A quality control program for mutation detection in KIT and PDGFRA in gastrointestinal stromal tumours

Background

Although most gastrointestinal stromal tumours (GIST) carry oncogenic mutations in KIT exons 9, 11, 13 and 17, or in platelet-derived growth factor receptor alpha (PDGFRA) exons 12, 14 and 18, around 10% of GIST are free of these mutations. Genotyping and accurate detection of KIT/PDGFRA mutations in GIST are becoming increasingly useful for clinicians in the management of the disease.

Method

To evaluate and improve laboratory practice in GIST mutation detection, we developed a mutational screening quality control program. Eleven laboratories were enrolled in this program and 50 DNA samples were analysed, each of them by four different laboratories, giving 200 mutational reports.

Results

In total, eight mutations were not detected by at least one laboratory. One false positive result was reported in one sample. Thus, the mean global rate of error with clinical implication based on 200 reports was 4.5%. Concerning specific polymorphisms detection, the rate varied from 0 to 100%, depending on the laboratory. The way mutations were reported was very heterogeneous, and some errors were detected.

Conclusion

This study demonstrated that such a program was necessary for laboratories to improve the quality of the analysis, because an error rate of 4.5% may have clinical consequences for the patient.     

Global meaning and meaning-related life attitudes: exploring their role in predicting depression, anxiety, and demoralization in cancer patients

Goal of work  

While significance of the concept of meaning in understanding adaptation to cancer is widely accepted, it has been little studied, especially in longitudinal data. This study aims to clarify the role of global meaning and meaning-related life attitudes (death acceptance and goal seeking) in predicting different aspects of psychological and existential distress by reference to a specified research model.     

Evaluation of micro-CT for emphysema assessment in mice: comparison with non-radiological techniques

Objectives

To define the potential, limitations and synergies of micro-CT and other non-radiological techniques for the quantification of emphysema and related processes in mice, by performing a complete characterization of the elastase-induced emphysema model.

Materials and methods

Ninety A/J mice (45 treated and 45 controls) were studied at different time points using breath-hold gated micro-CT, functional test parameters, RT-PCR for RNA cytokine expression, Luminex technology for cytokine plasma concentration and histomorphometry.

Results

Both histomorphometry and micro-CT imaging reflect rapid initial emphysema progression followed by steady-state development at decreasing rates. Cytokine measurements reveal an acute inflammatory response within the first 24?h that disappears after the first week. Limited systemic effect was observed based on plasma cytokine concentration. Lung compliance decreases during the acute inflammation phase and increases afterwards.

Conclusion

Histomorphometry is the most sensitive technique since it detects airspace enlargement before the other methods (1?h after treatment). Micro-CT correlates well with histology (r2?=?0.63) proving appropriate for longitudinal studies. Functional test parameters do not necessarily correlate with the extent of emphysema, as they can be influenced by acute inflammation. Finally, cytokine measurements correlate with the presence of inflammation in histology but not with emphysema.     

Laparoscopic Organ-Sparing Resection of Von Hippel-Lindau Disease-Associated Pancreatic Neuroendocrine Tumors

Background  

Pancreatic neuroendocrine tumors (PNETs) are a characteristic feature of the tumor syndromes multiple endocrine neoplasia type 1 (MEN-1) and von Hippel-Lindau disease (VHL). With VHL, about 10% of the patients exhibit PNETs by age 40 years. Metastatic potential is high if the tumors have grown to >3 cm in diameter. Optimal surgical treatment is still a challenge.     

German Association of Endocrine Surgeons practice guidelines for the surgical treatment of benign thyroid disease

Introduction

Benign thyroid disorders are among the most common diseases in Germany, affecting around 15 million people and leading to more than 100,000 thyroid surgeries per year. Since the first German guidelines for the surgical treatment of benign goiter were published in 1998, abundant new information has become available, significantly shifting surgical strategy towards more radical interventions. Additionally, minimally invasive techniques have been developed and gained wide usage. These circumstances demanded a revision of the guidelines.

Methods

Based on a review of relevant recent guidelines from other groups and additional literature, unpublished data, and clinical experience, the German Association of Endocrine Surgeons formulated new recommendations on the surgical treatment of benign thyroid diseases. These guidelines were developed through a formal expert consensus process and in collaboration with the German societies of Nuclear Medicine, Endocrinology, Pathology, and Phoniatrics & Pedaudiology as well as two patient organizations. Consensus was achieved through several moderated conferences of surgical experts and representatives of the collaborating medical societies and patient organizations.

Results

The revised guidelines for the surgical treatment of benign thyroid diseases include recommendations regarding the preoperative assessment necessary to determine when surgery is indicated. Recommendations regarding the extent of resection, surgical techniques, and perioperative management are also given in order to optimize patient outcomes.

Conclusions

Evidence-based recommendations for the surgical treatment of benign thyroid diseases have been created to aid the surgeon and to support optimal patient care, based on current knowledge. These recommendations comply with the Association of the Scientific Medical Societies in Germany requirements for S2k guidelines.     

Incidental Gallbladder Cancer by the AFC-GBC-2009 Study Group

Background  

Incidental gallbladder cancer (GBC) is frequently discovered on the specimen when cholecystectomy for a benign disease is performed. The objective of the present study was to assess the management of incidental GBC patients in a French registry.     

Navigated anterior cruciate ligament replacement: an experimental validation study

We wanted to test the following hypothesis: the location of the tibial and femoral ACL attachments measured by a navigation system differs from their actual anatomic location. A total of 10 gross specimens were studied. The standard navigated procedure was used. Metallic reference pins were implanted around the tibial and femoral ACL attachments and palpated with a navigated stylus. Their position was recorded in comparison with the same tibial or femoral reference point. All measurements were repeated with a caliper. Caliper and navigated measurements were compared with appropriate statistical tests at a 0.05 level of significance. There was a significant difference between caliper and navigated measurements at the tibia in absolute value (maximal range of 4 mm, mean difference about 2 mm), but the difference ratio was low (about 3%); there was no significant difference between caliper and navigated measurements at the femur. There was a strong correlation and a good agreement between caliper and navigated measurements. It is likely that these differences have few, if any, clinical relevance. We demonstrated that the navigation system used during the present study has the potential to enhance the precision of the intra-operative measurement of the tunnel placement during ACL replacement.     

Epigenetische Pathomechanismen der Epileptogenese

Recent studies point to a pathogenic role of epigenetic chromatin modifications during epileptogenesis. Epigenetic mechanisms are covalent posttranslational modifications of histone proteins and DNA, which can produce lasting alterations in chromatin structure and gene expression. They are increasingly recognized as fundamental regulatory processes in central nervous system development, synaptic plasticity, and memory, and also play a role in neurological disorders, such as schizophrenia or spinal muscular atrophy. The authors propose that the “methylation hypothesis??addresses the intriguing issue of seizure-induced epigenetic chromatin modifications, which aggravate the epileptogenic condition by targeting candidate epileptogenesis gene expression. Unravelling epigenetic pathomechanisms will open also new strategies to identify molecular targets for pharmacological treatment in epilepsies. This project will be supported by EpiGENet, one of four consortia from the newly established European EuroEPINOMICS initiative.