Die Behandlungspraxis bei Patienten mit isolierter stumpfer Milzverletzung: Eine Befragung der Schweizer Traumatologen

Zusammenfassung: Hintergrund: Das nicht-operative Management (NOM) des stumpfen Milztraumas hat sich in den vergangenen Jahren als Therapiekonzept etabliert. Es bestehen jedoch zahlreiche Kontroversen bezüglich der Überwachung und Nachsorge dieser Patienten. Ziel dieser Studie war es, mittels einer Umfrage bei Mitgliedern der Schweizerischen Gesellschaft für Allgemeine und Unfallchirurgie (SGAUC) die aktuelle Praxis bezüglich NOM beim isolierten Milztrauma zu erfassen und mögliche Diskrepanzen zur aktuellen Literatur zu eruieren. Studiendesign und Untersuchungsmethode: Sämtliche praktizierende Mitglieder der SGAUC wurden mittels schriftlichem Umfragebogen adressiert. Dieser enthielt Fragen zu Person und Klinik des Chirurgen, Fragen zu Diagnostik und Management während der Hospitalisation sowie zu radiologischen Verlaufskontrollen und zur stufenweisen Wiederaufnahme von Alltagsaktivitäten. Ergebnisse: An der Umfrage nahmen 52 von 165 (31,5%) praktizierenden Mitgliedern der SGAUC teil. Diese deckten 62,8% aller Schweizer Traumazentren ab. Vierzehn Befragte (26,9%) verfügen an ihrer Klinik über ein Protokoll zur Behandlung des Milztraumas. Als initiale Bildgebung beim hämodynamisch stabilen Patienten mit stumpfem Abdomaninaltrauma gaben 82,7% der Befragten die Sonographie an. Bei sonographischem Verdacht auf Milztrauma verzichteten allerdings 19,2% der Befragten auf eine weitergehende Diagnostik. Die Hälfte der Chirurgen gab außerdem an, bei sichtbarem Kontrastmittelextravasat aus der Milz keine weiteren therapeutischen Maßnahmen einzuleiten. 86,5% der Befragten würden Patienten mit niedriggradigem Milztrauma für durchschnittlich 1,6 (0-4Tage) in einem kontinuierlich-monitorisierten Bett überwachen. Keine Unterschiede wurden hinsichtlich der Aktivitätsrestriktion zwischen mittel- und hochgradigen Milztraumata gemacht. Schlussfolgerung: Aufgrund eines Mangels an evidenzbasierten Richtlinien zum NOM des Milztraumas gibt es eine beträchtliche Variabilität in der klinischen Praxis selbst unter erfahrenen Chirurgen. Die größten Diskrepanzen zu den Empfehlungen in der aktuellen Literatur waren zum einen der Verzicht auf eine Computertomographie bei Verdacht auf Milztrauma, zum anderen das konservative Vorgehen trotz nachgewiesenem Kontrastmittelaustrit

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Microglandular adenosis associated with triple-negative breast cancer is a neoplastic lesion of triple-negative phenotype harbouring TP53 somatic mutations

Microglandular adenosis (MGA) is a rare proliferative lesion of the breast composed of small glands lacking myoepithelial cells and lined by S100-positive, oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative epithelial cells. There is evidence to suggest that MGA may constitute a non-obligate precursor of triple-negative breast cancer (TNBC). We sought to define the genomic landscape of pure MGA and of MGA, atypical MGA (AMGA) and associated TNBCs, and to determine whether synchronous MGA, AMGA, and TNBCs would be clonally related. Two pure MGAs and eight cases of MGA and/or AMGA associated with in situ or invasive TNBC were collected, microdissected, and subjected to massively parallel sequencing targeting all coding regions of 236 genes recurrently mutated in breast cancer or related to DNA repair. Pure MGAs lacked clonal non-synonymous somatic mutations and displayed limited copy number alterations (CNAs); conversely, all MGAs (n = 7) and AMGAs (n = 3) associated with TNBC harboured at least one somatic non-synonymous mutation (range 3-14 and 1-10, respectively). In all cases where TNBCs were analyzed, identical TP53 mutations and similar patterns of gene CNAs were found in the MGA and/or AMGA and in the associated TNBC. In the MGA/AMGA associated with TNBC lacking TP53 mutations, somatic mutations affecting PI3K pathway-related genes (eg PTEN, PIK3CA, and INPP4B) and tyrosine kinase receptor signalling-related genes (eg ERBB3 and FGFR2) were identified. At diagnosis, MGAs associated with TNBC were found to display subclonal populations, and clonal shifts in the progression from MGA to AMGA and/or to TNBC were observed. Our results demonstrate the heterogeneity of MGAs, and that MGAs associated with TNBC, but not necessarily pure MGAs, are genetically advanced, clonal, and neoplastic lesions harbouring recurrent mutations in TP53 and/or other cancer genes, supporting the notion that a subset of MGAs and AMGAs may constitute non-obligate precursors of TNBCs

[Treatment practice in patients with isolated blunt splenic injuries : A survey of Swiss traumatologists.]

The non-operative management (NOM) of blunt splenic injuries has gained widespread acceptance. However, there are still many controversies regarding follow-up of these patients. The purpose of this study was to survey active members of the Swiss Society of General and Trauma Surgery (SGAUC) to determine their practices regarding the NOM of isolated splenic injuries