FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study

Background: In preclinical gastric cancer (GC) models, FGFR2 amplification was associated with increased tumour cell proliferation and survival, and drugs targeting this pathway are now in clinical trials. Methods: FGFR2 FISH was performed on 961 GCs from the United Kingdom, China and Korea, and the relationship with clinicopathological data and overlap with HER2 amplification were analysed. Results: The prevalence of FGFR2 amplification was similar between the three cohorts (UK 7.4%, China 4.6% and Korea 4.2%), and intratumoral heterogeneity was observed in 24% of FGFR2 amplified cases. FGFR2 amplification was associated with lymph node metastases (Po0.0001). FGFR2 amplification and polysomy were associated with poor overall survival (OS) in the Korean (OS: 1.83 vs 6.17 years, P ¼ 0.0073) and UK (OS: 0.45 vs 1.9 years, Po0.0001) cohorts, and FGFR2 amplification was an independent marker of poor survival in the UK cohort (P ¼ 0.0002). Co-amplification of FGFR2 and HER2 was rare, and when high-level amplifications did co-occur these were detected in distinct areas of the tumour. Conclusion: A similar incidence of FGFR2 amplification was found in Asian and UK GCs and was associated with lymphatic invasion and poor prognosis. This study also shows that HER2 and FGFR2 amplifications are mostly exclusive

Education and training of healthcare staff in the knowledge, attitudes and skills needed to work effectively with breastfeeding women:a systematic review

BACKGROUND: Current evidence suggests that women need effective support to breastfeed, but many healthcare staff lack the necessary knowledge, attitudes and skills. There is therefore a need for breastfeeding education and training for healthcare staff. The primary aim of this review is to determine whether education and training programs for healthcare staff have an effect on their knowledge and attitudes about supporting breastfeeding women. The secondary aim of this review was to identify whether any differences in type of training or discipline of staff mattered. METHODS: A systematic search of the literature was conducted using the Cochrane Pregnancy and Childbirth Group’s trial register. Randomised controlled trials comparing breastfeeding education and training for healthcare staff with no or usual training and education were included if they measured the impact on staff knowledge, attitudes or compliance with the Baby Friendly Hospital Initiative (BFHI). RESULTS: From the 1192 reports identified, four distinct studies were included. Three studies were two-arm cluster-randomised trials and one was a two-arm individual randomised trial. Of these, three contributed quantitative data from a total of 250 participants. Due to heterogeneity of outcome measures meta-analysis was not possible. Knowledge was included as an outcome in two studies and demonstrated small but significant positive effects. Attitudes towards breastfeeding was included as an outcome in two studies, however, results were inconsistent both in terms of how they were measured and the intervention effects. One study reported a small but significant positive effect on BFHI compliance. Study quality was generally deemed low with the majority of domains being judged as high or unclear risk of bias. CONCLUSIONS: This review identified a lack of good evidence on breastfeeding education and training for healthcare staff. There is therefore a critical need for research to address breastfeeding education and training needs of multidisciplinary healthcare staff in different contexts through large, well-conducted RCTs

Protein stabilization: a common consequence of mutations in independently derived v-Myc alleles.

Myc is overexpressed in many cancers as a result of gene rearrangement or amplification, but coding sequence changes which cluster in the N-terminal transactivation domain also appear to play a role in tumour progression. The prototypic v-Myc gene of MC29 virus differs from avian c-Myc by a series of mutations, including a change at a regulatory phosphorylation site within the mutational hotspot (thr-61) which is known to potentiate transformation in vitro. We now show that the mutation at thr-61 stabilizes the v-Myc protein (turnover difference) and that this single mutation is both necessary and sufficient for the phenotype. A major involvement of the proteasome in Myc degradation was confirmed, but surprisingly, a dilysine motif adjacent to thr-61 proved not to be the ubiquitin target. Two other v-Myc genes which carry a mutation at thr-61 (avian MH2) or a large deletion encompassing this domain (feline T17) were found to be stabilized to a similar extent as MC29, showing that stabilization is a common feature of independently derived Myc oncogenes. These results suggest a common selective process in the genesis of these three viral oncoproteins and a mechanistic link with Jun, Fos and Myb oncoproteins which are also stabilized relative to their cellular counterparts

A single unit lymphoma experience - Outcome in a Cape Town academic centre

To document outcome in Hodgkin and other lymphomas from a privately based academic centre the clinical records from 253 consecutive referrals were analysed. Diagnosis was according to World Health Organization criteria, prognosis assigned by the international index and therapy risk-stratified with results subject to appropriate statistical methodology. None of these patients underwent transplantation. For the cohort the median age was 55 years (range 11-94) and 63% were male. Constitutional symptoms were present in 22%; a quarter had previous chemotherapy and a third some form of irradiation prior to referral. Fifty-seven percent were stage I or II and 21% had nodal disease above and below the diaphragm whilst in the remainder cells were present in the circulation and this included the subset of chronic lymphocytic leukaemia - small lymphocytic lymphoma. Positron emission scanning was not available for these studies. Median survival for the cohort is 3.2 years and reduced to 1.3 years by the presence of unexplained fever, sweating or inappropriate weight loss. Further adverse factors included any prior treatment, intermediate or high-grade histopathology, risk factors defined by the International Prognostic Index as well as late Rai stages. Analysed by disease category Hodgkin lymphoma (n = 17) when managed according to the German Study Group protocols and hairy cell leukaemia (n = 10) treated with two chlorodeoxyadenosine - both had a stable plateau in excess of 90%. The corresponding figures for follicular variants (n = 31) was 72% in the low risk and 58% in the remainder when treated with cyclophosphamide, vincristine and prednisone. Curves for the aggressive or diffuse large B-cell lymphoma (n = 44) fell initially to 48%, but relapse continued in stages III and IV to the current level of 18% when receiving cyclophosphamide, hydroxydaunorubicin, vincristine and prednisone on the 21-day schedule. Chronic lymphocytic leukaemia - small lymphocytic lymphoma (n = 58) were initially given pulsed chlorambucil and sustained response was over 90% with low bulk, but declined to reach 30% as prognostic score rose. The miscellaneous categories (n < 5 each) managed variably, but using the same criteria, were pooled and are presently at 62% and 30% for high and low grades. It is concluded that precise diagnosis, accurate staging and therapy on standardised risk-stratified programmes, delivered uniformly by a single multidisciplinary group, creates the all-important centre effect; matching figures are unlikely to apply outside these disciplined circumstances. The expectation from patients and referring physicians alike is that, since lymphomas are potentially curable, such an approach to comprehensive management will be regarded as standard even in an under resourced or Third World country. It follows that late referral and prior therapy will adversely affect performance status and compromise life span: These alternative approaches are inappropriate and strongly discouraged. © 2007 Elsevier Ltd. All rights reserved.Articl