Our objective was to describe the clinical signs of 'possible' Creutzfeldt-Jakob disease (CJD) and to investigate whether current diagnostic criteria can accurately differentiate between different forms of dementia. We studied clinical data of 'definite' CJD, Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and vascular dementia (VD) patients. Two subgroups were used: the first consisted of patients with clinical signs compatible with 'possible' CJD but in whom another final diagnosis was made and a second group with a typical evolution of the respective dementia. More focal neurological deficits were observed in AD, DLB or VD patients initially classified as 'possible' CJD than in typical patients. A typical electroencephalogram showing periodic sharp wave complexes was observed in 26 (50%) CJD and 6% of other dementia patients. The 14-3-3 protein was detected in all CJD and 8% of other dementia patients. In patients with rapidly progressive dementia and focal neurological signs, CJD should be considered. When faced with the triad: dementia, myoclonus, and initial memory problems AD should be considered if the disease duration is longer than 1 year. The diagnosis of DLB is suggested, if Parkinsonism or fluctuations are present, whereas a focal onset and compatible brain imaging can indicate VD. Findings suggestive of CJD on EEG, brain imaging, and CSF do not exclude other dementias but make them very unlikely. These observations cannot only assist in the differential diagnosis of CJD but also with the identification of AD, DLB or VD patients with atypical clinical history.

The relation of protein deposition with glial cells and oxidative stress was studied in Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD) and neurologically healthy control patients. Three neocortical areas, the hippocampus, and the cerebellum of 20 CJD, 10 AD and 10 control patients were immunohistochemically examined for the presence of astroglia, microglia, and protein depositions. To investigate the level of oxidative stress the percentage of neurons with cytoplasmic hydroxylated DNA was determined. Astroglia, microglia and oxidative stress were located around amyloid-beta depositions and a clear quantitative relation was identified. These markers were only increased in the hippocampus of AD compared to controls. Quantitative analysis in these groups showed a correlation between the oxidative stress level and the number of microglia in the grey matter. All markers were increased in the grey matter and the cerebellum of CJD when compared to AD and controls. The highest numbers of lesions were observed in a CJD population with a rapid disease progression. Quantitative analysis showed a correlation between the oxidative stress level and all glial cells. Further analysis showed that the number of microglia was related to the intensity of the prion depositions. Glial cells in the brain are thought to be the main producers of oxidative stress, resulting in neuronal death. Our results confirm that this close relationship exists in both AD and CJD. We also show that an increased number of glial cells and therefore possibly oxidative stress is associated with the disease progression.

Short sentence: Treatment of early-stage lung cancer requires multidisciplinary cooperation and close interaction between respiratory physicians, medical oncologists, radiation oncologists and thoracic surgeons. Word count text: 6297 (without tables and references)Word count abstract: 188

Remediastinoscopy is a valuable restaging procedure after induction therapy. Persisting mediastinal nodal involvement proven at remediastinoscopy heralds a poor prognosis.

Remediastinoscopy is a valuable restaging procedure after induction therapy. Prognosis is poor in patients with persisting mediastinal nodal involvement, proven at repeat mediastinoscopy.

Surgical resection remains the standard of care for functionally operable early-stage non-small-cell lung cancer (NSCLC) and resectable stage IIIA disease. The role of invasive staging and restaging techniques is currently being debated, but they provide the largest biopsy samples which allow for precise mediastinal staging. Different types of operative procedures are currently available to the thoracic surgeon, and some of these interventions can be performed by video-assisted thoracic surgery (VATS) with the same oncological results as those by open thoracotomy. The principal aim of surgical treatment for NSCLC is to obtain a complete resection which has been precisely defined by a working group of the International Association for the Study of Lung Cancer (IASLC). Intraoperative staging of lung cancer is of utmost importance to decide on the extent of resection according to the intraoperative tumour (T) and nodal (N) status. Systematic nodal dissection is generally advocated to evaluate the hilar and mediastinal lymph nodes which are subdivided into seven zones according to the most recent 7th tumour-node-metastasis (TNM) classification. Lymph-node involvement not only determines prognosis but also the administration of adjuvant therapy.In 2011, a new multidisciplinary adenocarcinoma classification was published introducing the concepts of adenocarcinoma in situ and minimally invasive adenocarcinoma. This classification has profound surgical implications. The role of limited or sublobar resection, comprising anatomical segmentectomy and wide wedge resection, is reconsidered for early-stage lesions which are more frequently encountered with the recently introduced large screening programmes. Numerous retrospective non-randomised studies suggest that sublobar resection may be an acceptable surgical treatment for early lung cancers, also when performed by VATS.More tailored, personalised therapy has recently been introduced. Quality-of-life parameters and surgical quality indicators become increasingly important to determine the short-term and long-term impact of a surgical procedure. International databases currently collect extensive surgical data, allowing more precise calculation of mortality and morbidity according to predefined risk factors. Centralisation of care has been shown to improve results. Evidence-based guidelines should be further developed to provide optimal staging and therapeutic algorithms.

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