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Current trends in management of hepatitis B virus reactivation in the biologic therapy era

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World Journal of Gastroenterology 2011年第34期17卷 3881-3887页

作者： Claudio M Mastroianni Miriam Lichtner Rita Citton Cosmo Del Borgo Angela Rago Helene Martini Giuseppe Cimino Vincenzo Vullo Infectious Diseases Unit Fondazione Eleonora Lorillard Spencer Cenci Sapienza University SM Goretti Hospital Hematology Unit Sapienza University SM Goretti Hospital Department of Public Health and Infectious Diseases Sapienza University Policlinico Umberto I

Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.

关键词： Hepatitis B virus Virus reactivation Rituximab Tumor necrosis factor-α antagonists Biologic agents Antiviral drugs

Neoadjuvant chemoradiotherapy for locally advanced rectal cancer:The debate continues

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World Journal of Gastrointestinal Oncology 2014年第12期6卷 438-440页

作者： Francesca De Felice Daniela Musio Luciano Izzo Vincenzo Tombolini Department of Radiotherapy Policlinico Umberto I "Sapienza" University of Rome Department of Surgery "Pietro Valdoni" Policlinico Umberto I "Sapienza" University of Rome spencer-lorillard foundation 00161 Rome Italy

Rectal carcinoma represents the 30% of all colorectal cancers, with about 40000 new cases/years. In the past two decades, the management of rectal cancer has made important progress, highlighting the main role of a multimodality strategy approach, combining surgery, radiation therapy and chemotherapy. Nowadays, surgery remains the primary treatment and neoadjuvant chemoradiotherapy, based on fluoropyrimidine(5-FU) continuous infusion, is considered the standard in locally advanced rectal carcinoma. The aim is to reduce the incidence of local recurrence and to perform a conservative surgery. To improve these purposes different drugs combination have been tested in the neo-adjuvant setting. At American Society of Clinical Oncology 2014 an important abstract was presented focusing on the role of adding oxaliplatin to concomitant treatment, in patients with locally advanced rectal carcinoma. Rodel et al reported on the CAO/ARO/AIO-04 randomized phase Ⅲ trial that compared standard treatment with 5-FU and radiation therapy, to oxaliplatin plus 5-FU inassociation with radiation therapy. The addition of oxaliplatin to the neo-adjuvant treatment has been shown to improve disease-free survival from 71.2% to 75.9%(P = 0.03). This editorial was planned to clarify the optimal treatment in patients with locally advanced rectal cancer, considering the results from CAO/ARO/AIO-04 study.

关键词： Chemoradiotherapy Rectal cancer Locally advanced disease Neoadjuvant Debate

Multiple cells of origin in cholangiocarcinoma underlie biological,epidemiological and clinical heterogeneity

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World Journal of Gastrointestinal Oncology 2012年第5期4卷 94-102页

作者： Vincenzo Cardinale Guido Carpino Lola Reid Eugenio Gaudio Domenico Alvaro Department of MedicoSurgical Sciences and Biotechnologies Polo PontinoSapienza University of Rome00137 RomeItaly Department of Health Sciences University of Rome "Foro Italico"000135 RomeItaly Department of Anatomical HistologicalForensic Medicine and Orthopedics SciencesSapienza University of Rome000137 RomeItaly Department of Cell and Molecular Physiology Biomedical EngineeringProgram in Molecular Biology and BiotechnologyUNC School of MedicineChapel HillNC 27599United States eleonora lorillard spencer-cenci foundation 00156 RomeItaly

Recent histological and molecular characterization of cholangiocarcinoma(CCA) highlights the heterogeneity of this cancer that may emerge at different sites of the biliary tree and with different macroscopic or morphological ***,different stem cell niches have been recently described in the liver and biliarytree,suggesting this as the basis of the heterogeneity of intrahepatic(IH)-and extrahepatic(EH)-CCAs,which are two largely different tumors from both biological and epidemiological points of *** complexity of the organization of the liver stem cell compartments could underlie the CCA clinical-pathological heterogeneity and the criticisms in classifying primitive liver *** recent advances highlight a possible new classification of CCAs based on cells of origin and this responds to the need of generating homogenous diagnostic,prognostic and,hopefully,therapeutic categories of IH-and EH-CCAs.

关键词： Intrahepatic cholangiocarcinoma Extrahepatic cholangiocarcinoma Cholangiocarcinoma classification Cholangiolocarcinoma Cells of origin Cancer stem cells Peribiliary glands Biliary tree stem/progenitor cells Human hepatic stem cells Risk factors Targeted therapies

How to impute study-specific standard deviations in metaanalyses of skewed continuous endpoints?

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World Journal of Meta-Analysis 2015年第5期3卷 215-224页

作者： Teresa Greco Giuseppe Biondi-Zoccai Marco Gemma Claude Guérin Alberto Zangrillo Giovanni Landoni Laboratorio di Statistica Medica Biometria ed Epidemiologia "G.A.Maccacaro" Dipartimento di Scienze Cliniche e di Comunità University of Milan Anaesthesia and Intensive Care Department IRCCS San Raffaele Scientific Institute Department of Medico-Surgical Sciences and Biotechnologies Sapienza University of Rome eleonora lorillard spencer cenci foundation Meta-analysis and Evidence Based Medicine Training in Cardiology (METCARDIO) Medical Intensive Care Hospital de La Croix Rousse

AIM： To compare four methods to approximate mean and standard deviation （SD） when only medians and interquartile ranges are ***： We performed simulated meta-analyses on six datasets of 15, 30, 50, 100, 500, and 1000 trials, respectively. Subjects were iteratively generated from one of the following seven scenarios： five theoreti-cal continuous distributions [Normal, Normal （0, 1）, Gamma, Exponential, and Bimodal] and two real-life distributions of intensive care unit stay and hospital stay. For each simulation, we calculated the pooled estimates assembling the study-specific medians and SD approximations： Conservative SD, less conservativeSD, mean SD, or interquartile range. We provided a graphical evaluation of the standardized *** show which imputation method produced the best estimate, we ranked those differences and calculated the rate at which each estimate appeared as the best, second-best, third-best, or ***： Our results demonstrated that the best pooled estimate for the overall mean and SD was provided by the median and interquartile range （mean standardized estimates： 4.5 ± 2.2, P = 0.14） or by the median and the SD conservative estimate （mean standardized estimates： 4.5 ± 3.5, P = 0.13）. The less conservative approximation of SD appeared to be the worst method, exhibiting a significant difference from the reference method at the 90% confidence level. The method that ranked first most frequently is the interquartile range method （23/42 = 55%）, particularly when data were generated according to the Standard Normal, Gamma, and Exponential distributions. The second-best is the conservative SD method （15/42 = 36%）, particularly for data from a bimodal distributionand for the intensive care unit stay variable. CONCLUSION： Meta-analytic estimates are not signi-fcantly affected by approximating the missing values ofmean and SD with the correspondent values for medianand interquartile range.

关键词： Imputation Interquartile range Meta-analysis Randomized controlled trial Standard deviation