Precise Detection of Gene Mutations in Fine-Needle Aspiration Specimens of the Papillary Thyroid Microcarcinoma Using Next-Generation Sequencing.

PURPOSE: To assess the feasibility of next-generation sequencing (NGS) to detect mutations in BRAF, RAS, TERT promoter, and TP53 genes in ultrasound-guided fine-needle aspiration (FNA) biopsy samples of the papillary thyroid microcarcinoma (PTMC). METHODS: A total of 135 FNA samples out of 135 patients with suspected PTMC were submitted for mutation testing using NGS. NGS was successfully performed in 114 specimens, while the remaining 21 samples were excluded due to insufficient amount/poor quality of DNA and sequencing failure. Of those 114 samples, 72 who were confirmed as having PTMC by postoperative histopathology were enrolled in our study, and the other 42 who had a follow-up with ultrasound were excluded. Mutations of genes including BRAF, NRAS, HRAS, KRAS, TERT promoter, and TP53 were evaluated using NGS. The associations of gene mutations and clinicopathological characteristics of PTMC were analyzed. RESULTS: BRAF mutation was observed in 59 (81.94%) of 72 specimens. This mutation detected in BRAF was p.V600E (c.1799T>A) in exon 15 of all 59 specimens. NRAS mutation was identified in 1 (1.39%) specimen classified as Bethesda III and pathologically confirmed as a follicular variant PTMC. There were no mutations found in TERT promoter or TP53. The tumor with a maximum diameter (D max) larger than 5 mm was shown to be significantly correlated with the BRAF mutation in a multivariate analysis (OR 5.52, 95% CI 1.51-26.42, P = 0.033). But the BRAF mutation was not found to be significantly associated with the gender or age of patients with PTMC (P > 0.05). CONCLUSIONS: This study demonstrated that gene mutations in FNA specimens of PTMC could be successfully analyzed with a higher sensitivity using NGS compared to conventional methods for mutation detection. BRAF mutation of p.V600E was statistically associated with PTMC with a D max larger than 5 mm.

Follow-up study of high-dose praziquantel therapy for cerebral sparganosis.

BACKGROUND: Cerebral sparganosis is the most serious complication of human sparganosis. Currently, there is no standard for the treatment of inoperable patients. Conventional-dose praziquantel therapy is the most reported treatment. However, the therapeutic outcomes are not very effective. High-dose praziquantel therapy is a useful therapeutic choice for many parasitic diseases that is well tolerated by patients, but it has not been sufficiently evaluated for cerebral sparganosis. This study aims to observe the prognoses following high-dose praziquantel therapy in inoperable patients and the roles of MRI and peripheral eosinophil absolute counts during follow-up. METHODOLOGY: Baseline and follow-up epidemiological, clinical, radiological and therapeutic data related to 10 inoperable patients with cerebral sparganosis that were treated with repeated courses of high-dose praziquantel therapy, with each course consisting of 25 mg/kg thrice daily for 10 days were assessed, followed by analyses of the prognoses, MRI findings and peripheral eosinophil absolute counts. PRINCIPAL FINDINGS: Baseline clinical data: the clinical symptoms recorded included seizures, hemiparesis, headache, vomiting and altered mental status. Peripheral blood eosinophilia was found in 3 patients. The baseline radiological findings were as follows. Motile lesions were observed in 10 patients, including aggregated ring-like enhancements, tunnel signs, serpiginous and irregular enhancements. Nine of the 10 patients had varying degrees of white matter degeneration, cortical atrophy and ipsilateral ventricle dilation. The follow-up clinical data were as follows. Clinical symptom relief was found in 8 patients, symptoms were eliminated in 1 patient, and symptoms showed no change from baseline in 1 patient. Peripheral blood eosinophilia was found in 2 patients. The follow-up radiological findings were as follows. Motile lesions that were transformed into stable, chronic lesions were found in 8 patients, and motile lesions that were eliminated completely were found in 2 patients. CONCLUSIONS: High-dose praziquantel therapy for cerebral sparganosis is effective. The radiological outcomes of motile lesions are an important indicator during the treatment process, especially during follow-ups after clinical symptoms have improved. Peripheral eosinophil absolute counts cannot be used as an effective prognostic indicator.

The clinical presentation and collateral pathway development of congenital absence of the internal carotid artery.

OBJECTIVE: The objective of this study was to investigate the clinical presentation, risks, and collateral pathway development of the congenital absence of the internal carotid artery (ICA). METHODS: Sixty-four patients (10 new patients and 54 patients from the relevant literature) were studied. Data on demographic, clinical, and radiologic features were collected, followed by an analysis of the risks associated with ICA agenesis. RESULTS: There were 31 male and 33 female patients whose ages ranged from 5 months to 75 years, with a mean age of 31.1 years. The range of clinical symptoms recorded included transient ischemic attack (17 patients), subarachnoid hemorrhage (12 patients), developmental delay (13 patients), asymptomatic (8 patients), and other symptoms (15 patients). All 64 patients presented with absence of unilateral or bilateral ICAs, as measured by cervical computed tomography angiography or magnetic resonance angiography. The carotid canal was absent in all patients on computed tomography of the base of the skull, and abnormal development of collateral circulation pathways was observed. Five patients presented with basilar artery dilation on angiography. Aneurysms were observed in the angiography results from 16 patients. Ten patients presented with variations in the ophthalmic artery origin (the ophthalmic artery originated from the ipsilateral middle meningeal artery in six patients and from the ipsilateral middle cerebral artery in four patients). CONCLUSIONS: From analysis of our 10 cases of ICA agenesis and our review of the relevant literature, we conclude that young patients with ICA agenesis may present with developmental delay, subarachnoid hemorrhage, or other developmental abnormalities, whereas older patients most commonly present with transient neurologic events. Complications of carotid agenesis are related to specific anatomic subtypes and the resulting collateral circulation development.