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Low utility of plasma Nociceptin/orphanin FQ in the diagnosis of hepatocellular carcinoma

World Journal of Gastroenterology 2006年第29期12卷 4716-4720页

作者： Aldo Spadaro Antonino Ajello Carmelo Luigiano Carmela Morace Maria Letizia Resta Grazia Berlinghieri Salvatore Campo Claudio Scisca Angela Alibrandi Graziella D'arrigo Nunziata Alessi Oscar Ferraù Maria Antonietta Freni Dipartimento Clinico Sperimentale di Medicina e Farmacologia clinica medica Pad.CAOUVia Consolare Valeria No.1Messina 98125Italy

AIM： The utility of serum alpha-fetoprotein （α-FP） in the detection of hepatocellular carcinoma （HCC） is questionable. Very high circulating levels of nociceptin/ orphanin FQ （N/OFQ）, a ligand for a novel opioid receptor, have recently been reported in HCC. The aim of this study was to assess the role of plasma N/OFQ in the diagnosis of HCC arising in patients with liver cirrhosis. MeTHODS： Plasma N/OFQ levels were measured by eLISA in 58 patients （28 HCC and 30 liver cirrhosis） and in 25 healthy controls. The values were correlated with clinical and laboratory features including α-FP. Spearman index, biserial correlation coefficient, non parametric combination （NPC） test and discriminant stepwise analysis were used for statistical evaluation of data.ReSULTS： The upper normal limit of nociceptin was 122 pg/mL. Plasma levels above this cut-off were found in 21.4% of patients with HCC, in 23.3% of those with cirrhosis and in 8% of healthy subjects. α-FP serum levels〉200 ng/mL were found in 46.4% of the patients with HCC and in none of those with cirrhosis. No correlation was found between N/OFQ levels and any of the clinical and laboratory features, including α-FP. By NPC test, HCC and cirrhotic patients were different with regard to α-FP （P = 0.000） but not in terms of nociceptin （P = 0.595）. By point biserial correlation, HCC presence was positively correlated with α-FP （rpb = 0.52, P = 0.000） but not with N/OFQ （rpb = 0.16, P = 0.157）. In a discriminant analysis, α-FP was significant in the Wilks test （Y = -0.709 ＋ 0.03 α-FP） and properly classified 81% of all patients and 61% of HCC. N/OFQ had lower sensitivity, specificity and predictive values than α-FP. CONCLUSION： Nociceptin is increased in patients with chronic liver disease, independently of the presence of HCC, although the underlying mechanism has yet to be clarified. We conclude it is not a useful marker for HCC.

关键词： Hepatocellular carcinoma Nociceptin/orphanin FQ Liver cirrhosis Alpha-fetoprotein

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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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Adalimumab efficacy in enteropathic spondyloarthritis: A 12-mo observational multidisciplinary study

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World Journal of Gastroenterology 2017年第39期23卷 7139-7149页

作者： Michele Maria Luchetti Devis Benfaremo Francesco Ciccia Laura Bolognini Monia Ciferri Alessia Farinelli Matteo Rossini Piergiorgio Mosca Giovanni Triolo Armando Gabrielli Dipartimento Scienze Cliniche e Molecolari Clinica MedicaUniversità Politecnica delle Marche Dipartimento Biomedico di Medicina Interna e Specialistica Sezione di Reumatologia Università degli Studi di Palermo Dipartimento Gastro-enterologico e dei Trapianti Polo Ospedaliero--Universitario 'Umberto I-G.M. Lancisi- G. Salesi'

AIM To report adalimumab(Ada) efficacy on articulargastrointestinal disease and health-related quality of life(HRQo L) in patients with enteropathic spondyloarthritis(eS).MeTHODS A cohort of 52 patients with eS was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes(PROs) of the HRQo L questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor(TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests:(1) Ankylosing Spondylitis Disease Activity ScoreC-Reactive Protein(ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index(BASDAI), Bath Ankylosing Spondylitis Functional Index(BASFI) and Bath Ankylosing Spondylitis Metrology Index(BASMI) for articular activity;(2) Inflammatory Bowel Disease Questionnaire(IBDQ), Crohn's Disease Activity Index(CDAI) and partial Mayo(p Mayo) score for gastrointestinal symptoms and activity; and(3) Health Assessment Questionnaire(HAQ), Patient Global Assessment(PGA) and Short Form-36 health survey(SF-36) questionnaires for PROs of the HRQo *** Integrated evaluation and management of the patients affected by eS, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 eS patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQo L scores, showed a significant improvement having been achieved at the earli

关键词： Clinimetric assessment Patient reported outcomes Inflammatory bowel diseases enteropathic spondyloarthritis Tumor necrosis factor-inhibitors Multidisciplinary evaluation

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Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib

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World Journal of Gastroenterology 2014年第3期20卷 786-794页

作者： Andrea L Inghilesi Donatella Gallori Lorenzo Antonuzzo Paolo Forte Daniela Tomcikova Umberto Arena Stefano Colagrande Silvia Pradella Bernardo Fani elena Gianni Luca Boni Giacomo Laffi Francesco Di Costanzo Fabio Marra Dipartimento di Medicina Sperimentale e clinica Università degli Studi di Firenze Oncologia medica Azienda Ospedaliero-Universitaria Careggi Gastroenterologia 2 Azienda Ospedaliero-Universitaria Careggi Centro per il Coordinamento delle Sperimentazioni Cliniche Istituto Toscano Tumoriand Azienda Ospedaliero-Universitaria Careggi Dipartimento di Scienze Biomediche Sperimentali e ClinicheUniversità degli Studi di Firenze

AIM: To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma (HCC) in patients with established cirrhosis.

关键词： Hepatocellular carcinoma Sorafenib Cirrhosis Adverse events Barcelona Clinic Liver Cancer

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Post-transplantation hepatocellular carcinoma recurrence: Patterns and relation between vascularity and differentiation degree

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World Journal of Hepatology 2015年第2期7卷 276-284页

作者： Annarita Pecchi Giulia Besutti Mario De Santis Cinzia Del Giovane Sofia Nosseir Giuseppe Tarantino Fabrizio Di Benedetto Pietro Torricelli Dipartimento di Diagnostica per Immagini Azienda Ospedaliero-Universitaria Policlinico di Modena Unità di Statistica medica Dipartimento di Medicina Diagnostica Clinica e Sanità Pubblica Università di Modena e Reggio Emilia Dipartimento dei Laboratori Anatomia Patologica e Medicina Legale Università degli studi di Modena e Reggio Emilia Dipartimento Chirurgico Medico Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico Oncologico e di Medicina Rigenerativa Università di Modena e Reggio Emilia

AIM: To evaluate the relationship between hepatocellular carcinoma(HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation ***: This retrospective study included 165 patients(143 men, 22 women; median age 56.8 years, range 28-70.4 years) transplanted for HCC who had a follow-up period longer than 2 mo. Pre-transplantation dynamic computed tomography or magnetic resonance examinations were retrospectively reviewed, classifying HCC imaging enhancement pattern into hypervascular and hypovascular based on presence of wash-in during arterial phase. All pathologic reports of the explanted livers were reviewed, collecting data about HCC differentiation degree. The association between imaging vascular pattern and pathological grade was estimated using the Fisher exact test. All follow-up clinical and imaging data were reviewed for evidence of recurrence. Recurrence rate was calculated and imaging features of recurrent tumor were collected, classifying early and late recurrences based on timing(ears after transplantation) and intrahepatic, extrahepatic and both intrahepatic and extrahepatic recurrences based onlocation. All intrahepatic recurrences were classified as hypervascular or hypovascular and the differentiation degree was collected where available. The presence of variations in imaging enhancement pattern and pathological grade between the primary tumor and the intrahepatic recurrence was evaluated and the association between imaging and histopatholgical variations was estimated by using the χ2 test. ReSULTS: Of the 163 patients with imaging evidence of viable tumor, 156(95.7%) had hypervascular and 7(4.3%) hypovascular HCC. Among the 125 patients with evidence of viable tumor in the explanted liver, 19(15.2%) had grade 1, 56(44.8%) grade 2, 40(32%) grade 3 and 4(3.2%) grade 4 HCC, while the differentiation degree was not assessable for 6 patients(4.8%). A significant association was

关键词： Contrast media Hepatocellular carcinoma Liver transplantation Cell differentiation Recurrence

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Human cytomegalovirus and epstein-Barr virus infection in inflammatory bowel disease:Need for mucosal viral load measurement

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World Journal of Gastroenterology 2015年第6期21卷 1915-1926页

作者： Rachele Ciccocioppo Francesca Racca Stefania Paolucci Giulia Campanini Lodovica Pozzi elena Betti Roberta Riboni Alessandro Vanoli Fausto Baldanti Gino Roberto Corazza Centre for the Study and Cure of Inflammatory Bowel Disease Clinica Medica I IRCCS San Matteo Hospital Foundation University of Pavia SS Virologia Molecolare - SC Virologia e Microbiologia Fondazione IRCCS Policlinico San Matteo Servizio di endoscopia Digestiva Fondazione IRCCS Policlinico San Matteo Servizio di Anatomia Patologica Fondazione IRCCS Policlinico San Matteo

AIM:To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus(HCMV)and epstein-Barr virus(eBV)infection in inflammatory bowel disease(IBD).MeTHODS:A cohort of 40 IBD patients(17 refractory)and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample *** infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry,and correlations with clinical and endoscopic indexes of activity,and risk factors were ***:All refractory patients carried detectable levels of HCMV and/or eBV mucosal load as comparedto 13/23(56.5%)non-refractory and 13/40(32.5%)*** median DNA value was significantly higher in refractory(HCMV 286 and eBV 5.440 copies/105cells)than in non-refractory(HCMV 0 and eBV 6copies/105 cells;Pents and controls(HCMV and eBV 0 copies/105 cells;Pefractory patients showed DNA peak values≥103 copies/105 cells in diseased mucosa in comparison to non-diseased mucosa(PeBV),while non-refractory patients and controls invariably displayed levels below this threshold,thus allowing us to differentiate viral colitis from mucosal ***,the mucosal load positively correlated with the values found in the peripheral blood,whilst no correlation with the number of positive cells at immunohistochemistry was *** use was identified as a significant risk factor for both HCMV(P=0.018)and eBV(P=0.002)***,a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis,whilst refractory patients with eBV colitis did not show any improvement despite steroid tapering and discontinuation of the other ***:Viral colitis appeared to contribute to mucosal lesions in refractory IBD,and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specime

关键词： Inflammatory bowel disease quantitative real-time

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Damage-associated molecular patterns in inflammatory bowel disease:From biomarkers to therapeutic targets

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World Journal of Gastroenterology 2018年第41期24卷 4622-4634页

作者： Hayandra Ferreira Nanini Claudio Bernardazzi Fernando Castro Heitor Siffert Pereira de Souza Servico de Gastroenterologia e Laboratorio Multidisciplinar de Pesquisa Departamento de Clinica MedicaHospital Universitario Clementino Fraga FilhoUniversidade Federal do Rio de JaneiroRio de JaneiroRJ 21941-913Brazil D’Or Institute for Research and education(IDOR) Rua Diniz Cordeiro 30BotafogoRio de JaneiroRJ 22281-100Brazil

The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. These components include environmental elements and gut microbiota a dysbiosis. For decades, immune abnormalities have been investigated as critically important in IBD pathogenesis, and attempts to develop effective therapies have predominantly targeted the immune system. Nevertheless, immune events represent only one of the constituents contributing to IBD pathogenesis within the context of the complex cellular and molecular network underlying chronic intestinal inflammation. These factors need to be appreciated within the milieu of nonimmune components. Damage-associated molecular patterns (DAMPs), which are essentially endogenous stress proteins expressed or released as a result of cell or tissue damage, have been shown to act as direct proinflammatory mediators. excessive or persistent signalling mediated by such molecules can underlie several chronic inflammatory disorders, including IBD. The release of endogenous DAMPs amplifies the inflammatory response driven by immune and non-immune cells and promotes epigenetic reprogramming in *** effects determine pathologic changes,which may sustain chronic intestinal inflammation and also underlie specific disease *** addition to highlighting the potential use of DAMPs such as calprotectin as biomarkers,research on DAMPs may reveal novel mechanistic associations in IBD pathogenesis and is expected to uncover putative therapeutic targets.

关键词： Damage-associated molecular patterns environmental factors epigenetics Inflammatory bowel disease Therapeutic targets

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palliative care and end-stage colorectal cancer management:The surgeon meets the oncologist

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World Journal of Gastroenterology 2014年第24期20卷 7602-7621页

作者： Renato Costi Francesco Leonardi Daniele Zanoni Vincenzo Violi Luigi Roncoroni Istituto di clinica Chirurgica Generale e Terapia Chirurgica Dipartimento di Scienze ChirurgicheUniversità di ParmaAzienda Ospedaliero-Universitaria di Parma43126 ParmaItaly Dipartimento Polispecialistico 1 Unità Operativa di Oncologia MedicaAzienda Ospedaliero-Universitaria di Parma43126 ParmaItaly Dipartimento di Chirurgia Generale e Specialistica Ospedale di VaioAzienda Unità Sanitaria Locale di Parma43036 Fidenza (Parma)Italy

Colorectal cancer (CRC) is a common neoplasia in the Western countries, with considerable morbidity and mortality. every fifth patient with CRC presents with metastatic disease, which is not curable with radical intent in roughly 80% of cases. Traditionally approached surgically, by resection of the primitive tumor or stoma, the management to incurable stage IV CRC patients has significantly changed over the last three decades and is nowadays multidisciplinary, with a pivotal role played by chemotherapy (CHT). This latter have allowed for a dramatic increase in survival, whereas the role of colonic and liver surgery is nowadays matter of debate. Although any generalization is difficult, two main situations are considered, asymptomatic (or minimally symptomatic) and severely symptomatic patients needing aggressive management, including emergency cases. In asymptomatic patients, new CHT regimens allow today long survival in selected patients, also exceeding two years. The role of colonic resection in this group has been challenged in recent years, as it is not clear whether the resection of primary CRC may imply a further increase in survival, thus justifying surgery-related morbidity/mortality in such a class of short-living patients. Secondary surgery of liver metastasis is gaining acceptance since, under new generation CHT regimens, an increasing amount of patients with distant metastasis initially considered non resectable become resectable, with a significant increase in long term survival. The management of CRC emergency patients still represents a major issue in Western countries, and is associated to high morbidity/mortality. Obstruction is traditionally approached surgically by colonic resection, stoma or internal by-pass, although nowadays CRC stenting is a feasible option. Nevertheless, CRC stent has peculiar contraindications and complications, and its long-term cost-effectiveness is questionable, especially in the light of recently increased survival. Per

关键词： Colorectal cancer Palliative care Multimodal treatment Chemotherapy Surgery Stenting Radiotherapy

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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

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Anti-tumor necrosis factor α therapy associates to type 17 helper T lymphocytes immunological shift and significant microbial changes in dextran sodium sulphate colitis

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World Journal of Gastroenterology 2019年第12期25卷 1465-1477页

作者： Valentina Petito Cristina Graziani Loris R Lopetuso Marco Fossati Alessandra Battaglia Vincenzo Arena Domenico Scannone Gianluca Quaranta Andrea Quagliariello Federica Del Chierico Lorenza Putignani Luca Masucci Maurizio Sanguinetti Alessandro Sgambato Antonio Gasbarrini Franco Scaldaferri Istituto di Patologia Speciale medica Università Cattolica del Sacro Cuore UOC di Medicina Interna e Gastroenterologia Area di Gastroenterologia e Oncologia Medica Dipartimento di Scienze Gastroenterologiche Endocrino-Metaboliche e Nefro-Urologiche Fondazione Policlinico Universitario "A. Gemelli" IRCCS Dipartimento delle Scienze della Salute della Donna e del Bambino Fondazione Policlinico Universitario "A. Gemelli" IRCCS Istituto di clinica Ostetrica e Ginecologica Università Cattolica del Sacro Cuore U.O.S.A. Gineco-Patologia e Patologia Mammaria Fondazione Policlinico Universitario "A. Gemelli" IRCCS Istituto di Anatomia Patologica Università Cattolica del Sacro Cuore Dipartimento di Anatomia Patologica e Istologia Fondazione Policlinico Universitario "A. Gemelli" IRCCS Dipartimento di Microbiologia Fondazione Policlinico Universitario "A. Gemelli" IRCCS Istituto di Microbiologia Università Cattolica del Sacro Cuore Unità di Microbioma Umano Ospedale Pediatrico Bambino Gesù IRCCS Unità di Parassitologia Ospedale Pediatrico Bambino Gesù IRCCS Istituto di Patologia Generale Università Cattolica del Sacro Cuore

BACKGROUND Anti-tumor necrosis factor α(TNFα) represents the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe ulcerative colitis. On the other side gut microbiota plays a crucial role in pathogenesis of ulcerative colitis but few information exists on how microbiota changes following anti-TNFα therapy and on microbiota role in mucosal *** To elucidate whether gut microbiota and immune system changes appear following anti TNFα therapy during dextran sulfate sodium(DSS) *** eighty C57 BL/6 mice were divided into four groups: "No DSS", "No DSS + antiTNFα", "DSS" and "DSS + anti-TNFα". "DSS" and "DSS + anti-TNFα" were treated for 5 d with 3% DSS. At day 3, mice whithin "No DSS+anti-TNFα" and"DSS+anti-TNFα" group received 5 mg/kg of an anti-TNFα agent. Forty mice were sacrificed at day 5, forty at day 12, after one week of recovery post DSS. The severity of colitis was assessed by a clinical score(Disease Activity Index), colon length and histology. Bacteria such as Bacteroides, Clostridiaceae, enterococcaceae and Fecalibacterium prausnitzii(F. prausnitzii) were evaluated by quantitative *** 1 helper T lymphocytes(Th1), type 17 helper T lymphocytes(Th17) and CD4+ regulatory T lymphocytes(Treg) distributions in the mesenteric lymph node(MLN) were studied by flow *** Bacteria associated with a healthy state(i.e., such as Bacteroides, Clostridiaceae and F. prausnitzii) decreased during colitis and increased in course of anti-TNFαtreatment. Conversely, microorganisms belonging to enterococcaceae genera,which are linked to inflammatory processes, showed an opposite ***, in colitic mice treated with anti-TNFα microbial changes were associated with an initial increase(day 5 of the colitis) in Treg cells and a consequent decrease(day 12 post DSS) in Th1 and Th17 frequency cells. Healthy mice treated with anti-TNFα showed the same histological, microbial and immune featur

关键词： Gut microbiota Dextran sodium sulphate colitis Immune system T cells Mesenchymal lymphnode Tumor necrosis factor α

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