Plasmatic microRNA levels by ddPCR as peripheral biomarkers for IDH-wild type glioblastomas: a pilot study

BACKGROUND: Glioblastoma (GBM) is the most frequent malignant brain tumour in adults with a dismal prognosis and peripheral biomarkers may be useful and effective in managing patients with GBM. The main aim of our study was the use of ddPCR to assess the absolute quantification of the plasmatic levels of three miRNAs as possible GBM-specific biomarkers. We focused on: miR-21-5p, an onco-miR overexpressed in blood, tumour tissue and cell cultures derived from patients affected by GBM, miR-23b-3p and miR-34a-5p, tumour suppressor miRs dysregulated in GMB. MATERIALS AND METHODS: Eight patients presenting with firstly-diagnosed IDH-wild type GBM and 10 age- and gender-matched healthy control donors (hC) have been enrolled in the study. Peripheral blood samples were collected at diagnosis and one month after surgery. Total RNA was isolated from plasma by means of miRNeasy Serum/Plasma Kit (Qiagen), according to the manufacturer’s instructions. Digital droplet PCR (ddPCR) was performed to assess the absolute quantification of each miRNA level according to the QX200 ddPCR protocol. RESULTS: The expression analysis revealed: i) different levels of each miRNA in hC: 98.74 copies/L (±123.60), 2.56 copies/L (±5.57), 0.73 copies/L (±0.85) for miR-21-5p, miR-23b-3p and miR-34a-5p, respectively; ii) a trend of downregulation of miR-21-5p and miR-23b-3p in GMB patients at diagnosis compared to hC; iii) a trend of upregulation of each miRNA in GMB patients one month after surgery compared with the levels measured at diagnosis, in particular 3.02, 6.2 and 1.7 fold increase for miR-21-5p, miR-23b-3p and miR-34a-5p, respectively. CONCLUSIONS: In this pilot study we reported higher amounts of circulating miR-21-5p, miR-23b-3p and miR-34a-5p in plasma of patients affected by IDH-wild type GBM one month after surgery compared to the levels at diagnosis

Determination of plasmatic microRNA levels by ddPCR as peripheral biomarkers for IDH-wild type glioblastomas: a pilot study

BACKGROUND: Glioblastoma (GBM) is the most frequent malignant brain tumour in adults with a dismal prognosis. Peripheral biomarkers may be useful and effective in managing patients affected by GBM. The aim of our study was to analyse the plasmatic levels of three miRNAs as possible GBM-specific biomarkers. We focused on miR-21-5p – an onco-miR overexpressed in blood, tumour tissue and cell cultures derived from patients affected by GBM – miR-23b-3p – overexpressed in GBM, especially under hypoxic conditions – and miR-34a-5p – a tumour suppressor miR downregulated in tumour tissue and serum of patients with GBM. MATERIALS AND METHODS: Eight patients presenting with firstly-diagnosed IDH-wild type GBM and 10 age- and gender-matched healthy volunteers (hV) have been enrolled in the study. Peripheral blood samples were collected at diagnosis and one month after surgery. Total RNA was isolated from plasma by means of miRNeasy Serum/Plasma Kit (Qiagen), according to the manufacturer’s instructions. Digital droplet PCR (ddPCR) was performed for each miRNA according to the QX200 EvaGreen ddPCR protocol. RESULTS: The circulating concentrations of miR-21-5p were in mean 24.00 (28.44) and 72.40 (147.88) copies/L in patients with GBM at diagnosis and one month after surgery (p=0.38), respectively, compared with 98.74 copies/L ( 123.60) quantified in hV (p=0.09; p=0.69). The mean peripheral levels of miR-23b-3p were 0.49 copies/L (0.49) at diagnosis and 3.02 copies/L (6.88) one month after surgery (p=0.32) in patients with GBM, and 2.56 copies/L (5.57) in hV (p=0.31; p=0.88). Analysing plasmatic expression of miR-34a-5p, 1.11 (1.55) and 1.85 copies/L (1.87) were measured on average at diagnosis and one month after surgery in patients with GBM (p=0.41), while 0.73 copies/L (0.85) in hV (p=0.52; p=0.11). CONCLUSIONS: We preliminarily reported higher concentrations of circulating miR-21-5p, miR-23b-3p and miR-34a-5p in plasma of patients affected by IDH-wild type GBM one month after surgery compared to the levels at diagnosis

Primary glomus tumour of the pituitary gland: diagnostic challenges of a rare and potentially aggressive neoplasm

From Springer Nature via Jisc Publications RouterHistory: received 2020-06-05, rev-recd 2020-08-14, accepted 2020-08-24, registration 2020-09-02, pub-electronic 2020-09-12, online 2020-09-12, pub-print 2021-05Publication status: PublishedFunder: University of ManchesterAbstract: Primary non-neuroendocrine tumours of the pituitary gland and sella are rare lesions often challenging to diagnose. We describe two cases of clinically aggressive primary glomus tumour of the pituitary gland. The lesions occurred in a 63-year-old male and a 30-year-old female who presented with headache, blurred vision and hypopituitarism. Neuroimaging demonstrated large sellar and suprasellar tumours invading the surrounding structures. Histologically, the lesions were characterised by angiocentric sheets and nests of atypical cells that expressed vimentin, smooth muscle actin and CD34. Perivascular deposition of collagen IV was also a feature. Case 2 expressed synaptophysin. INI-1 (SMARCB1) expression was preserved. Both lesions were mitotically active and demonstrated a Ki-67 labelling index of 30%. Next-generation sequencing performed in case 1 showed no mutations in the reading frame of 37 commonly mutated oncogenes, including BRAF and KRAS. Four pituitary glomus tumours have previously been reported, none of which showed features of malignant glomus tumour. Similar to our two patients, three previous examples displayed aggressive behaviour

How I do it - The "drum skin" duraplasty technique after foramen magnum decompression for Chiari malformations

BackgroundChiari malformations are a spectrum of posterior cranial fossa anomalies characterized by herniation of the cerebellar tonsils through the foramen magnum. Surgery is the treatment of choice for selected patients with good postoperative outcomes.MethodsWe describe foramen magnum decompression (FMD) with dural opening and a "drum skin" duraplasty technique.ConclusionsIn our experience, FMD with "drum skin" duraplasty is a safe and effective procedure, reducing the risk of CSF leakage and arachnoidal adhesions and yielding better long-term clinical and radiological outcomes than other traditional techniques