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Casoni G.L.,GB Morgagni Hospital | Tomassetti S.,GB Morgagni Hospital | Cavazza A.,S. Maria Nuova Hospital I.R.C.C.S | Colby T.V.,Mayo Medical School | And 10 more authors.

Background: Histology is a key element for the multidisciplinary diagnosis of fibrotic diffuse parenchymal lung diseases (f-DPLD) when the clinical-radiological picture is nondiagnostic. Transbronchial lung cryobiopsy (TBLC) have been shown to be useful for obtaining large and well-preserved biopsies of lung parenchyma, but experience with TBLC in f-DPLD is limited. Objectives: To evaluate safety, feasibility and diagnostic yield of TBLC in f-DPLD. Method: Prospective study of 69 cases of TBLC using flexible cryoprobe in the clinical-radiological setting of f-DPLD with nondiagnostic high resolution computed tomography (HRCT) features. Results: Safety: pneumothorax occurred in 19 patients (28%). One patient (1.4%) died of acute exacerbation. Feasibility: adequate cryobiopsies were obtained in 68 cases (99%). The median size of cryobiopsies was 43.11 mm2 (range, 11.94-76.25). Diagnostic yield: among adequate TBLC the pathologists were confident ("high confidence") that histopathologic criteria sufficient to define a specific pattern in 52 patients (76%), including 36 of 47 with UIP (77%) and 9 nonspecific interstitial pneumonia (6 fibrosing and 3 cellular), 2 desquamative interstitial pneumonia/respiratory bronchiolitis-interstitial lung disease, 1 organizing pneumonia, 1 eosinophilic pneumonia, 1 diffuse alveolar damage, 1 hypersensitivity pneumonitis and 1 follicular bronchiolitis. In 11 diagnoses of UIP the pathologists were less confident ("low confidence"). Agreement between pathologists in the detection of UIP was very good with a Kappa coefficient of 0.83 (95% CI, 0.69-0.97). Using the current consensus guidelines for clinical-radiologic-pathologic correlation 32% (20/63) of cases were classified as Idiopathic Pulmonary Fibrosis (IPF), 30% (19/63) as possible IPF, 25% (16/63) as other f-DPLDs and 13% (8/63) were unclassifiable. Conclusions: TBLC in the diagnosis of f-DPLD appears safe and feasible. TBLC has a good diagnostic yield in the clinical-radiological setting of f-DPLD without diagnostic HRCT features of usual interstitial pneumonia. Future studies should consider TBLC as a potential alternative to SLBx in f-DPLD. © 2014 Casoni et al. Source

Brunasso A.M.G.,Medical University of Graz | Puntoni M.,Biostatistics and Clinical Trials Unit | Aberer W.,Medical University of Graz | Delfino C.,University of Florence | And 2 more authors.
British Journal of Dermatology

Background In 2007 the International Psoriasis Council proposed that palmoplantar pustulosis (PPP) should be considered a separate condition from psoriasis, despite the presence of certain phenotypes common in both diseases. Objectives To describe and compare demographic and clinical characteristics among patients with PPP and palmoplantar plaque psoriasis. Methods This was a retrospective case series study from 2005 to 2010. The following data were obtained: age, sex, family history, smoking habits, nail involvement, joint involvement, disease duration, lesion morphology (plaque or pustular), histological diagnosis, comorbidities, and Physician's Global Assessment (PGA) score for extrapalmoplantar lesions. The sample size calculation indicated that 80 patients, 40 patients for each group (palmoplantar plaque psoriasis and PPP) were needed to see clinically relevant differences between groups. Results Ninety patients were selected, 51 with palmoplantar plaque psoriasis and 39 with PPP. No statistically significant differences were registered between patients affected by PPP and palmoplantar plaque psoriasis as regards age at onset of the disease (48 vs. 44 years; P = 0·4), disease duration (6 vs. 10 years; P = 0·1), family history of psoriasis (28% vs. 33%; P = 0·7), concomitant arthritis (26% vs. 25%; P = 1·0), or smoking habits (54% vs. 41%; P = 0·2). We observed a female predominance (P = 0·01) and a lesser frequency of nail involvement (P = 0·03) in patients affected by PPP. Conclusions Our data suggest a close relationship between PPP and psoriasis. The existing data concerning epidemiology, clinical presentation, genetics, histopathology and pathogenesis do not permit a clear distinction between these two entities, which seem to coincide in many aspects. PPP appears to have a marked predilection among female smokers. What's already known about this topic? Recently, palmoplantar pustulosis (PPP) has been proposed as a separate condition from psoriasis. What does this study add? We were not able to find significant differences between patients with PPP and those with palmoplantar plaque psoriasis regarding psoriasis, anamnesis, comorbidities or associated extrapalmoplantar psoriasis lesions. Our data suggest a close relationship between PPP and psoriasis. Available data concerning epidemiology, genetics, histopathology and pathogenesis do not permit a clear distinction between psoriasis and PPP. © 2013 The Authors. BJD © 2013 British Association of Dermatologists. Source

Ibrahim T.,Osteoncology Center | Sacanna E.,Osteoncology Center | Gaudio M.,Pathology Unit | Mercatali L.,Osteoncology Center | And 7 more authors.
Clinical Breast Cancer

Background: The RANK/RANKL/OPG system is active in primary cancers such as breast, prostate, and also in their bone metastases. CXCR4 chemokine receptor is highly expressed in human breast cancer cells and is believed to facilitate the homing of tumor cells to organs such as bone that express high levels of its ligand SDF1. Our study aimed to investigate whether the analysis of these markers with an inexpensive and simple test can help to predict bone metastases in breast cancer patients. Patients and Methods: Marker expression was evaluated by immunohistochemical staining in paraffin-embedded tissue sections of primary breast cancers from 40 individuals: 20 patients with bone metastases (BM), 10 with visceral metastases (VM; considered together as the relapsed group), and 10 with no evidence of disease (NED). Results: RANKL was not detected in tumor cells. OPG- and RANK-positive tumors are found with similar frequency in NED (20%) and in relapsed patients (23% and 17%, respectively). However, in the latter subgroup, only RANK positivity was always associated with bone relapse. The frequency of CXCR4-positive tumors was three-fold higher in relapsed (30%) than in NED (10%) patients and positivity was always linked to bone metastases. Considering NED and VM patients together versus BM patients, we observed that CXCR4 expression, alone (P =.008) or in combination with RANK (P <.001), identified patients destined to relapse to bone. Conclusion: Our results provide the first clinical evidence to support a pivotal role of combined CXCR4 and RANK expression in predicting bone relapse. © 2011 Elsevier Inc. All rights reserved. Source

Saragoni L.,Hospital G.B. Morgagni L. Pierantoni | Morgagni P.,Hospital G.B. Morgagni L. Pierantoni | Gardini A.,Hospital G.B. Morgagni L. Pierantoni | Marfisi C.,Hospital G.B. Morgagni L. Pierantoni | And 3 more authors.
Gastric Cancer

Background: The prevention and early diagnosis of gastric cancer permit clinicians to discover the tumor in the initial phase, during which time it can be completely eradicated, endoscopically or surgically. Since Murakami gave the definition of early gastric cancer (EGC) in 1971, many authors have identified various subtypes of EGC with different morphological characteristics and clinical behaviour. Methods: We evaluated retrospectively 530 patients: the median follow-up time was 10.4 months (range 0.3-29.2). All tumors were classified according to the macroscopic and microscopic criteria proposed by the Japanese Society of Gastroenterology and Endoscopy and Lauren, respectively. The infiltrative growth pattern was evaluated according to Kodama's classification. Only tumor-related death was considered as an endpoint of interest for the survival analysis. Results: The overall survival rates of our patients were 94 % (95 % CI, 92-96) and 90 % (95 % CI, 87-93) at 5 and 10 years, respectively. Only 44 patients (8.3 %) died of the disease. Kodama's type (p < 0.0001), lymph node status, both for number and pathological stage according to the 7th Edition of TNM (p < 0.0001), and depth of infiltration (p = 0.0006) were significant prognostic factors in univariate analysis. The multivariate analysis identified Kodama's PENA type (HR, 3.91; 95 % CI, 2.08-7.33; p < 0.0001) and lymph node status for more than three positive nodes versus negative nodes (HR, 12.78; 95 % CI, 5.37-30.43; p < 0.0001) as the only independent prognostic factors in our series. Conclusion: Lymph node status, especially when more than three lymph nodes are involved, is the most important prognostic factor in EGC. However, it is also important to evaluate the infiltrative growth pattern of the cancers in their early phase according to Kodama's classification, considering PEN A type lesions to be more aggressive than the other EGC types. Then, we propose new elements for an updated definition and classification of EGC, with an important clinical impact on the treatment of patients. © 2013 The International Gastric Cancer Association and The Japanese Gastric Cancer Association. Source

Brunasso A.M.G.,Medical University of Graz | Puntoni M.,Biostatistics and Clinical Trials Unit | Gulia A.,University of LAquila | Massone C.,Medical University of Graz

Objectives: To identify all of the patients affected by chronic hepatitis C infection treated with TNF-a blockers (adalimumab, certolizumab pegol, etanercept, golimumab and infliximab) in order to evaluate the safety profile. Methods: A systematic review of the literature from January 1990 to October 2010. Results: In total, 37 publications with data on 153 patients who were treated with anti-TNF-a agents in the setting of HCV infection were found. The mean anti-TNF-a treatment duration was 11.9 months. Ninety-one patients had RA, 22 had psoriasis, 6 had Crohn's disease and 14 patients had other chronic inflammatory diseases. To date, etanercept is the biological agent that has been most extensively used in the patients with HCV infection, with only one definitely confirmed case of HCV hepatitis worsening and five suspected cases (elevation of transaminases not associated with an increase in the HCV viral load and vice versa) in 110 treated patients. Treatment with this agent resulted in stable levels of liver transaminases and a stable viral load in 74 patients, with an improvement in HCV chronic liver disease in combination with IFN_ribavirin therapy in 29 patients. Conclusions: The safety profile of anti-TNF-a agents in the setting of HCV infection seems to be acceptable, even if differences in the hepatotoxic profile are apparent between different agents. In the absence of long-term and large, controlled clinical trials a definitive statement on the safety of anti-TNF-a therapies in the setting of chronic HCV infection cannot be made. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. Source

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