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Percutaneous electrochemotherapy in the treatment of portal vein tumor thrombosis at hepatic hilum in patients with hepatocellular carcinoma in cirrhosis: A feasibility study

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World Journal of Gastroenterology 2017年第5期23卷 906-918页

作者： Luciano tarantino Giuseppina Busto Aurelio Nasto Raffaele Fristachi Luigi Cacace Maria Talamo Catello Accardo Sara Bortone paolo Gallo paolo tarantino Riccardo Aurelio Nasto Matteo Nicola Dario Di Minno Pasquale Ambrosino Department of Surgery Interventional Hepatology UnitAndrea Tortora Hospital Department of Oncology Andrea Tortora Hospital Department of Surgery Unit of General Surgery and OncologyAndrea Tortora Hospital Department of Pathology Andrea Tortora Hospital Department of Radiology Andrea Tortora Hospital Department of Advanced Biomedical Sciences Division of CardiologyFederico II University Unit of Cell and Molecular Biology in Cardiovascular Diseases Centro Cardiologico MonzinoIRCCS Department of Clinical Medicine and Surgery Federico II University

AIMTo treated with electrochemotherapy (ECT) a prospective case series of patients with liver cirrhosis and Vp3-Vp4- portal vein tumor thrombus (PVTT) from hepatocellular carcinoma (HCC), in order to evaluate the feasibility, safety and efficacy of this new non thermal ablative technique in those *** patients (5 males and 1 female), aged 61-85 years (mean age, 70 years), four in Child-Pugh A and two in Child-Pugh B class, entered our study series. All patients were studied with three-phase computed tomography (CT), contrast enhanced ultrasound (CEUS) and ultrasound-guided percutaneous biopsy of the thrombus before ECT. All patients underwent ECT treatment (Cliniporator Vitae®, IGEA SpA, Carpi, Modena, Italy) of Vp3-Vp4 PVTT in a single session. At the end of the procedure a post-treatment biopsy of the thrombus was performed. Scheduled follow-up in all patients entailed: CEUS within 24 h after treatment; triphasic contrast-enhanced CT and CEUS at 3 mo after treatment and every six months ***-treatment CEUS showed complete absence of enhancement of the treated thrombus in all cases. Post-treatment biopsy showed apoptosis and necrosis of tumor cells in all cases. The follow-up ranged from 9 to 20 mo (median, 14 mo). In 2 patients, the follow-up CT and CEUS demonstrated complete patency of the treated portal vein. Other 3 patients showed a persistent avascular non-tumoral shrinked thrombus at CEUS and CT during follow-up. No local recurrence was observed at follow-up CT and CEUS in 5/6 patients. One patient was lost to follow-up because of death from gastrointestinal hemorrage 5 wk after *** patients with cirrhosis, ECT seems effective and safe for curative treatment of Vp3-Vp4 PVTT from HCC.

关键词： Hepatocellular carcinoma Portal vein tumor thrombosis Electrochemotherapy

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Opportunities and challenges of implementing Pharmacogenomics in cancer drug development

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Cancer Drug Resistance 2019年第1期2卷 43-52页

作者： paolo tarantino Dario Trapani Stefania Morganti Emanuela Ferraro Giulia Viale paolo D’Amico Bruno Achutti Duso Giuseppe Curigliano Division of Early Drug Development for Innovative Therapies IEOEuropean Institute of Oncology IRCCSMilan 20141Italy Department of Oncology and Haematology(DIPO) University of MilanMilan 20122Italy

Cancer drug development is a time and resources consuming *** 90%of drugs entering clinical trials fail due to lack of efficacy and/or safety issues,more often after conspicuous research and economic *** of the discarded drugs might be beneficial only in a subgroup of the study patients,and some adverse events might be prevented by identifying those patients more vulnerable to *** implementation of pharmacogenomic biomarkers allows the categorization of patients,to predict efficacy and toxicity and to optimize the drug development *** seventy FDA approved drugs currently present one or more genetic biomarker to keep in consideration,and with the progress of Precision Medicine tailoring therapies on individuals’genomic landscape promises to become a new standard of cancer *** the current article we review the role of pharmacogenomics in cancer drug development,underlying the advantages and challenges of their implementation.

关键词： Pharmacogenomics cancer drug development precision medicine clinical trials

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Hepatitis C virus lymphotropism and peculiar immunological phenotype:Effects on natural history and antiviral therapy

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World Journal of Gastroenterology 2009年第19期15卷 2305-2308页

作者： paolo Conca Giovanni tarantino Department of Clinical and Experimental Medicine Federico University Medical School of Naples

Hepatitis C virus （HCV） has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential lap in the pathogenesis of virus-related autoimmune and lymphoproliferative disorders, ranging from clonal expansion of B-cells with organ-and non-organ-specific autoantibody production up to overt non-Hodgkin＇s lymphoma along a continuous step-by-step model of B-cell lymphomagenesis, where the intermediated mixed cryoglobulinemia could be considered as a stage of suppressible antigen-driven lymphoproliferation. HCV infection of lymphoid ceils could set up privileged reservoirs able to interfere with the host viral clearance efficiency and may be implicated in viral recurrence after apparently successful antiviral therapy. The HCV long-lasting extrahepatic replicative state generates an abnormal systemic immunological response, easily detectable by searching simple laboratory and clinical parameters, mainly represented by vasculitis-like skin features and *** presence or absence of this hypersensitivity pattern seems to correlate with the antiviral response and could be identified as a novel immunological cofactor. Further research is required to fully verify the real impact on therapeutic choice/regimen.

关键词： Hepatitis C virus Lymphotropism Naturalhistory Antiviral therapy Immunological co-factor

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Chasing the right path: tips, tricks and challenges of robotic approach to posterior segments

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Hepatobiliary Surgery and Nutrition 2019年第5期8卷 512-514页

作者： Fabrizio Di Benedetto Giuseppe tarantino paolo Magistri Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModenaMOItaly

The advent of minimally invasive technologies to approachliver diseases changed some paradigms of liver surgeryduring the last two *** allow to safely treatpatients with poor liver function,portal hypertension andcirrhosis,reducing the risk of decompensation(1).However,those potential benefits resulted to be in contrast with theactual application of such technologies in the real-life(2,3).

关键词： liver diseases surgery

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Does protracted antiviral therapy impact on HCV-related liver cirrhosis progression?

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World Journal of Gastroenterology 2007年第36期13卷 4903-4908页

作者： Giovanni tarantino Antonio Gentile Domenico Capone Vincenzo Basile Marianna tarantino Matteo Nicola Dario Di Minno Alberto Cuocolo paolo Conca Department of Clinical and Experimental Medicine Federico Ⅱ University Medical School of Naples Naples 80131 Italy Department of Biomorphological and Functional Sciences Pharmacology Section of Neuroscience Department Federico Ⅱ University Medical School of Naples Naples 80131 Italy

AIM: To study the outcomes of patients with compensated hepatitis C virus-related cirrhosis. METHODS: Twenty-four grade A5 and 11 grade A6 of Child-Pugh classification cirrhotic patients with active virus replication, treated for a mean period of 31.3 ± 5.1 mo with moderate doses of interferon-alpha and ribavirin, were compared to a cohort of 36 patients with similar characteristics, without antiviral treatment. Salivary caffeine concentration, a liver test of microsomal function, was determined at the starting and thrice in course of therapy after a mean period of 11 ± 1.6 mo, meanwhile the resistive index of splenic artery at ultra sound Doppler, an indirect index of portal hypertension, was only measured at the beginning and the end of study. RESULTS: Eight out of the 24 A5- (33.3%) and 5 out of the 11 A6- (45.45%) treated-cirrhotic patients showed a significant improvement in the total overnight salivary caffeine assessment. A reduction up to 20% of the resistive index of splenic artery was obtained in 3 out of the 8 A5- (37.5%) and in 2 out of the 5 A6- (40%) cirrhotic patients with an improved liver function, which showed a clear tendency to decrease at the end of therapy. The hepatitis C virus clearance was achieved in 3 out of the 24 (12.5%) A5- and 1 out of the 11 (0.091%) A6-patients after a median period of 8.5 mo combined therapy. In the cohort of non-treated cirrhotic patients, not only the considered parameters remained unchanged, but 3 patients (8.3%) had a worsening ofthe Child-Pugh score (P = 0.001).CONCLUSION: A prolonged antiviral therapy with moderate dosages of interferon-alpha and ribavirin shows a trend to stable liver function or to ameliorate the residual liver function, the entity of portal hypertension and the compensation status at acceptable costs.

关键词： Liver cirrhosis Hepatitis C virus infection Antiviral therapy

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Contrast-enhanced sonography versus biopsy for the differential diagnosis of thrombosis in hepatocellular carcinoma patients

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World Journal of Gastroenterology 2009年第18期15卷 2245-2251页

作者： paolo Sorrentino Salvatore D'Angelo Luciano tarantino Umberto Ferbo Alessandra Bracigliano Raffaela Vecchione Liver Unit Clinical and Experimental HepatologyDepartment of Internal MedicineS.G.Moscati Hospital83100 AvellinoItaly Department of Biomorphological Science University of Naples Federico Ⅱ80131 NaplesItaly Hepatology and Interventional Ultrasound Unit S.Giovanni di Dio HospitalASL 380027 FrattamaggioreNaplesItaly Institute of Pathology S.G.Moscati Hospital83100 AvellinoItaly

AIM:To clarify which method has accuracy:2nd gen-eration contrast-enhanced ultrasound or biopsy of portal vein thrombus in the differential diagnosis of portal vein ***:One hundred and eighty-six patients with hepatocellular carcinoma and portal vein thrombosis underwent in blinded fashion a 2nd generation contrast-enhanced ultrasound and biopsy of portal vein thrombus;both results were examined on the basis of the follow-up of patients compared to ***:One hundred and eight patients completed the *** thrombosis on 2nd generation contrast-enhanced ultrasound was characterised by progressive hypoenhancing of the thrombus;in malignant portal vein thrombosis there was a precocious homo-geneous enhancement of the *** follow-up there were 50 of 108 patients with benign thrombosis:all were correctly diagnosed by both *** were 58 of 108 patients with malignant thrombosis:amongst these,52 were correctly diagnosed by both methods,the remainder did not present malignant cells on portal vein thrombus biopsy and showed on 2nd generation contrast-enhanced ultrasound an inho-mogeneous enhancement pattern.A new biopsy during the follow-up,guided to the area of thrombus that showed up on 2nd generation contrast-enhanced ultra-sound,demonstrated an enhancing pattern indicating malignant ***:In patients with hepatocellular carcinoma complicated by portal vein thrombosis,2nd generation contrast-enhanced ultrasound of portal vein thrombus is very useful in assessing the benign or malignant nature of the *** biopsy of thrombus is usually accurate but presents some sampling errors,so,when pathological results are required,2nd generation contrast-enhanced ultrasound could guide the sampling needle to the correct area of the thrombus.

关键词： Hepatocellular carcinoma 2nd generationcontrast enhanced ultrasound Contrast enhancedsonography Malignant thrombosis Portal vein biopsy

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Surgery in biliary lithiasis: from the traditional “open” approach to laparoscopy and the“rendezvous” technique

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Hepatobiliary & Pancreatic Diseases International 2017年第6期16卷 595-601页

作者： Giuseppe tarantino paolo Magistri Roberto Ballarin Giacomo Assirati Antonio Di Cataldo Fabrizio Di Benedetto Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University of Modena and Reggio Emilia 41124 ModenaItaly Department of General Surgery Sapienza-University of Rome 00189 Rome Italy Department of Surgical Sciences Organ Transplantation and Advanced Technologies University of Catania95124 Catania Italy

BACKGROUND:According to the current literature, biliary lithiasis is a worldwide-diffused condition that affects almost 20% of the general population. The rate of common bile duct stones(CBDS) in patients with symptomatic cholelithiasis is estimated to be 10% to 33%, depending on patient’s *** to stones in the gallbladder, the natural history of secondary CBDS is still not completely understood. It is not clear whether an asymptomatic choledocholithiasis requires treatment or not. For many years, open cholecystectomy with choledochotomy and/or surgical sphincterotomy and cleaning of the bile duct were the gold standard to treat both pathologies. Development of both endoscopic retrograde cholangiopancreatography(ERCP) and laparoscopic surgery,together with improvements in diagnostic procedures, influenced new approaches to the management of CBDS in association with *** SOURCES:We decided to systematically review the literature in order to identify all the current therapeutic options for CBDS. A systematic literature search was performed independently by two authors using Pub Med, EMBASE, Scopus and the Cochrane Library ***:The therapeutic approach nowadays varies greatly according to the availability of experience and expertise in each center, and includes open or laparoscopic common bile duct exploration, various combinations of laparoscopic cholecystectomy and ERCP and combined laparoendoscopic ***:Although ERCP followed by laparoscopic cholecystectomy is currently preferred in the majority of hospitals worldwide, the optimal treatment for concomitant gallstones and CBDS is still under debate, and greatly varies among different centers.

关键词： biliary obstruction bile duct stones gallstones endoscopic retrograde cholangiopancreatography laparoscopic cholecystectomy

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Flow cytometry assay of myeloid dendritic cells (mDCs)in peripheral blood during acute hepatitis C:Possible pathogenetic mechanisms

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World Journal of Gastroenterology 2006年第7期12卷 1105-1109页

作者： Alessandro Perrella Luigi Atripaldi Pasquale Bellopede Tommaso Patarino Costanza Sbreglia Giovanni tarantino paolo Sorrentino paolo Conca Luca Ruggiero Oreste Perrella Department Infectious Disease and Immunology Hospital D.CotugnoNaplesItaly Department Institute for Cancer Genetics Columbia University

AIM： To asses the expression of myeloid dendritic cells （CD11c＋） subset during acute HCV hepatitis and its possible involvement in natural history of the infection.METHODS： We enrolled 11 patients with acute hepatitis C （AHC）（Group A）, 10 patients with acute hepatitis A （AHA）（as infective control-Group B） and 10 healthy donors （group C） in this study. All patients underwent selective flow cytometry gating strategies to assess the peripheral number of the myeloid dendritic cells （mDCs） to understand the possible role and differences during acute hepatitis.RESULTS： Eight of 11 patients with acute HCV hepatitis did not show any increase of mDCs compared to healthy individuals, while a significant decrease of mDCs was found in absolute cell count （z=-2.37, P〈0.05） and percentage （z=-2.30; P〈 0.05） as compared with AHA. On the contrary, The remaining three patients of the group A had a higher mDCs number and percentage as occur in group B. Interestingly, after six months, those patients did not show any increase of mDCs subset were chronically infected, while the three subjects with an increase of peripheral mDCs, as in HAV acute infection, resolved the illness.CONCLUSION： The lack of increase of mDCs during acute hepatitis C might be an important factor involved in chronicization of the infection.

关键词： Myeloid dendritic cells HCV CD4+ CD11c+ HCV-RNA HAV

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Robotic liver surgery is the optimal approach as bridge to transplantation

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World Journal of Hepatology 2017年第4期9卷 224-226页

作者： paolo Magistri Giuseppe tarantino Roberto Ballarin Andrea Coratti Fabrizio Di Benedetto Department of Medical and Surgical Sciences and Translational Medicine Sapienza - University of Rome Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University of Modena and Reggio Emilia Department of Oncology Division of Oncological and Robotic General Surgery Careggi University Hospital

The role of minimally invasive liver surgery as a bridge to transplantation is very promising but still underestimated. However, it should be noted that surgical approach for hepatocellular carcinomas(HCC) is not merely a technical or technological issue. Nowadays, the epidemiology of HCC is evolving due to the increasing role of non-alcoholic fatty-liver-disease, and the emerging concerns on direct-acting antivirals against hepatitis C virus in terms of HCC incidence. Therefore, a fully multidisciplinary study of the cirrhotic patient is currently more important than ever before, and the management of those patients should be reserved to tertiary referral hepatobiliary centers. In particular, minimally invasive approach to the liver showed several advantages compared to the classical open procedure, in terms of:(1) the small impact on abdominal wall;(2) the gentle manipulation on the liver;(3) the limited surgical trauma; and(4) the respect of venous shunts. Therefore, more direct indications should be outlined also in the Barcelona Clinic Liver Cancer model. We believe that treatment of HCC in cirrhotic patients should be reserved to tertiary referral hepatobiliary centers, that should offer patient-tailored approaches to the liver disease, in order to provide the best care for each case, according to the individual comorbidities, risk factors, and personal quality of life expectations.

关键词： Hepatocellular carcinomas Liver transplant Robotic surgery Bridge to transplantation Da vinci Barcelona Clinic Liver Cancer Patient safety

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Hepatic steatosis in overweight/obese females: New screening method for those at risk

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World Journal of Gastroenterology 2009年第45期15卷 5693-5699页

作者： Giovanni tarantino Genoveffa Pizza Annamaria Colao Fabrizio Pasanisi paolo Conca Patrizia Colicchio Carmine Finelli Franco Contaldo Carolina Di Somma Silvia Savastano Department of Clinical and Experimental Medicine Federico Ⅱ University Medical School of Naples Department of Molecular and Clinical Endocrinology and Oncology Section of Endocrinology Federico Ⅱ University Medical School of Naples

AIM: To identify which parameters could help to distinguish the "metabolically benign obesity", which is not accompanied by insulin resistance (IR) and early ***: Eighty two of 124 overweight/obese females formed the study population, which was divided into two groups (52 and 30 subjects, respectively) with and without IR according to a HO meostatic Metabolic Assessment (HOMA) cut-off of 2, and were studied in a cross-sectional manner. The main outcome measures were waist circumference, serum uric acid, high-density lipoprotein-cholesterol and triglycerides, alanine amino-transferase, blood pressure and the two imaging para-meters, hepatic steatosis and longitudinal diameter of the spleen, which were measured in relation to the presence/absence of IR. RESULTS: A variable grade of visceral obesity was observed in all subjects with the exception of *** of a severe grade was represented more in the group of IR individuals (P = 0.01). Hepatic steatosis, revealed at ultrasound, was more pronounced in IR than in non-IR subjects (P = 0.005). The two groups also demonstrated a clear difference in longitudinal spleen diameter and blood pressure, with raised and signif icant values in the IR group. Metabolic syndrome was frequent in the IR group, and was not modified when adjusted for menopause (P = 0.001). At linear regression, the β values of waist circumference and body mass index predicting HOMA were 0.295, P = 0.007 and 0.41, P = 0.0001, respectively. Measures of spleen longitudinal diameter were well predicted by body mass index (BMI) values, β = 0.35, P = 0.01, and by HOMA, β = 0.41, P = 0.0001. Blood pressure was predicted by HOMA values, β = 0.39, P = 0.0001). HOMA and hepatic steatosis were highly associated (rho = 0.34, P = 0.002). Interestingly, IR patients were almost twice as likely to have hepatic steatosis as non-IR patients. Among the MS criteria, blood pressure was very accurate in identifying the presence of IR (AUROC for systo

关键词： Body mass index Cardiovascular disease Fatty liver Insulin resistance Metabolic f itness Obesity

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