Metabolic delineation of IDH1 wild-type glioblastoma surgical anatomy: how to plan the tumor extent of resection.

PURPOSE: Magnetic resonance imaging (MRI) is the current standard for preoperative planning of glioblastoma (GBM) surgery. However, recent data on the use of 11 C-methionine positron emission tomography (11[C]-MET PET) suggest its role in providing additional information beyond MRI. The purpose of this study is to establish if there is a correlation between anatomical and metabolic data. METHODS: We retrieved all GBM cases treated from 2014 to January 2021. Preoperative MRI (Enhancing Nodule -EN-, FLAIR and Total Tumor Volume -TTV-), PET volumes and histological samples obtained from the different tumor regions were evaluated to analyze potential correlations between anatomical, metabolic and pathological data. RESULTS: 150 patients underwent surgery for GBM and 49 of these were also studied preoperatively with 11[C]-MET PET; PET volume was evaluated in 47 patients. In 33 patients (70.21%) preoperative 11[C]-MET PET volume > preoperative EN volume and in 11 (23.4%) preoperative 11[C]-MET PET volume > preoperative TTV. We found a significant correlation between preoperative TTVs and PET volumes (p = 0.016) as well as between preoperative EN volumes and PET volumes (p = < 0.001). Histologically, 109 samples were evaluated. ENs samples exhibited the conventional GBM morphology while samples from the FLAIR regions showed white matter tissue, with focal to diffuse tumor cells infiltration and areas of reactive astrogliosis. CONCLUSION: We submit that 11[C]-MET PET volume generally overcome EN. The presence of neoplastic cells confirm these metabolic data. It should be considered in the surgical planning to achieve a Supra Total Resection (SupTR).

Direct Transpedicular C2 Fixation for the Surgical Management of Hangman's Fractures: A "Second Youth" for the Judet Approach.

PURPOSE: The optimal management of hangman's fractures is controversial and the standard of care has been neither established nor supported by strong evidence. The Judet approach has been introduced in 1970 as surgical option to treat selected cases of hangman's fractures, harboring the advantage to preserve motion of the craniovertebral junction and to restore the C2 vertebra anatomy by insertion of transpedicular screws through the fracture line. This paper reviews the literature on hangman's fractures surgically managed by Judet approach, and reports two new illustrative cases. METHODS: The PubMed database was searched for the review process. After initial screening of abstracts and papers, 13 manuscripts were included in the present review.Two cases of hangman's fractures, a Levine-Edwards type I and a type IIA, respectively, treated with direct transpedicular C2 screw fixation are reported. Surgical steps of the Judet approach are also described. RESULTS: Our literature review revealed that the technique described by Judet is gaining appeal only in recent years and there is no consensus on surgical indications.No surgery-related complications were observed in the two reported cases. Patients experienced a significant reduction of neck pain postoperatively. Motion of craniovertebral junction was preserved in both patients at 3-, 6-, and 12-month follow-ups. CONCLUSIONS: Direct transpedicular osteosynthesis of C2-pars interarticularis fracture has been already demonstrated as effective in type II and IIA hangman's fractures. The application of such technique in selected patients with atypical type I fractures should also be considered in order to achieve early mobilization and avoid external fixation.

Anatomical distribution of cancer stem cells between enhancing nodule and FLAIR hyperintensity in supratentorial glioblastoma: time to recalibrate the surgical target?

It is ge nerally accepted that glioblastoma (GBM) arise from cancer stem cells (CSC); however, there is little evidence on their anatomical distribution. We investigated the expression and distribution of SOX-2-positive and CD133-positive CSCs both in the enhancing nodule (EN) of GBM and in the FLAIR hyperintensity zones on a surgical, histopathological series of 33 GBMs. The inclusion criterion was the intraoperative sampling of different tumor regions individualized, thanks to neuronavigation and positivity to intraoperative fluorescence with the use of 5-aminolevulinic acid (5-ALA). Thirty-three patients (20 males and 13 females with a mean age at diagnosis of 56 years) met the inclusion criterion. A total of 109 histological samples were evaluated, 52 for ENs and 57 for FLAIR hyperintensity zone. Considering the quantitative distribution of levels of intensity of staining (IS), ES (extent score), and immunoreactivity score (IRS), no difference was found between ENs and FLAIR regions for both the SOX-2 biomarker (respectively, IS p = 0.851, ES p = 0.561, IRS p = 1.000) and the CD133 biomarker (IS p = 0.653, ES p = 0.409, IRS p = 0.881). This evidence suggests to recalibrate the target of surgery for FLAIRECTOMY and 5-ALA could improve the possibility to achieve this goal.

Recurrent high-grade glioma surgery: a multimodal intraoperative protocol to safely increase extent of tumor resection and analysis of its impact on patient outcome.

OBJECTIVE: No consensus exists on the best treatment for recurrent high-grade glioma (HGG), particularly in terms of surgical indications, and scant data are available on the integrated use of multiple technologies to overcome intraoperative limits and pitfalls related to artifacts secondary to previous surgery and radiotherapy. Here, the authors report on their experience with the integration of multiple intraoperative tools in recurrent HGG surgery, analyzing their pros and cons as well as their effectiveness in increasing the extent of tumor resection. In addition, they present a review of the relevant literature on this topic. METHODS: The authors reviewed all cases in which recurrent HGG had been histologically diagnosed after a first surgery and the patient had undergone a second surgery involving neuronavigation with MRI, intraoperative CT (iCT), 11C-methionine-positron emission tomography (11C-MET-PET), 5-aminolevulinic acid (5-ALA) fluorescence, intraoperative neurophysiological monitoring (IONM), and intraoperative navigated ultrasound (iUS). All cases were classified according to tumor functional grade (1, noneloquent area; 2, near an eloquent area; 3, eloquent area). RESULTS: Twenty patients with recurrent HGG were operated on using a multimodal protocol. The recurrent tumor functional grade was 1 in 4 patients, 2 in 8 patients, and 3 in the remaining 8 patients. In all patients but 2, 100% EOTR was obtained. Intraoperative 5-ALA fluorescence and navigated iUS showed low specificity and sensitivity. iCT detected tumor remnants in 3 cases. Postoperatively, 6 patients (30%) had worsening neurological conditions: 4 recovered within 90 days, 1 partially recovered, and 1 experienced a permanent deficit. The median Karnofsky Performance Status remained substantially unchanged over the follow-up period. The mean progression-free survival after the second surgery was 7.7 months (range 2-11 months). The mean overall survival was 25.4 months (range 10-52 months), excluding 2 long survivors. Two patients died within 60 days after surgery, and 3 patients were still under follow-up at the end of this study. CONCLUSIONS: This is the first study reporting the integration of neuronavigation, 5-ALA fluorescence, iUS, iCT, 11C-MET-PET, and IOM during microsurgical resection of recurrent glioma. The authors believe that the proposed multimodal protocol is useful to increase the safety, effectiveness, and EOTR in patients with recurrent HGG and brain alterations secondary to radio- and chemotherapy.

Decision-Making Challenge of Ping-Pong Fractures in Children: Case Exemplification and Systematic Review of Literature.

Ping-pong fractures have become less frequent, and no definite predictors to determine which fractures will elevate spontaneously and which should undergo surgical treatment have been clearly defined. Herein, the authors present a revision of the literature, in which 54 papers were included, with a total of 228 children studied. Patients who underwent surgery accounted for 30%; elevation through obstetrical vacuum or other aspiration systems was applied in 30%; and spontaneous resolution occurred in 40%; in 4 patients, percutaneous microscrew elevation was applied. Overall, in 96.4% of patients, the outcome was favorable because we found no significant increase in the incidence of post-traumatic seizures or neurologic sequelae with no significant differences between treated patients and spontaneous elevation. Statistical analysis showed no significant differences among the different treatment methods (P = 0.53). Our results suggest that simple compound ping-pong fractures without brain compression, hematomas, or dural tears could benefit from conservative management. In cases of nonspontaneous resolution after 6 months, operative strategies should be performed, considering that there is no evidence of differences between vacuum elevation and surgical elevation.

High Grade Glioma Treatment in Elderly People: Is It Different Than in Younger Patients? Analysis of Surgical Management Guided by an Intraoperative Multimodal Approach and Its Impact on Clinical Outcome.

OBJECTIVE: Age is considered a negative prognostic factor for High Grade Gliomas (HGGs) and many neurosurgeons remain skeptical about the benefits of aggressive treatment. New surgical and technological improvements may allow extended safe resection, with lower level of post-operative complications. This opportunity opens the unsolved question about the most appropriate HGG treatment in elderly patients. The aim of this study is to analyze if HGG maximal safe resection guided by an intraoperative multimodal imaging protocol coupled with neuromonitoring is associated with differences in outcome in elderly patients versus younger ones. METHODS: We reviewed 100 patients, 53 (53%) males and 47 (47%) females, with median (IQR) age of 64 (57; 72) years. Eight patients were diagnosed with Anaplastic Astrocytoma (AA), 92 with Glioblastoma (GBM). Surgery was aimed to achieve safe maximal resection. An intraoperative multimodal imaging protocol, including neuronavigation, neurophysiological monitoring, 5-ALA fluorescence, 11C MET-PET, navigated i-US system and i-CT, was used, and its impact on EOTR and clinical outcome in elderly patients was analyzed. We divided patients in two groups according to their age: <65 and >65 years, and surgical and clinical results (EOTR, post-operative KPS, OS and PFS) were compared. Yet, to better understand age-related differences, the same patient cohort was also divided into <70 and >70 years and all the above data reanalyzed. RESULTS: In the first cohort division, we did not found KPS difference over time and survival analysis did not show significant difference between the two groups (p = 0.36 for OS and p = 0.49 for PFS). Same results were obtained increasing the age cut-off for age up to 70 years (p = 0.52 for OS and p = 0.92 for PFS). CONCLUSIONS: Our data demonstrate that there is not statistically significant difference in post-operative EOTR, KPS, OS, and PFS between younger and elderly patients treated with extensive tumor resection aided by a intraoperative multimodal protocol.

Pros and cons of a minimally invasive percutaneous subdural drainage system for evacuation of chronic subdural hematoma under local anesthesia.

OBJECTIVE: Chronic subdural hematoma (CSH) is a common neurosurgical disease among elderly population with concomitant degenerative neurological disorders. This is a retrospective series-control analysis of prospectively collected data, aiming to show advantages and indications of a minimally invasive, percutaneous drainage system for CSH. PATIENTS AND METHODS: We retrospectively analyse the clinical and radiological data of a minimally invasive, percutaneous draining system (Integra ™) used in fifteen patients (Group A; mean age: 75.7) with CSH, and compare them with those obtained from two retrospective series of patients: the first one (Group B 15 patients, mean age 77.1) treated with standard, single-burr hole technique for subdural drainage under general anaesthesia; the second one (Group C 15 patients, mean age 76.4) treated with standard, single-burr hole technique for subdural drainage under local anaesthesia and mild sedation. All The percutaneous procedures (Group A) were performed under local anaesthesia. RESULTS: Mean follow-up was 10.9 (range 3-14), 18.2 (range 10-29) and 15.2 (range 8-28) months in Group A, B and C respectively. Three of 15 and in Group B experienced a worsening of pre-existing neurodegenerative disorders after general anaesthesia. One patient in group C suffering from Parkinson's disease experienced a worsening of gait disturbances. Post-operative CT scans were performed at 48 h and 21 days after the operation. An early post-operative CT-scan, obtained immediately after surgical procedure, was performed in all Group A patients. No differences in CSH evacuation were observed comparing the three groups. Two recurrent hematomas, one in group A and one in group B, required revision. Post-operative hospitalization was similar (5.1 vs 5.7 vs 5.6 days, respectively, in group A, B and C) but analgesics use was lower in Group A. CONCLUSION: Pre-operative evaluation of radiological features of CSDHs is crucial in determining the right indication for a minimally invasive drainage. Minimally invasive treatments of CSH may reduce the use of anaesthetic drugs and worsening of pre-existing neurodegenerative disorders.