Absence of WDR13 in p53-Null Mice Increases Longevity

Absence of WDR13 is known to be involved in pancreatic, colon and uterine hyperproliferation. However, a recent study showed its antiproliferative role liver regeneration in response to hepatotoxins. These findings intrigued to study the role of WDR13-null condition in Trp53 knockout mouse to study the tumour predisposition and survival. We report absence of Wdr13 in Trp53-null background alleviates the tumour load, in turn increasing total survival in mouse model.

Clinical characterization of children and adolescents with NF1 microdeletions

Purpose An estimated 5–11% of patients with neurofibromatosis type 1 (NF1) harbour NF1 microdeletions encompassing the NF1 gene and its flanking regions. The purpose of this study was to evaluate the clinical phenotype in children and adolescents with NF1 microdeletions. Methods We retrospectively analysed 30 children and adolescents with NF1 microdeletions pertaining to externally visible neurofibromas. The internal tumour load was determined by volumetry of whole-body magnetic resonance imaging (MRI) in 20 children and adolescents with NF1 microdeletions. Furthermore, the prevalence of global developmental delay, autism spectrum disorder and attention deficit hyperactivity disorder (ADHD) were evaluated. Results Children and adolescents with NF1 microdeletions had significantly more often cutaneous, subcutaneous and externally visible plexiform neurofibromas than age-matched patients with intragenic NF1 mutations. Internal neurofibromas were detected in all 20 children and adolescents with NF1 microdeletions analysed by whole-body MRI. By contrast, only 17 (61%) of 28 age-matched NF1 patients without microdeletions had internal tumours. The total internal tumour load was significantly higher in NF1 microdeletion patients than in NF1 patients without microdeletions. Global developmental delay was observed in 28 (93%) of 30 children with NF1 microdeletions investigated. The mean full-scale intelligence quotient in our patient group was 77.7 which is significantly lower than that of patients with intragenic NF1 mutations. ADHD was diagnosed in 15 (88%) of 17 children and adolescents with NF1 microdeletion. Furthermore, 17 (71%) of the 24 patients investigated had T-scores ≥ 60 up to 75, indicative of mild to moderate autistic symptoms, which are consequently significantly more frequent in patients with NF1 microdeletions than in the general NF1 population. Also, the mean total T-score was significantly higher in patients with NF1 microdeletions than in the general NF1 population. Conclusion Our findings indicate that already at a very young age, NF1 microdeletions patients frequently exhibit a severe disease manifestation which requires specialized long-term clinical care.

hypercalcaemia due to a calcitriol-producing neuroendocrine tumour

In this case report, we describe a 40-year-old patient with a large grade 2 pancreatic neuroendocrine tumour (pNET) with spleen metastasis. Albeit radical resection, he developed liver metastasis after 2 years, for which he underwent radio frequency ablation and embolization, and was treated successfully with different subsequent lines of systemic therapy. Eight years after the initial diagnosis, he was admitted for symptomatic and refractory hypercalcaemia, due to calcitriol synthesis by the liver metastasis. After tumour load reduction by hemihepatectomy, there was an initial normalization of hypercalcaemia, until it recurred after 18 months. In this period, the liver metastasis had progressed despite chemo- and immunotherapy. Patient underwent an additional extend hemihepatectomy, from which he recovered well with normalization of calcium levels. This case illustrates the hormonal plasticity of pNETs and shows how prolonged survival can be achieved for metastatic pNET by multimodality approach.