The mean annual incidence of children with CNS tumours was 4.2/100,000 and has not increased during the study period. Survival rate for brain tumours at 10 years follow-up was 72%.

SUMMARYNeuroblastoma is a childhood extracranial solid tumour that is associated with a number of genetic changes. Included in these genetic alterations are mutations in the kinase domain of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (RTK), which have been found in both somatic and familial neuroblastoma. In order to treat patients accordingly requires characterisation of these mutations in terms of their response to ALK tyrosine kinase inhibitors (TKIs). Here, we report the identification and characterisation of two novel neuroblastoma ALK mutations (A1099T and R1464STOP), which we have investigated together with several previously reported but uncharacterised ALK mutations (T1087I, D1091N, T1151M, M1166R, F1174I and A1234T). In order to understand the potential role of these ALK mutations in neuroblastoma progression, we have employed cell culture-based systems together with the model organism Drosophila as a readout for ligand-independent activity. Mutation of ALK at position 1174 (F1174I) generates a gain-of-function receptor capable of activating intracellular targets such as ERK (extracellular signal regulated kinase) and STAT3 (signal transducer and activator of transcription 3) in a ligand-independent manner. Analysis of these previously uncharacterised ALK mutants and comparison with ALKF1174 mutants suggests that ALK mutations observed in neuroblastoma fall into three classes. These classes are: (i) gain-of-function ligand-independent mutations such as ALKF1174l, (ii) kinase-dead ALK mutants, e.g. ALKI1250T (Schönherr et al., 2011a) and (iii) ALK mutations that are ligand-dependent in nature. Irrespective of the nature of the observed ALK mutants, in every case the activity of the mutant ALK receptors could be abrogated by the ALK inhibitor crizotinib (Xalkori/PF-02341066), albeit with differing levels of sensitivity.

percutaneous therapeutic interventions under X-ray control were performed in patients with exudative complications. Results: Sensitivity, specificity and diagnostic accuracy of ultrasound imaging were respectively 84.7%, 73.4% and 78.8%. Sensitivity, specificity and diagnostic efficiency of cytological and microbiological examination of our data were, respectively, 86.9%, 95.2% and 91.6%. 737 miniinvasive percutaneous interventions were hold totaly. The implementation of miniinvasive percutaneous interventions helped to stop the disease process and to avoid open surgical procedures in 91.7% of cases. Conclusion: Fine-needle diagnostic puncture is a highly informative method for diagnosis of the nature and details of tissue damage and pathological process phase. The timely refining ultrasound diagnosis of various clinical and morphological forms of acute pancreatitis combined with diagnostic fine-needle puncture conducting allows to approach differentiately to the implementation of miniinvasive percutaneous interventions and to justify a strategic position in the surgical treatment of destructive pancreatitis.

Autosomal recessive osteopetrosis (ARO) is a heterogeneous disorder, characterized by defective osteoclastic resorption of bone that results in increased bone density. We have studied nine individuals with an intermediate form of ARO, from the county of Västerbotten in Northern Sweden. All afflicted individuals had an onset in early infancy with optic atrophy, and in four patients anemia was present at diagnosis. Tonsillar herniation, foramen magnum stenosis, and severe osteomyelitis of the jaw were common clinical features. Whole exome sequencing, verified by Sanger sequencing, identified a splice site mutation c.212 + 1 G > T in the SNX10 gene encoding sorting nexin 10. Sequence analysis of the SNX10 transcript in patients revealed activation of a cryptic splice site in intron 4 resulting in a frame shift and a premature stop (p.S66Nfs * 15). Haplotype analysis showed that all cases originated from a single mutational event, and the age of the mutation was estimated to be approximately 950 years. Functional analysis of osteoclast progenitors isolated from peripheral blood of patients revealed that stimulation with receptor activator of nuclear factor kappa-B ligand (RANKL) resulted in a robust formation of large, multinucleated osteoclasts which generated sealing zones; however these osteoclasts exhibited defective ruffled borders and were unable to resorb bone in vitro.

BackgroundIncidental gallbladder cancer (IGBC) is an unexpected finding when a cholecystectomy is performed upon a benign indication, and the use of routine or selective histological analysis of gallbladder specimen is still debated. The aim of this study was to investigate whether the proportion of submitted gallbladder specimens for pathological investigation influences the proportion of IGBC found, and what possible factors preoperatively or perioperatively could influence the selection process.MethodsAll cholecystectomies between January 2007 and September 2014 registered in the Swedish Registry of Gallstone Surgery and ERCP (GallRiks) were included. Proportion of histological analysis was divided into four subgroups (0–25%, >25–50%, >50–75%, >75–100%).ResultsA total of 81,349 cholecystectomies were registered, and 36,010 (44.3%) gallbladder specimens were sent for histological analysis. A total of 213 cases of IGBC were discovered, which constituted 0.26% of all cholecystectomies performed and 0.59% of the number of gallbladder specimens sent for histological analysis. Hospitals submitting >75–100% of the gallbladder specimens had significantly more IGBC/1000 cholecystectomies performed (p = 0.003). Hospitals with the most selective approach had a significantly higher proportion of IGBC/1000 gallbladders that were sent for histological analysis (p < 0.001). Factors such as higher age (p < 0.001), female gender (p = 0.048) and macroscopic cholecystitis (p < 0.001) were more common in gallbladder specimens from hospitals that had a selective approach to histological analysis.ConclusionA routine approach to histological analysis in cholecystectomies with a benign indication for surgery can uncover a higher proportion of IGBC cases. When a selective approach is used, risk factors should be taken into account.