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Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake?

World Journal of Gastroenterology 2018年第2期24卷 274-289页

作者： Rossella Reddavid Silvia Sofia Paolo Chiaro Fabio Colli renza trapani Laura Esposito Mario Solej Maurizio Degiuli Surgical Oncology and Digestive Surgery Department of Oncology University of Turin San Luigi University Hospital Department of Surgical Sciences Digestive and Oncological Surgery University of Turin Molinette Hospital

AIM To investigate the neoadjuvant chemotherapy(NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.METHODS We proceeded to a review of the literature with Pub Med, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials(RCTs) comparing NAC followed by surgery(NAC + S) with surgery alone(SA) for gastric cancer(GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association(JGCA) performed in both arms, disease-specific(DSS) and disease-free survival(DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment. RESULTS We identified a total of 16 randomized controlled trials comparing NAC + S(n = 1089) with SA(n = 973) published in the period from January 1993-March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node(LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. Inthe third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the "Study Treatment" protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction(EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper stomach cancer. Additionally, several patients d

关键词： gastric cancer neoadjuvant chemotherapy perioperative chemotherapy D2 lymphadenectomy randomized control trial

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Transperineal laser ablation of the prostate as a treatment for benign prostatic hyperplasia and prostate cancer: The results of a Delphi consensus project

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Asian Journal of Urology 2024年第2期11卷 271-279页

作者： Andrea Cocci Marta Pezzoli Fernando Bianco Franco Blefari Pierluigi Bove Francois Cornud Gaetano De Rienzo Paolo Destefanis Danilo Di trapani Alessandro Giacobbe Luca Giovanessi Antonino Laganà Giovanni Lughezzani Guglielmo Manenti Gianluca Muto Gianluigi Patelli Novello Pinzi Stefano Regusci Giorgio I.Russo Juan I.M.Salamanca Matteo Salvi Luigi Silvestri Fabrizio Verweij Eric Walser Riccardo GBertolo Valerio Iacovelli Alessandro Bertaccini Debora Marchiori Hugo Davila Pasquale Ditonno Paolo Gontero Gennaro Iapicca Theo M De Reijke Vito Ricapito Pierluca Pellegrini Andrea Minervini Sergio Serni Francesco Sessa Department of Urology Careggi HospitalUniversity of FlorenceFlorenceItaly Urology Section University of FlorenceFlorenceItaly Urological Research Network MiamiFLUSA Urology Section Prato HospitalPratoItaly Torvergata Oncoscience Research Centre of Excellence TORDepartment of Experimental MedicineUniversity of Rome Tor VergataRomeItaly Department of Urology San Carlo di Nancy HospitalRomeItaly Department of Radiology Hôpital CochinParis Descartes UniversityParisFrance Urology and Andrology Unit II Department of Emergency and Organ TransplantationUniversity of BariBariItaly Unit of Urology Cittàdella Salute e della Scienza HospitalUniversity of TurinTurinItaly Urology Unit Buccheri La Ferla Fatebenefratelli HospitalPalermoItaly Department of Urology Humanitas Gradenigo HospitalTurinItaly Urology Unit Surgical DepartmentFondazione Poliambulanza Istituto OspedalieroBresciaItaly Departement of Urology “S.Giovanni Evangelista”HospitalTivoliItaly Humanitas Clinical and Research CentereIRCCS Department of UrologyRozzanoItaly Department of Biomedical Sciences Humanitas UniversityPieve EmanueleItaly Department of Biomedicine and Prevention University of Rome“Tor Vergata”RomeItaly Department of Diagnostic Imaging and Interventional Radiology University of Rome“Tor Vergata”RomeItaly Department of Interventional Radiology Pesenti-Fenaroli Hospital-ASST Bergamo EstAlzano LombardoItaly Department of Urology University of SienaSienaItaly Swiss International Prostate Center GenevaSwitzerland Clinique Générale Beaulieu GenevaSwitzerland Department of Urology University of CataniaItaly Department of Urology Puerta de Hierro-Majadahonda University HospitalMadridSpain Lyx Institute of Urology Universidad Francisco de VitoriaMadridSpain Department of Medico-Surgical Sciences and Biotechnologies Sapienza University of RomeFaculty of Pharmacy and MedicineUrology Unit ICOTLatinaItaly Department of Urology European Institute of Oncology(IEO)IRCCSMilanItaly Department of Radiology D

Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method.Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized.Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from 80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations.Conclusion: Ech

关键词： Transperineal laser ablation Prostatecancer Benignprostatic hyperplasia Delphi consensus

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Treatment of hepatitis B virus infection in children and adolescents

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World Journal of Gastroenterology 2021年第36期27卷 6053-6063页

作者： Mariangela Stinco Chiara Rubino Sandra trapani Giuseppe Indolfi Department of Health Sciences Pediatric SectionMeyer Children’s University HospitalFlorence 50139Italy Department Neurofarba University of Florence and Meyer Children’s University HospitalFlorence 50139Italy

Hepatitis B virus(HBV)infection is one of the main causes of morbidity and mortality worldwide.Most children acquire the infection perinatally or during early childhood and develop a chronic hepatitis characterized by a high viral replication and a low-inflammation phase of infection,with normal or only slightly raised aminotransferases.Although a conservative approach in children is usually recommended,different therapies exist and different therapeutic approaches are possible.The main goals of antiviral treatment for children with chronic HBV infection are to suppress viral replication and to warn the disease progression to cirrhosis and hepatocellular carcinoma,although these complications are rare in children.Both United States Food and Drug Administration(USFDA)and European Medicines Agency(EMA)have approved interferon alfa-2b for children aged 1 year and older,pegylated interferon alfa-2a and lamivudine for children aged 3 years and older,entecavir for use in children aged 2 years and older,and adefovir for use in those 12 years of age and older.Tenofovir disoproxil fumarate is approved by EMA for children aged 2 years and older and by USFDA for treatment in children aged 12 years and older.Finally,EMA has approved the use of tenofovir alafenamide for treatment of children aged 12 years and older or for children weighing more than 35 kg independent of age.This narrative review will provide the framework for summarizing indications to antiviral therapy in the management of chronic HBV infection in children and adolescents.

关键词： Hepatitis B Children Adolescents Antiviral therapy Tenofovir disoproxil fumarate Entecavir Interferon

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IFN-γ^(+) cytotoxic CD4^(+) T lymphocytes are involved in thepathogenesis of colitis induced by IL-23 and the foodcolorant Red 40

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Cellular & Molecular Immunology 2022年第7期19卷 777-790页

作者： Lili Chen Zhengxiang He Bernardo S.Reis Jesse D.Gelles Jerry Edward Chipuk Adrian T.Ting Julie A.Spicer Joseph A.trapani Glaucia C.Furtado Sergio A.Lira Precision Immunology Institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA Laboratory of Mucosal Immunology The Rockefeller UniversityNew YorkNY 10065USA Department of Oncological Sciences Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA The Tisch Cancer Institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA The Diabetes Obesityand Metabolism InstituteIcahn School of Medicine at Mount SinaiNew YorkNY 10029USA Department of Immunology Mayo ClinicRochesterMN 55905USA Auckland Cancer Society Research Centre Faculty of Medical and Health SciencesThe University of AucklandPrivate Bag 92019Auckland 1142New Zealand Cancer Immunology Program Peter MacCallum Cancer Centre305 Grattan StreetMelbourneVIC 3000Australia

The food colorant Red 40 is an environmental risk factor for colitis development in mice with increased expression of interleukin(IL)-23.This immune response is mediated by CD4^(+)T cells,but mechanistic insights into how these CD4^(+)T cells trigger andperpetuate colitis have remained elusive.Here,using single-cell transcriptomic analysis,we found that several CD4^(+)T-cell subsetsare present in the intestines of colitic mice,including an interferon(IFN)-γ-producing subset.In vivo challenge of primed mice withRed 40 promoted rapid activation of CD4^(+)T cells and caused marked intestinal epithelial cell(IEC)apoptosis that was attenuated bydepletion of CD4^(+)cells and blockade of IFN-γ.Ex vivo experiments showed that intestinal CD4^(+)T cells from colitic mice directlypromoted apoptosis of IECs and intestinal enteroids.CD4^(+)T cell-mediated cytotoxicity was contact-dependent and required FasL,which promoted caspase-dependent cell death in target IECs.Genetic ablation of IFN-γconstrained IL-23-and Red 40-inducedcolitis development,and blockade of IFN-γinhibited epithelial cell death in vivo.These results advance the understanding of themechanisms regulating colitis development caused by IL-23 and food colorants and identify IFN-γ^(+)cytotoxic CD4^(+)T cells as a newpotential therapeutic target for colitis.

关键词： Allura Red IL23 Cytotoxic CD4^(+)T cells CD4^(+)CTL Inflammation Epithelium damage Colitis

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Deep mine cooling,a case for Northern Ontario:Part Ⅰ

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International Journal of Mining Science and Technology 2016年第6期26卷 721-727页

作者： D. Millar K. trapani A. Romero MIRARCO 935 Ramsey Lake Rd Sudbury P3E 2C6 Canada Laurentian University 935 Ramsey Lake Rd Sudbury P3E 2C6 Canada

Cooling energy needs,for mines in Northern Ontario,are mainly driven by the mining depth and its operation.Part I of this research focusses on the thermal energy loads in deep mines as a result of the virgin rock temperature,mining operations and climatic conditions.A breakdown of the various heat sources is outlined,for an underground mine producing 3500 tonnes per day of broken rock,taking into consideration the latent and sensible portions of that heat to properly assess the wet bulb global temperature.The resulting thermal loads indicate that cooling efforts would be needed both at surface and underground to maintain the temperature underground within the legal threshold.In winter the air might also have to be heated at surface and cooled underground,to ensure that icing does not occur in the inlet ventilation shaft-the main reason why cooling cannot be focussed solely at surface.

关键词：安大略矿井降温深部案例原岩温度开采深度气候条件破碎岩石

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A comprehensive evaluation of sexual and reproductive outcomes following robot-assisted retroperitoneal lymph node dissection for nonseminomatous germ cell tumor

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Asian Journal of Andrology 2022年第6期24卷 579-583页

作者： Francesco A Mistretta Ottavio de Cobelli Paolo Verze Francesco Botticelli Letizia Jannello Stefano Luzzago Gabriele Cozzi Roberto Bianchi Ettore Di trapani Matteo Ferro Giovanni Cordima Danilo Bottero Deliu Victor Matei Vincenzo Mirone Gennaro Musi Department of Urology European Institute of OncologyIRccSMilan 20141Italy Department of Oncology and Hemato-Oncology University of MilanMilan 20122Italy Department of Urology University of NaplesFederico IlNaples 80138Italy

Sexual disorders following retroperitoneal pelvic lymph node dissection(RPLND)for testis tumor can affect the quality of life of patients.The aim of the current study was to investigate several different andrological outcomes,which may be influenced by robot-assisted(RA)RPLND.From January 2012 to March 2020,32 patients underwent RA-RPLND for stage I nonseminomatous testis cancer or postchemotherapy(PC)residual mass.Modified unilateral RPLND nerve-sparing template was always used.Major variables of interest were erectile dysfunction(ED),premature ejaculation(PE),dry ejaculation(DE),or orgasm alteration.Finally,fertility as well as the fecundation process(sexual intercourse or medically assisted procreation[MAP])was investigated.Ten patients(31.3%)presented an andrological disorder of any type after RA-RPLND.Hypospermia was present in 4(12.5%)patients,DE(International Index of Erectile Function-5[IIEF-5]<25)in 3(9.4%)patients,and ED in 3(9.4%)patients.No PE or orgasmic alterations were described.Similar median age at surgery,body mass index(BMI),number of nodes removed,scholar status,and preoperative risk factor rates were identified between groups.Of all these 10 patients,6(60.0%)were treated at the beginning of our robotic experience(2012-2016).Of all 32 patients,5(15.6%)attempted to have a child after RA-RPLND.All of these 5 patients have successfully fathered children,but 2(40.0%)required a MAP.In conclusion,a nonnegligible number of andrological complications occurred after RA-RPLND,mainly represented by ejaculation disorders,but ED occurrence and overall sexual satisfaction deficit should be definitely considered.No negative impact on fertility was described after RA-RPLND.

关键词： andrology lymph node excision nonseminomatous germ cell tumor robotics testicular cancer

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Kounis syndrome:a clinical entity penetrating from pediatrics to geriatrics

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Journal of Geriatric Cardiology 2020年第5期17卷 294-299页

作者： Mattia Giovannini Ioanna Koniari Francesca Mori Silvia Ricci Luciano De Simone Silvia Favilli Sandra trapani Giuseppe Indolfi Nicholas George Kounis Elio Novembre Allergy Unit Department of Pediatrics Meyer Children’s University Hospital Electrophysiology and Device Department University Hospital of South Manchester NHS Foundation Trust Department of Health Sciences University of Florence Meyer Children’s Hospital Pediatric Cardiology Unit Meyer Children’s University Hospital Department of Neurofarba University of Florence Meyer Children’s Hospital Department of Cardiology Patras University School of Medicine

1 Introduction Kounis syndrome constitutes a coronary hypersensitivity disorder defined by the association of an anaphylactoid,anaphylactic,allergic or hypersensitivity reaction with an acute coronary syndrome,in a physiopathological context involving various interrelated and interacting inflammatory cells,such as mast-cells,eosinophils and platelets.[1,2]Similar entities to Kounis syndrome might involve cerebral and mesenteric arteries.

关键词： Age Classification Coronary artery disease Kounis syndrome Myocardial infarction

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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 process.Around 90%of drugs entering clinical trials fail due to lack of efficacy and/or safety issues,more often after conspicuous research and economic efforts.Part 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 toxicities.The implementation of pharmacogenomic biomarkers allows the categorization of patients,to predict efficacy and toxicity and to optimize the drug development process.Around 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 care.In 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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Regulation and deregulation of cholesterol homeostasis: The liver as a metabolic "power station"

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World Journal of Hepatology 2012年第6期4卷 184-190页

作者： Laura trapani Marco Segatto Valentina Pallottini Department of Biology University Roma Tre Viale Marconi 446 00146 Rome Italy

Cholesterol plays several structural and metabolic roles that are vital for human biology. It spreads along the entire plasma membrane of the cell, modulating fluidity and concentrating in specialized sphingolipid-rich domains called rafts and caveolae. Cholesterol is also a substrate for steroid hormones. However, too much cholesterol can lead to pathological pictures such as atherosclerosis, which is a consequence of the accumu- lation of cholesterol into the cells of the artery wall. The liver is considered to be the metabolic power station of mammalians, where cholesterol homeostasis relies on an intricate network of cellular processes whose deregulations can lead to several life-threatening pathologies, such as familial and age-related hypercholesterolemia. Cholesterol homeostasis maintenance is carried out by: biosynthesis, via 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity; uptake, through low density lipoprotein receptors (LDLr); lipoprotein release in the blood; storage by esterification; and degradation and conversion into bile acids. Both HMGR and LDLr are transcribed as a function of cellular sterol amount by a family of transcription factors called sterol regulatory element binding proteins that are responsible for the maintenance of cholesterol homeostasis through an intricate mechanism of regulation. Cholesterol obtained by hepatic de novo synthesis can be esterified and incorporated into apolipoprotein B-100-containing very low density lipoproteins, which are then secreted into the bloodstream for transport to peripheral tissues. Moreover, dietary cholesterol is transferred from the intestine to the liver by high density lipoproteins (HDLs); all HDL particles are internalized in the liver, interacting with the hepatic scavenger receptor (SR-B1). Here we provide an updated overview of liver cholesterol metabolism regulation and deregulation and the causes of cholesterol metabolism-related diseases. Moreover, current pharmacological treatment and novel hypocho-lesterolemic strategie

关键词： Cholesterol 3-hydroxy-3-methylglutaryl coenzyme A reductase Hypercholesterolemia Low density lipoprotein receptors Liver

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New compounds able to control hepatic cholesterol metabolism:Is it possible to avoid statin treatment in aged people?

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World Journal of Hepatology 2013年第12期5卷 676-684页

作者： Laura trapani Marco Segatto Valentina Pallottini Department of Science Section Biomedical Science and TechnologiesUniversity Roma Tre

Aging is characterized by the loss of homeostasis that leads to changes in the biochemical composition of tissues, reduced ability to respond adaptively to en- vironmental stimuli, and increased susceptibility and vulnerability to diseases including coronary artery dis- eases, carotid artery disease and brain vessel disease. Hypercholesterolemia is one of the primary risk factors for these pathologies, whose incidence is highly related to aging. Almost 25% of men and 42% of women older than 65 years have a serum total cholesterol level greater than 240 mg/dL. The mechanisms behind this age-related increase in plasma cholesterol are still incompletely understood, thus, the control of plasma cholesterol content in aged people is more challenging than in adults. In this review the different pharmaco- logical approaches to reduce plasma cholesterol levels, particularly in aged people, will be discussed. In brief, current therapies are mostly based on the prescription of statins(3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) that are pretty effective but that exert sev- eral side effects. More attention should be given to po- tential drug interactions, potential age-related changes in drug pharmacokinetics, adverse effects such as my-opathy and competing risks when statins are prescribed to old patients. In combination or in alternative to sta- tin therapy, other agents might be required to reduce low density lipoprotein(LDL) cholesterol levels. Among the available drugs, the most commonly prescribed are those addressed to reduce cholesterol absorption, to modulate lipoprotein lipase activity and bile acid se- questrants: even these pharmacological interventions are not exempt from side effects. The use of antioxi- dants or organoselenium compounds and the discovery of new proteins able to modulate exclusively LDL re- ceptor recycling such as Proprotein convertase subtilisin kexin 9 and SEC24 offer new pharmacological approaches to selectively reduce the main causes of dyslipidemia.

关键词： Aging Cholesterol Hypercholesterolemia

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