PubMed | Operative Unit of Pathology, Operative Unit of Molecular Biology, University of Bologna, Cervical Screening Unit and 2 more.
Type: Journal Article | Journal: Journal of clinical pathology | Year: 2016
Identification of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinomas is the single most important predictor of clinical response and outcome using EGFR tyrosine kinase inhibitors (TKIs). EGFR E746-A750del and L858R mutations are the most common gene alterations, also predicting the best clinical response to TKIs. We evaluated the accuracy of EGFR mutation-specific antibodies in a large cohort of lung adenocarcinomas, with different molecular settings and types of tissue samples.300 lung adenocarcinomas diagnosed on cytology (48 cell blocks), biopsy (157 cases) and surgical resections (95 cases) were selected. All cases were investigated for EGFR by sequencing and two mutation-specific antibodies (clone 6B6 for E746-A750del; clone 43B2 for L858R) were tested using an automated immunostainer. Discordant results were investigated by next-generation sequencing (NGS).Overall sensitivity and specificity of mutant-specific antibodies were 58.6% and 98.0%, respectively, and they increased up to 84% and 100% if only tumours harbouring E746-A750del were considered. In 13 discordant cases, NGS confirmed immunohistochemistry results in eight samples.The EGFR mutation-specific antibodies have a fair/good sensitivity and good/high specificity in identifying classic mutations, but they cannot replace molecular tests. The antibodies work equally well on biopsies and cell blocks, possibly permitting a rapid screening in cases with poor material.
PubMed | Medical Oncology, Marche Polytechnic University, Cannizzaro Hospital, Regina Elena Cancer Institute and 13 more.
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017
415 Background: The Retrospective analysis of Sorafenib (So) as the first- or second- target therapy (RESET) study in metastatic renal cell carcinoma (mRCC) patients assessed the use and safety of sorafenib under daily-life treatment conditions in a community-based patient population in Italian centers.RESET was a retrospective, observational, non-interventional field study in mRCC patients. Treatment decisions were determined by each physician according to local prescribing guidelines and clinical practice. Patients for whom a decision to treat with sorafenib single agent as first- or second- target therapy (TT) for mRCC has been made, were eligible for inclusion. Patients that started So treatment between January 1, 2008 and December 31, 2010 were included. Data collection started retrospectively in 2012, in order to have a period of observation of at least 1 year up to 31st Dec 2011. Endpoints included safety, overall survival (OS), progression-free survival (PFS), response rate (RR), and treatment duration. Subgroup analyses included age, Eastern Cooperative Oncology Group performance status, prior therapy, number of metastases, and line of TT with So.From February to Jululy 2012, 358 pts from 37 Italian centers were enrolled. The most common grade 3 drug-related adverse events were hand-foot skin reaction (6.3%), rash (2.3%), hypertension, fatigue, and diarrhea (1.7% each). In the overall population, median OS was 17.2 months (mos) (95% CI 15.5 - 19.6 mos) and median PFS was 5.9 mos (95% CI 5.0-6.8 mos). Median duration of treatment with So was 5.09 mos. Complete response was observed in 3 (0.8%) pts, partial response in 53(15.0%) pts and stable disease in 139(39.4%) pts. In pts receiving So as first- or second- TT, median OS was 19.9 mos (95% CI 15.4-25.3 mos) and 16.6 mos (95% CI 13.1-18.4 mos) respectively, and median PFS was 6.6 mos (95% CI 4.9-9.3 mos) and 5.3 mos (95% CI 4.4-6.2 mos) respectively.The efficacy and safety of So under routine clinical practice conditions in the setting of community-based practice in Italy were similar to that reported in prospective clinical trials. The efficacy of So was observed in the subgroup of pts receiving So as either the first or second TT for mRCC.
PubMed | Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggiero dAragona, Ospedale Villa Sofia, Sant'Anna School of Advanced Studies, UOC Cardiologia Clinica e Riabilitativa Azienda Ospedaliera Bianchi Melacrino Morelli and 4 more.
Type: | Journal: The American journal of cardiology | Year: 2016
Patients with asymptomatic heart failure (HF; stage A and B) are characterized by maladaptive left ventricular (LV) remodeling. Classic 4-group classification of remodeling considers only LV mass index and relative wall thickness as variables. Complex remodeling classification (CRC) includes also LV end-diastolic volume index. Main aim was to assess the prognostic impact of CRC in stage A and B HF. A total of 1,750 asymptomatic subjects underwent echocardiographic examination as a screening evaluation in the presence of cardiovascular risk factors. LV dysfunction, both systolic (ejection fraction) and diastolic (transmitral flow velocity pattern), was evaluated, together with LV remodeling. We considered a composite end point: all-cause death, myocardial infarction, coronary revascularizations, cerebrovascular events, and acute pulmonary edema. CRC was suitable for 1,729 patients (men 53.6%; age 58.3 13years). Two hundred thirty-eight patients presented systolic dysfunction (ejection fraction <50%) and 483 diastolic dysfunction. According to the CRC, 891 patients were normals or presented with physiologic hypertrophy, 273 concentric remodeling, 47 eccentric remodeling, 350 concentric hypertrophy, 29mixed hypertrophy, 86 dilated hypertrophy, and 53 eccentric hypertrophy. Age and gender distribution was noticed (p <0.001). After a median follow-up of 21months, Kaplan-Meier analysis showed different survival distribution (p <0.001) of the CRC patterns. In multivariate Cox regression (adjusted for age, gender, history of stable ischemic heart disease, classic remodeling classification, systolic, and diastolic dysfunction), CRC was independent predictor of primary end point (p= 0.044, hazard ratio 1.101, 95% CI 1.003 to 1.21), confirmed in a logistic regression (p <0.03). In conclusion, CRC could help physicians in prognostic stratification of patients in stage A and B HF.
Violini R.,Azienda Ospedaliera S. Camillo Forlanini |
Vairo U.,Azienda Ospedaliero Universitaria Policlinico |
Hijazi Z.M.,Rush University Medical Center
Catheterization and Cardiovascular Interventions | Year: 2013
This report describes the use of the Edwards Sapien THV in a patient who had a short regurgitant/stenotic homograft with early bifurcation stenoses of the pulmonary arteries. A 48-mm AndraStent was positioned in the right pulmonary artery-homograft jailing the left pulmonary artery (LPA). To have an unobstructed access to the LPA, the stent strut leading to the LPA was broken using high-pressure balloon. A 23-mm Edwards Sapien THV was positioned in the stented homograft just proximal to the LPA origin with resolution of the stenosis and regurgitation. © 2012 Wiley Periodicals, Inc.
PubMed | University Ziekenhuizen Leuven, University of Bologna, Pediatric Hematology Oncology and Transplantation, Pediatric Hematology Oncology and 6 more.
Type: Journal Article | Journal: PloS one | Year: 2016
Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients.By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD.Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM.
Cesinaro A.M.,Azienda Ospedaliero Universitaria Policlinico
APMIS | Year: 2012
Fibroplasia is a peculiar stromal reaction at the base of melanocytic lesions, particularly observed in so-called dysplastic nevi. This study evaluates a series of clinico-pathological features in nevi with fibroplasia, their frequence in comparison to usual nevi, and the association of fibroplasia with the risk for the development of melanoma. A total of 209 consecutive nevi showing fibroplasia, belonging to 203 patients, was reviewed. Nevi with fibroplasia were more frequent in men, about half of the lesions belonged to patients aged 11-40 years, and the highest number (52%) were located on the posterior trunk. Lesions 6 mm or greater were 152 (72.73%). Junctional and compound nevi were 52 (24.8%), and 157 (75.2%), respectively. Inflammatory infiltrate was present in 67.8% of cases, melanophages in 56.4%, a lentiginous pattern in 31.1%, focal pagetoid infiltration in three lesions. Nevi with fibroplasia constituted 4.27% of all junctional and compound nevi diagnosed in the same period. A total of 23 patients (11.3%) had a personal history of melanoma. The total number of nevi excised from the 203 patients ranged between 1 and 21, and significantly correlated with the patient's personal history of melanoma (p < 0.001). Fibroplasia is relatively infrequent in melanocytic nevi, it does not appear related to a process of senescence of the lesion, and does not represent a particularly strong predictor of risk of melanoma. © 2012 The Authors APMIS © 2012 APMIS.
Cesinaro A.M.,Azienda Ospedaliero Universitaria Policlinico |
Bettelli S.,Azienda Ospedaliero Universitaria Policlinico |
Maccio L.,Azienda Ospedaliero Universitaria Policlinico |
Milani M.,Azienda Ospedaliero Universitaria Policlinico
American Journal of Dermatopathology | Year: 2014
Mantle cell lymphoma rarely affects the skin and is usually a secondary involvement. The present case illustrates a primary cutaneous mantle cell lymphoma of the leg, with blastoid morphology and aberrant expression of CD10 and bcl-6, which was misinterpreted at the beginning as diffuse large B-cell lymphoma. A larger panel of immunohistochemical markers, including cyclin-D1, and molecular investigation showing the typical translocation (t11;14), pointed toward the correct diagnosis. Cutaneous diffuse B-cell lymphomas with unusual morphology should be interpreted cautiously, and the diagnosis made on the basis of an appropriate panel of antibodies and molecular studies. © 2014 Lippincott Williams & Wilkins.
Signorelli F.,University of Catanzaro |
Guyotat J.,Hopital Neurologique et Neurochirurgical P. Wertheimer |
Elisevich K.,Ford Motor Company |
Barbagallo G.M.V.,Azienda Ospedaliero Universitaria Policlinico
Acta Neurochirurgica | Year: 2010
The insular lobe is a functionally complex structure, harbouring peculiar anatomical and vascular features and specific neuronal connectivity with surrounding cerebral structures. It is situated in the depth of the Sylvian fissure and can be affected by either low-grade or high-grade gliomas. Because of its complexity, surgery of insular tumours has been traditionally regarded as hazardous. Nonetheless, currently improved diagnostic, neurophysiological and surgical tools allow the neurosurgeon to perform surgery of insular gliomas in a safer way, thus bringing forward the pioneering work performed by neurosurgeons in the past two decades.The aim of this paper is to provide the reader with an updated review of the anatomy, the clinical picture, diagnosis and surgical management of insular gliomas. © 2009 Springer-Verlag.
Cesinaro A.M.,Azienda Ospedaliero Universitaria Policlinico |
Lonardi S.,University of Brescia |
Facchetti F.,University of Brescia
American Journal of Surgical Pathology | Year: 2013
The pathogenesis of granuloma faciale (GF), framed in the group of cutaneous vasculopathic dermatitis, is poorly understood. The present study investigated whether GF might be part of the spectrum of IgG4-related sclerosing diseases (IgG4-RD). Erythema elevatum diutinum (EED), believed to belong to the same group of disorders as GF, was also studied for comparison. Thirty-one biopsies of GF obtained from 25 patients (18 men, 7 women) and 5 cases of EED (4 women and 1 man) were analyzed morphologically and for the expression of IgG and IgG4 by immunohistochemistry. The distribution of Th1, T regulatory and Th2 T-cell subsets, respectively, identified by anti-T-bet, anti-FoxP3, and anti-GATA-3 antibodies, was also evaluated. The dermal inflammatory infiltrate in GF contained eosinophils and plasma cells in variable proportions. Obliterative venulitis was found in 16 cases, and storiform fibrosis, a typical feature of IgG4-RD, was observed in 8 cases and was prominent in 3 of them. On immunohistochemical analysis 7 of 31 biopsies (22.6%) from 6 GF patients fulfilled the criteria for IgG4-RD (IgG4/IgG ratio >40%, and absolute number of IgG4 per high-power field >50). Interestingly, the 6 patients were male, and 4 showed recurrent and/or multiple lesions. In an additional 5 cases, only the IgG4/IgG ratio was abnormal. None of the 5 EED cases fulfilled the criteria for IgG4-RD. The T-cell subsets in GF were quite variable in number, GATA-3 lymphocytes were generally more abundant, but no relationship with the number of IgG4 plasma cells was found. The study indicates that a significant number of GF cases are associated with an abnormal content of IgG4 plasma cells; this association was particularly obvious in male patients and in cases presenting with multiple or recurrent lesions. As morphologic changes typically found in IgG4-RD, such as obliterative vascular inflammation and storiform sclerosis, are found in GF, we suggest that GF might represent a localized form of IgG4-RD. Copyright © 2012 by Lippincott Williams &Wilkins.
PubMed | University of Modena and Reggio Emilia and Azienda Ospedaliero Universitaria Policlinico
Type: Journal Article | Journal: The Journal of dermatology | Year: 2016
We report the case of a 74-year-old man affected by an unusual variant of pemphigus. He presented with a crusty and scaly lesion of the nose. We performed reflectance confocal microscopy and optical coherence tomography on the lesion, which suggested an unexpected diagnosis of pemphigus. Therefore, to confirm our diagnostic suspicions, we executed indirect immunofluorescence and two biopsies, one for histopathological examination and one for direct immunofluorescence. Histopathological evaluation showed acantholysis with formation of clefts in the granular and spinous layers of the epidermis. Direct immunofluorescence revealed immunoglobulin G and C3 deposit to the full thickness of the epidermis. Indirect immunofluorescence showed intercellular antibodies at a titer of 1:40 in the suprabasal epidermis. The immunoblot analysis using epidermal extract revealed the presence of circulating antibodies directed to 130- and 160-kDa antigens in the patients serum. These two antigens were evidenced from nitrocellulose membrane with colorimetric AP systems, which highlighted the presence of autoantibodies against desmoglein (Dsg)1 and Dsg3 (sodium dodecylsulfate polyacrylamide gel electrophoresis). We also performed an enzyme-linked immunoassay. All these findings suggested that this patients pemphigus had features of both vulgaris and foliaceus variants.