The effectiveness of cinacalcet: a randomized, open label study in chronic hemodialysis patients with severe secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is associated with high incidences of cardiovascular disease, bone fracture, and mortality. This study was conducted to demonstrate the effectiveness of cinacalcet treatment on chronic kidney disease-mineral bone disorder (CKD-MBD) markers in chronic hemodialysis patients with severe SHPT. METHODS: In phase 1, 30 adult HD patients were randomized to cinacalcet or control groups for 12 weeks to explore the achievement of >30% reduction of iPTH. In phase 2, 45 patients were participated to further explore the effect of cinacalcet on CKD-MBD parameters for 24-week follow up and 12 additional weeks after cinacalcet discontinuation. RESULTS: In phase 1, the baseline serum iPTH levels were not different [1374 (955, 1639) pg/mL in the control group vs. 1191 (1005, 1884) pg/mL in the cinacalcet group], the percentage of patients achieving iPTH target were significantly higher in the treatment group [80% vs. 13%, p = .001]. In phase 2, the significant reductions of iPTH, FGF-23, tartrate-resistant acid phosphatase 5b, and slightly decreased size of parathyroid gland and stabilized vascular calcification were observed at 24-week follow up and markedly rebounded after discontinuation of cinacalcet. CONCLUSIONS: The effectiveness of cinacalcet were still obviously demonstrated even in chronic HD patients with severe SHPT. In addition, the improvements of bone markers and FGF-23, and stabilization of vascular calcification were observed. Therefore, cinacalcet can provide salutary effects on CKD-MBD in severe SHPT and might be an initially effective PTH-lowering therapy prior to surgical parathyroidectomy as well as an alternative treatment in the patients unsuitable for surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02056730. Date of registration: February 4, 2014.

New insights into neurocutaneous melanosis.

BACKGROUND: Neurocutaneous melanosis is a rare disorder in which children with large cutaneous melanotic nevi have associated melanosis in the brain. Although many affected children have structurally normal brains, some have associated developmental disorders or brain anomalies. OBJECTIVES: To determine the range of extent of brain melanosis as assessed by magnetic resonance imaging (MRI) and to investigate the frequency and types of associated brain anomalies. MATERIALS AND METHODS: We retrospectively reviewed brain and spine MRIs of 80 patients with congenital melanocytic nevi (range: 1 day to 22 years of age) affiliated with Nevus Outreach Inc. from 1998 to 2017. Central nervous system (CNS) melanosis was diagnosed when a mass with abnormal parenchymal T1 hyperintensity was seen. The locations of abnormal signal, associated malformations, the presence of contrast enhancement and, in patients with more than one MRI, changes over time were recorded. Associations among findings were analyzed using chi-square test or Fisher exact test. RESULTS: Brain abnormalities were identified in 33 patients. The most common finding was melanosis in the amygdala, which was found in 31 patients (an isolated finding in 14 patients). Nineteen patients had melanosis in the brainstem, cerebellum, cerebral cortex or thalamus. Cerebral and/or spinal leptomeningeal enhancement was uncommon (five patients). Hindbrain melanosis was associated with cerebellar and pontine hypoplasia (P=0.012). Brain melanosis was most easily seen on T1 images prior to myelination; reduced/loss of visibility was noted as the CNS matured. CONCLUSION: Brain melanosis is a common manifestation in children with large cutaneous melanotic nevi, most commonly found in the anterior temporal lobes (amygdala), brainstem, cerebellum and cerebral cortex. Hindbrain melanosis is associated with hypoplasia of the affected structures. Early imaging is optimal to provide the greatest sensitivity for diagnosis and to guide proper management.

KRAS Mutation in Pediatric Intracranial Germ Cell Tumors.

BACKGROUND: Intracranial germ cell tumors (IGCTs) are rare, highly curable neoplasms. KRAS is a gene in the KIT/RAS signaling pathway, and KRAS mutations have been reported in patients diagnosed with IGCTs. OBJECTIVES: To describe the clinicopathologic and molecular features of KRAS mutation and the treatment outcome of children diagnosed with IGCTs. METHODS: Patients diagnosed with IGCTs at the Department of Pediatrics, King Chulalongkorn Memorial Hospital from 2007 to 2016 were retrospectively reviewed. DNA was extracted from formalin-fixed, paraffin-embedded tissue and used for molecular study. Mutations in codons 12, 13, and 61 of the KRAS gene were detected using the cobas® KRAS mutation test and pyrosequencing. RESULTS: Eighteen patients were diagnosed with IGCTs (11 males and 7 females): nine with germinomas and nine with non-germinomatous GCTs (NGGCTs). The age range of the patients was 5-14 years (median 10.5 years). Elevated markers were revealed in approximately 25% of the patients. Four patients (two with germinomas and two with NGGCTs) had leptomeningeal involvement. All patients underwent tumor biopsy and received neoadjuvant chemotherapy. Radiotherapy was administered in 16 patients, and craniospinal radiation was administered only in patients with leptomeningeal metastasis. With a median follow-up of 26 months, overall survival was 88.9% in the patients with germinomas and 37% in the patients with NGGCTs. Mutation of the KRAS gene was detected using pyrosequencing in one patient. The mutation located at codon 61, with frequency 38.3% units, nucleotide substitution CAA > CTA, and amino acid substitution, was Q61L. The patient carrying the mutant gene was diagnosed with germinoma with cerebrospinal fluid metastasis and eventually died from treatment-related toxicity. CONCLUSION: Our study revealed the treatment outcomes of IGCTs in Thai children. The metastatic germinoma patient with KRAS codon 61 mutation had a poor outcome, supporting that Q61L has a clinical correlation with IGCTs.

A case of PHACE syndrome with growth hormone deficiency and abnormal thyroid functions.

Background PHACE syndrome is a rare vascular neurocutaneous disorder characterized by posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies and eye anomalies. Growth hormone deficiency (GHD) has been infrequently described. Case presentation We report a girl with PHACE syndrome. Endocrine abnormalities including abnormal thyroid functions and GHD have recently been described in similar cases. Conclusions This case suggests the necessity to screen pituitary functions in all patients with PHACE syndrome with abnormal hypothalamus and pituitary (HP) anatomy. Likewise, growth parameters and thyroid function test (TFT) should be monitored in all patients with PHACE syndrome at regular intervals.