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Ileal lesions in patients with ulcerative colitis after ileo-rectal anastomosis:Relationship with colonic metaplasia

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World Journal of Gastroenterology 2008年第34期14卷 5290-5300页

作者： Livia Biancone Emma Calabrese Giampiero Palmieri Carmelina Petruzziello Sara Onali Giuseppe Sigismondo Sica Marta Cossignani Giovanna Condino Kiron Moy Das Francesco Pallone Cattedra di Gastroenterologia Dipartimento di Medicina InternaUniversità di "Tor Vergata" Cattedra di Anatomia ed Istologia Patologica Università di "Tor Vergata" Cattedra di Gastroenterologia Dipartimento di Medicina InternaUniversità di "Tor Vergata" Cattedra di Chirurgia Generale Università di "Tor Vergata" Cattedra di Gastroenterologia Dipartimento di Medicina Interna Università di "Tor Vergata" GI Unit Department of Gastroenterology & Hepatology University of Medicine & Dentistry of New Brunswick

AIM:To assess whether in ulcerative colitis (UC) patients with ileo-rectal anastomosis (IRA), ileal lesions may develop in the neo-terminal-ileum and their possible relation with phenotypic changes towards colonic epithelium. METHODS: A total of 19 patients with IRA under regular follow up were enrolled, including 11 UC and 8 controls (6 Crohn’s disease, CD; 1 familial adenomatous polyposis, FAP; 1 colon cancer, colon K). Ileal lesions were identifi ed by ileoscopy with biopsies taken from the ileum (involved and uninvolved) and from the rectal stump. Staining included HE and immunohistochemistry using monoclonal antibodies against colonic epithelial protein CEP (Das-1) and human tropomyosin isoform 5, hTM5 (CG3). Possible relation between development of colonic metaplasia and ileal lesions was ***: Stenosing adenocarcinoma of the rectal stump was detected in 1 UC patient. The neo-terminal ileum was therefore investigated in 10/11 UC patients. Ileal ulcers were detected in 7/10 UC, associated with colonic metaplasia in 4/7 (57.1%) and Das-1 and CG3 reactivity in 3/4 UC. In controls, recurrence occurred in 4/6 CD, associated with colonic metaplasia in 3/4 and reactivity with Das-1 and CG3 in 2/3. CONCLUSION: Present fi ndings suggest that in UC, ileal lesions associated with changes towards colonic epithelium may develop also after IRA. Changes of the ileal content after colectomy may contribute to the development of colonic metaplasia, leading to ileal lesions both in the pouch and in the neo-terminal ileum after IRA.

关键词： Ulcerative colitis Ileo-rectal anastomosis Ileal lesions Colonic metaplasia

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When sepsis affects the heart: A case report and literature review

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World Journal of Clinical Cases 2015年第8期3卷 743-750页

作者： Giuseppe Clemente Antonino Tuttolomondo Daniela Colomba Rosaria Pecoraro Chiara Renda Vittoriano Della Corte Carlo Maida Irene Simonetta Antonio Pinto U.O.C.di medicina interna e Cardioangiologia University of Palermo

A 59-year-old nursing home patient with Down syndrome was brought to the internal medicine department of our hospital due to fever, cough without expectorate, and dyspnea. A thoracic computed tomography revealed the presence of bilateral basal parenchymal opacities. Her condition deteriorated after admission and troponin reached a peak serum concentration of 16.9 ng/m L. The patient was in cardiogenic shock. In addition to fluid resuscitation, vaso-active amine infusion was administered to achieve hemodynamic stabilization. The differential diagnosis investigated possible pulmonary embolism, myocardial infarction, and myocarditis. Furthermore, a second transthoracic echocardiogram suggested Tako-Tsubo syndrome. This is a septic patient. The purpose of this manuscript is to review studies which formerly examined the possible association between high levels of troponin and mortality to see if it can be considered a positive predictive factor of fatal prognosis as the case of thrombocytopenia, already a positive independent predictive factor of multiple organ failure syndrome, and generally to characterize risk profile in a septic patient.

关键词： Sepsis Shock Hypotension Troponin Myocardial dysfunction

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Biochemical mechanisms in drug-induced liver injury:Certainties and doubts

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World Journal of Gastroenterology 2009年第39期15卷 4865-4876页

作者： Ignazio Grattagliano Leonilde Bonfrate Catia V Diogo Helen H Wang David QH Wang Piero Portincasa Clinica Medica "A.Murri" Dipartimento di Medicina Interna e Medicina PubblicaUniversity of Bari Medical School department of Zoology Center for Neurosciences and Cell BiologyUniversity of Coimbra department of Medicine Liver Center and Gastroenterology DivisionBeth Israel Deaconess Medical CenterHarvard Medical School and Harvard Digestive Diseases Center

Drug-induced liver injury is a significant and still unresolved clinical problem. Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development. Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites. Aging, preexisting liver disease, enzyme induction or inhibition, genetic variances, local 02 supply and, above all, the intrinsic molecular properties of the drug may affect this process. Necrotic death follows antioxidant consumption and oxidation of intracellular proteins, which determine increased permeability of mitochondrial membranes, loss of potential, decreased ATP synthesis, inhibition of Ca^2＋-dependent ATPase, reduced capability to sequester Ca^2＋ within mitochondria, and membrane bleb formation. Conversely, activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis. Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage. Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis, in which different HLA genotypes might play a major role. This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage. Future perspectives including new frontiers for research are discussed.

关键词： Adverse effects Apoptosis Drug toxicity Liver diseases Microsomes Mitochondria Necrosis

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Clinical features and epidemiology of spondyloarthritides associated with inflammatory bowel disease

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World Journal of Gastroenterology 2009年第20期15卷 2449-2455页

作者： Carlo Salvarani Walter Fries Rheumatology Unit Department of Interna Medicine department of internal Medicine and MedicaTherapy University of Messina

Inflammation of axial and/or peripheral joints is one of the most frequent extra-intestinal manifestations complicating the clinical course and therapeutic approach in inflammatory bowel diseases(IBD).The frequency of these complications seems to be similar for both diseases, Crohn's disease and ulcerative *** associated with IBD belongs to the category of *** involvement ranges from isolated inflammatory back pain to ankylosing spondylitis, whereas peripheral arthritis is noted in pauciarticular and in polyarticular *** radiological involvement of the sacroiliac joints is reported to occur in up to 50% of *** musculoskeletal manifestations such as buttock pain, dactylitis, calcaneal enthesitis, and thoracic pain are frequently underdiagnosed and, consequently, are not treated *** diagnostic approaches and criteria have been proposed over the past 40 years in an attempt to correctly classify and diagnose such *** correct recognition of spondylarthropathies needs an integrated multidisciplinary approach in order to identify common therapeutic strategies, especially in the era of the new biologic therapies.

关键词： Crohn disease Ankylosing spondylitis Ulcerative colitis Spondylarthropathies Arthritis Enthesopathy

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Gastric cancer and the epoch of immunotherapy approaches

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World Journal of Gastroenterology 2015年第19期21卷 5778-5793页

作者： Elena Niccolai Antonio Taddei Domenico Prisco Amedeo Amedei department of Experimental and Clinical Medicine University of Florence department of Surgery and Translational Medicine University of Florence department of Biomedicine Azienda Ospedaliera Universitaria Careggi SOD medicina interna Interdisciplinare-DAI Neuromuscoloscheletrico e degli organi di senso Azienda Ospedaliera Universitaria Careggi

The incidence of gastric cancer(GC) fell dramatically over the last 50 years, but according to IARC-Globocan 2008, it is the third most frequent cause of cancerrelated deaths with a case fatality GC ratio higher than other common malignancies. Surgical resection is the primary curative treatment for GC though the overall 5-year survival rate remains poor(approximately 20%-25%). To improve the outcome of resectable gastric cancer, different treatment strategies have been evaluated such as adjuvant or perioperative chemotherapy. In resected gastric cancer, the addition of radiotherapy to chemotherapy does not appear to provide any additional benefit. Moreover, in metastatic patients, chemotherapy is the mainstay of palliative therapy with a median overall survival of 8-10 mo and objective response rates of merely 20%-40%. Therefore, the potential for making key beneficial progress is to investigate the GC molecular biology to realize innovative therapeutic strategies, such as specific immunotherapy. In this review, we provide a panoramic view of the different immune-based strategies used for gastric cancer treatment and the results obtained in the most significant clinical trials. In detail, firstly we describe the therapeutic approaches that utilize the monoclonal antibodies while in the second part we analyze the cell-based immunotherapies.

关键词： Gastric cancer Immunotherapy Monoclonalantibodies T cells Dendritic cells NK cells

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Beyond the joint: Subclinical atherosclerosis in rheumatoid arthritis

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World Journal of Orthopedics 2014年第3期5卷 328-335页

作者： Antongiulio Scarno Fabio Massimo Perrotta Francesca Cardini Alessia Carboni Gianmarco Annibali Ennio Lubrano Antonio Spadaro UOC medicina E Dipartimento di Medicina Interna e Specialità MedicheSapienza-Università di Roma-Azienda Policlinico Umberto I00161 RomeItaly UOC di Reumatologia Dipartimento di Medicina Interna e Specialità MedicheSapienza-Università di Roma - Azienda Policlinico Umberto I00161 RomeItaly Academic Rheumatology Unit Department of Medicine and Health SciencesUniversity of Molise86100 CampobassoItaly

Rheumatoid arthritis is a chronic autoimmune inflammatory disease associated with increased cardiovascular risk and higher mortality in respect to general *** joint disease,inflammation is the major determinant of accelerated atherosclerosis observed in rheumatoid *** review the relationship between inflammation,atherosclerosis and cardiovascular risk in rheumatoid arthritis,focusing on the assessment of subclinical atherosclerosis by functional and morphological *** tools include flow mediated dilatation,carotid intima-media thickness,ankle/brachial index,coronary calcium content,pulse wave analysis and serum biomarker of subclinical atherosclerosis.

关键词： Atherosclerosis Rheumatoid arthritis Flow mediated dilatiation Intima-media thickness Inflammation

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Gut epithelial barrier dysfunction in humanimmunodeficiency virus-hepatitis C virus coinfectedpatients:Influence on innate and acquired immunity

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World Journal of Gastroenterology 2016年第4期22卷 1433-1448页

作者： Mercedes Márquez Clotilde Fernández Gutiérrez delÁlamo JoséAntonio Girón-González department of internal Medicine Infectious Disease UnitPuerta del Mar University HospitalUniversity of Cadiz11009 CádizSpain Servicio de medicina interna Hospital Universitario Puerta del Mar11009 CádizSpain

Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus(HIV)-infected patients have several non-acquired immunodeficiency syndrome(AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus(HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.

关键词： human immunodeficiency virus infection hepatitis C virus infection Innate immunity Acquiredimmunity Gut barrier

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Clinical impact of selective transarterial chemoembolization on hepatocellular carcinoma:A cohort study

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World Journal of Gastroenterology 2009年第15期15卷 1843-1848页

作者： Rodolfo Sacco Marco Bertini Pasquale Petruzzi Michele Bertoni Irene Bargellini Giampaolo Bresci Graziana Federici Luigi Gambardella Salvatore Metrangolo Giuseppe Parisi Antonio Romano Antonio Scaramuzzino Emanuele Tumino Alessandro Silvestri Emanuele Altomare Claudio Vignali Alfonso Capria Gastroenterology department Pisa University Hospital Institute of interna Medicine University of Foggia department of Diagnostic and Interventional Radiology Pisa University Hospital

AIM： To prospectively long term clinical impact evaluate the short and of selective transarterial chemoembolization （TACE） on fiver function in patients with hepatocellular carcinoma （HCC）. To assess side effects in relation to treatments. To analyze the overall survival and HCC progression free survival probability. METHODS： One hundred and seventeen cirrhotic patients with HCC were enrolled. Baseline liver function included Child-Pugh score and serum levels of alanine- aminotransferase （ALT）, prothrombin time （PT） and bilirubin. According to Cancer Liver Italian Program （CLIP） and Barcelona Clinic Liver Cancer （BCLC） staging systems, 71 patients were eligible for TACE; 32 had previously received treatment for HCC. No significant differences in liver function were observed between previously treated and not treated patients. TACE was performed by selective catheterization of the arteries nourishing the lesions. While hospitalized, patients underwent clinical, hematologic and ultrasonographic assessments. One month after TACE a CT scan was performed to assess tumor response. A second TACE was performed ＂on demand＂ Liver function tests were checked in all patients every four months. RESULTS： After first TACE, the mean Child-Pugh score increased from a mean baseline 5.62 ±1.12 to 6.11 ±1.57 at discharge time （P 〈 0.0001）, decreasing after four months to 5.81 ± 0.73 （not significant）. ALT, PT and bilirubin significantly （P 〈 0.0001） increased 24 h after TACE and progressively decreased until discharge. After the second TACE, variations in Child-Pugh score, ALT, PT and bilirubin were comparable to that described after the first TACE. No major complications were observed. The mean follow-up was 14.7 ＋ 6.3 mo （median： 16 mo）. Only one patient died. No other patient experienced important long term worsening of clinical status. The overall survival probability at twenty-four months was 98.18% with a correspondent HCC progression free survival probability of 69%. CONCLUSION：

关键词： Hepatocellular carcinoma Transarterialchemoembolization Liver function Liver cirrhosis Child-Pugh score

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Management of portopulmonary hypertension:New perspectives

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World Journal of Gastroenterology 2013年第45期19卷 8252-8257页

作者： Luigi Mancuso Francesca Scordato Michela Pieri Eliana Valerio Andrea Mancuso department of Cardiologia Ospedale Cervello90100 Palermo Italy Cardiologia Clinica Candela 90100 Palermo Italy Epatologia e Gastroenterologia Ospedale Niguarda Cà Granda Milano 20162 Milano Italy medicina interna 1 ARNAS Civico 90100 Palermo Italy

Portopulmonary hypertension(PPHTN)is a known complication of ***-to-severe PPHTN implies an extremely poor *** occurs in 5%-10%of patients referred for liver transplantation(LT),and probably with an higher incidence in patients with large portosystemic *** with moderate-tosevere pulmonary hypertension have been previously excluded from LT because of the extremely high surgical risk and since the post-transplant outcome reported was ***,new perspectives in the management of patients with portopulmonary hypertension are *** fact,some pulmonary vasoactive drugs have become routine in the treatment of patients with idiopathic pulmonary *** drugs,particularly epoprostenol,have been recently introduced in the treatment of patients with PPHTN,and have been shown to be effective in reducing pulmonary artery pressure as well as pulmonary vascular ***,recent studies seem to demonstrate that treatment with pulmonary vasoactive drugs could allow liver transplantation with acceptable surgical risks and excellent *** there are not large series nor prospective studies addressing this topic,the clinical scenario of patients with PPHTN seems to be positively changing.

关键词： Portopulmonary hypertension Cirrhosis Liver transplantation Management Epoprostenol

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Metabolic shift in liver: Correlation between perfusion temperature and hypoxia inducible factor-1α

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World Journal of Gastroenterology 2015年第4期21卷 1108-1116页

作者： Andrea Ferrigno Laura Giuseppina Di Pasqua Alberto Bianchi Plinio Richelmi Mariapia VairettiAndrea Ferrigno Unit of Cellular and Molecular Pharmacology and Toxicology Department of Interna Medicine and TherapeuticsUniversity of PaviaPavia 27100 Italy

AIM: To study at what temperature the oxygen carried by the perfusate meets liver requirements in a model of organ perfusion. METHODS: in this study, we correlated hypoxia induciblefactor(Hi F)-1α expression to the perfusion temperature and the hepatic oxygen uptake in a model of isolated perfused rat liver. Livers from Wistar rats were perfused for 6 h with an oxygenated medium at 10, 20, 30 and 37 ℃. Oxygen uptake was measured by an oxygen probe; lactate dehydrogenase activity, lactate release and glycogen were measured spectrophotometrically; bile flow was gravitationally determined; p H of the perfusate was also evaluated; Hi F-1α m RNA and protein expression were analyzed by real time-polymerase chain reaction and ELi SA, respectively. RESULTS: Livers perfused at 10 and 20 ℃ showed no difference in lactate dehydrogenase release after 6 h of perfusion(0.96 ± 0.23 vs 0.93 ± 0.09 m U/min per g) and had lower hepatic damage as compared to 30 and 37 ℃(5.63 ± 0.76 vs 527.69 ± 45.27 m U/min per g, respectively, P s < 0.01). After 6 h, tissue ATP was significantly higher in livers perfused at 10 and 20 ℃than in livers perfused at 30 and 37 ℃(0.89 ± 0.06 and 1.16 ± 0.05 vs 0.57 ± 0.09 and 0.33 ± 0.08 nmol/mg, respectively, P s < 0.01). No sign of hypoxia was observed at 10 and 20 ℃, as highlighted by low lactate release respect to livers perfused at 30 and 37 ℃(121.4 ± 12.6 and 146.3 ± 7.3 vs 281.8 ± 45.3 and 1094.5 ± 71.7 nmol/m L, respectively, P s < 0.02), and low relative Hi F-1α m RNA(0.40 ± 0.08 and 0.20 ± 0.03 vs 0.60 ± 0.20 and 1.47 ± 0.30, respectively, P s < 0.05) and protein(3.72 ± 0.16 and 3.65 ± 0.06 vs 4.43 ± 0.41 and 6.44 ± 0.82, respectively, P s < 0.05) ***: Livers perfused at 10 and 20 ℃ show no sign of liver injury or anaerobiosis, in contrast to livers perfused at 30 and 37 ℃.

关键词： Anaerobiosis Hypoxia inducible factor-1 α ischemia

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