58 research outputs found
Refractory and relapsed paediatric ACC in the MET studies – a challenging situation necessitating novel diagnostic and therapeutic concepts
Background
Paediatric adrenocortical carcinomas (ACC) are highly aggressive malignancies with a dismal prognosis in advanced and metastatic disease. Little is known about outcome of patients with refractory and relapsed (r/r) disease.
Procedure
National retrospective multicentre study including r/r ACC diagnosed in patients aged <18 years registered in the MET studies between January 1997 and December 2021
Results
A total of 16 patients (5 male; median age 12.9 years) with refractory disease were included. Median time to progression was 0.6 years [0.0-1.3]. Site of progression was locoregional (n=1), distant (n=3), and combined (n=12). 3-year overall (OS) and progression-free (PFS) survival were both 0%.
Thirty patients with relapse (11 male; median age 7.3 years) were identified. Median time to relapse was 0.7 years [0.1-3.2]. Site of relapse was locoregional (n=8), distant (n=15), and combined (n=7). At last follow-up, 20 patients had died of disease or complications or were alive with disease, 10 patients were in second complete remission (median follow-up: 6.8 years [0-10.5]). 3-year OS and PFS following relapse were 39.1% and 31.9%. Survival was superior in patients with distant relapse (59.6%) compared to locoregional (28.6%) and combined (14.3%) (p=0.028) and in patients with complete surgical resection of all sites of recurrence (70.0%) compared to incomplete (21.4%) and no surgery (0%) (p=0.003).
Conclusions
For patients nonresponsive to first-line therapy or who experience relapse, prognosis is dismal and options are scarce. Site of relapse and resectability define prognosis. Novel therapeutic concepts are needed to improve the outcome of paediatric patients with r/r ACC
Outcome for pediatric adreno-cortical tumors is best predicted by the COG stage and five-item microscopic score — report from the German MET studies
Background: Adrenocortical tumors (ACTs) encompassing the adrenocortical adenoma (ACA), carcinoma (ACC), and tumors of undetermined malignant potential (ACx) are rare endocrine neoplasms with a poor prognosis. We report on pediatric ACT patients registered with the Malignant Endocrine Tumor studies and explore the EXPeRT recommendations for management. Patients: Data from the ACT patients (<18 years) were analyzed. For the risk prediction, the patients were retrospectively assigned to the COG stages and the five-item score. Results: By December 2021, 161 patients with ACT (ACA n = 51, ACx n = 19, and ACC n = 91) had been reported (the median age at the diagnosis was 4.3 years with a range of 0.1–17.8), with lymph node and distant metastases in 10.7% and 18.9% of the patients with ACC/ACx. The mean follow-up was 4.5 years (with a range of 0–16.7). The three-year overall (OS) and event-free survival (EFS) rates were 65.5% and 50.6%. In the univariate analyses, the OS was impaired for patients aged ≥ 4 years (p = 0.001) with the initial biopsy (p = 0.016), tumor spillage (p = 0.028), incomplete tumor resection (p < 0.001), unfavorable histology (p = 0.047), and COG stages III/IV (p = 0.002). Multivariate analysis revealed COG stages III/IV and an unfavorable five-item score as independent negative prognostic factors for the EFS and OS. Conclusions: Age defines the clinical presentation and prognosis in pediatric ACTs. The outcome is best predicted by the COG stage and five-item score
Addressing gaps in care of people with conditions affecting sex development and maturation
Differences of sex development are conditions with discrepancies between chromosomal, gonadal and phenotypic sex. In congenital hypogonadotropic hypogonadism, a lack of gonadotropin activity results primarily in the absence of pubertal development with prenatal sex development being (almost) unaffected in most patients. To expedite progress in the care of people affected by differences of sex development and congenital hypogonadotropic hypogonadism, the European Union has funded a number of scientific networks. Two Actions of the Cooperation of Science and Technology (COST) programmes - DSDnet (BM1303) and GnRH Network (BM1105) - provided the framework for ground-breaking research and allowed the development of position papers on diagnostic procedures and special laboratory analyses as well as clinical management. Both Actions developed educational programmes to increase expertise and promote interest in this area of science and medicine. In this Perspective article, we discuss the success of the COST Actions DSDnet and GnRH Network and the European Reference Network for Rare Endocrine Conditions (Endo-ERN), and provide recommendations for future research
Extraction of pure components from overlapped signals in gas chromatography-mass spectrometry (GC-MS)
Gas chromatography-mass spectrometry (GC-MS) is a widely used analytical technique for the identification and quantification of trace chemicals in complex mixtures. When complex samples are analyzed by GC-MS it is common to observe co-elution of two or more components, resulting in an overlap of signal peaks observed in the total ion chromatogram. In such situations manual signal analysis is often the most reliable means for the extraction of pure component signals; however, a systematic manual analysis over a number of samples is both tedious and prone to error. In the past 30 years a number of computational approaches were proposed to assist in the process of the extraction of pure signals from co-eluting GC-MS components. This includes empirical methods, comparison with library spectra, eigenvalue analysis, regression and others. However, to date no approach has been recognized as best, nor accepted as standard. This situation hampers general GC-MS capabilities, and in particular has implications for the development of robust, high-throughput GC-MS analytical protocols required in metabolic profiling and biomarker discovery. Here we first discuss the nature of GC-MS data, and then review some of the approaches proposed for the extraction of pure signals from co-eluting components. We summarize and classify different approaches to this problem, and examine why so many approaches proposed in the past have failed to live up to their full promise. Finally, we give some thoughts on the future developments in this field, and suggest that the progress in general computing capabilities attained in the past two decades has opened new horizons for tackling this important problem
Mass spectrometric analysis of androstan-17β-ol-3-one and androstadiene-17β-ol-3-one isomers
Disorders of sex development: effect of molecular diagnostics
Disorders of sex development (DSDs) are a diverse group of conditions that can be challenging to diagnose accurately using standard phenotypic and biochemical approaches. Obtaining a specific diagnosis can be important for identifying potentially life-threatening associated disorders, as well as providing information to guide parents in deciding on the most appropriate management for their child. Within the past 5 years, advances in molecular methodologies have helped to identify several novel causes of DSDs; molecular tests to aid diagnosis and genetic counselling have now been adopted into clinical practice. Occasionally, genetic profiling of embryos prior to implantation as an adjunct to assisted reproduction, prenatal diagnosis of at-risk pregnancies and confirmatory testing of positive results found during newborn biochemical screening are performed. Of the available genetic tests, the candidate gene approach is the most popular. New high-throughput DNA analysis could enable a genetic diagnosis to be made when the aetiology is unknown or many differential diagnoses are possible. Nonetheless, concerns exist about the use of genetic tests. For instance, a diagnosis is not always possible even using new molecular approaches (which can be worrying for the parents) and incidental information obtained during the test might cause anxiety. Careful selection of the genetic test indicated for each condition remains important for good clinical practice. The purpose of this Review is to describe advances in molecular biological techniques for diagnosing DSDs
Recommended from our members
Curing Behavior of Thermosets for the Use in a Combined Selective Laser Sintering Process of Polymers
Selective laser sintering (SLS) of polymers is an additive manufacturing process,
which enables the production of functional technical components. Unfortunately, the SLS
process is restricted regarding the materials that can be processed and thus resulting
component properties are limited.
The investigations in this study illustrates a totally new additive manufacturing process
which combines reactive liquids like thermoset resins and thermoplastics to generates multi
material SLS parts. To introduce thermoset resins into the regular SLS process, the time-temperature-dependent curing behavior of the thermoset and the infiltration behavior has to be
understood in order to assess the process behavior. The curing behavior was analyzed by
rotational viscosimeter. Furthermore, the fundamental infiltration behavior was analyzed with
micro dosing infiltration experiments. Finally, a thermoset resin in combination with a dosing
system was chosen for integration in a laser sintering system.Mechanical Engineerin
Recommended from our members
Aging Behavior of Polyamide 12: Interrelation Between Bulk Characteristics and Part Properties
The high process temperatures in combination with long building times during the laser
sintering process lead to chemical and physical aging mechanisms on the polymeric feed
material. The unmolten partcake material, which acts as a supporting structure, can be removed
after each building process and reused for further processes. However, material as well as bulk
properties are changed due to thermal and mechanical load during the laser sintering process.
Within this paper the interrelation between the aging state, bulk values and resulting
part properties like porosity, surface roughness and mechanical behavior are derived. Therefore,
polyamide 12 powder is used for at least five processing cycles without refreshing. Before and
after each building process, bulk characteristics and changes of the particle surface were
determined. Specimens were manufactured during the laser sintering process in order to study
the part density, roughness and mechanical behavior.Mechanical Engineerin
Recommended from our members
Understanding the Influence of Energy-Density of the Layer Dependent Part Properties in Laser-Sintering of PA12
As the demand for individualization and complex parts is continuously growing, laser-sintering of
polymers is on the edge from a pure prototyping technology to manufacturing parts for applications in series
production. The influences on resulting parts and layer depending part properties are well known in the
literature but the understanding of the interaction between process parameters and layer dependent properties
is missing and limiting the dimensioning. Within this study, tensile bars with different amounts of layers and
energy densities were produced and investigated for the resulting mechanical properties, roughness, density
and the degree of particle melt. The results showed a strong interaction between the energy density and amount
of layers, which results in differences in the fracture behavior as well as the mechanical properties. Therefore,
the presented results enable the prediction of necessary part thickness for dimensioning thin parts with laser-sintering.Mechanical Engineerin
- …