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Trecca A.,USI Group | Marinozzi G.,Digestive Endoscopy Unit | Villanacci V.,Spedali Civili of Brescia | Salemme M.,Spedali Civili of Brescia | Bassotti G.,University of Perugia
Techniques in Coloproctology | Year: 2014

Endoscopic submucosal dissection (ESD) is gaining popularity worldwide in the treatment of neoplastic lesions of the gastrointestinal tract. However, the experience in Western countries is quite limited and restricted to large or academic centers. Besides, this approach requires an optimal pathological assessment. The aim of this study was to report our experience with colonic ESD using a new device that allows complete handling of the resected specimens and especially of lateral margins, for pathological analysis. In a 1-year period, 14 patients (6 men, 8 women, age range 50–82 years) underwent colonic ESD in a non-academic hospital. The endoscopic procedure was carried out successfully en bloc in more than 90 % of cases. Perforation requiring surgery occurred in one patient (7 %). Pathological assessment with the new device allowed entire and complete examination of both the deep and lateral margins of the excised specimens. Colonic ESD is a viable option for non-surgical treatment of large bowel lesions even in relatively small centers and in non-academic settings. The new device allows good handling of the specimens, and it seems to be useful for the entire examination of the resection margins. © 2014, Springer-Verlag Italia Srl.


Mazzuoli S.,San Nicola Pellegrino Hospital Trani | Guglielmi F.W.,San Nicola Pellegrino Hospital Trani | Antonelli E.,University of Perugia | Salemme M.,Spedali Civili of Brescia | And 2 more authors.
Digestive and Liver Disease | Year: 2013

Since the introduction of biological therapy, endoscopic and histological remission, i.e. mucosal healing, has become an important therapeutic goal in Crohn's Disease and Ulcerative Colitis. Mucosal healing is associated with lower rates of hospitalization and surgery, although its role in preventing progression and changing the natural history of the disease has not been clearly demonstrated. A precise definition of mucosal healing has not yet been established, although the concept used in clinical trials is the "complete absence of all inflammatory and ulcerative lesions in all segments of gut" at endoscopy. This definition does not include mucosal improvement and does not distinguish among grades of mucosal healing. In both Crohn's Disease and Ulcerative Colitis trials, several qualitative and quantitative numeric endoscopic indices have been proposed to measure and distinguish endoscopic changes. In addition, the microscopic features associated with inflammatory bowel diseases are considerably modified by the course of the disease and the treatments adopted. However, it is not yet clear whether microscopic healing should be a primary endpoint in clinical trials. In this paper we discuss endoscopic and histological findings and the limitations of the endoscopic and histological indices as a basis for a standardised diagnosis of mucosal healing. © 2013 Editrice Gastroenterologica Italiana S.r.l.


PubMed | Aix - Marseille University, University of Genoa, Spedali Civili of Brescia and IRCCS Bambino Gesu Childrens Hospital
Type: Journal Article | Journal: The Journal of allergy and clinical immunology | Year: 2016

Programmed death 1 (PD-1) is an immunologic checkpoint that limits immune responses by delivering potent inhibitory signals to Tcells on interaction with specific ligands expressed on tumor/virus-infected cells, thus contributing to immune escape mechanisms. Therapeutic PD-1 blockade has been shown to mediate tumor eradication with impressive clinical results. Little is known about the expression/function of PD-1 on human natural killer (NK) cells.We sought to clarify whether human NK cells can express PD-1 and analyze their phenotypic/functional features.We performed multiparametric cytofluorimetric analysis of PD-1We provide unequivocal evidence that PD-1 is highly expressed (PD-1We have identified and characterized a novel subpopulation of human NK cells expressing high levels of PD-1. These cells have the phenotypic characteristics of fully mature NK cells and are increased in patients with ovarian carcinoma. They display low proliferative responses and impaired antitumor activity that can be partially restored by antibody-mediated disruption of PD-1/programmed death ligand interaction.


Appelman H.D.,University of Michigan | Matejcic M.,International Center for Genetic Engineering and Biotechnology | Parker M.I.,International Center for Genetic Engineering and Biotechnology | Riddell R.H.,Mount Sinai Hospital | And 3 more authors.
Annals of the New York Academy of Sciences | Year: 2014

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the evolution of low-grade squamous and glandular dysplasia to invasive carcinoma; the mutational spectra of Barrett's esophagus and adenocarcinoma; the risk of p53-immunoreactive glandular dysplasia compared to non-immunoreactive mucosa for progression to cancer; the role of lectins in progression to adenocarcinoma; and the role of racemase immunoreactivity in the prediction of risk of adenocarcinoma. © 2014 New York Academy of Sciences.


Filippi M.,San Raffaele Scientific Institute | Riccitelli G.,San Raffaele Scientific Institute | Mattioli F.,Spedali Civili of Brescia | Capra R.,Multiple Sclerosis Center | And 7 more authors.
Radiology | Year: 2012

Purpose: To evaluate brain changes after cognitive rehabilitation in patients with clinically stable relapsing-remitting (RR) multiple sclerosis (MS) by using neuropsychologic assessment and structural and functional magnetic resonance (MR) imaging techniques. Materials and Methods: The study was conducted with approval of the involved institutional review boards. Written informed consent was obtained from each participant. Twenty patients with RR MS and cognitive deficits at baseline were randomly assigned to undergo treatment (n = 10), which entailed computer-assisted cognitive rehabilitation of attention and information processing and executive functions, or to serve as a control subjects (n = 10) without cognitive rehabilitation. All patients underwent a standardized neuropsychologic assessment and MR imaging at baseline and after 12 weeks. Changes in gray matter (GM) volumes on three-dimensional T1-weighted images and changes in normal-appearing white matter (NAWM) architecture on diffusion-weighted images were assessed. Changes in functional activity at functional MR imaging during the Stroop task and at rest were also investigated by using linear models. Results: As compared with their performance at baseline, the patients in the treatment group improved at tests of attention and information processing and executive functions. Neither structural modifications to GM volume nor modifications to NAWM architecture were detected at follow-up in both groups. Functional MR imaging demonstrated modifications of the activity of the posterior cingulate cortex (PCC)/precuneus and dorsolateral prefrontal cortex (PFC) during the Stroop task, as well as modifications of the activity of the anterior cingulum, PCC and/or precuneus, left dorsolateral PFC, and right inferior parietal lobule at rest in the treatment group compared with the control group. In the treatment group, functional MR imaging changes were correlated with cognitive improvement (P < .0001 to .01). Conclusion: Rehabilitation of attention and information processing and executive functions in RR MS may be effected through enhanced recruitment of brain networks subserving the trained functions. © RSNA, 2012.


Canavese G.,University of Turin | Bassotti G.,University of Perugia | Astegiano M.,Gastroenterology and Hepatology Section | Castellano I.,University of Turin | And 3 more authors.
World Journal of Gastroenterology | Year: 2013

Following the international guidelines criteria an adequate "diagnostic conclusion" of inflammatory bowel disease (IBD) can be achieved only if clinical, endoscopic and laboratory findings, together with sample technical adequacy and unequivocal histomorphological signs of the disease are available. Thus, a conclusive diagnosis requires a complex combination of clinical, endoscopic and histological data. A considerable number of endoscopic biopsies obtained from IBD patients do not meet the above-mentioned requirements. The aim of the present proposal is to introduce a binary system of evaluation in the "diagnostic conclusion" of the histopathological report that will help to simplify the clinical decisions and consequent patient management. In patients with no history of disease, the pathologist should classify the biopsies in "Diagnostic", when the criteria established by the international guidelines are satisfied and "not diagnostic" when one or more of the above-mentioned criteria are not met. The term "not diagnostic" should replace "highly suggestive" and "probable". This new terminology could avoid ambiguous expressions that encourage the clinician to classify the patient as affected by IBD without fulfilling all of the requirements for an accurate diagnostic approach. © 2013 Baishideng. All rights reserved.


Spena G.,University of Brescia | D'Agata F.,University of Turin | Panciani P.P.,University of Brescia | Di Monale M.B.,Spedali Civili of Brescia | Fontanella M.M.,University of Brescia
PLoS ONE | Year: 2013

Background: To date, few parameters have been found that can aid in patient selection and surgical strategy for eloquent area gliomas. Aims: The aim of the study was to analyze preoperative and intraoperative factors that can predict functional outcome and extent of resection in eloquent area tumors. Patients and Methods: A retrospective analysis was conducted on 60 patients harboring supratentorial gliomas in eloquent areas undergoing awake surgery. The analysis considered clinical, neuroradiologic (morphologic), intraoperative, and postoperative factors. End-points were extent of resection (EOR) as well as functional short- and long-term outcome. Postoperatively, MRI objectively established the EOR. x2 analyses were used to evaluate parameters that could be predictive. Multivariate logistic regression analyses were used to evaluate the best combination to predict binary positive outcomes. Results: In 90% of the cases, subcortical stimulation was positive in the margins of the surgical cavity. Postoperatively, 51% of the patients deteriorated but 90% of the patients regained their preoperative neurological score. Factors negatively affecting EOR were volume, degree of subcortical infiltration, and presence of paresis (P<0.01). Sharp margins and cystic components were more amenable to gross total resection (P<0.01). Contrast enhancement (P<0.02), higher grade (P<0.01), paresis (P<0.01), and residual tumor in the cortex (P<0.02) negatively affected long-term functional outcomes, whereas postoperative deterioration could not be predicted for any factor other than paresis. Subcortical stimulation did not correlate with deterioration, both postoperatively (P<0.08) and at follow-up (P<0.042). Conclusions: Biological and morphological factors such as type of margins, volume, preoperative neurological status, cystic components, histology and the type of infiltration into the white matter must be considered when planning intraoperative mapping. © 2013 Spena et al.


Girolomoni G.,University of Verona | Altomare G.,University of Milan | Ayala F.,University of Naples Federico II | Berardesca E.,Dermatologic Institute S Maria E S Gallicano | And 5 more authors.
Immunopharmacology and Immunotoxicology | Year: 2012

Context: The efficacy and favorable safety profile of anti-tumor necrosis factor (TNF) agents in the treatment of psoriasis and psoriatic arthritis (PsA) are supported by several randomized controlled studies and meta-analyses. However, some concerns on the long-term safety of these drugs still exist, as these studies generally included small patient numbers and were performed in selected patient populations. Objective: This review presents and discusses current evidence on the safety of anti-TNFα agents in patients with psoriasis and PsA, with a focus on European registry studies and case reports of particular importance. Methods: Key studies on the safety of anti-TNFα agents in the treatment of adult patients with psoriasis or PsA were identified by a MEDLINE search (last updated 10 November 2011) based on several interrelated queries, with a focus on European registries. Other studies and case reports were included if deemed relevant. Studies concerning other conditions, such as rheumatoid arthritis (RA), were included as appropriate when data in psoriatic disease were unavailable or insufficient. Results: Available data on the safety of anti-TNFα agents such as etanercept in psoriasis and PsA appear reassuring, even if some concerns still exist. Most notably, data suggest a higher incidence of infection and lymphoma amongst patients treated with the anti-TNFα monoclonal antibodies infliximab and adalimumab compared with etanercept. Conclusion: The overall safety profile of monoclonal antibodies in patients with psoriasis, PsA and RA seems less favorable than that of etanercept, particularly in terms of risk of infection and hepatotoxicity. © 2012 Informa Healthcare USA, Inc.


Gotti D.,University of Brescia | Danesi M.,University of Brescia | Calabresi A.,University of Brescia | Ferraresi A.,University of Brescia | And 6 more authors.
AIDS Patient Care and STDs | Year: 2013

HIV-infected patients are at increased risk for developing HIV-related Hodgkin lymphoma (HIV-HL) despite the success of combination antiretroviral therapy (cART). To study the incidence of HIV-HL in HIV-patients with respect to the general population of Brescia, Italy, we conducted a single-center cohort study of HIV-patients followed from 1999 to 2009. The incidence of HIV-HL was compared to the incidence in the general population of Brescia using standardized incidence ratios (SIRs). Poisson analysis was used to study the association between covariates and HL. A total of 5085 HIV-patients were observed among 30,946 person-years; 30 patients developed HIV-HL. The incidence rate was 9.9 (95% confidence interval [CI], 6.7-14.1) per 10,000 person-years of follow-up. HL was substantially more frequent in HIV-patients than in the general population living in the same district area [standardized incidence rate, SIR=21.8 (95% CI, 15.33-31)]. The risk of HIV-HL tended to increase with lowering CD4+ cell counts at time of HL diagnosis [adjusted incidence relative risk (IRR) for CD4 cell count<50 cells/μL: 41.70, p<0.001]. HL risk had been elevated during the 6 months after combination antiretroviral therapy (cART) initiation (IRR: 26.65, p<0.001). Twenty-two HIV-HL cases were matched to 3280 controls. In the year preceding HIV-HL diagnosis the mean change in CD4+ cell counts between cases and controls was significantly different (-99 cells/μL for cases vs. +37 cells/μL for controls, p<0.0001). Compared with the general population, HIV-infected patients showed an increased risk for developing HL. The risk of HIV-HL increased significantly in the first months after cART initiation. © 2013, Mary Ann Liebert, Inc.


Zarattini G.,University of Brescia | Buffoli P.,University of Brescia | Isabelli G.,Spedali Civili of Brescia | Marchese M.,University of Brescia
Clinical Cases in Mineral and Bone Metabolism | Year: 2014

This paper shows a case of pregnancy-associated osteoporosis (PAO) with seven vertebral compression fractures treated with strontium ranelate and supplementation of calcium and cholecalciferol. Clinical evaluation, laboratory and radiological results are analyzed in the case-report to demonstrate that strontium ranelate is a good option to restore quickly the value of bone mineral density in the treatment of a case of PAO.

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