Molecular diagnosis of pancreatic cancer: where do we stand?

Pancreatic cancer remains a disease with a dismal prognosis due mostly to its late diagnosis. An early diagnosis would have a significant impact on the prognosis and, eventually, on the incidence of the disease itself. Many progresses have been made in the molecular diagnosis of pancreatic cancer. High risk patients would likely benefits from biologic screening, before the general population. Most of the markers remain limited to phase I and II studies. The challenges include the lack of specificity of some of the markers, as well as the lack of standardization within the laboratories. Further research is necessary prior to the application of the currently known biomarkers for the diagnosis of pancreatic cancer

Strong correlation between diet and development of colorectal cancer.

Multiple factors have been described among the causes of non-hereditary colorectal cancer. In Western countries, the most common risk factors include upper-middle socioeconomic status and dietary regimens rich in proteins and animal fats. High consumption of red meats, smoked foods, cold cuts, or canned foods is believed to contribute to carcinogenesis as they directly affect epithlial turnover and cause metabolism of biliary acids. Dietary fibers have protective effects in that they capture the fats and biliary acids, thereby inhibiting their activity. Tobacco smoking acts both locally and systemically on the colorectal mucosa through the production of carcinogenic agents. Finally, the action of alcohol, in association with nicotine addiction, also increases the risk of developing colorectal tumors. Knowledge of dietary and environmental factors is of paramount importance in implementing preventive strategies for colorectal cancer

Clinical and biological markers in gastric cancer: update and perspectives.

Gastric cancer is the second cause of death from cancer worldwide and the only chance to reach better outcomes lays on an early diagnosis. The need for non-invasive, low-cost tests is invoked also in countries in which imaging and endoscopic screening have already showed the ability to improve early diagnosis and overall survival. Genomic medicine could allow a better understanding of regulatory pathways driving the development and growth of gastric cancer and the characterization of specific molecular targets actually stimulate new drug developments. The knowledge of the role of Helicobacter pylori (HP) in gastric tumor pathogenesis has put new insides in the understanding of this peculiar disease and enriched the field of gastric biomarkers

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects

Repair of Parastomal Hernias with Biologic Grafts: A Systematic Review

Contains fulltext : 98303.pdf (publisher's version ) (Open Access)BACKGROUND: Biologic grafts are increasingly used instead of synthetic mesh for parastomal hernia repair due to concerns of synthetic mesh-related complications. This systematic review was designed to evaluate the use of these collagen-based scaffolds for the repair of parastomal hernias. METHODS: Studies were retrieved after searching the electronic databases MEDLINE, EMBASE and Cochrane CENTRAL. The search terms 'paracolostomy', 'paraileostomy', 'parastomal', 'colostomy', 'ileostomy', 'hernia', 'defect', 'closure', 'repair' and 'reconstruction' were used. Selection of studies and assessment of methodological quality were performed with a modified MINORS index. All reports on repair of parastomal hernias using a collagen-based biologic scaffold to reinforce or bridge the defect were included. Outcomes were recurrence rate, mortality and morbidity. RESULTS: Four retrospective studies with a combined enrolment of 57 patients were included. Recurrence occurred in 15.7% (95% confidence interval [CI] 7.8-25.9) of patients and wound-related complications in 26.2% (95% CI 14.7-39.5). No mortality or graft infections were reported. CONCLUSIONS: The use of reinforcing or bridging biologic grafts during parastomal hernia repair results in acceptable rates of recurrence and complications. However, given the similar rates of recurrence and complications achieved using synthetic mesh in this scenario, the evidence does not support use of biologic grafts

Clinical, Diagnostic and Therapeutic Aspects of Implantable Cardiac Electronic Device Infections. A Five-Year Retrospective Analysis and Comparison with Literature.

Background: Infections related to implantable cardiac electronic devices (IICEDs) are increasing in incidence. Aim of our study was to evaluate: epidemiological characteristics, risk factors and type of device in patients who developed ICEDs compared to the control group; b. microbial causes and resistances; c. main signs and symptoms, laboratory and instrumental investigations; d. treatment and prognosis. Material and Methods: the study was conducted with a retrospective method, analysing all cases of IICEDs registered in our ward from April 2009 to May 2014. For each patient, were evaluated epidemiological and clinical characteristics, risk factors, diagnostic procedures, aetiology and antibiotic assays, treatment and outcome. Results: In the investigated period, 22 cases of IICEDs were registered. Demographic factors didn’t affect the risk of ICEDs. Hypertension, usually considered a risk factor, resulted to be a protective factor (p=0.0329). Age younger than 65 years, female gender, altered BMI, diabetes, dyslipidemia and smoking appear to increase the risk of IICEDs, although not significantly. The oral anticoagulant therapy was found to be a predictive negative factor (p=0.0012) as well as the type of implanted device, with particular regard to intracardiac defibrillator and biventricular devices. CoNS were isolated in 68% of cases, Staphylococcus aureus in 25% and Enterococcus faecalis in 3.5%. A polimicrobial aetiology was registered in one case (3.5%). Among the CoNS, S. epidermidis was the most represented (28.55%), followed by S. hominis (14.3%) and S. haemoliticus (14.7%). The antibiotic assays showed a high proportion of methicillin resistance (34.8%) mainly related to S. epidermidis (71.4%) followed by S. aureus (14.3%). Rifampicin was found to be resistant in 8 cases (100%) by susceptibility testing. The treatment of ICEDs showed an important heterogeneity and a very long time waiting (12.22 months) between the diagnosis and the removal of the device. Of the 22 treated patients 7 died; 3 of them were older than 90 years while 4 were aged between 61 to 68 years. Conclusion: young age, smoking and altered BMI are factors associated to the development of IICEDs, even if not statistically significant. Hypertension resulted a statistically protective factor. The suspension of oral anticoagulation therapy and assumption of perioperative heparin was found to be statistically associated with the risk of IICEDs development, because it increases the risk of hematoma formation. According to literature data, the majority of the isolated microorganisms were Staphylococci (68% CoNS and 25% S. aureus) with high rates of methicillin (34.8%) and rifampicin (100%) resistance. The difference between systemic infections and infections localized to the generator pocket is not easily distinguishable, confirming the therapeutic need of the device removal in case of infection

Evaluation and comparison of deoxyribonucleic acid typing methods on human tissue fixed with different fixatives

Abstract. Commonly employed fixing fluids result in very satisfactory histomorphologic analysis; however, they don't allow deoxyribonucleic acid (DNA) typing methods to provide good results. This study investigated the effect of eight fixatives on DNA extracted from placenta samples. Fresh tissue (placenta) specimens were fixed by immersion in different fixing fluids for different periods (from 24 h to 60 days). Different DNA extraction methods were assayed. Gene Amp 2400 and 9700 Thermal Cyclers coupled to AmpFLSTR Identifier kit (Applied Biosystems), that allows the simultaneous amplification of 15 STRs loci, was used for quantification. Amplified products were analyzed by capillary electrophoresis on ABI PRISM 310 and 3100 Genetic Analyzers (Applied Biosystems).