岩浆的氧化性是当前研究的焦点.本文综合分析了全球范围内已发表的弧岩浆中钒(V)和钪(Sc)的比值(V/Sc)数据,并收集了V和Sc在矿物和... 详细信息

斑岩型铜矿床是全球铜(Cu)、钼(Mo)和金(Au)资源的主要供应源,其形成过程受到多种地质因素的控制,尤其是岩浆的氧化性是当前研究的焦点.本文综合分析了全球范围内已发表的弧岩浆中钒(V)和钪(Sc)的比值(V/Sc)数据,并收集了V和Sc在矿物和硅酸盐熔体中的分配系数.通过探讨V/Sc比值与岩浆氧逸度(f O2)之间的相关性,评估了不同厚度弧地壳中岩浆的氧化性特征.研究结果表明,磁铁矿的分离结晶是降低残余岩浆的V/Sc比值的关键因素.此外,磁铁矿结晶开始时的镁值(Mg#)与岩浆氧化性呈现显著的正相关性.利用这一规律,进一步评估第四纪弧岩浆的氧化性,发现在地壳厚度超过20km的成熟岛弧和大陆弧中,岩浆随着地壳厚度的增加趋向于更高的氧逸度.这表明在这些环境中,石榴石和角闪石的地壳内分异作用增强了岩浆的氧化性;相比之下,地壳厚度小于20km的薄弧中的岩浆则可能由于更多的俯冲板片氧化性物质输入,展现出比厚弧岩浆更高的氧化性.这些发现表明,俯冲动力学和地壳厚度在决定弧岩浆氧化性及其形成斑岩型铜矿的能力方面起着至关重要的作用.高度氧化的原始弧岩浆由于在岩浆演化的早期阶段经历磁铁矿结晶,从而导致硫化物饱和,这一过程导致铜的早期亏损,因此不利于斑岩型铜矿的形成.相反,在厚弧中磁铁矿结晶被广泛抑制,使硫化物大量饱和出现在岩浆晚期阶段,因此更有利于保留演化岩浆中铜的成矿潜力.本研究深入探讨了地壳内分异作用和俯冲带物质输入对弧岩浆氧化性的双重影响,并基于V/Sc比值变化规律的系统研究,为斑岩型铜矿床的成矿潜力提供了新的地球化学指示.

关键词：岩浆演化 V/Sc变化规律磁铁矿氧逸度斑岩铜矿

Crustal magma oxidation state and endowments in porphyry copper deposits

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Science China Earth Sciences 2025年第1期 226-236页

作者： Yumin AI massimo CHIARADIA Chao WU Huayong CHEN Key Laboratory of Mineralogy and Metallogeny Guangzhou Institute of Geochemistry Chinese Academy of Sciences University of Chinese Academy of Sciences Department of Earth Sciences University of Geneva Guangdong Provincial Key Laboratory of Mineral Physics and Materials

Porphyry copper deposits（PCDs） supply the majority of the world's copper（Cu） as well as significant amounts of molybdenum（Mo） and gold（Au）. The formation of these deposits is controlled by a variety of geological factors, among which the magmatic oxidation is one of the focuses of current research. This study investigates the redox characteristics of arc magmas by analyzing the ratio of vanadium（V） to scandium（Sc） and its correlation with the oxygen fugacity （fO2） of magmas from arcs of various crustal thicknesses globally. We compiled an extensive dataset of published V/Sc values and studied the partition coefficients of Vand Sc between minerals and silicate melts across various magmatic environments. The results demonstrate that fractional crystallization of magnetite markedly reduces V/Sc values of the residual melt. Furthermore, magnesium number（Mg#） at the onset of magnetite fractionation is strongly positively correlated with fO2of the equilibrium magma. Based on this,the oxidation of arc magmas from different crustal thicknesses can be evaluated. The result suggests that magmas generated in crusts thicker than 20 km tend to be more oxidized with increasing crust thickness. This trend is attributed to enhanced intracrustal differentiation processes involving garnet and amphibole, particularly in mature island and continental arcs. In contrast,magmas in thinner arc crusts（<20 km）, which are significantly influenced by subducted slab materials, display higher oxidation states than most of their thicker crust counterparts. These findings suggest that both subduction dynamics and crustal thickness play a vital role in determining the oxidation state of arc magmas and, consequently, their capacity to generate PCDs. Highly oxidized, primitive arc magmas are less favorable for PCD formation due to that they tend to experience magnetite fractionation and thus sulfide saturation in the early stage of magma evolution, a process leading to copper depletion. On the contra

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