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BACKGROUND: Nucleic acid testing (NAT) for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) has been implemented in several European countries and in the United States, while hepatitis B virus (HBV) NAT is still being questioned by opinions both in favor and against such an option, depending on the HBV endemicity, health care resources, and expected benefits. STUDY DESIGN AND METHODS: This survey was aimed to assess the NAT impact in improving the safety of blood supply in Italy, 6 years after implementation. The study involved 93 Italian transfusion centers and was carried out in 2001 through 2006. A total of 10,776,288 units were tested for the presence of HCV RNA, 7,932,430 for HIV RNA, and 3,405,497 for HBV DNA, respectively. RESULTS: Twenty-seven donations or 2.5 per million tested were HCV RNA–positive/anti-HCV–negative; 14 or 1.8 per million units tested were HIV RNA–positive/anti-HIV–negative; and 197 or 57.8 per million donations tested were HBV DNA–positive/hepatitis B surface antigen–negative. Of the latter, 8 (2.3/106) were collected from donors in the window phase of infection and 189 (55.5/106) from donors with occult HBV. Sixty-eight percent of the latter donors had hepatitis B surface antibody, 74.5 percent of whom with concentrations considered protective (≥10 mIU/mL). CONCLUSION: NAT implementation has improved blood safety by reducing the risk of entering 2.5 HCV and 1.8 HIV infectious units per million donations into the blood supply. The yield of NAT in detecting infectious blood before transfusion was higher for HBV than for HCV or HIV. However, the benefit of HBV NAT in terms of avoided HBV-related morbidity and mortality in blood recipients needs to be further evaluated.

During the 1990s, with the general tendency to develop minimally invasive operations, an endoscopic approach has been applied to neck surgery for both parathyroidectomy and thyroidectomy. The most widely spread minimally invasive technique for thyroidectomy is minimally invasive video assisted thyroidectomy (MIVAT), described and developed for the first time at our institution in 1998. Ideal candidates for MIVAT are patients with a thyroid volume lower than 25ml with nodules smaller than 35 mm. Consequently, MIVAT will present restricted indications, being suitable only for the treatment of about 10-15% of the whole standard surgical case load. Thus, together with small follicular lesions, "low risk" papillary carcinoma will result the main indication for MIVAT, being this small cancer usually harboured in normal glands of young females. On the other hand, in case of locally invasive carcinomas and/or lymph node metastasis the procedure must be immediately converted to the conventional technique. MIVAT also is not indicated for the treatment of medullary and anaplastic carcinomas. Recent prospective randomized studies clearly demonstrate that MIVAT allows achieving same clearance at the thyroid bed level and same outcome as conventional technique, when dealing with "low risk" papillary carcinoma. At the same time, patients can benefit from the main advantages of this minimally invasive technique: lower postoperative pain, faster postoperative recovery and excellent cosmetic outcome.

In 1997 a Minimally Invasive Video Assisted Technique for Parathyroidectomy (MIVAP) was developed in the University of Pisa. In this review we examine the last three years of MIVAP (240 cases) in order to identify the advantages and the limits of the procedure after the first-period development of the technique.In our experience, 65% of patients affected by primary hyperparathyroidism (PHPT) turned out to be eligible for MIVAP. During the first years several selection criteria were strictly followed; more recently, some initially absolute contraindications to the operation have been interpreted more flexibly. Mean operative time is 35 minutes. 18 conversions (7.5%) to traditional open cervicotomy were needed and in 4 cases (1.6%) no affected parathyroid tissue was removed.At present, we consider absolutely necessary for MIVAP: preoperative localization of an adenoma with at least one imaging study (US or MIBI scintiscan) and the availability of QPTH intraoperative assay. No absolute contraindications other than the size of the lesions and the suspect of parthyroid carcinoma are identified for patients with PHPT. Moreover, MIVAP has proved to have further advantages when compared to other mini invasive procedures such as the demonstrated possibility to perform a traditional bilateral exploration, when indicated. Nevertheless, a great degree of experience is requested for this procedure. In conclusion, MIVAP permits to significantly reduce postoperative pain, size of the incision, days of hospitalisation and, finally, the cost of the entire procedure without affecting in any way the success rate of the traditional operation and without an increase of the complications.

This study reviews four years of Minimally Invasive Video Assisted Thyroidectomy (MIVAT) technique and compares the results to those of traditional thyroid surgery.Between 1999 and 2002, a series of 427 patients were submitted to MIVAT at our Department. Selection criteria were: thyroid nodule maximum diameter of 3.5 cm, total thyroid volume under 25 cc, no signs associated thyroiditis, diagnosis of benign thyroid disease or "low risk" thyroid tumor, no evidence of nodal disease of the neck.We operated on 362 females and 65 males and the mean age of the population was 39.6 years (range 10-77). A total thyroidectomy was performed in 208 cases, and 219 patients underwent a single-side procedure. Mean operative time was 30.4 minutes for lobectomy (range 20-140 minutes) and 50.2 for total thyroidectomy (range 35-140). Complications were represented by definitive recurrent nerve palsy in 3 patients (0.7%) and one case of definitive hypoparathyroidism (0.4%). A wound infection is reported in 3 cases and we had no major bleeding that required surgical revision. A conversion to open procedure was performed in 5 cases (1.2%); mean hospitalisation was 1.28 days (range: 1-4).This series demonstrates that MIVAT is not different to conventional open surgery in terms of complications, radicality of the procedure and operative time. Moreover, even if not statistically proved, MIVAT appears to offer some advantages in terms of cosmetic results and postoperative pain. In conclusion, we believe that MIVAT is a perfectly reproducible and safe technique for both benign and low-risk malignant thyroid disease, when correct indications are strictly followed.

Metadata only record Globally, many poor households rely on agriculture for their livelihoods, and this remains true even when livelihoods are diversified. Poor households are also most vulnerable to undernutrition, including lack of micronutrients. Over the last decades, a variety of organizations have aimed to harness agriculture for nutrition. Agricultural approaches have the potential to substantially impact nutritional outcomes in a sustainable way, but there is insufficient understanding of the evidence base for this potential impact and of how best to achieve this potential. This chapter aims to consolidate the available evidence linking agricultural interventions to nutrition outcomes. First, the chapter describes five pathways through which agricultural interventions can impact nutrition: consumption of own production; increases in income; reductions in market prices; shifts in consumer preferences; and shifts in control of resources. Second, we review four types of studies that provide insights about links between agriculture and nutrition: early studies of agricultural commercialization; studies of women in agriculture; studies of horticultural interventions; and studies of livestock and aquaculture interventions. Consistent themes include the importance of integrating well-designed behaviour-change communications and careful consideration of gender dimensions. Third, we present two case studies that show how well-designed interventions can successfully diversify diets and/or impact micronutrient intakes and nutritional status outcomes; the second case study illustrates impact at scale. The review yields lessons for design of future interventions and for evaluation design, and identifies critical areas for future work, which include investigations of cost-effectiveness, scaling up processes and sustainability. (CAB Abstracts).

Tumour-associated Macrophages (TAM) present two different polarizations: classical (M1) characterized by immunostimulation activity and tumour suppression; alternative (M2) characterized by tumour promotion and immune suppression. In this retrospective study, we evaluated the correlation between the two forms of TAM with survival time in radically resected gastric cancer patients. A total of 52 chemo- and radio- naive patients were included. Two slides were prepared for each patient and double-stained for CD68/NOS2 (M1) or CD68/CD163 (M2) and five representative high-power fields per slide were evaluated for TAM count. The median value of the two macrophage populations density and the median value of M1/M2 ratio were used as cut-off. Twenty-seven patients with M1 density above-the-median had a significantly higher survival compared to those below the median. Twenty-six patients with M1/M2 ratio above the median showed median OS of 27.2 months compared to 15.5 months of the patients below the median. No association between M2 macrophage density and patient’s outcome was found. In multivariate analysis, M1/M2 was a positive independent predictor of survival. The M1 macrophage density and M1/M2 ratio, as con- firmed in multivariate analysis, are factors that can help in predicting patients survival time after radical surgery for gastric cancer.

Aims: To demonstrate the antiproliferative and pro-apoptotic activity of the novel pyrazolopyrimidine derivative multiple tyrosine kinase inhibitor CLM3, alone and in combination with SN-38 (the active metabolite of irinotecan), on endothelial and tumor cells and to show its mechanism of action. Methods: Proliferation and apoptotic assays were performed on microvascular endothelial (HMVEC-d) and lung (A549) and thyroid cancer (8305C, TT) cell lines exposed to CLM3 and to the simultaneous combination with SN38 for 72 h. Cell-based phospho-VEGFR-2, phospho-EGFR and phospho-RET inhibition assays were performed and ERK1/2 and Akt phosphorylation were quantified by ELISA kits. Cyclin D1 gene expression was performed with real-time PCR and cyclin D1 intracellular concentrations were measured by ELISA. Results: A strong effect on antiproliferative and pro-apoptotic activity was found with the CLM3 on endothelial and cancer cells, synergistically enhanced by SN38. Phospho-VEGFR-2, phospho-EGFR and phospho-RET levels significantly decreased after CLM3 treatments in activated endothelial and cancer cells; ERK1/2 and Akt phosphorylation were significantly inhibited by lower concentrations of the pyrazolopyrimidine drug in endothelial cells if compared to cancer cells. Moreover, CLM3 treatment greatly inhibited the expression of the cyclin D1 gene in endothelial and cancer cells, decreasing the cyclin D1 protein intracellular concentration. Conclusions: The pyrazolopyrimidine derivative CLM3 demonstrated a highly significant and promising antiproliferative and proapoptotic activity, alone and in combination with SN-38, for activated endothelial and cancer cells. These effects are mainly due to its inhibition of phosphorylation of VEGFR-2, EGFR and RET tyrosine kinases and their related signaling pathways. © 2011 Elsevier Inc. All rights reserved.

Let $mu_n$ be a probability measure on the Borel $sigma$-field on $D[0,1]$ with respect to Skorohod distance, $ngeq 0$. Necessary and sufficient conditions for the following statement are provided. On some probability space, there are $D[0,1]$-valued random variables $X_n$ such that $X_nsimmu_n$ for all $ngeq 0$ and $ ormX_n-X_0 ightarrow 0$ in probability, where $ ormcdot$ is the sup-norm. Such conditions do not require $mu_0$ separable under $ ormcdot$. Applications to exchangeable empirical processes and to pure jump processes are given as well.

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This article reports on recent advances on metastatic breast cancer. Detection, prognostic factors, predictors of response to therapy and therapy, with particular regard to targeted therapies, were examined. Detection: Unlike current guidelines that yet do not routinely recommend intensive clinical-instrumental post-operative follow-up of breast cancer patients, relatively large data collected in the last decades have shown that an intensive post-operative follow-up with 'dynamic evaluation' of a suitable tumour marker panel precedes a few months as average the clinical and/or instrumental sign of a pending relapse in most relapsed patients and largely limits the use of the common instrumental examinations. Prognosis and therapy predictors: Disease-free interval (DFI) ≤ 24 months, adjuvant chemotherapy, liver and distant soft tissue involvement or DFI > 24 months and disease confined to bony skeleton are prognostic factors more often correlated with relatively poor or prolonged survival, respectively. Estrogen receptor (ER) expression in primary tumour and at the relapse correlates strongly with response to salvage hormone therapy and data from large trials showed that 38-59% of ER and/or PR+ post-menopausal patients had clinical benefit from first line tamoxifen or aromatase inhibitors. An inverse correlation of ER with epidermal growth factor receptor (EGFR) has been found. The co-expression of HER-2/neu and/or elevated serum HER-2/neu protein level were associated with a low rate and shorter duration of response of ER+ patients to first line hormone therapy. Accordingly, ER-EGFR- compared with ER-EGFR+ tumours are usually more responsive to endocrine therapy. High class III beta-tubulin expression or fall in insulin-like growth factor binding protein-3 (IGFBP-3) from baseline levels have been found to significantly predict resistance to chemotherapeutic agents. Therapy: Liposomes as carrier of doxorubicin (Caelix, Evacet, Myocet) is one approach to decrease the anthracycline-related cardiac toxicity. Weekly paclitaxel or docetaxel and oral formulation of vinorelbine and 5-fluorouracil (5-FU) (capecitabine) provide new effective and well tolerated options that reach greater dose intensity and cumulative dose than with the conventional schedules. As to the so called 'tailored' or targeted therapies, the more potent and highly selective third generation of aromatase inhibitors (letrozole, anastrozole, exemestane) targeting ER+ tumours by estrogen deprivation, challenge tamoxifen as current standard first line therapy in postmenopausals. One pilot study showed that stimulation of cellular immunity by the addition of beta-interferon-interleukin-2 sequence in patients on clinical benefit on first line tamoxifen significantly prolonged median overall survival (OS) and duration of response compared to that observed in similar patients only treated with tamoxifen. Trastuzumab, a humanised monoclonal antibody to extracellular domain of HER-2, plus conventional chemotherapy has become a standard of care for women with overexpressing HER-2 tumours. Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor (VEGF) that in refractory metastatic breast cancer doubled the response rate of capecitabine although it did not affect survival. Finally, the so called 'oligometastatic' and a few stage IV diseases are conditions amenable to be rendered with no evidence of disease (NED) after local surgery and/or radiation. In both, as well as in complete responders to chemotherapy, minimal residual disease (m.r.d.) likely continues to be present. Recent data suggest that 'biological' therapy (immunomodulators and/or retinoids with or without hormone therapy), might be suitable to be successfully tested in these patients as maintenance treatment given soon after local intervention or chemotherapy. © 2006 Elsevier Masson SAS. All rights reserved.

A novel human thyroid papillary carcinoma cell line (FB-2) has been established and characterized. FB-2 cells harbor the RET/PTC1 chimeric oncogene in which the RET kinase domain is fused to the H4 gene. FB-2 cells neither formed colonies in semisolid media nor induced tumors after heterotransplant into severe combined immunodeficient mice. However, HMGI(Y), HMGI-C and c-myc genes, which are associated to thyroid cell transformation, were abundantly expressed in FB-2 cells but not in normal thyroid cells. FB-2 cells only partially retained the differentiated thyroid phenotype. In fact, the PAX-8 gene, which codes for a transcriptional factor required for thyroid cell differentiation, was expressed, while thyroglobulin, TSH-receptor and thyroperoxidase genes were not. Moreover, FB-2 cells produced high levels of interleukin (IL)-6 and IL-8.