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Incidentally Discovered Hcc (iHcc) in Explant Liver-Histopathologic Features and clinical Outcome

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Journal of cancer Therapy 2013年第2期4卷 394-398页

作者： Renumathy Dhanasekaran Davinderbir S. Pannu Alpna Limaye Ivan Zendejas Roberto J. Firpi consuelo Soldevila-Pico giuseppe Morelli Virginia c. clark Amitabh Suman David R. Nelson Roniel cabrera Department of Medicine University of Florida Gainesville USA Department of Surgery University of Florida Gainesville USA Division of Gastroenterology Hepatology and Nutrition University of Florida Gainesville USA

Incidentally discovered hepatocellular carcinomas (iHcc) are tumors which are discovered on the explanted liver which were not present on imaging prior to transplant. The natural history, histopathologic characteristics and prognosis of iHcc are not clearly defined. Methods: A retrospective analysis was performed to compare the characteristics of iHcc and established Hcc within Milan criteria (eHcc) in patients who underwent liver transplantation at our center between 2000 and 2010. Results: During the study period a total of 975 adult patients were transplanted in our center;124 (12.7%) patients had eHcc and 26 (2.6%) patients had iHcc. A larger number of patients with iHcc (73.1%) had ascites when compared to eHcc (41.3%) (p = 0.035). Patients with iHcc had a higher mean bilirubin (p 0.001) and mean INR (p = 0.05) than patients with eHcc. Around 70% of patients with iHcc had a Model for End Stage Liver Disease (MELD) score greater than 15 at the time of listing while only 25% of patients with eHcc had a MELD greater than 15 at listing (p 0.001).The mean alphafetoprotein (AFP) in patients with iHcc was significantly lower (11.6 ± 16.5) than the patients with eHcc (564.9 ± 2180;p = 0.024). In patients with iHcc, 30.8% had a multiple tumors and 23% had bilobar involvement. The average number of tumors was 1.6 and the cumulative tumor size was 2.1 cm (SD 1.4). The cumulative tumor size in iHcc was significantly smaller than in eHcc (mean 3.9 cm) (p = 0.035). American Joint committee on cancer (AJcc) T1 tumor stage was found in 58% of patients with iHcc and 48.4% of patients with eHcc (p = 0.829).The median survival was 9.47 years for iHcc (95% cI 7.0 - 11.9) and 8.7 years (95% cI 6.1 - 11.4) for eHcc (p = 0.328). While none of the patients with iHcc had recurrence of Hcc, the incidence of recurrence in patients with eHcc was 6.4%. conclusion: iHcc occurred in patients with more advanced liver disease than eHcc. AFP was usually not elevated in patients with iHcc. The c

关键词： Incidental Hcc Recurrence Survival

New Molecular Targets in Metastatic Prostate cancer

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Journal of cancer Therapy 2016年第6期7卷 388-401页

作者： Francesco Pantano Giulia Ribelli Michele Iuliani Marco Fioramonti Mark Leakos Alice Zoccoli Daniele Santini Giovanni Muto giuseppe Tonini Medical Oncology Campus Bio-Medico University of Rome Rome Italy Translational Oncology Laboratory Campus Bio-Medico University of Rome Rome Italy Department of Urology Campus Bio-Medico University of Rome Rome Italy

Prostate cancer (Pca) is the second leading cause of cancer death in men. Despite initial responses, almost all patients progress to castration-resistant prostate cancer (cRPc). Over the past decade, increased understanding of the mechanisms that drive resistance to castration has led to the development of next-generation androgen receptor targeting agents such as abiraterone acetate and enzalutamide. Moreover in the last few years, results from large Phase III trials led to the approval of an α-emitter (radium-223), the bone resorption-targeting drug denosumab and an immunotherapy (sipuleucel-T) that showed improvements in terms of overall survival. In the field of metastatic cRPc, other novel therapeutics have recently been proven to extend survival via distinct mechanisms of action such as the new and more potent classes of androgen inhibitors, ortonel, ARN-509 and galeterone, the endothelin A receptor antagonist zibotentan, the Src inhibitor dasatinib, the c-MET inhibitor cabozantinib and the immune checkpoint inhibitor ipilimumab. This review aims to revisit the evolution of androgen receptor targeting therapeutics and to discuss other important alternative biologic pathways that have given rise to new agents in metastatic prostate cancer.

关键词： Prostate cancer Target Therapy

Primary clarithromycin resistance to Helicobacter pylori : Is this the main reason for triple therapy failure?

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World Journal of Gastrointestinal Pathophysiology 2013年第3期4卷 43-46页

作者： Floriana Giorgio Mariabeatrice Principi Vincenzo De Francesco Angelo Zullo giuseppe Losurdo Alfredo Di Leo Enzo Ierardi Division of Gastroenterology Department of Medical and Surgical Sciences University of Foggia 71100 Foggia Italy Division of Gastroenterology Department of Emergency and Organ Transplantation University of Bari 70124 Bari Italy Department of Gastroenterology and Digestive Endoscopy 'Nuovo Regina Margherita' Hospital 00153 Rome Italy

conventional triple therapies for Helicobacter pylori (H. pylori ) eradication have recently shown a disappointing reduction in effectiveness in many countries. The main reason for failure was found to be bacterial resistance to one of the most commonly used antibiotics, clarithromycin. An additional problem for conventional triple therapy is the high rate of resistance to metronidazole found in Europe, America and Asia. In Italy, in the last 15 years a 2-fold increase in resistance has occurred. A recent study of the whole of Italy included about 20 patients from each region at the first endoscopic diagnosis of H. pylori infection. The most surprising result was the patchy distribution of resistance, which was almost absent in two regions (one northern and one southern), although the highest prevalence was found in some regions of the South. In the paediatricpopulation we found a 25% prevalence of resistance in a sample of H. pylori positive children observed between 2002 and 2007, mirroring data obtained in southern European countries. clarithromycin resistance assessment is currently based on phenotypic detection performed after culture the agar dilution method or E-test, and genotypic methods based on polymerase chain reaction (PcR). In a recent comparative study we found a 71.2% agreement between the two methods. culture-free techniques are highly accurate in finding even minimal traces of genotypically resistant strains. Moreover, PcR-based tools are accurate in detecting a heteroresistant status, defined as the co-existence of some strains that are susceptible and some resistant to the same antibiotic in an individual patient. Three point mutations, namely A2143G , A2142G and A2142c , are responsible for 90% of cases of primary clarithromycin resistance in H. pylori strains isolated in Western countries, although we previously demonstrated that the presence of the A2143G mutation, but not A2142G or A2142c , significantly lowered the H. pylori eradication rate

关键词： Helicobacter pylori clarithromycin Genotypic resistance Phenotypic resistance Therapy failure cost Resistance epidemiology

THE cONTRIBUTION OF ELEcTRIcAL cONDUcTIVITY,DIELEcTRIc PERMITTIVITY AND DOMAIN SWITcHING IN FERROELEcTRIc HYSTERESIS LOOPS

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Journal of Advanced Dielectrics 2011年第1期1卷 107-118页

作者： HAIXUE YAN FAWAD INAM giuseppe VIOLA HUANPO NING HONGTAO ZHANG QINGHUI JIANG TAO ZENG ZHIPENG GAO MIKE J REEcE School of Engineering and Materials Science Queen Mary University of London Mile End Road LondonE14NSUK Nanoforce Technology Ltd Mile End Road LondonE14NSUK Department of Materials University of Oxford OxfordOX13PHUK School of Materials Science and Engineering University of Jinan Shandong 250022P.R.China

Triangular voltage waveform was employed to distinguish the contributions of dielectric permittivity,electric conductivity and domain switching in current-electricfield *** the same time,it is shown how those contributions can affect the shape of the electric displacement-electricfield loops(D-E loops).The effects of frequency,temperature and microstructure(point defects,grain size and texture)on the ferroelectric properties of several ferroelectric compositions is reported,***_(3);lead zirconate titanate(PZT);lead-free Na_(0.5)K_(0.5)NbO_(3);perovskite-like layer structured A_(2)B_(2)O_(7)with super high curie point(T_(c));Aurivillius phase ferroelectric Bi_(3.15)Nd_(0.85)Ti_(3)O_(12);and multiferroic Bi_(0.89)La_(0.05)Tb_(0.06)FeO_(3).This systematic study provides an instructive outline in the measurement of ferroelectric properties and the analysis and interpretation of experimental data.

关键词： Polarization ferroelectrics conductivity permittivity domain

chronic hepatitis c:This and the new era of treatment

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World Journal of Hepatology 2016年第2期8卷 92-106页

作者： Gaetano Bertino Annalisa Ardiri Maria Proiti giuseppe Rigano Evelise Frazzetto Shirin Demma MariaIrene Ruggeri Laura Scuderi Giulia Malaguarnera Nicoletta Bertino Venerando Rapisarda Isidoro Di carlo Adriana Toro Federico Salomone Mariano Malaguarnera Emanuele Bertino Michele Malaguarnera Hepatology Unit-Department of clinical and Experimental Medicine University of Catania95123 CataniaItaly Internal Medicine Unit ARNAS Civic Hospital90142 PalermoItaly Research centre“La Grande Senesce” University of Catania95100 CataniaItaly Department of Biomedical Sciences University of Catania95100 CataniaItaly Faculty of Pharmacy University of Catania95123 CataniaItaly Occupational Medicine Unit Department of Clinical and Experimental MedicineUniversity of Catania95100 CataniaItaly Department of Surgical Sciences Organ Transplantation and Advanced TechnologiesUniversity of Catania95100 CataniaItaly Gastroenterology Unit Acireale Hospital95024 AcirealeCataniaItaly

Over the last years it has started a real revolution in the treatment of chronic hepatitis c. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects.

关键词： Direct-acting antiviral agents Nucleosideinhibitors Boceprevir Sofosbuvir Telaprevir Hepatitisc Simeprevir Daclatasvir Ledipasvir Faldaprevir Ritonavir Ombitasvir Dasabuvir

Future Directions in Metastatic castration Resistant Prostate cancer (mcRPc): clinical Rationale and Use of New-Generation Hormonal Therapies

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Journal of cancer Therapy 2013年第3期4卷 698-703页

作者： Paolo Grassi Elena Verzoni Rosanna Montone Isabella Testa Enrico Garanzini Pamela Biondani Sara Pusceddu Filippo de Braud giuseppe Procopio Department of Medical Oncology Fondazione IRCCS Istituto Nazionale Tumori Milan Italy

Several recent studies in mcRPc have identified the mechanisms of tumoral growth after the disease becomes unresponsive to standard hormonal therapy. These studies have highlighted the importance of residual intratumoral androgens in maintaining androgen receptor (AR) transcriptional activity in mcRPc [1]. Based on this findings, it has been possible to develop drugs, blocking the key enzyme in the biosynthesis of androgens through the inhibition of cytochrome p450 17 (cYP17) such as Abiraterone Acetate (AA) and drugs which directly target the AR including Enzalutamide (E) and Orteronel. Before this new knowledge, mcRPc treatment benefited from chemotherapy with taxanes. Recently a new taxane, cabazitaxel (c), was approved in second line setting in association with prednisone. Retrospective analyses have tried to clarify the current role of chemotherapy in mcRPc patients and the right chemotherapy sequence of use of chemotherapy compared to new hormonal agents. Moreover, it would be important to address changes in the endpoints used in clinical trials, based on the stage of disease including the presence tumor-related symptoms, in order to identify the right therapeutic strategy.

关键词： Metastatic castration Resistant Prostate cancer Abiraterone cabazitaxel Enzalutamide

Systemic inflammation and immune response after laparotomy vs laparoscopy in patients with acute cholecystitis, complicated by peritonitis

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World Journal of Gastrointestinal Surgery 2013年第4期5卷 73-82页

作者： Federico Sista Mario Schietroma giuseppe De Santis Antonella Mattei Emanuela Marina cecilia Federica Piccione Sergio Leardi Francesco carlei Gianfranco Amicucci Department of Surgery University of L'Aquila Department of Medicine Health and Environment Sciences University of L'Aquila

AIM: To evaluate acute cholecystitis, complicated by peritonitis, acute phase response and immunological status in patients treated by laparoscopic or open approach. METHODS: From January 2002 to May 2012, we conducted a prospective randomized study on 45 consecutive patients (27 women, 18 men; mean age 58 years). These subjects were taken from a total of 681 patients who were hospitalised presenting similar preoperative findings: acute upper abdominal pain with tenderness, involuntary guarding under the right hypochondrium and/or in the flank; fever higher than 38 ℃, leukocytosis greater than 10 × 10 9 /L or both, and ultrasonographic evidence of calculous cholecystitis possibly complicated by peritonitis. These patients had undergone cholecystectomy for acute calculous cholecystitis,complicated by bile peritonitis. Randomly, 23 patients were assigned to laparoscopic cholecystectomy (Lc), and 22 patients to open cholecystectomy (Oc). Blood samples were collected from all patients before operation and at days 1, 3 and 6 after surgery. Serum bacteraemia, endotoxaemia, white blood cells (WBcs), WBc subpopulations, human leukocyte antigen-DR (HLA-DR), neutrophil elastase, interleukin-1 (IL-1) and IL-6, and c-reactive protein (cRP) were measured at 0, 30, 60, 90, 120 and 180 min, at 4, 6, 12, 24 h, and then daily (8 A.M.) until post-operative day ***: The two groups were comparable in the severity of peritoneal contamination as indicated by the viable bacterial count (open group = 90% of positive cultures vs laparoscopic group = 87%) and endotoxin level (open group = 33.21 ± 6.32 pg/mL vs laparoscopic group = 35.02 ± 7.23 pg/mL). Four subjects in the Oc group (18.1%) and 1 subject (4.3%) in the Lc group (P cess. Severe leukocytosis (range 15.8-19.6/mL) was observed only after Oc but not after Lc, mostly due to an increase in neutrophils (days 1 and 3, P c and

关键词： Systemic inflammation Immune response Laparoscopy cholecystectomy Bile peritonitis

Microscopic colitis in patients with mild duodenal damage:A new clinical and pathological entity(“lymphocytic enterocolitis”)?

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World Journal of Gastrointestinal Pathophysiology 2016年第4期7卷 307-313页

作者： Gabriele Antonio Bonagura Davide giuseppe Ribaldone Sharmila Fagoonee Nicoletta Sapone Gian Paolo caviglia Giorgio Maria Saracco Marco Astegiano Rinaldo Pellicano Unit of Gastroenterology and Hepatology Molinette Hospital Institute for Biostructures and Bioimages-cNR c/o Molecular Biotechnology center University of Torino Department of Medical Sciences University of Turin Department of Oncology University of Torino

AIM To evaluate the potential association between mild duodenal damage and microscopic colitis(Mc).METHODS We retrospectively included 105 consecutive patients with type I Marsh-Oberhuber duodenal damage and negativity for immunoglobulin A anti-endomysium and anti-tissue *** following parameters were analyzed:Sex,age at execution of esophagogastroduodenoscopy,duodenal damage,and number of intraepithelial lymphocytes at biopsies,prevalenceof Helicobacter pylori infection,age at execution of colonoscopy,macroscopic and microscopic features of colonoscopy,family history of gastrointestinal and autoimmune diseases,smoking habits,biochemical parameters of inflammation and autoimmunity,use of proton pump inhibitors or nonsteroidal anti-inflammatory drugs,adverse reactions to drugs or foods,pathologies known to be associated with celiac disease or Mc,living on a gluten-free diet or on a gluten-low diet for at least 1 *** colonoscopy was performed in 59 patients,but only in 48 of them biopsies were taken in the entire *** the latter cohort,the diagnosis of Mc was met in 25(52.1%) patients while in 18 patients other pathologic findings were reported:13(27%) cases of nonspecific inflammatory bowel disease,2(4.2%) cases of crohn's disease,2(4.2%) cases of eosinophilic gastroenteritis,and 1(2.1%) case of autoimmune ***(10.4%) patients had a normal colonoscopic *** the groups by age,and considering only patients who underwent colonoscopy(42.7 ± 15.5 years) vs those who did not undergo colonoscopy(36.9 ± 10.6 years),a statistical difference was found(P = 0.039).Focusing on symptoms,diarrhea was statistically more prevalent in Mc group than in patients who did not undergo colonoscopy(P = 0.03).cONcLUSION Mild duodenal damage is associated with Mc in more than half of the *** association supports the hypothesis of a link between these two entities.

关键词： Autoimmune diseases celiac disease Helicobacter pylori Intraepithelial lymphocytes Lymphocytic colitis Lymphocytic enterocolitis Microscopic colitis

Hepatocellular carcinoma and the risk of occupational exposure

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World Journal of Hepatology 2016年第13期8卷 573-590页

作者： Venerando Rapisarda carla Loreto Michele Malaguarnera Annalisa Ardiri Maria Proiti giuseppe Rigano Evelise Frazzetto Maria Irene Ruggeri Giulia Malaguarnera Nicoletta Bertino Mariano Malaguarnera Vito Emanuele catania Isidoro Di carlo Adriana Toro Emanuele Bertino Dario Mangano Gaetano Bertino Occupational Medi-cine Unit Department of Clinical and Experimental MedicineUniversity of Catania Department of Biomedical Sciences Human Anatomy and Histology Section University of Catania Department of Biomedical Sciences University of Catania Hepatology Unit Department of Clinical and Experimental Medicine University of Catania Internal Medicine Unit ARNAS civic Hospital Research centre "La Grande Senescenza" University of Catania Faculty of Pharmacy University of Catania Department of Surgical Sciences Organ Transplantation and Advanced TechnologiesUniversity of Catania

Hepatocellular carcinoma(Hcc)is the most common type of liver *** main risk factors for Hcc are alcoholism,hepatitis B virus,hepatitis c virus,nonalcoholic steatohepatitis,obesity,type 2 diabetes,cirrhosis,aflatoxin,hemochromatosis,Wilson’s disease and *** exposure to chemicals is another risk factor for *** the relationship between occupational risk and Hcc is unclear and the reports are fragmented and *** review aims to summarize the current knowledge regarding the association of infective and non-infective occupational risk exposure and Hcc in order to encourage further research and draw attention to this global occupational public health problem.

关键词： Hepatocellular carcinoma Autophagy Epigenetic events Hepatitis B virus Hepatitis c virus Occupational exposure chemical agents Mitophagy Arsenic cadmium