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In routine clinical practice, hepatitis C virus-infected patients can prematurely discontinue the prescribed regimen for several reasons. The aim of our study was to investigate sustained virological response (SVR12) rates in patients who prematurely discontinued directly acting antiviral (DAA) regimens and to assess the shortest effective duration of DAA able to lead to SVR12. We retrospectively collected the SVR rates of patients, registered in the NAVIGATORE-Lombardia Network database from January 2015, who discontinued DAAs before the predefined end of treatment. Overall, we included 365 patients, males were the majority (213, 58.4%), mean age was 60.5years, and 53 (14.5%) patients were HIV-co-infected. Liver cirrhosis was observed in 251 (68.8%) subjects, and the most represented genotypes were 1b (n=168, 46%) and 3 (n=59, 16.2%). DAA was discontinued a median of 1 (IQR 1–4) weeks before the predefined EOT, with 164 (44.9%) patients stopping DAAs at least 2weeks before the planned schedule. In patients with F0–F3 liver fibrosis, lower rates of SVR12 were observed in patients treated for

Tommaso Susini,1 Barbara Berti,1 Carlo Carriero,1 Ketty Tavella,2 Jacopo Nori,3 Ermanno Vanzi,3 Cecilia Molino,1 Mariarosaria Di Tommaso,1 Marco Santini,1 Valeria Saladino,4 Simonetta Bianchi4 1Department of Health Science, Gynecology Section, 2Department of Health Science, Chemotherapy Section, University of Florence, Italy; 3Diagnostic Senology Unit, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy; 4Department of Surgery and Translational Medicine, Pathology Unit, University of Florence, Italy Purpose: Anthracyclines and taxanes are considered the standard for neoadjuvant chemotherapy of breast cancer, although they are often associated with serious side effects and wide variability of individual response. In this study, we analyzed the value of topoisomerase II alpha (TOP2A) and transducin-like enhancer of split 3 (TLE3) as predictive markers of response to therapy with anthracyclines and taxanes. Materials and methods: TOP2A and TLE3 protein expressions were evaluated using immunohistochemistry on 28 samples, obtained by core needle biopsy in patients with locally advanced breast carcinoma, subsequently subjected to epirubicin- and paclitaxel-based neoadjuvant chemotherapy. The immunohistochemical staining was correlated with the clinical response measured by the tumor size reduction evaluated by breast magnetic resonance imaging, prior and after chemotherapy, and by pathologic evaluation of the surgical specimen. Results: Neoadjuvant chemotherapy achieved a size reduction in 26/28 tumors (92.9%), with an average percentage decrease of 45.6%. A downstaging was achieved in 71.4% of the cases of locally advanced carcinoma. TOP2A positivity was correlated with a greater reduction in tumor diameter (P=0.06); negative staining for TLE3 was predictive of a better response to neoadjuvant chemotherapy (P=0.07). A higher reduction in tumor diameter (P=0.03) was also found for tumors that were concurrently TLE3-negative and TOP2A-positive. Conclusion: TOP2A and TLE3 showed a correlation with response to neoadjuvant chemotherapy. While TOP2A is a well-known marker of response to anthracyclines-based chemotherapy, TLE3 is a new putative predictor of response to taxanes. Data from the current study suggest that TOP2A and TLE3 warrant further investigation in a larger series as predictors of response to neoadjuvant chemotherapy for locally advanced breast carcinoma. Keywords: breast carcinoma, advanced stage disease, immunohistochemical markers

AIM: The aim of the study was to investigate the utility of NT-proBNP measurement for the stratification of presurgical cardiac risk. METHODS: Cardiac risk before elective non-cardiac surgery was evaluated in 82 consecutive patients. From each patient a venous blood sample was drawn to determinate NT-proBNP levels. Patients were followed up over three months in order to detect the occurrence of cardiac adverse events. RESULTS: NT-proBNP was positively correlated (P

INTRODUCTION: the report describes the features of a low cost, open mini-invasive procedure for cholecystectomy in a sample of 121 consecutive high risk elderly (ASA score 3 to 5). PATIENTS AND METHODS: the surgery is performed through a 3 - 4 cm right subcostal skin incision. An optimal exposition of the operating field was achieved thanks to an innovative three valve retractor. RESULTS: a mean hospital stay of 3,02 days, low complication rate and 2,4% mortality are the results of the described procedure. CONCLUSIONS: in high risk elderly the results are extremely encouraging, particularly in comparison with both laparoscopic and traditional open cholecystectomy. The open minisurgical cholecystectomy could be considered a cost-effective alternative to laparoscopy, with excellent results in this subset of patients. The described mini-surgical procedure can also integrate the laparoscopic in case of conversion.

In this laboratory activity, the Fiber Optic Reflectance Spectroscopy (FORS) and the Optical Microscopy (MO) techniques will be introduced. After a brief introduction about the theory, instrumentations and applications of both techniques, the students will see the application of the following equipment: -Digivision 1.3 megapixel USB digital optical microscope -Ocean Optics USB2000 + XR1 portable reflection UV-vis spectrophotometer with DH-mini UV-Vis-NIR source and reflection probe. The acquisition of MO images and of FORS spectra will be performed on pigments of some archeological ceramics, stones with and without a protective and on patina of metal alloys. The MO images of each artifacts will be discussed. Data analysis of FORS spectra will be illustrated. The colour parameters will be also calculated and some considerations about their meaning will be made.

In the last 10 years, cancer stem cells have interested the scientific community because this small tumorigenic population is also associated with tumor progression in human patients and specific targeting of cancer stem cells could be a strategy to eradicate cancers currently resistant to conventional therapy. Clinical studies have recently demonstrated that adding immune therapy to chemotherapy has survival benefits in comparison with chemotherapy alone that can sensitize tumors to immune cell-mediated killing (e.g., increasing sensitivity of tumor cells to subsequent cytotoxicity by T cells via upregulation of death receptors DR5 and Fas). However, loss of MHC molecules is often observed in cancer cells, rendering tumor cells resistant to CD8 T-cell-mediated cytotoxicity. For this reason, we review the role of other T-cell subsets, such as γδ T and NK cells that are able to efficiently recognize and kill tumor cells and that could be used in passive or active immunotherapy in cancer stem cell eradication.

Paragangliomas (PGs) of the head and neck region are typically benign, slow-growing neuroendocrine tumours. At times, they may exhibit unusual histological features, such as prominent stromal sclerosis (sclerosing PG), which may raise concerns of malignancy. We describe a case of sclerosing PG of the carotid body, emphasizing the value of immunohistochemical stains for differential diagnosis. A 43-year-old woman presented with a painless lump on the neck. A magnetic resonance imaging scan demonstrated a hypervascular lesion of the carotid body, which was surgically excised. Grossly, the lesion measured 1.8 cm at maximum diameter. On microscopic examination, irregular nests and tiny bundles of neoplastic cells were found between thick bands of fibrous tissue. Focal nuclear cytomegaly and marked pleomorphism were noted. Neoplastic cells proved to be immunoreactive for chromogranin, synaptophysin and neuron specific enolase, but negative for cytokeratins, smooth muscle actin and CD34. Ultrastructurally, numerous mitochondria, rough endoplasmic reticulum structures and endocrine granules were seen in the cytoplasm of the tumour cells. On consideration of the above-mentioned clinico-pathological and ultrastructural findings a diagnosis of sclerosing PG was established. Sclerosing PG is a rare entity which may mimic a malignant neoplasm. The recognition of this unusual morphological variant of PG, together with appropriate immunostains, leads to the correct diagnosis.

Leukocytes are thought to play an important role in the pathogenesis of inflammatory bowel diseases; granulocyte monocyte adsorptive (GMA) apheresis, an extracorporeal technique aimed at removing activated circulating leukocytes from the blood, may represent a safe and effective therapeutic tool in these patients. The Italian Registry of Therapeutic Apheresis performed an observational, multicentric study involving 24 Gastroenterology Units. In this study, laboratory data and clinical outcomes of 230 patients (148 males, mean age 43.5 years) affected with ulcerative colitis (UC, n 5 194) or Crohn’s disease (CD, n 5 36) who underwent one or more cycles of GMA were analyzed. Each cycle consisted of five GMA treatments. The patients were followed up for a mean of 8.7 (min. 3 to max. 12) months. At 3 months, positive outcome was achieved in 77.7% of UC patients (72.0% remission, 5.7% clinical response) and 61.3% of CD patients (54.8% remission, 6.5% clinical response). The cumulative proportion of positive outcome at 12 months was 87.1% for UC patients (83.7% remission, 3.4% clinical response) and 77.4% for CD patients (74.2% remission, 3.2% clinical response). No single clinical or laboratory parameter among those analyzed (age, sex, disease characteristics, history of smoking, medication history, baseline values of clinical activity index (CAI)/Crohn’s disease activity index (CDAI), hemoglobin, white blood cells count, and erythrocyte sedimentation rate) was independently associated with clinical outcome. The procedure was well tolerated with no significant adverse effects registered. J. Clin. Apheresis 26:332–337, 2011.

Background: Until few years ago, all neoplastic cells within a tumour were suggested to have tumorigenic capacity, but recent evidences hint to the possibility that such feature is confined to a subset of Cancer Initiating Cells (CICs), also called Cancer Stem Cells (CSCs). These cells are the reservoir of the heterogeneous populations of differentiated cancer cells constituting the tumour bulk. Mechanisms shared with somatic stem cells, such as quiescence, self-renewal ability, asymmetric division and multidrug resistance, allow to these cells to drive tumour growth and to evade conventional therapy. Objective: Here, we give a brief overview on the origin of CICs, the mechanisms involved in chemoresistance and therapeutic implications. Conclusion: Current cancer treatments, based on the assumption that tumour cell population responds homogeneously, have been developed to eradicate proliferating cells. The new model of tumorigenesis entails significant therapeutic implications, in fact if a small fraction of CICs survives conventional therapy it may lead to recurrence after month or years of apparent remission. Selective targeting of CICs could eliminate the tumour from the root, overcoming the emergence of clones capable of evading traditional therapy and increasing overall disease free survival.

This study examines how family functioning, the parent-child relationship and personal factors are related to happiness in 1549 children aged 7 to 14 years old (53% females) in Italy. Children and pre-adolescents completed a set of questionnaires on self-rated happiness, self-concept and loneliness. At least one of their parents filled in questionnaires on family functioning, attachment and their child’s happiness level. No gender differences were found in the direct measure of happiness, but younger participants were happier than older participants, according to both the children’s and parents’ evaluations. Happiness is influenced by positive self-concept, self-esteem and low levels of satisfaction but family functioning does not seem to play a major role. The clinical and social implications of the study are discussed., peer-reviewed