San Giovanni al Natisone, Italy
San Giovanni al Natisone, Italy

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Foltran F.,University of Padua | Ballali S.,Prochild ONLUS | Passali F.M.,University of Rome Tor Vergata | Morra B.,San Giovanni Battista Molinette Hospital | And 4 more authors.
International Journal of Pediatric Otorhinolaryngology | Year: 2012

Background: Very recently, some attempts have been made to start a systematic collection of foreign bodies (FB) in view of using them to characterize the risk of chocking in terms of size, shape and consistency of the FB. However, most of the epidemiologic evidence on foreign bodies in children comes from single-center retrospective studies, without any systematic geographical and temporal coverage. This paper is aimed at providing an estimate of the distribution of foreign body's injuries in children according to gender, age, type of FB, site of obstruction, clinical presentation, diagnostic/therapeutic procedures, complications, as emerging from a meta-analytic review of published papers. Methods: A free text search on PubMed database ((foreign bodies) OR (foreign body)) AND ((aspiration) OR (airways) OR (tracheobronchial) OR (nasal) OR (inhalation) OR (obstruction) OR (choking) OR (inhaled) OR (aspirations) OR (nose) OR (throat) OR (asphyxiation)) AND ((children) OR (child)) finalized to identify all English written articles referring to foreign body inhalation over a 30. years period (1978-2008) was performed. The target of the analysis has been defined as the proportion of injuries as reported in the studies, stratified according to children demographic characteristics, type of FB, site of obstruction. The pooled proportions of FB were calculated using the DerSimonian and Laird approach. Results: 1699 papers were retrieved and 1063 were judged pertinent; 214 English written case series were identified, among them 174 articles were available and have been included in the analysis. Airway foreign body most commonly occurs in young children, almost 20% of children who have inhaled foreign bodies being between 0 and 3. years of age. Organic FB, particularly nuts, are the most documented objects while, among inorganic FBs, the greatest pooled proportion has been recorded for magnets, which can be particularly destructive in each location. Non specific symptoms or a complete absence of symptoms are not unusual, justifying mistaken or delayed diagnosis. Acute and chronic complications seem to occur in almost 15% of patients. Conclusions: Even if an enormous heterogeneity among primary studies seems to exist and even if the absence of variables standardized definitions across case series, including class age definition and symptoms and signs descriptions, seriously impairs studies comparability, our results testify the relevant morbidity associated with foreign body inhalation in children, stressing the importance of preventive measures. © 2012 Elsevier Ireland Ltd.


Rolfo C.,University of Antwerp | Giovannetti E.,VU University Amsterdam | Hong D.S.,University of Houston | Bivona T.,University of California at San Francisco | And 14 more authors.
Cancer Treatment Reviews | Year: 2014

Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs. Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal-epithelial transition factor (MET) amplification, epithelial-mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeutic strategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking of multiple members of the ErbB family. Several molecules which target multiple ErbB receptors are being investigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitinib and lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance (T790M) mutations, are currently under clinical development. Other therapeutic strategies include inhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 or poly (ADP-ribose) polymerase in addition to mammalian target of rapamycin (mTOR), monoclonal antibodies against the insulin-like growth factor-1 receptor, and fulvestrant-mediated oestrogen receptor regulation. Conclusion: Improved understanding of mechanisms underlying resistance to EGFR TKIs emphasises the importance of a genotype-guided approach to therapy. Elucidation of resistance mechanisms is indeed crucial to target innovative therapeutic approaches and to improve the efficacy of anticancer regimes in NSCLC. © 2014 Elsevier Ltd.


Ferrario A.,University of Milan | Pulsoni A.,University of Rome La Sapienza | Olivero B.,University of Milan | Rossi G.,Spedali Civili | And 11 more authors.
Cancer | Year: 2012

BACKGROUND: Indolent nonfollicular non-Hodgkin B-cell lymphomas (INFLs) are clonal mature B-cell proliferations for which treatment has not been defined to date. METHODS: In this phase 2 study of patients with advanced INFL, the authors evaluated the efficacy and safety of first-line rituximab, fludarabine, and cyclophosphamide (FCR) as induction immunochemotherapy (rituximab 375 mg/m 2 intravenously on day 1 of each cycle and on days 1 and 14 of cycles 4 and 5; fludarabine 25 mg/m 2 intravenously on days 2-4, cyclophosphamide 250 mg/m 2 intravenously on Days 2-4) every 28 days for 6 cycles followed by a maintenance phase with 4 infusions of rituximab (375 mg/m 2 intravenously on day 1) every 2 months for responders. RESULTS: Forty-seven patients were enrolled. Among 46 evaluable patients (28 men; median age, 59 years), 19 were diagnosed with lymphoplasmacytic lymphoma, 21 were diagnosed with small lymphocytic lymphoma, and 6 were diagnosed with nodal marginal zone lymphoma. The overall response rate after maintenance was 89.1% with a 67.4% complete remission (CR) rate (CR/unconfirmed CR) and a 21.7% partial response rate. After a median follow-up of 40.9 months, the failure-free survival and progression-free survival rates both were 90.1%, and the overall survival rate was 97.4%. The main toxicity was hematologic, and related grade 3 and 4 neutropenia was observed in 55.3% of patients. CONCLUSIONS: FCR induction therapy followed by a short maintenance phase is a highly effective regimen with acceptable toxicity. Cancer 2012. © 2011 American Cancer Society. Indolent nonfollicular non-Hodgkin B-cell lymphomas are clonal mature B-cell proliferations for which treatment has not been defined to date. The combination of rituximab, fludarabine, and cyclophosphamide as induction immunochemotherapy followed by a short maintenance phase with rituximab is a highly effective regimen with acceptable toxicity in this subset of lymphomas. Copyright © 2011 American Cancer Society.


Oderda G.,University of Novara | Marietti M.,San Giovanni Battista Molinette Hospital | Pellicano R.,San Giovanni Battista Molinette Hospital
Minerva Pediatrica | Year: 2015

Helicobacter pylori (H. pylori) infection is a large worldwide infection usually acquired during childhood, whose prevalence in pediatric population varies, with lower incidence rates in developed countries compared to developing countries (up to 10-15% and 70%, respectively). Diagnosis can be performed both with endoscopic-based methods and noninvasive diagnostic tests, such as urea breath test and fecal antigen. Current guidelines recommend endoscopic evaluation of the young patients, in order to determine the underlying cause of abdmonal pain. Even in case of suspected functional pain, patient should not be investigated for infection, unless upper endoscopy is performed to rule out organic causes. Nowadays, in pediatric population, applications of noninvasive tests are limited to verifying eradication after therapy and to investigating the presence of infection in asymptomatic patients with first-degree relatives affected by gastric cancer. Since correlation between abdominal pain and H. pylori gastritis, in absence of peptic ulcer disease is still debated, "test and treat" strategy is not recommended in children. As for adults, treatment regimens are based on the combination of proton-pump inhibitor and two or more antibiotics, for 7-14 days, depending on resistance rates of geographic areas.


De Rosa F.G.,University of Turin | Motta I.,University of Turin | Audisio E.,San Giovanni Battista Molinette Hospital | Frairia C.,San Giovanni Battista Molinette Hospital | And 3 more authors.
BMC Infectious Diseases | Year: 2013

Background: Infections are a common cause of morbidity and mortality in patients with acute myeloid leukemia (AML). The evidence for efficacy of antibiotic prophylaxis in reducing the mortality rates and the incidence of bacterial infections was also reported by a systematic review published by Cochrane in 2012. The objective of our study was to report the incidence and the etiology of bloodstream infections in patients with AML undergoing levofloxacin prophylaxis during neutropenic episodes.Methods: This was a retrospective study of patients with diagnosis of AML during 2001-2007.Results: A total of 81 patients were included in the study. Two hundred and ninetyone neutropenic episodes were studied, of which 181 were febrile. Bacteria isolated from blood cultures were mostly Gram-positives during the induction (80%) and Gram-negatives during the consolidation (72.4%) phases of chemotherapy. Resistance to ciprofloxacin was found in 78.9% of isolated E. coli and it was higher during consolidation and higher than the hospital rate. The production of extended spectrum betalactamases (ESBL) in E. coli strains was reported in 12.1%, below the reported hospital rate during the study period.Conclusions: Regular microbiology surveillance is needed to better understand the impact of levofloxacin prophylaxis in neutropenic patients. Our study shows that Gram-positive bacteria are predominant during the induction phase of chemotherapy and Gram-negatives during the consolidation. The rate of fluoroquinolone resistance in the latter setting, even higher than the hospital rate, may suggest to reconsider levofloxacin prophylaxis. © 2013 De Rosa et al.; licensee BioMed Central Ltd.


Ojetti V.,Catholic University | Pellicano R.,San Giovanni Battista Molinette Hospital | Fagoonee S.,University of Turin | Migneco A.,Catholic University | And 2 more authors.
Minerva Medica | Year: 2010

The bacterium Helicobacter pylori (H. pylori), prime causal agent of gastroduodenal diseases, has been involved in various aspects of several extragastric manifestations. Although currently available data do not provide proof of its role in most of them, a potential relationship cannot be ruled out. In the present review, the consistency of a role of H. pylori infection in the pathogenesis of diabetes mellitus (DM) as well as in the gastric abnormalities of diabetics is analyzed and critically discussed. Several controversies emerge from the epidemiological data. The clinical consequence of H. pylori infection in terms of metabolic control seems to be low. Regarding interventional studies, the bacterial eradication rate is significantly lower in DM patients than in controls. The difference in the eradication rate observed between adults and children affected by diabetes could be due to the fact that the latter have no history of repeated infectious diseases and antibiotic treatments, with minor antibiotic-resistant H. pylori strain selection. Finally, a higher H. pylori re-infection rate in DM patients than in general population has been shown.


Rolfo C.,University of Antwerp | Raez L.E.,Memorial Cancer Institute | Bronte G.,University of Palermo | Santos E.S.,Lynn Cancer Institute | And 4 more authors.
Expert Opinion on Investigational Drugs | Year: 2013

Introduction: Several new targeted agents with anti-angiogenic properties have been developed recently, including vandetanib, sunitinib, sorafenib, bevacizumab and others. Tumor development, progression, metastasis are strongly linked to angiogenesis. Targeted agents like bevacizumab, a monoclonal antibody which targets VEGF, have been fully developed in several solid tumors. These new agents strongly advocate that targeting angiogenesis is one of the best approaches for cancer therapy. Areas covered: Those agents that target additional pro-angiogenic intracellular signaling pathways beyond VEGF signaling have also the potential to contribute to anticancer therapies. The authors present here nintedanib (BIBF 1120), a triple angiokinase inhibitor. It targets not only VEGFRs, but also FGFR and PDGFR. All the available clinical information regarding Phase I-II trials and the toxicity and efficacy of BIBF 1120 both as single agent and in combination with cytotoxic agents in non-small cell lung cancer (NSCLC) is reviewed and discussed here. Expert opinion: Up till now, Phase I and II trials with nintedanib showed an improvement for survival of advanced NSCLC patients. Tolerability profile seems to be acceptable in these clinical trials. However, Phase III trials are mandatory to translate these findings into clinical practice. The research for predictive biomarkers could improve the success of these anti-angiogenic agents. © 2013 Informa UK, Ltd.


Adriani A.,San Giovanni Battista Molinette Hospital | Repici A.,IRCCS Instituto Clinico Humanitas | Hickman I.,Princess Alexandra Hospital | Pellicano R.,San Giovanni Battista Molinette Hospital
Minerva Medica | Year: 2014

Helicobacter pylori (H. pylori) has been conclusively related to several gastroduodenal diseases. The possible role of the bacterium in the development of extragastric manifestations has been investigated in the past few years. To identify all publications on the association between H. pylori and respiratory diseases, a MEDLINE search of all studies published in English from 1965 to 2013 was conducted. All data are based on case-control studies. Controversial findings of H. pylori seroprevalence have been obtained in patients with bronchial asthma, lung cancer, pulmonary tuberculosis, sarcoidosis, cystic fibrosis, chronic bronchitis and bronchiectasis. At present, on epidemiological bases, there is no definite evidence of a causal relationship between H. pylori infection and respiratory diseases. There is a low consideration of confounding factors as poorer socioeconomic status and tobacco use. The activation of proinflammatory cytokines by H. pylori might be a possible pathogenetic mechanism. However, there are no convincing data about the influence of H. pylori on the inflammatory changes of the bronchoepithelium so far. Further studies are needed on the impact of H. pylori eradication, on the prevention, development and natural history of these disorders.


Vandone A.M.,Coes Subalpine Oncohematology Cancer Center | Donadio M.,Coes Subalpine Oncohematology Cancer Center | Mozzati M.,San Giovanni Battista Molinette Hospital | Ardine M.,Coes Subalpine Oncohematology Cancer Center | And 4 more authors.
Annals of Oncology | Year: 2012

Background: Osteonecrosis of the jaw (ONJ) is associated with bisphosphonate (BP) therapy and invasive dental care. An Interdisciplinary Care Group (ICG) was created to evaluate dental risk factors and the efficacy of a preventive restorative dental care in the reduction of ONJ risk.Patients and methods: This prospective single-center study included patients with bone metastases from solid tumors. Patients who received at least one BP infusion between October 2005 and 31 August 2009 underwent one or more ICG evaluation and regular dental examinations. We also retrospectively evaluated patients with bone metastases from solid tumors who did not undergo dental preventive measures.Results: Of 269 patients, 211 had received at least one infusion of BP therapy: 62% were BP naive and 38% had previous BP exposure. Of these 211 patients followed for 47 months, 6 patients developed ONJ (2.8%). Of 200 patients included in the retrospective analysis, 11 patients developed ONJ (5.5%).Conclusions: In comparison with published ONJ rates and those extrapolated from the retrospective analysis, the observed ONJ rate in the prospective group was lower, suggesting that implementation of a preventive dental program may reduce the risk of ONJ in metastatic patients treated with i.v. BP therapy. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Casadei R.,University of Bologna | Ricci C.,University of Bologna | Silvestri S.,San Giovanni Battista Molinette Hospital | Campra D.,San Giovanni Battista Molinette Hospital | And 5 more authors.
Pancreatology | Year: 2013

Objective: To evaluate Peng's binding pancreaticojejunostomy as a safe technique which avoids anastomotic leakage after a pancreaticoduodenectomy. Methods: Prospective, observational, dual-institutional study, of patients who underwent a Peng's binding pancreaticojejunostomy was conducted. It was compared with an historical control group of patients who underwent duct to mucosa pancreaticojejunostomy. Overall postoperative mortality, morbidity, postoperative pancreatic fistulas, postpancreatectomy hemorrhage, reoperation, length and costs of hospital stay were collected. Factors related with pancreatic fistula were: sex, age, comorbidities, body mass index, American Society of Anesthesiologists score, type of resection, extension of resection, characteristics of the pancreatic remnant, pathological diagnosis and surgeons. Univariate and multivariate analyzes were carried out. Results: Sixty-nine patients who underwent binding pancreaticojejunostomy were reported. The control group consisted of 52 patients. The mean length of hospital stay was significantly shorter in the control group than in binding group (p = 0.003). Multivariate analyzes showed that soft pancreatic remnant was significantly related to an increasing rate of postoperative pancreatic fistula (OR 3.7-CI 1.1-12.8- P = 0.034) while the type of pancreatic anastomosis was not significantly related with the occurrence of postoperative pancreatic fistula. Conclusions: In the European population, the binding pancreaticojejunostomy according to Peng did not preclude or reduce the postoperative pancreatic fistula rate. Copyright © 2013, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.

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