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Hepatocellular carcinoma: Where are we?

World Journal of Experimental Medicine 2016年第1期6卷 21-36页

作者： Roberto Mazzanti Umberto Arena Renato Tassi Department of Experimental and Clinical Medicine School of Sciences of Human Health University of Florence

Hepatocellular carcinoma(HCC) is the second cause of death due to malignancy in the world, following lung cancer. The geographic distribution of this disease accompanies its principal risk factors: Chronic hepatitis B virus and hepatitis C virus infection, alcoholism, aflatoxin B1 intoxication, liver cirrhosis, and some genetic attributes. Recently, type Ⅱ diabetes has been shown to be a risk factor for HCC together with obesity and metabolic syndrome. Although the risk factors are quite well known and it is possible to diagnose HCC when the tumor is less than 1 cm diameter, it remains elusive at the beginning and treatment is often unsuccessful. Liver transplantation is thus far considered the best treatment for HCC as it cures HCC and the underlying liver disease. Using the Milan criteria, overall survival after liver transplantation for HCC is about 70% after 5 years. Many attempts have been made to go beyond the Milan Criteria and according to recent works reasonably good results have been achieved by using a histochemical marker such as cytokeratine 19 and the so-called "up to seven criteria" to divide patients into categories according to their risk of relapse. In addition to liver transplantation other therapies have been proposed such as resection, tumor ablation by different means, embolization and chemotherapy. An important step in the treatment of advanced HCC has been the introduction of sorafenib, the first oral, systemic drug that has provided significant improvement in survival. Treatment of HCC patients must be multidisciplinary and by using the different approaches discussed in this review it is possible to offer prolonged survival and quite good and sometimes even excellent quality of life to many patients.

关键词： Hepatocellular carcinoma Treatment Liver cancer Epidemiology Liver transplantation Percutaneous ethanol injection Chemoembolization Chemotherapy Radiofrequency ablation

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Quick and easy assessment of sarcopenia in cirrhosis: Can ultrasound be the solution?

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World Journal of Gastroenterology 2024年第17期30卷 2287-2293页

作者： Francesca Campani Tancredi Vincenzo Li Cavoli Umberto Arena Fabio Marra Erica Nicola Lynch Claudia Campani Department of Health Science University Hospital CareggiUniversity of FlorenceFlorence 50134Italy Internal Medicine and Liver Unit University Hospital CareggiUniversity of FlorenceFlorence 50134Italy Department of Experimental and Clinical Medicine University of FlorenceFlorence 50134Italy Gastroenterology Research Unit Department of Experimental and Clinical Biomedical Sciences“Mario Serio”University of FlorenceFlorence 50134Italy Department of Medical Biotechnologies University of SienaSiena 53100Italy

Cirrhosis is frequently associated with sarcopenia,with reported rates of over 80%in patients with decompensated alcohol-related liver disease.Sarcopenia nega-tively impacts the prognosis of cirrhotic patients and affects the response to treatment of patients with hepatocellular carcinoma(HCC).For these reasons,identifying an easy-to-perform method to assess sarcopenia in is a key element in the optimization of care in this patient population.Assessment of muscle mass by computed tomography is considered the standard of care for the diagnosis of sarcopenia,but exposure to radiation and high costs limit its application in this setting,especially for repeated assessments.We believe that ultrasound,a cheap and harmless technique also used for HCC screening in cirrhotic patients,could have an expanding role in the diagnosis and follow-up of sarcopenia in these patients.

关键词： Sarcopenia Ultrasound Cirrhosis Hepatocellular carcinoma Computed tomography

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Evaluation of the prognostic value of liver stiffness in patients with hepatitis C virus treated with triple or dual antiviral therapy:A prospective pilot study

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World Journal of Gastroenterology 2015年第10期21卷 3013-3019页

作者： Cristina Stasi Alessia Piluso Umberto Arena Elena Salomoni Paolo Montalto Monica Monti Barbara Boldrini Giampaolo Corti Fabio Marra Giacomo Laffi Stefano Milani Anna Linda Zignego Department of Experimental and Clinical Medicine University of Florence Health Agency of Tuscany Gastrointestinal Endoscopy Unit Ospedale SS Cosma e Damiano Department of Biomedical Experimental and Clinical sciencesUniversity of Florence

AIM:To evaluate the association between liver stiffness(LS) prior to the initiation of dual/triple therapy and viral response.METHODS:LS was measured in all patients before treatment was administered.The therapeutic approach was based on hepatic,virological,and immunological evaluations and considered the fact that patients with severe fibrosis(F3)or compensated cirrhosis(F4)in Child-Pugh class A are the primary candidates for triple therapy.In total,65 hepatitis C virus(HCV)patients were treated with Peg-interferon/ribavirin(Peg-IFN/RBV);24patients were classified as genotypes 1/4(36.92%),and41 patients were classified as genotypes 2/3(63.08%)(dual therapy).In addition,20 HCV treatment-experienced genotype 1 patients were treated with Peg IFN-RBV and boceprevir(triple therapy).Wilcoxon rank-sum tests were used to compare the groups.RESULTS:LS significantly differed between dual therapy and triple therapy(P=0.002).The mean LS value before dual therapy treatment was 8.61±5.79k Pa and was significantly different between patients achieving a sustained virologic response(SVR)24weeks after therapy and those who did not(7.23±5.18 k Pa vs 11.72±5.99 k Pa,respectively,P=0.0003).The relative risk of non-response to therapy was 4.45(95%CI:2.32-8.55).The attributable risk of non-response to therapy was 49%.The mean LSvalue before triple therapy treatment was 13.29±8.57k Pa and was significantly different between patients achieving and not achieving SVR24(9.41±5.05 vs19.11±9.74,respectively;P=0.008).The relative risk of non-response to therapy was 5.57%(95%CI:1.50-20.65).The attributable risk of non-response to therapy(70%)was increased compared with dual therapy patients.Pre-treatment stiffness>12 k Pa was significantly associated with non-SVR(P<0.025)in both groups.CONCLUSION:Pre-treatment liver stiffness may be useful for predicting the response to treatment in patients treated with either dual or triple anti-HCV therapy.

关键词： Antiviral therapy Chronic hepatitis C Fibrosis Liv

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Evaluating the best treatment for multifocal hepatocellular carcinoma:A propensity score-matched analysis

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World Journal of Gastroenterology 2022年第29期28卷 3981-3993页

作者： Matteo Risaliti Ilenia Bartolini Claudia Campani Umberto Arena Carlotta Xodo Valentina Adotti Martina Rosi Antonio Taddei Paolo Muiesan Amedeo Amedei Giacomo Batignani Fabio Marra Department of Experimental and Clinical Medicine AOU CareggiFlorence 50134Italy

BACKGROUND Hepatocellular carcinoma(HCC)is a common tumour often diagnosed with a multifocal presentation.Patients with multifocal HCC represent a heterogeneous group.Although Trans-Arterial ChemoEmbolization(TACE)is the most frequently employed treatment for these patients,previous data suggested that liver resection(LR)could be a safe and effective procedure.AIM To compare LR and TACE in patients with multifocal HCC in terms of procedurerelated morbidity and oncologic outcomes.METHODS All patients with multifocal HCC who underwent LR or TACE as the first procedure between May 2011 and March 2021 were enrolled.The decision to perform surgery or TACE was made after a multidisciplinary team evaluation.Only patients in Child-Pugh class A or B7 and stage B(according to the Barcelona Clinic Liver Cancer staging system,without severe portal hypertension,vascular invasion,or extrahepatic spread)were included in the final analysis.Propensity score matching was used to adjust the baseline differences between patients undergoing LR and the TACE group[number and diameter of lesions,presence of cirrhosis,alpha-fetoprotein(AFP)levels,and Model for End-Stage Liver Disease score].The Kaplan-Meier method was used to estimate overall survival(OS)and disease-free survival(DFS).The outcomes of LR and TACE were compared using the log-rank test.RESULTS After matching,30 patients were eligible for the final analysis,15 in each group.Morbidity rates were 42.9% and 40% for LR and TACE,respectively(P=0.876).Median OS was not different in the LR and TACE groups(53 mo vs 18 mo,P=0.312),while DFS was significantly longer with LR(19 mo vs 0 mo,P=0.0001).Subgroup analysis showed that patients in the Italian Liver Cancer(ITA.LI.CA)B2 stage,with AFP levels lower than 400 ng/mL,less than 3 lesions,and lesions bigger than 41 mm,benefited more from LR in terms of DFS.Patients classified as ITA.LI.CA B3,with AFP levels higher than 400 ng/mL and with more than 3 lesions,appeared to receive more benefit from TACE in terms of OS.CONCLUSION In a small

关键词： Hepatocellular carcinoma Multifocal hepatocellular carcinoma Liver resection Trans-arterial chemoembolization Guidelines Liver tumour management

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Long-term albumin infusion improves survival in patients with cirrhosis and ascites: An unblinded randomized trial

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World Journal of Gastroenterology 2006年第9期12卷 1403-1407页

作者： Roberto Giulio Romanelli Giorgio La Villa Giuseppe Barletta Francesco Vizzutti Fabio Lanini Umberto Arena Vieri Boddi Roberto Tarquini Pietro Pantaleo Paolo Gentilini Giacomo Laffi Department of Internal Medicine University of Florence School of Medicine FlorenceItaly Department of Heart and Vessels University of Florence School of Medicine FlorenceItaly Department of Public Health University of Florence School of Medicine FlorenceItaly Giacomo Laffi Department of Internal Medicine University of Florence School of Medicine Florence Italy

瞄准：在幸存上调查长期的白朊管理的效果，腹水的复发和另外的复杂并发症的发作。方法：为第一发作的腹水招收的 100 个连续病人被使随机化加人的白朊收到利尿剂第一年和 25 g 里的 25 g/wk 每二 wk 此后(组 1 ) 或利尿剂独自一个(组 2... 详细信息

瞄准：在幸存上调查长期的白朊管理的效果，腹水的复发和另外的复杂并发症的发作。方法：为第一发作的腹水招收的 100 个连续病人被使随机化加人的白朊收到利尿剂第一年和 25 g 里的 25 g/wk 每二 wk 此后(组 1 ) 或利尿剂独自一个(组 2 ) 。没有肝移植，主要端点是幸存。第二等的端点是腹水的复发和另外的复杂并发症的出现。结果：中部的后续是 84 (2-120 ) 瞬间。对待白朊的病人有显著地更大的累积幸存率(Breslow test=7.05， P=0.0078 ) 并且腹水复发的更低的概率(51% 对 94% ， P<0.0001 ) 。长期的白朊注入导致了 16 瞬间的幸存的吝啬的增加。结论：在第一发作的腹水以后的长期的白朊管理显著地改进病人的幸存并且减少腹水复发的风险。

关键词：白蛋白硬化腹水病理机制

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Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib

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World Journal of Gastroenterology 2014年第3期20卷 786-794页

作者： Andrea L Inghilesi Donatella Gallori Lorenzo Antonuzzo Paolo Forte Daniela Tomcikova Umberto Arena Stefano Colagrande Silvia Pradella Bernardo Fani Elena Gianni Luca Boni Giacomo Laffi Francesco Di Costanzo Fabio Marra Dipartimento di Medicina Sperimentale e Clinica Università degli Studi di Firenze Oncologia Medica Azienda Ospedaliero-Universitaria Careggi Gastroenterologia 2 Azienda Ospedaliero-Universitaria Careggi Centro per il Coordinamento delle Sperimentazioni Cliniche Istituto Toscano Tumoriand Azienda Ospedaliero-Universitaria Careggi Dipartimento di Scienze Biomediche Sperimentali e ClinicheUniversità degli Studi di Firenze

AIM:To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma(HCC)in patients with established cirrhosis.METHODS:From October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled.According to the Barcelona Clinic Liver Cancer(BCLC)classification,patients were in the advanced stage(BCLC-C)or in the intermediate stage(BCLC-B)but unfit or unresponsive to other therapeutic strategies.Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo,and analyzed according to the modified Response Evaluation Criteria in Solid Tumors.Sorafenib was administered at 800 mg/d,until radiological progression or occurrence of unacceptable adverse events(AEs).Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival.RESULTS:Forty-four patients were enrolled,15 had intermediate HCC and 14 a Child-Pugh score of B7.AEs caused treatment interruption in 19 patients(43%),and median treatment duration was shorter in this subset(5 wk vs 19 wk,P<0.001)and in the BCLC-C subgroup(13 wk vs 40 wk,P=0.015).No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years.After 16 wk of treatment,18 patients(41%)had stable disease or partial response.Patients with viral infection or BCLC-C were at higher risk of disease progression.ECOG,extrahepatic spread,macrovascular invasion,alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival.CONCLUSION:In patients with cirrhosis and HCC treated with sorafenib,AEs are a common cause of early treatment withdrawal.Vascular invasion and extrahepatic spread condition early response to treatment and survival.Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter

关键词： Hepatocellular carcinoma Sorafenib Cirrhosis Adver

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When Edge Computing Meets IoT Systems: Analysis of Case Studies

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China Communications 2020年第10期17卷 50-63页

作者： Fabio arena Giovanni Pau Faculty of Engineering and Architecture Kore University of EnnaCittadella UniversitariaEnna 94100Italy

On a macroscopic level,an edge computing architecture looks like a distributed and decentralized IT(Information Technology)architecture.More in detail,it could be defined as a mesh network of micro data centers capable of processing and storing critical data locally,and to transmit all data received and/or processed to a central data center or a cloud storage repository.This network topology,also taking advantage of the availability on the market of cost-effective small form factor(SFF)electronic components and systems decreasing,brings the essential components of processing,storage,and networking closer to the sources that generate the data.The typical use case is that of Internet of Things(IoT)devices and implementations,which often face latency problems,lack of bandwidth,reliability,which cannot be addressed through the conventional cloud model.In this context,the edge computing architecture can reduce the size of data to be sent to the cloud,processing critical data,sensitive to latency,at the point of origin,via a smart device,or sending it to an intermediate server,located nearby.The aim of this paper is to report some of the main aspects and significant features of edge computing and analyzing several popular case studies.

关键词： edge computing fog computing cloud computing analysis internet of things

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Exploring the contribution of the mitochondrial disulfide relay system to Parkinson’s disease:the PINK1/CHCHD4 interplay

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Neural Regeneration Research 2021年第11期16卷 2222-2224页

作者： Giuseppe arena Nazanine Modjtahedi Rejko Kruger Translational Neuroscience group Luxembourg Centre for Systems Biomedicine(LCSB)University of LuxembourgEsch-sur-AlzetteLuxembourg UniversitéParis-Saclay Gustave Roussy InstituteCNRSMetabolic and systemic aspects of oncogenesis for new therapeutic approachesVillejuifFrance Parkinson Research Clinic Centre Hospitalier du Luxembourg(CHL)Esch-sur-AlzetteLuxembourg Transversal Translational Medicine Luxembourg Institute of Health(LIH)Esch-sur-AlzetteLuxembourg

Parkinson’s disease(PD)is a common movement disorder of the elderly caused by the degeneration of dopaminergic neurons in the substantia nigra pars compacta of the brain.Both environmental and genetic factors pointed out mitochondrial dysfunction as a major cause of neurodegeneration in PD.Pioneering studies using mitochondrial toxins revealed their ability to trigger dopaminergic cell death and irreversible parkinsonism in different animal models(Poewe et al.,2017).Typical features of mitochondrial dysfunction have been also observed in the human brain of idiopathic PD cases,showing alterations of respiratory chain complex I and IV activity,accumulation of mtDNA deletions and increased oxidative stress(Bender et al.,2006).Moreover,a number of genes found mutated in familial PD forms encode for proteins involved in the maintenance of mitochondrial homeostasis and quality control.Among these,the PINK1 gene encodes a mitochondrial serine/threonine kinase implicated in key neuroprotective functions,including mitophagy,regulation of mitochondrial transport,control of the mitochondria/endoplasmic reticulum crosstalk and calcium homeostasis(Brunelli et al.,2020).

关键词： PINK1 homeostasis protective

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一个人也要好好吃饭

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女友(校园) 2022年第1期 48-51页

作者：妙妙 arena

有人曾经统计过,一个人吃饭最大的难处是什么?得票最高的不是"一个人吃饭总是会做多剩下",而是"一个人吃饭会带来浓浓的孤独感"。其实想要打败这种孤独感,首先要摒弃掉追求速度、随便吃点的心理,因为美食不仅能够填饱肚子,更能够治愈孤...

有人曾经统计过,一个人吃饭最大的难处是什么?得票最高的不是"一个人吃饭总是会做多剩下",而是"一个人吃饭会带来浓浓的孤独感"。其实想要打败这种孤独感,首先要摒弃掉追求速度、随便吃点的心理,因为美食不仅能够填饱肚子,更能够治愈孤单,即使是一个人吃饭,也不要将就哦!今天我们就请来了"简的花园牛排屋"的主厨毛少泽,为大家认认真真设计从前菜到甜品的一整套一人食餐食,希望大家在新年里好好吃饭、好好工作、好好爱自己。

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Vibro-acoustic characteristics of multifunctional carbon fiber reinforced panel

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Defence Technology（防务技术） 2023年第6期24卷 129-139页

作者： Liberata Guadagno Marialuigia Raimondo Luigi Vertuccio Giuseppina Barra Maurizio arena Massimo Viscardi Department of Industrial Engineering University of SalernoVia Giovanni Paolo II13284084FiscianoSAItaly Department of Engineering University of Campania“Luigi Vanvitelli”Via Roma 29I-81031AversaItaly Department of Industrial Engineering Aerospace SectionUniversity of Naples“Federico Ⅱ”Via Claudio 2180125NaplesItaly

This paper deals with the assessment of vibro-acoustic properties of a multifunctional carbon fiber reinfo rced panel manu factured by bulk infu sion,a modified resin film infusion process.The components of the epoxy resin were chosen to contrast the electrical insulating property and poor flame resistance of the epoxy resins impregnating carbon woven fabric.To confer electrical conductivity to the resin a percentage of 0.5 wt%of Multi-Wall Carbon Nanotubes(MWCNTs)was dispersed in the resin,whereas to increase flame resistance a percentage of 5 wt%of Glycidil Polyhedral Oligomeric Silsesquioxanes(GPOSS)was solubilized in the epoxy mixture.Furthermore,as hardener agents,a mixture of 4,4’-DiaminoDiphenyl Sulfone(DDS)(53.4 wt%)and Bis(3-Aminophenyl)Methyl Phosphine Oxide(BAMPO)(46.7 wt%)was used.The values of the electrical conductivity were found satisfactory enough,being4.02×10^(-2)S/m for the multifunctional resin and 1.39×10^(4)S/m for the in-plane conductivity of the panel,whereas the Limiting Oxygen Index(LOI)value of the multifunctional resin was found to increase from 27%to 36%.Considering these promising results,an experimental assessment of the vibro-acoustic properties of the manufactured multifunctional panel was also performed.The panel was tested mainly to evaluate its low-frequency vibration damping and sound insulation characteristics.The manufactured panel demonstrated an improved efficiency if compared to a baseline configuration,presenting almost the double modal damping and a gain of 10 dB on the global noise reduction.

关键词： Composite materials Electrical properties Damping Tunneling atomic force microscopy(TUNA) Vibro-acoustic properties

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