. Development of a method to provide organ and effective dose coefficients to reference adults for any CT scanner based on values of
measured both in air and in standard CT dosimetry phantoms.
. ...Results from previous Monte Carlo simulations for a range of contemporary CT scanners have been analyzed to provide linear models relating values of organ dose (normalized to
), for each slab of 3 reference phantoms (ICRP Male/Female, and AH hermaphrodite), to similarly normalized values of
in standard CT dosimetry phantoms. Three methods have been investigated to apply the models to values of
for a 'new' scanner not previously simulated: a Generic approach using averaged normalized organ dose profiles for whole body exposure of the phantoms; and two processes for matching the scanner, on the basis of normalized organ doses or effective dose (
), to one of the 102 sets of dose coefficients previously calculated for 12 contemporary CT scanner models, from 4 manufacturers, operating under a range of conditions.
. The merit of each method has been quantitatively assessed when applied to both the present contemporary scanners with each test data set being excluded in turn during the matching process, and also to 3 previously-simulated older scanners. Whereas all three methods appear viable, with all doses being within 1% and 10% for the contemporary and old scanners respectively, matching to
is overall the approach preferred in practice, yielding an uncertainty of around 6% in estimated values of
. The present methodology also provides superior performance when compared against some other common normalization factors for
.
. The CT dose model and the data sets will be incorporated into a new CT dosimetry tool that will be made available from UKHSA in support of facilitating improvements in patient protection.
Provide analyses of new organ dose coefficients (hereafter also referred to as normalized doses) for CT that have been developed to update the widely-utilized collection of data published 30 years ...ago in NRPB-SR250.
In order to reflect changes in technology, and also ICRP recommendations concerning use of the computational phantoms adult male (AM) and adult female (AF), 102 series of new Monte Carlo simulations have been performed covering the range of operating conditions for 12 contemporary models of CT scanner from 4 manufacturers. Normalized doses (relative to free air on axis) have been determined for 39 organs, and for every 8 mm or 4.84 mm slab of AM and AF, respectively.
Analyses of results confirm the significant influence (by up to a few tens of percent), on values of normalized organ (or contributions to effective dose (
)), for whole body exposure arising from selection of tube voltage and beam shaping filter. Use of partial (when available) rather than a Full fan beam reduced both organ and effective dose by up to 7%. Normalized doses to AF were larger than corresponding figures for AM by up to 30% for organs and by 10% for
. Additional simulations for whole body exposure have also demonstrated that: practical simplifications in the main modelling (point source, single slice thickness, neglect of patient couch and immobility of phantom arms) have sufficiently small (<5%) effect on
; mis-centring of the phantom away from the axis of rotation by 5 mm (in any direction) leads to changes in normalized organ dose and
by up to 20% and 6%, respectively; and angular tube current modulation can result in reductions by up to 35% and <15% in normalized organ dose and
, respectively, for 100% cosine variation.
These analyses help advance understanding of the influence of operational scanner settings on organ dose coefficients for contemporary CT, in support of improved patient protection. The results will allow the future development of a new dose estimation tool.
The prognosis of patients with colorectal cancer is poor, especially when there is distant metastatic disease. Local ablation of tumor by radiofrequency ablation (RFA) has emerged as a safe and ...effective new treatment modality, but its long-term efficacy may be hindered by renewed local tumor growth at the site of RFA. The objectives of this study were to identify risk factors for local RFA failure and to define exclusion criteria for RFA treatment of colorectal liver metastases.
A total of 199 lesions in 87 patients were ablated with RFA. Factors influencing local failure rates were identified and compared with data from the literature.
The local failure rate was 47.2%, and the average time to local disease progression was 6.5 months. Factors that significantly correlated with increased failure rates were metachronous occurrence of liver metastases, large mean lesion size, and central tumor location.
Because accurate electrode placement is pivotal in achieving adequate tumor necrosis, RFA should not be performed percutaneously when electrode placement is impaired. We suggest that lesions >5 cm and lesions located near great vessels or adjacent organs should be treated with open RFA, thus allowing vascular inflow occlusion and complete mobilization of the liver. Lesions that are difficult to reach by electrodes should be approached by an open procedure.
1 Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands
2 Faculty of Medicine & CHU, Nancy Université, France
3 Department of Hematology and Oncology, Fondazione IRCCS ...Policlinico San Matteo, Pavia, and University of Pavia, Italy
4 Laboratoire dHématologie, CHU Dupuytren, Limoges, France
5 Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
6 Department of Hematology Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany
7 Department of Hematology and Oncology, Georg-August-University, Göttingen, Germany
8 Sanquin Research at CLB, Amsterdam, The Netherlands
9 Kings College Hospital, London, United Kingdom
10 Department of Hematology, St Radboud University Medical Center, Nijmegen, The Netherlands
11 MLL Munich Leukemia Laboratory, Munich, Germany
12 Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
13 Division of Hematology, Department of Medicine, Nippon Medical School, Tokyo, Japan
14 Servicio Central de Citometría, Centro de Investigación del Cáncer, Instituto de Biologia Celular y Molecular del Cáncer (CSIC/USAL) and Department of Medicine, Universidad de Salamanca, Spain
15 Department of Pathology, Karolinska University Hospital, Stockholm, Sweden
16 HMDS, St. Jamess University Hospital, Leeds, United Kingdom
17 Department of Hematology, Fundación Jiménez Díaz, Madrid, Spain
18 Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
19 Department of Hematology, Weatherall Institute of Molecular Medicine University of Oxford and John Radcliffe Hospital, Oxford, United Kingdom
20 Hematologics, Inc., Seattle, WA, USA
Correspondence: Arjan A. van de Loosdrecht, MD, PhD, Department of Hematology, VU-Institute of Cancer and Immunology, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. E-mail: a.vandeloosdrecht{at}vumc.nl
The myelodysplastic syndromes are a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more cell lineages and increased risk of evolution to acute myeloid leukemia (AML). Recent advances in immunophenotyping of hematopoietic progenitor and maturing cells in dysplastic bone marrow point to a useful role for multiparameter flow cytometry (FCM) in the diagnosis and prognostication of myelodysplastic syndromes. In March 2008, representatives from 18 European institutes participated in a European LeukemiaNet (ELN) workshop held in Amsterdam as a first step towards standardization of FCM in myelodysplastic syndromes. Consensus was reached regarding standard methods for cell sampling, handling and processing. The group also defined minimal combinations of antibodies to analyze aberrant immunophenotypes and thus dysplasia. Examples are altered numbers of CD34 + precursors, aberrant expression of markers on myeloblasts, maturing myeloid cells, monocytes or erythroid precursors and the expression of lineage infidelity markers. When applied in practice, aberrant FCM patterns correlate well with morphology, the subclassification of myelodysplastic syndromes, and prognostic scoring systems. However, the group also concluded that despite strong evidence for an impact of FCM in myelodysplastic syndromes, further (prospective) validation of markers and immunophenotypic patterns are required against control patient groups as well as further standardization in multi-center studies. Standardization of FCM in myelodysplastic syndromes may thus contribute to improved diagnosis and prognostication of myelodysplastic syndromes in the future.
Key words: myelodysplastic syndromes, flow cytometry, standardization, ELN, consensus.
Related Article
Flow cytometry immunophenotyping for diagnosis of myelodysplastic syndrome
Mario Cazzola
Haematologica 2009 94: 1041-1043.
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Group A streptococci (GAS), or Streptococcus pyogenes, are associated with a remarkable variety of diseases, ranging from superficial infections to life-threatening diseases such as toxic-shock-like ...syndrome (TSS). GAS strains belonging to M types M1 and M3 are associated with TSS. This study aims to obtain insight into the gene profiles underlying different M types and disease manifestations. Genomic differences between 76 clinically well characterized GAS strains collected in The Netherlands were examined using a mixed-genome microarray. Inter-M-type genomic differences clearly outweighed intra-M-type genome variation. Phages were major contributors to observed genome diversification. We identified four novel genes, including two genes encoding fibronectin-binding-like proteins, which are highly specific to a subset of M types and thus may contribute to M-type-associated disease manifestations. All M12 strains were characterized by the unique absence of the citrate lyase complex and reduced growth under hypoxic, nutrient-deprived conditions. Furthermore, six virulence factors, including genes encoding a complement-inhibiting protein (sic), an exotoxin (speA), iron(III) binding factor, collagen binding factor (cpa), and fibrinogen binding factor (prt2-like), were unique to M1 and/or M3 strains. These virulence factors may contribute to the potential of these strains to cause TSS. Finally, in contrast to M-type-specific virulence profiles, we did not identify a common virulence profile among strains associated with TSS irrespective of their M type.
Invasive group A streptococcal (GAS) disease reemerged in The Netherlands in the late 1980s. To seek an explanation for this resurgence, the genetic compositions of 22 M1 and 19 M28 GAS strains ...isolated in The Netherlands between 1960s and the mid-1990s were analyzed by using a mixed-genome DNA microarray. During this four-decade period, M1 and especially M28 strains acquired prophages on at least eight occasions. All prophages carried a superantigen (speA2, speC, speK) or a streptodornase (sdaD2, sdn), both associated with invasive GAS disease. Invasive and noninvasive GAS strains did not differ in prophage acquisition, suggesting that there was an overall increase in the pathogenicity of M1 and M28 strains over the last four decades rather than emergence of hypervirulent subclones. The increased overall pathogenic potential may have contributed to the reemergence of invasive GAS disease in The Netherlands.
Nasal colonization by Staphylococcus aureus is an important risk factor for the development of a nosocomial infection. Acquisition of nasal colonization by S. aureus increases mortality in ...hospitalized patients, but little is known about the transmission dynamics of S. aureus. To study S. aureus transmission, colonization and colonization persistence, we developed a murine transmission model. In 20 cages, 2 out of 10 mice were nasally inoculated (at 5×10(8) c.f.u. per mouse) with either meticillin-susceptible S. aureus (MSSA) (10 cages) or meticillin-resistant S. aureus (MRSA) (10 cages). On days 5, 15, 25 and 40, all mice in a cage were swabbed or sacrificed and nasal colonization and c.f.u. were determined in all 10 mice by nasal dissection or by nasal swab. Spread and subsequent stable colonization by both MSSA and MRSA from colonized to uncolonized mice within a cage was seen. At day 5, an increased number of colonized mice were observed in the MSSA group compared to the MRSA group (P = 0.003). On day 40, the mean number of c.f.u. per mouse was higher for MRSA than for MSSA (P = 0.06). Faecal-oral transmission was shown to be a possibly important transmission route in this model. These results suggest a more rapid spread of MSSA compared to MRSA. However, MRSA shows a more stable nasal colonization after a longer period of time.
The therapeutic effect of a single, oral dose of itraconazole was studied in rats inoculated intravaginally with Candida albicans and in which an established vaginal infection was present. We used ...light microscopy, transmission and scanning electron microscopy to document the structural alterations in the 3 days after treatment. The most important observations include the speed (within 24 hours) with which itraconazole inhibits the further penetration of the fungus into the vaginal squamous epithelium, the ability of the drug to reach and structurally alter intracellularly located fungal elements, and the prolonged drug effect of a single dose leading to complete eradication of the fungus from the vagina within 3 days.
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