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Role of liver biopsy in hepatocellular carcinoma

World Journal of Gastroenterology 2019年第40期25卷 6041-6052页

作者： Luca Di Tommaso Marco Spadaccini Matteo Donadon Nicola Personeni Abubaker Elamin Alessio Aghemo Ana Lleo Pathology Unit Humanitas Clinical and Research Center IRCCSRozzano 20089Italy Department of Biomedical Sciences Humanitas UniversityPieve Emanuele 20090Italy Division of Hepatobiliary and General Surgery Department of General SurgeryHumanitas Clinical and Research Center IRCCSRozzano 20089Italy Division of Medical Oncology and Hematology Humanitas Cancer CenterHumanitas Clinical and Research Center IRCCSRozzano 20089Italy Division of Internal Medicine and Hepatology Department of GastroenterologyHumanitas Clinical and Research Center IRCCSRozzano 20089Italy

The role of liver biopsy in the diagnosis of hepatocellular carcinoma(HCC)has been challenged over time by the ability of imaging techniques to characterize liver lesions in patients with known *** fact,in the diagnostic algorithm for this tumor,histology is currently relegated to controversial ***,the risk of complications,such as tumor seeding and bleeding,as well as inadequate sampling have further limited the use of liver biopsy for HCC ***,there is growing evidence of prognostic and therapeutic information available from microscopic and molecular analysis of HCC and,as the information content of the tissue sample increases,the advantages of liver biopsy might modify the current risk/benefit *** herein review the role and potentiality of liver biopsy in the diagnosis and management of *** the potentiality of precision medicine comes to the management of HCC,it will be crucial to have rapid pathways to define prognosis,and even treatment,by identifying the patients who could most benefit from target-driven *** of the above reasons suggest that the current role of liver biopsy in the management of HCC needs substantial reconsideration.

关键词： Hepatocellular carcinoma Liver biopsy Prognostic factors Liver cancer Recurrence Liquid biopsy

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Unravel hepatic artery infusion chemotherapy in patients with resected colorectal liver metastases

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Hepatobiliary Surgery and Nutrition 2021年第2期10卷 257-260页

作者： Matteo Donadon Lorenza Rimassa Guido Torzilli Department of Biomedical Sciences Humanitas UniversityPieve EmanueleMilanItaly Department of Hepatobiliary and General Surgery IRCCS Humanitas Research HospitalRozzanoMilanItaly humanitas Cancer Center IRCCS Humanitas Research HospitalRozzanoMilanItaly

Over the past years,important progresses have been made in the treatment of patients with colorectal liver metastases(CLM).Now,5-year overall survival rate may exceed 50%by using the combination of multimodality therapies among which modern systemic chemotherapy,with or without monoclonal antibodies,and hepatic resection are the cornerstones(1,2).In such multimodality,hepatic artery infusion(HAI)has been proposed since many years with the rationale of increasing the concentration of chemotherapy agents in the liver(3).However,HAI still remains infrequently used,in particular in the adjuvant setting mainly because of the requirement of a multidisciplinary team to manage therapy,and the more widespread use of systemic chemotherapy-in particular following the perioperative“sandwich”schema(4).

关键词： infusion chemotherapy hepatic

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Non-alcoholic fatty liver disease,non-alcoholic steatohepatitis,metabolic syndrome and hepatocellular carcinoma——a composite scenario

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Hepatobiliary Surgery and Nutrition 2018年第2期7卷 130-133页

作者： Luca Viganò Ana Lleo Alessio Aghemo Division of Hepatobiliary and General Surgery Department of SurgeryHumanitas Clinical and Research CenterHumanitas UniversityRozzanoMilanItaly Department of Biomedical Sciences Humanitas UniversityRozzanoMilanItaly Division of Internal Medicine and Hepatology Department of Internal MedicineHumanitas Clinical and Research CenterHumanitas UniversityRozzanoMilanItaly

Hepatocellular carcinoma(HCC)is the fifth most common cancer and the second leading cause of cancer-related death *** data suggest that the epidemiology of HCC is changing;while the frequencies of hepatitis B virus(HBV)-and hepatitis C virus(HCV)-related HCC are progressively decreasing owing to the development of nucleo(t)side-based therapies and directly acting antiviral agents,respectively,the frequency of cryptogenic HCC continues to increase(15–30%of cases)(1).The rise of cryptogenic HCC is mainly related to non-alcoholic fatty liver disease(NAFLD)(1,2).NAFLD encompasses a wide spectrum of liver injuries,ranging from steatosis to non-alcoholic steatohepatitis(NASH),which may progress to cirrhosis(1,3).

关键词： epidemiology liver NAFLD death

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Minimal access liver surgery: from the escalation, to the boundaries, searching for the rules

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Hepatobiliary Surgery and Nutrition 2019年第6期8卷 637-639页

作者： Guido Torzilli Division of Hepatobiliary&General Surgery Department of SurgeryHumanitas Research HospitalHumanitas UniversityMilanoItaly

Minimal access liver surgery(MALS),is now routinely performed worldwide,and procedures like limited resections of antero-inferior segments and left lateral sectionectomy could be retained as standard once performed laparoscopically(1).It is a common believe that MALS procedures mean shorter and better postoperative outcome,and essentially more safety compared to the open ***,MALS procedures facing with complex disease presentations are increasingly proposed(2).In this escalation of MALS in the panorama of the surgical offer available for patients with liver tumors open liver surgery(OLS)seems somehow passed *** this setting,the paper of Tong et *** to set clinically based criteria for allowing to foresee the risk of conversion and morbidity once a MALS is planned(3).At least the attempt is worth to be awarded while the results should be validated by means of further studies able to test the scoring system the authors *** sure there is the merit to investigate the burden of MALS,which implies the recognition of a limit and subsequently the need for its precise definition.A definition which,as anything in medicine,could not be considered definitive,since it will probably evolve with expertise and technology as it has been the case in the last 10-15 ***,pointing out the existence of a limit superimposes caution to any effort to get over the burden unless the attempt is based on a solid *** sure,in this sense,the authors have provided an instrument for the surgical community which conveys limits to which any surgeon has to face with.

关键词： routine instrument searching

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Post-hepatectomy biliary fistula: from risk factors to the role of drain placement and management—still a lot to be answered

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Hepatobiliary Surgery and Nutrition 2019年第4期8卷 417-418页

作者： Guido Costa Matteo Donadon Guido Torzilli Department of Hepatobiliary and General Surgery Humanitas University & Humanitas Clinical and Research Center – IRCCS Rozzano Milan Italy

Hepatic resection represents the gold-standard treatment for different liver diseases. Among postoperative complications, bile leak remains one of the most common sources of morbidity, which can lead to an increase of hospital stay, need of invasive procedure and potentially death (1). The definition and acknowledge of risk factors for the development of biliary fistula as well as its early detection and optimal management is, in this sense, of crucial importance.

关键词： fistula biliary death

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The elegance of a macrophage

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Cellular & Molecular Immunology 2018年第3期15卷 196-198页

作者： Maria De Santis Massimo Locati Carlo Selmi Rheumatology and Clinical Immunology Humanitas Research HospitalRozzanoItaly Laboratory of Leukocyte Biology Humanitas Research HospitalRozzanoItaly BIOMETRA Department University of MilanMilanItaly

In the latest issue of Nature Immunology,Piccolo et al.1 elegantly explored the effect of coexisting interferon-γ(IFN-γ)and interleukin 4(IL-4)antagonistic signals on macrophage transcriptional and epigenetic profiles and,interestingly,identified a plastic cross-talk as opposed to mutually exclusive programs between M1 and M2 polarized *** results support the fascinating hypothesis that transcriptional and epigenetic reprogramming overcame genetics to drive the evolution of eukaryotic organisms.A rapid reshaping of chromatin acetylation redirected the expression of hundreds of genes under the control of a few transcription factors in response to two coexisting but opposing signals that indicated inflammation and its resolution simultaneously.

关键词： macrophage interferon inflammation

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Is precision medicine for colorectal liver metastases still a utopia?New perspectives by modern biomarkers,radiomics,and artificial intelligence

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World Journal of Gastroenterology 2022年第6期28卷 608-623页

作者： Luca Viganò Visala S Jayakody Arachchige Francesco Fiz Department of Hepatobiliary and General Surgery IRCCS Humanitas Research HospitalRozzano 20089MIItaly Department of Biomedical Sciences Humanitas UniversityPieve Emanuele 20072MIItaly Nuclear Medicine IRCCS Humanitas Research HospitalRozzano 20089MIItaly

The management of patients with liver metastases from colorectal cancer is still *** therapeutic options and treatment strategies are available for an extremely heterogeneous clinical *** prediction of patients’outcomes and of the effectiveness of chemotherapy and loco-regional treatments are crucial to reach a precision medicine *** has been an unmet need for a long time,but recent studies have opened new *** morphological biomarkers have been *** dynamic evaluation of the metastases across a time interval,with or without chemotherapy,provided a reliable assessment of the tumor *** have been explored and,thanks to their strong association with prognosis,have the potential to drive treatment *** liver-tumor interface has been identified as one of the main determinants of tumor progression,and its components,in particular the immune infiltrate,are the focus of major *** mining and analyses provided new insights on tumor biology and are expected to have a relevant impact on clinical *** intelligence is a further step *** present paper depicts the evolution of clinical decision-making for patients affected by colorectal liver metastases,facing modern biomarkers and innovative opportunities that will characterize the evolution of clinical research and practice in the next few years.

关键词： Colorectal liver metastases Biomarkers Genetics Immune infiltrate Radiomics Artificial Intelligence

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Tauroursodeoxycholic acid: a potential therapeutic tool in neurodegenerative diseases

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Translational Neurodegeneration 2022年第1期11卷 444-460页

作者： Kareem Khalaf Paolo Tornese Antoniangela Cocco Alberto Albanese Department of Neurology IRCCS Humanitas Research HospitalRozzanoMIItaly

Most neurodegenerative disorders are diseases of protein homeostasis, with misfolded aggregates accumulating. The neurodegenerative process is mediated by numerous metabolic pathways, most of which lead to apoptosis. In recent years, hydrophilic bile acids, particularly tauroursodeoxycholic acid (TUDCA), have shown important anti-apoptotic and neuroprotective activities, with numerous experimental and clinical evidence suggesting their possible therapeutic use as disease-modifiers in neurodegenerative diseases. Experimental evidence on the mechanisms underlying TUDCA’s neuroprotective action derives from animal models of Alzheimer’s disease, Parkinson’s disease, Huntington’s diseases, amyotrophic lateral sclerosis (ALS) and cerebral ischemia. Preclinical studies indicate that TUDCA exerts its effects not only by regulating and inhibiting the apoptotic cascade, but also by reducing oxidative stress, protecting the mitochondria, producing an anti-neuroinflammatory action, and acting as a chemical chaperone to maintain the stability and correct folding of proteins. Furthermore, data from phase II clinical trials have shown TUDCA to be safe and a potential disease-modifier in ALS. ALS is the first neurodegenerative disease being treated with hydrophilic bile acids. While further clinical evidence is being accumulated for the other diseases, TUDCA stands as a promising treatment for neurodegenerative diseases.

关键词： Amyotrophic lateral sclerosis Alzheimer’s disease Bile acids Disease-modifying Huntington’s disease Neurodegeneration Neuroprotection Parkinson’s disease Ursodeoxycholic acid Tauroursodeoxycholic acid

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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

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lmmunotherapy in hepatobiliary tumors: search for the missing pieces of the puzzle

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Hepatobiliary Surgery and Nutrition 2020年第1期9卷 86-88页

作者： Matteo Donadon Federica Marchesi Lorenza Rimassa Guido Torzilli Department of Hepatobiliary and General Surgery Humanitas Clinical and Research Center-IRCCSRozzanoMilanItaly Department of Biomedical Sciences Humanitas UniversityPieve EmanueleMilanItaly Department of Immunology and Inflammation Humanitas Clinical and Research Center-IRCCSRozzanoMilanItaly Department of Biotechnology and Translational Medicine University of MilanMilanItaly humanitas Cancer Center Humanitas Clinical and Research Center-IRCCSRozzanoMilanItaly

In the current era of immunotherapy, the treatment of hepatobiliary cancers is rapidly evolving. The use of immunotherapeutic approaches, which include peptide-based vaccines, checkpoint inhibitors and antibodies, particularly applies to advanced hepatobiliary cancers, for which the availability of limited therapeutic options encourages the adoption of alternative strategies. Thanks to the published/presented, although conflicting, results of some of the clinical trials on this topic together with the incoming results of some other trials, clinicians involved in the cure of hepatobiliary cancer patients need to understand the basic and advanced applications of immunotherapies (1-6).

关键词： hepato biliary therapeutic

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