Late onset erythropoietic porphyria

A 51-year-old Japanese man and his 56-year-old sister of consanguineous parents had skin lesions with areas of dark-brown pigmentation and blisters with minimal trauma on sun-exposed skin which resembled those seen in porphyria cutanea tarda. Their fresh urine was wine-red in colour and fluoresced with ultraviolet light. The peripheral blood contained fluorocytes and porphyrin analysis of the red blood cells, urine and faeces of the patients revealed an increase of the isotype I of uro- and coproporphyrin and normal concentrations of delta-aminolaevulinate and porphobilinogen, suggesting the diagnosis of erythropoietic porphyria. No other members of this family had symptoms or biochemical findings suggestive of porphyria. We consider these two cases to be that of late onset erythropoietic porphyria.     

Prognostic Factors and Histopathological Features of Pediatric Intracranial Ependymomas: Nationwide Brain Tumor Registry-based Study of Japan

To assess the clinicopathological features and prognostic factors of pediatric intracranial ependymomas and to explore the current diagnostic practice, we analyzed clinical data from the Brain Tumor Registry of Japan (BTRJ). Data of fifty children under 18 years of age diagnosed with intracranial ependymoma were extracted from the BTRJ database. Cases were reviewed for overall survival (OS) and progression-free survival (PFS), with attention to gender, preoperative Karnofsky performance status score, location of the tumor, the extent of resection, World Health Organization (WHO) histopathological grading, and adjuvant therapy. The median age at diagnosis was 6.1 years, ranging from 7 months to 17.6 years. Based on the WHO histopathological grading, 27 patients were classified under grade 2 (54%) and 23 patients were classified under grade 3 (46%). Gross total resection (GTR) was achieved in 30 patients (60%). The median follow-up time was 65 months. Five-year PFS and OS were 47.2 ± 7.3% and 73.3 ± 6.7%, respectively. GTR was associated with longer OS (P = 0.02). The histopathological grading was not an independent prognostic factor for the OS. Mitosis and microvascular proliferation were higher among patients with grade 3 than in those with grade 2, which aided in deciding the WHO grade. This nationwide study revealed the characteristics and outcomes of patients with childhood ependymomas. GTR was the factor most consistently associated with improved survival. In contrast, the histopathological grading in this cohort was not a significant prognostic factor. More reproducible and practical criteria for the diagnosis of intracranial ependymomas should be further pursued in future studies.     

Challenges in the Treatment of Severe Traumatic Brain Injury Based on Data in the Japan Neurotrauma Data Bank

The Japan Neurotrauma Data Bank is a source of epidemiological data for patients with severe traumatic brain injury (TBI) and is sponsored by the Japan Society of Neurotraumatology. In this report, we examined the changes in the treatment of severe TBI in Japan based on data of the Japan Neurotrauma Data Bank. Controlling and decreasing intracranial pressure (ICP) are the primary objective of severe TBI treatment. Brain-oriented whole-body control or neurocritical care, including control of cerebral perfusion pressure, respiration, and infusion, are also increasingly considered important because cerebral tissues require oxygenation to improve the outcomes of patients with severe TBI. The introduction of neurocritical care in Japan was delayed compared with that in Western countries. However, the rate of ICP monitoring increased from 28.0% in 2009 to 36.7% in 2015 and is currently likely to be higher. Neurocritical care has also become more common, but the functional prognosis of patients has not significantly improved in Japan. Changes in the background of patients with severe TBI suggest the need for improvement of acute-phase treatment for elderly patients. Appropriate social rehabilitation from the subacute to chronic phases and introduction of cellular therapeutics are also needed for patients with TBI.     

PPARα activator irbesartan suppresses the proliferation of endometrial carcinoma cells via SREBP1 and ARID1A

Endometrial carcinoma (EMC) is associated with obesity; however, the underlying mechanisms have not yet been elucidated. Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor that is involved in lipid, glucose, and energy metabolism. PPARα reportedly functions as a tumor suppressor through its effects on lipid metabolism; however, the involvement of PPARα in the development of EMC remains unclear. The present study demonstrated that the immunohistochemical expression of nuclear PPARα was lower in EMC than in normal endometrial tissues, suggesting the tumor suppressive nature of PPARα. A treatment with the PPARα activator, irbesartan, inhibited the EMC cell lines, Ishikawa and HEC1A, by down-regulating sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FAS) and up-regulating the tumor suppressor genes p21 and p27, antioxidant enzymes, and AT-rich interaction domain 1A (ARID1A). These results indicate the potential of the activation of PPARα as a novel therapeutic approach against EMC.