Molecular diagnosis of diffuse glioma using a chip-based digital PCR system to analyze IDH, TERT, and H3 mutations in the cerebrospinal fluid.

PURPOSE: Conventional genetic analyzers require surgically obtained tumor tissues to confirm the molecular diagnosis of diffuse glioma. Recent technical breakthroughs have enabled increased utilization of cell-free tumor DNA (ctDNA) in body fluids as a reliable resource for molecular diagnosis in various cancers. Here, we tested the application of a chip-based digital PCR system for the less invasive diagnosis (i.e., liquid biopsy) of diffuse glioma using the cerebrospinal fluid (CSF). METHODS: CSF samples from 34 patients with diffuse glioma were collected from the surgical field during craniotomy. Preoperative lumbar CSF collection was also performed in 11 patients. Extracted ctDNA was used to analyze diagnostic point mutations in IDH1 R132H, TERT promoter (C228T and C250T), and H3F3A (K27M) on the QuantStudio® 3D Digital PCR System. These results were compared with their corresponding tumor DNA samples. RESULTS: We detected either of the diagnostic mutations in tumor DNA samples from 28 of 34 patients. Among them, we achieved precise molecular diagnoses using intracranial CSF in 20 (71%). Univariate analyses revealed that the World Health Organization (WHO) grade (p = 0.0034), radiographic enhancement (p = 0.0006), and Mib1 index (p = 0.01) were significant predictors of precise CSF-based molecular diagnosis. We precisely diagnosed WHO grade III or IV diffuse gliomas using lumbar CSF obtained from 6 (87%) of 7 patients with tumors harboring any mutation. CONCLUSION: We established a novel, non-invasive molecular diagnostic method using a chip-based digital PCR system targeting ctDNA derived from CSF with high sensitivity and specificity, especially for high-grade gliomas

Volumetric study reveals the relationship between outcome and early radiographic response during bevacizumab-containing chemoradiotherapy for unresectable glioblastoma.

PURPOSE: Although we have shown the clinical benefit of bevacizumab (BEV) in the treatment of unresectable newly diagnosed glioblastomas (nd-GBM), the relationship between early radiographic response and survival outcome remains unclear. We performed a volumetric study of early radiographic responses in nd-GBM treated with BEV. METHODS: Twenty-two patients with unresectable nd-GBM treated with BEV during concurrent temozolomide radiotherapy were analyzed. An experienced neuroradiologist interpreted early responses on fluid-attenuated inversion recovery (FLAIR) and gadolinium-enhanced T1-weighted images (GdT1WI). Volumetric changes were evaluated using diffusion-weighted imaging (DWI) and GdT1WI according to the Response Assessment in Neuro-Oncology (RANO) criteria. The results were categorized into improved (complete response [CR] or partial response [PR]) or non-improved (stable disease [SD] or progressive disease [PD]) groups; outcomes were compared using Kaplan-Meier analysis. RESULTS: The volumetric GdT1WI improvement was a significant predictive factor for overall survival (OS) prolongation (p = 0.0093, median OS: 24.7 vs. 13.6 months); however, FLAIR and DWI images were not predictive. The threshold for the neuroradiologists interpretation of improvement in GdT1WI was nearly 20% of volume reduction, which was lesser than 50%, the definition of PR applied in the RANO criteria. However, even less stringent neuroradiologist interpretation could successfully predict OS prolongation (improved vs. non-improved: p = 0.0067, median OS: 17.6 vs. 8.3 months). Significant impact of OS on the early response in volumetric GdT1WI was observed within the cut-off range of 20-50% (20%, p = 0.0315; 30%, p = 0.087; 40%, p = 0.0456). CONCLUSIONS: Early response during BEV-containing chemoradiation can be a predictive indicator of patient outcome in unresectable nd-GBM

Lumboperitoneal shunt using fluoroscopy and a peel-away sheath

Background: After placement of the spinal catheter into the spinal canal during lumboperitoneal shunt (LPS) placement, the spinal catheter needs to be connected to the programmable valve. Although surgeons always try to secure the spinal catheter position during procedures, it may be accidentally pulled and displaced. This article aimed to introduce a “one-piece method” of LPS using fluoroscopy and peel-away sheath without connecting the spinal catheter to the programmable valve. Methods: An abdominal shunt catheter, valve, and spinal shunt catheter were connected and tunneled to the back for insertion into the lumbar spinal subarachnoid space. The spinal catheter was cut to a length of 15 cm. Lumbar puncture was performed using a 14-gauge Tuohy needle inserted at the L2-3 intervertebral space using an image-guided paramedian technique, and a 0.035-inch guidewire was passed gently through the Tuohy needle under fluoroscopic guidance. The Tuohy needle was withdrawn, and a 5-Fr peel-away sheath was advanced over the wire. The dilator and guide wire were removed, the distal end of the 5-Fr peel-away sheath was checked to ensure that the cerebrospinal fluid flowed out, and the spinal shunt catheter was passed down the sheath. After confirming under fluoroscopic guidance that the catheter was properly positioned, the peel-away sheath was removed. Results: LPS was performed using this method in seven patients without complications. Conclusion: This simple “one-piece method” using fluoroscopy and peel-away sheath is safe and effective for positioning the spinal catheter

Unilateral C1 Posterior Arch Screw-C2 Laminar Screw Posterior Fixation for Vertebral Artery Preservation in Bow Hunter’s Syndrome

Pedicle or lateral mass screws, which are usually used to fix atlantoaxial instability, increase the risk of vertebral artery (VA) injury in patients with bone or arterial anomalies or osteoporotic bone. Here, we report the use of a unilateral C1 posterior arch screw-C2 laminar screw posterior fixation with a contralateral C1 lateral mass screw for VA preservation in a patient with bow hunter’s syndrome (BHS). A 65-year-old male presented with recurrent loss of consciousness in the right rotational and backward-bending head positions for 1 year. Cerebral angiography in the same head position showed that the left VA was disrupted at C1/2 and the right VA was hypoplastic. The patient was diagnosed with BHS. C1-2 posterior fixation and iliac bone grafting were performed. The left VA was on the dominant side, and the VA was in a high position; thus, a C1 posterior arch screw was selected for the left side, a C1 lateral mass screw was selected for the right side, and a C2 laminar screw with O-arm navigation and a C-arm was used to prevent arterial injury. Intraoperative findings revealed no VA injury, and postoperative computed tomography showed the screw at the planned site. In a patient with BHS, posterior fixation with a unilateral C1 posterior arch screw-C2 laminar screw prevented VA injury because the screw could be inserted while avoiding the VA

Predictors of recurrence and postoperative outcomes in patients with non-skull base meningiomas based on modern neurosurgical standards

Background: Advances in neurosurgical techniques and neuroimaging resolution questions the modern-day reliability of the Simpson grade for predicting meningioma recurrence. Therefore, we evaluated the reliability of predictors for recurrence and outcomes in detail in patients with non-skull base meningiomas (NSBMs). Methods: We retrospectively analyzed data from consecutive 175 NSBMs underwent surgical resection. We performed Kaplan–Meier analyses of recurrence-free survival (RFS) according to Simpson and World Health Organization (WHO) grades. Predictors of RFS and clinical deterioration were estimated by univariate and multivariate analyses. Correlation between the Simpson grade and change in Karnofsky Performance Scale scores was assessed by Fisher's exact test. Results: Log-rank tests revealed significant correlations of both the Simpson and WHO grades with RFS for the overall cohort, convexity, and falx/tentorium meningioma. Unlike patients undergoing Simpson grade I and II resections, RFS in patients with WHO grade I and II/III tumors differed significantly from the early postoperative stage. Multivariate analysis identified tumor size, Simpson grade, and MIB-1 labeling index as significant predictors of RFS. Clinical deterioration was more frequent among patients undergoing less aggressive resection. Tumor location was the only significant predictor of clinical deterioration. Conclusions: Our findings indicate that tumor size, Simpson and WHO grades, and MIB-1 labeling index are significant predictors of NSBM recurrence. Moreover, the risk of recurrence markedly decreases within the follow-up duration of 80 months. Aggressive resection appears to minimize the risk of recurrence without evidence of clinical deterioration. Follow-up schedules should be based on the WHO grade and extent of resection. Keywords: Meningioma, Non-skull base, Outcome, Recurrence, Simpson grade, WHO grad