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Immune-mediated bile duct injury:The case of primary biliary cirrhosis

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World Journal of Gastrointestinal Pathophysiology 2010年第4期1卷 118-128页

作者： Carlo Selmi Andrea Affronti Laura Ferrari Pietro Invernizzi Division of Internal Medicine and Hepatobiliary Immunopathology Unit IRCCS Istituto Clinico Humanitas Laura Ferrari Department of Translational MedicineUniversitàdegli Studi di Milano Department of Translational Medicine Universitàdegli Studi di Milano

Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies and autoreactive T ***,the conditionis universally named primary biliary cirrhosis(PBC).The disease etiology and pathogenesis remain largely unknown despite the proposed lines of *** twin study and numerous epidemiology reportssuggest that both a susceptible genetic background and environmental factors determine disease onsetwhile a recent genome-wide association study proposed highly significant associations with several commongenetic polymorphisms in subgroups of *** infectious agents and chemicals may contribute to the disease onset and perpetuation in a geneticallysusceptible host,possibly through molecular ***,several murine models have been proposed and include strains in which PBC is genetically determined or induced by immunization with chemicals and *** a pathogenetic standpoint,new exciting data have demonstrated the unique apoptotic features of bile duct cells that allow the mitochondrial autoantigens to be taken up in their intact form within apoptotic *** are convinced that the application of the most recent molecular techniques will soon pro-vide developments in PBC etiology and pathogenesis with likely implications in diagnostics and therapeutics.

关键词： Autoimmune cholangitis Anti-mitochondrial antibody Epithelial cell apoptosis Innate immunity

Nonalcoholic fatty liver disease prevalence in an Italian cohort of patients with hidradenitis suppurativa: A multi-center retrospective analysis

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World Journal of Hepatology 2019年第4期11卷 391-401页

作者： Giovanni Damiani Sebastiano Leone Kristen Fajgenbaum Nicola L Bragazzi Alessia Pacifico Rosalynn RZ Conic Paolo DM Pigatto Carlo Maiorana Pierpaolo Poli Emilio Berti Maria C Pace Piergiorgio Malagoli Vincenzo Bettoli Marco Fiore Department of Dermatology Case Western Reserve University Young Dermatologists Italian Network (YDIN) Centro Studi GISED Clinical Dermatology IRCCS Galeazzi Orthopaedic Institute Department of Biomedical Surgical and Dental SciencesUniversity of Milan Division of Infectious Diseases "San Giuseppe Moscati" Hospital University of North Carolina School of Medicine School of Public Health Department of Health Sciences (DISSAL)University of Genoa San Gallicano Dermatological Institute IRCCS Center for Jawbone Atrophies Policlinico Hospital University of Milan School of Dentistry Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti Università degli Studi di Milano Unità Operativa di Dermatologia IRCCS Fondazione Ca’ GrandaOspedale Maggiore Policlinico Department of Women Child and General and Specialized SurgeryUniversity of Campania "Luigi Vanvitelli" Dermatology Unit Azienda Ospedaliera San Donato Milanese Department of Clinical and Experimental Dermatology O.C. of DermatologyAzienda Ospedaliero-Universitaria di Ferrara

BACKGROUND Nonalcoholic fatty liver disease(NAFLD) includes two distinct conditions, with different histologic features and prognosis: non-alcoholic fatty liver(NAFL) and non-alcoholic steatohepatitis(NASH). Furthermore, NASH is the more aggressive necro-inflammatory form, which may accumulate fibrosis and result in End stage liver disease(ESLD). NAFLD is also linked to systemic inflammatory conditions such as psoriasis. NAFLD is currently the most common cause of ESLD in Western countries, becoming a serious public health *** suppurativa(HS) is a systemic inflammatory/autoinflammatory disease of the terminal follicular epithelium of the apocrine gland with a prevalence of 0.05% to 4.10%. Due to its systemic inflammatory behavior several comorbidities were recently associated, however liver ones were scarcely *** To evaluate the prevalence and characteristics of NASH/NAFL in HS *** This retrospective study is a sub-analysis of a larger study carried out in 4 Italian dermatological centers. In this cohort, there were 83 patients: 51 patients with HS only, 20 patients with HS/NAFL and 12 with HS/*** Inflammatory comorbidities were present in 3.9% of HS only patients, 25% of HS/NAFL patients and 58.3% of HS/NASH patients(P < 0.001). Similarly, mean Autoinflammatory Disease Damage Index(ADDI) was significantly higher among patients with HS/NASH(5.3 ± 2.2, P < 0.001) compared to patients with HS/NAFL or HS only(2.8 ± 1.6 and 2.6 ± 1.4 respectively). Furthermore, ADDI correlates with IHS4 in HS, HS/NAFL and HS/NASH. Diabetic patients have higher Hurley score than not diabetic ones. Ultrasound examination was significantly different in the three *** HS patients displayed a high prevalence of NASH/NAFLD and ultrasound examination should be particularly addressed to patients that display high ADDI scores.

关键词： Non-alcoholic steatohepatitis Non-alcoholic fatty liver Nonalcoholic fatty liver disease End stage liver disease Hidradenitis suppurativa

circadian clock circuitry in colorectal cancer

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World Journal of Gastroenterology 2014年第15期20卷 4197-4207页

作者： Gianluigi Mazzoccoli Manlio Vinciguerra Gennaro Papa Ada Piepoli Department of Medical Sciences Division of Internal Medicine and Chronobiology UnitIRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza"71013 San Giovanni Rotondo FoggiaItaly istituto EuroMEditerraneo di Scienza e Tecnologia (IEMEST) 90100 PalermoItaly Division of Medicine Royal Free CampusInstitute for Liver and Digestive HealthUniversity College LondonLondon NW3 2PFUnited Kingdom Department of Surgical Sciences Division of UrologyUniversity of Chieti66100 ChietiItaly Department of Medical Sciences Research Laboratory and Division of GastroenterologyIRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza"71013 San Giovanni Rotondo FoggiaItaly

Colorectal cancer is the most prevalent among digestive system *** relies on disrupted control of cellular processes,such as metabolism,proliferation,DNA damage recognition and repair,and ***,tissue,organ and body physiology is characterized by periodic fluctuations driven by biological clocks operating through the clock gene *** of molecular clockworks and cellular oscillators is involved in tumorigenesis,and altered expression of clock genes has been found in cancer *** studies have shown that circadian disruption,that is,alteration of bodily temporal organization,is a cancer risk factor,and an increased incidence of colorectal neoplastic disease is reported in shift *** this review we describe the involvement of the circadian clock circuitry in colorectal carcinogenesis and the therapeutic strategies addressing temporal deregulation in colorectal cancer.

关键词： Colorectal cancer Circadian rhythm Clock gene

Repeat liver surgery by laparoscopy for a malignant recurrence after previous open or laparoscopic resection

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Hepatoma Research 2015年第1期1卷 30-35页

作者： Luigi Cioffi Andrea Belli Corrado Fantini Alberto D’Agostino Gianluca Russo Giulio Belli Department of General and Hepato-Pancreato-Biliary Surgery Loreto Nuovo Hospital80142 NaplesItaly Department of Abdominal Oncology Division of Surgical OncologyIstituto Nazionale Tumori Fondazione G.Pascale-IRCCS80131 NaplesItaly

Aim:This paper reported the experience of one center on repeat laparoscopic liver surgery for metastasis and hepatocellular carcinoma(HCC)with a review of the ***:This retrospective study included 24 patients who underwent laparoscopic re-intervention(hepatic resection and radiofrequency ablation)for recurrent HCC in cirrhosis(n=17)and for recurrent malignant metastases(n=7)after a previous open or laparoscopic *** were divided into two groups according to the fi rst surgical *** 1 underwent open resection and laparoscopic procedure(7 patients),and Group 2 underwent laparoscopic resection and laparoscopic procedure(17 patients).Results:Mean operative time for re-intervention was signifi cantly longer for Group 1(220.14±80.06 min)than for Group 2(150±56.18 min;P=0.001),whereas the mean blood loss and mean hospital stay were comparable in both *** to Dindo-Clavien classifi cation,overall morbidity ranged between Grade I and IIIa and was similar in both ***:This study suggests that repeat laparoscopic surgery for recurrent hepatic malignant diseases in selected patients is a feasible and safe procedure with good short-term outcomes,but further prospective studies are needed to support these results.

关键词： Recurrence repeat liver surgery resection

Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer

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World Journal of Gastroenterology 2016年第28期22卷 6345-6361页

作者： Vincenzo Sforza Erika Martinelli Fortunato Ciardiello Valentina Gambardella Stefania Napolitano Giulia Martini Carminia della Corte Claudia Cardone Marianna L Ferrara Alfonso Reginelli Giuseppina Liguori Giulio Belli Teresa Troiani Oncologia medica Dipartimento di Medicina Clinica e Sperimentale "F. Magrassi e A. Lanzara" Seconda Università degli Studi di Napoli Department of Medical Oncology Biomedical Research Institute INCLIVA University of Valencia Department of Internal and Experimental Medicine Magrassi-Lanzara Institute of Radiology Seconda Università di Napoli Department of Pathology Istituto Nazionale Tumori "Fond. Pascale" - IRCCS Department of General and Hepato-Pancreato-Biliary Surgery S. M. Loreto Nuovo Hospital

The prognosis of patients with metastatic colorectal cancer (mCRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies (moAbs) cetuximab and panitumumab, directed against the epidermal growth factor receptor (EGFR), undoubtedly represent a major step forward in the treatment of mCRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase III clinical trials among different lines of treatment. However, the anti-EGFR moAbs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary (or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-EGFR drugs biochemically converge into MEK-ERK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-EGFR moAbs together with the various strategies evaluated to prevent, overcame or revert them.

关键词： Metastatic colorectal cancer Epidermal growth factor receptor Resistance Mutation KRAS NRAS BRAF PIK3CA MET Monoclonal antibodies

First-line pazopanib in patients with advanced non-clear cell renal carcinoma:An Italian case series

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World Journal of Clinical Oncology 2021年第11期12卷 1037-1046页

作者： Sebastiano Buti Melissa Bersanelli Francesco Massari Ugo De Giorgi Orazio Caffo Gaetano Aurilio Umberto Basso Giacomo Carteni Claudia Caserta Luca Galli Francesco Boccardo Giuseppe Procopio Gaetano Facchini Giuseppe Fornarini Alfredo Berruti Elena Fea Emanuele Naglieri Fausto Petrelli Roberto Iacovelli Camillo Porta Alessandra Mosca Medical Oncology Unit University Hospital of ParmaParma 43126Italy Medicine and Surgery Department University of ParmaParma 43126Italy Division of Oncology Policlinico Sant’Orsola-Malpighi HospitalBologna 40138Italy Department of Oncology IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori(I.R.S.T.)Meldola 47014Italy Department of Medical Oncology Santa Chiara HospitalTrento 38122Italy Department of Medical Oncology Division of Urogenital and Head and Neck TumoursEuropean Institute of Oncology IRCCSMilan 20141Italy Medical Oncology Unit 3 Istituto Oncologico Veneto IOV IRCCSCastelfranco VenetoPadova 31033Italy Division of Oncology Azienda Ospedaliera di Rilievo Nazionale A.CardarelliNapoli 80131Italy Medical Oncology Unit Azienda Ospedaliera S.MariaTerni 05100Italy Oncology Unit 2 University Hospital of PisaPisa 56126Italy Academic Unit of Medical Oncology IRCCS San Martino Polyclinic HospitalGenova 16132Italy Medical Oncology Genitourinary Section Fondazione IRCCS Istituto Nazionale Dei TumoriMilan 20133Italy Departmental Unit of Clinical and Experimental Uro-Andrologic Oncology Istituto Nazionale Tumori IRCCS Fondazione G.PascaleNapoli 80131Italy Medical Oncology Unit Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)Ospedale Policlinico San MartinoGenova 16132Italy University of Brescia ASST-Spedali CiviliBresciaBrescia 25123Italy Medical Oncology Unit S Croce and Carle Teaching HospitalCuneo 12100Italy Division of Medical Oncology Istituto Tumori G Paolo IIIRCCSBari 70124Italy Medical Oncology Unit ASST Bergamo OvestTreviglioBergamo 24047Italy Medical Oncology Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00161Italy Division of Oncology AOU Consorziale Policlinico di BariBari 70124Italy Department of Biomedical Sciences and Human Oncology University of Bari"A.Moro"Bari 70124Italy Multidisciplinary Outpatient Oncology Clinic Candiolo Cancer InstituteFPO-IRCCSCandioloTurin 10060Italy

BACKGROUND Non-clear cell(ncc)metastatic renal-cell carcinoma(RCC)has dismal results with standard systemic therapies and a generally worse prognosis when compared to its clear-cell *** systemic combination therapies have emerged for metastatic RCC(mRCC),but the pivotal phase III trials excluded patients with nccRCC,which constitute about 30%of metastatic RCC *** To provide a piece of real-life evidence on the use of pazopanib in this patient *** The present study is a multicenter retrospective observational analysis aiming to assess the activity,efficacy,and safety of pazopanib as first-line therapy for advanced nccRCC patients treated in a real-life *** Overall,48 patients were *** the median follow-up of 40.6 mo,the objective response rate was 27.1%,the disease control rate was 83.3%,and the median progression-free survival and overall survival were 12.3(95%confidence interval[CI]:3.6-20.9)and 27.7(95%CI:18.2-37.1)mo,*** 3 adverse events occurred in 20%of patients,and no grade 4 or 5 toxicities were *** Pazopanib should be considered as a good first-line option for metastatic RCC with variant histology.

关键词： Pazopanib Non-clear cell Kidney cancer Renal-cell carcinoma Variant histology Tyrosine kinase inhibitors

The EuroLifeNet Study: How Different Microenvironments Influence Personal Exposure to PM<sub>2.5</sub>among High-School Students in Milan

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Open Journal of Air Pollution 2015年第1期4卷 16-25页

作者： Alessandro Borgini Cristian Ricci Martina Bertoldi Paolo Crosignani Andrea Tittarelli Fondazione irccs istituto Nazionale dei Tumori Cancer Registry and Environmental Epidemiology Unit Via Venezian 1 Milan Italy Institut für Epidemiologie und Praventivmedizin Universitat Regensburg Fakultat für Medizin Regensburg Germany

Epidemiological studies show that long-term exposure to PM is associated with an increased risk of cancer. The EuroLifeNet study measured the personal exposure to PM2.5 in 90 pupils attending three schools in Milan, using a portable nephelometer, over a three-week period spanning November and December 2006. Background levels explained 40% of the variability of the exposure. Methods: As a second part of that study we analyzed the role of different microenvironments as determinants of personal exposure to PM2.5. Results: Exposure was influenced by the time of day, zone of the city and different microenvironments. Exposure was higher indoors than out, and indoors it was higher in the kitchen, particularly during cooking. In outdoor environments exposure was higher at bus stops where road traffic was heavy. Conclusions: Even though background concentration can be a good predictor of personal exposure to PM, students’ personal exposure is strongly influenced by different microenvironments and should be considered in population studies. The EuroLifeNet experience gives a contribution to personal exposure measure methodology.

关键词： Personal Exposure Air Pollution Fine Particles Students Schools Indoor/Outdoor Microenvironments

Coronary stenting:A matter of revascularization

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World Journal of Cardiology 2017年第3期9卷 207-211页

作者： Aldo Bonaventura Fabrizio Montecucco Luca Liberale First Clinic of Internal Medicine Department of Internal MedicineUniversity of Genoa School of Medicine and IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro16132 GenoaItaly

In the last few decades, the recommended treatment for coronary artery disease has been dramatically improved by percutaneous coronary intervention(PCI) and the use of balloon catheters, bare metal stents(BMSs), and drug-eluting stents(DESs). Catheter balloons were burdened by acute vessel occlusion or target-lesion restenosis. BMSs greatly reduced those problems holding up the vessel structure, but showed high rates of instent re-stenosis, which is characterized by neo-intimal hyperplasia and vessel remodeling leading to a renarrowing of the vessel diameter. This challenge was overtaken by first-generation DESs, which reduced restenosis rates to nearly 5%, but demonstrated delayed arterial healing and risk for late in-stent thrombosis, with inflammatory cells playing a pivotal role. Finally, new-generation DESs, characterized by innovations in design, metal composition, surface polymers, and antiproliferative drugs, finally reduced the risk for stent thrombosis and greatly improved revascularization outcomes. New advances include bioresorbable stents potentially changing the future of revascularization techniques as the concept bases upon the degradation of the stent scaffold to inert particles after its function expired, thus theoretically eliminating risks linked with both stent thrombosis and re-stenosis. Talking about DESs also dictates to consider dual antiplatelet therapy(DAPT), which is a fundamental moment in view of the good outcome duration, but also deals with bleeding complications. The better management of patients undergoing PCI should include the use of DESs and a DAPT finely tailored in consideration of the potentially developing bleeding risk in accordance with the indications from last updated guidelines.

关键词： Drug-eluting stent Bare metal stent In stent re-stenosis Stent thrombosis Coronary artery disease

Cardiovascular magnetic resonance of cardiac tumors and masses

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World Journal of Cardiology 2021年第11期13卷 628-649页

作者： Marco Gatti Tommaso D’Angelo Giuseppe Muscogiuri Serena Dell'aversana Alessandro Andreis Andrea Carisio Fatemeh Darvizeh Davide Tore Gianluca Pontone Riccardo Faletti Radiology Unit Department of Surgical SciencesUniversity of TurinTurin 10126Italy Department of Biomedical Sciences and Morphological and Functional Imaging “G.Martino”University Hospital MessinaMessina 98100Ita Department of Radiology IRCCS Istituto Auxologico ItalianoSan Luca HospitalMilan 20149Italy Department of Radiology S.Maria Delle Grazie HospitalPozzuoli 80078Italy Department of Medical Sciences University of TurinTurin 10126Italy School of Medicine Vita-Salute San Raffaele UniversityMilan 20121Italy Department of Cardiovascular Imaging Centro Cardiologico MonzinoIRCCSMilan 20138Italy

Cardiac masses diagnosis and treatment are a true challenge,although they are infrequently encountered in clinical *** encompass a broad set of lesions that include neoplastic(primary and secondary),non-neoplastic masses and *** clinical presentation of cardiac tumors is highly variable and depends on several factors such as size,location,relation with other structures and *** presumptive diagnosis is made based on a preliminary non-invasive diagnostic work-up due to technical difficulties and risks associated with biopsy,which is still the diagnostic gold *** findings should always be interpreted in the clinical context to avoid misdiagnosis,particularly in specific conditions(e.g.,infective endocarditis or thrombi).The modern multi-modality imaging techniques has a key role not only for the initial assessment and differential diagnosis but also for management and surveillance of the cardiac *** magnetic resonance(CMR)allows an optimal non-invasive localization of the lesion,providing multiplanar information on its relation to surrounding ***,with the additional feature of tissue characterization,CMR can be highly effective to distinguish pseudomasses from masses,as well as benign from malignant lesions,with further differential diagnosis of the *** histopathological assessment is important to make a definitive diagnosis,CMR plays a key role in the diagnosis of suspected cardiac masses with a great impact on patient *** literature review aims to provide a comprehensive overview of cardiac masses,from clinical and imaging protocol to pathological findings.

关键词： Cine magnetic resonance imaging Multiparametric magnetic resonance imaging Heart neoplasm Multimodal imaging Late-gadolinium enhancement Early gadolinium enhancement