Efficacy and Safety of Carmustine Wafer Implantation After Ventricular Opening in Glioblastomas, Isocitrate Dehydrogenase-Wildtype, in Adults.

BACKGROUND AND OBJECTIVES: We assessed the impact of ventricular opening on postoperative complications and survival of carmustine wafer implantation during surgery of newly diagnosed supratentorial glioblastomas, isocitrate dehydrogenase (IDH)-wildtype in adults. METHODS: We performed an observational, retrospective, single-center cohort study at a tertiary surgical neuro-oncological center between January 2006 and December 2021. RESULTS: One hundred ninety-four patients who benefited from a first-line surgical resection with carmustine wafer implantation were included. Seventy patients (36.1%) had a ventricular opening. We showed that ventricular opening (1) did not increase overall postoperative complication rates (P = .201); (2) did not worsen the early postoperative Karnofsky Performance Status score (P = .068); (3) did not increase the time interval from surgery to adjuvant oncological treatment (P = .458); (4) did not affect the completion of the standard radiochemotherapy protocol (P = .164); (5) did not affect progression-free survival (P = .059); and (6) did not affect overall survival (P = .142). CONCLUSION: In this study, ventricular opening during first-line surgical resection did not affect the survival and postoperative complications after use of carmustine wafer implantation in adult patients with a newly diagnosed supratentorial glioblastoma, IDH-wildtype. This warrants a prospective and multicentric study to clearly assess the impact of the ventricular opening after carmustine wafer implantation in glioblastoma, IDH-wildtype.

Carmustine wafer implantation for supratentorial glioblastomas, IDH-wildtype in "extreme" neurosurgical conditions.

We assessed the feasibility of Carmustine wafer implantation in "extreme" conditions (i.e. patients > 80 years and Karnofsky Performance Status score < 50) and of implantation ≥ 12 Carmustine wafers in adult patients harbouring a newly diagnosed supratentorial glioblastoma, IDH-wildtype. We performed an observational, retrospective single-centre cohort study at a tertiary surgical neuro-oncological centre between January 2006 and December 2021. Four hundred eighty patients who benefited from a surgical resection at first-line treatment were included. We showed that Carmustine wafer implantation in patients > 80 years, in patients with a Karnofsky performance status score < 50, and that implantation ≥ 12 Carmustine wafers (1) did not increase overall postoperative complication rates, (2) did not affect the completion of standard radiochemotherapy protocol, (3) did not worsen the postoperative Karnofsky Performance Status scores, and (4) did not significantly affect the time to oncological treatment. We showed that the implantation of ≥ 12 Carmustine wafers improved progression-free survival (31.0 versus 10.0 months, p = 0.025) and overall survival (39.0 versus 16.5 months, p = 0.041) without increasing postoperative complication rates. Carmustine wafer implantation during the surgical resection of a newly diagnosed supratentorial glioblastoma, IDH-wildtype is safe and efficient in patients > 80 years and in patients with preoperative Karnofsky Performance Status score < 50. The number of Carmustine wafers should be adapted (up to 16 in our experience) to the resection cavity to improve survival without increasing postoperative overall complication rates.

Predictors of postoperative epidural hematomas after custom-made porous hydroxyapatite cranioplasty: a single-center experience of 194 consecutive cases.

Cranioplasty is important for improving cosmesis and functional recovery after decompressive craniectomy. We assessed the incidence and predictors of post-cranioplasty epidural hematomas requiring surgical evacuation. A single-institution, retrospective study enrolled 194 consecutive patients who underwent a cranioplasty using custom-made hydroxyapatite between February 2008 and April 2022. Variables associated with postoperative epidural hematoma requiring surgical evacuation at the p < 0.1 level in unadjusted analysis were entered into multivariable analyses. Nine patients (4.6%) experienced postoperative epidural hematomas requiring evacuation, with time interval between craniectomy and cranioplasty <6 months (adjusted odds ratio (aOR), 20.75, p = 0.047), cranioplasty-to-bone shift > half of the bone thickness (aOR, 17.53, p = 0.008), >10 mm difference between pre-cranioplasty and post-cranioplasty midline brain shift contralateral to the cranioplasty (aOR, 17.26, p < 0.001), and non-resorbable duraplasty (aOR, 17.43, p = 0.011) identified as independent predictors. Seventeen patients (8.8%) experienced post-cranioplasty hydrocephalus requiring shunt placement. Twenty-six patients (13.4%) experienced postoperative infection. Sixteen patients (8.2%) had postoperative epileptic seizures. The identification of independent predictors of post-cranioplasty epidural hematomas requiring surgical evacuation will help identify at-risk patients, guide prophylactic care, and reduce morbidity of this common and important procedure.

A Preoperative Scoring System to Predict Function-Based Resection Limitation Due to Insufficient Participation During Awake Surgery.

BACKGROUND: Failure in achieving a function-based resection related to the insufficient patient's participation is a drawback of awake surgery. OBJECTIVE: To assess preoperative parameters predicting the risk of patient insufficient intraoperative cooperation leading to the arrest of the awake resection. METHODS: Observational, retrospective, multicentric cohort analysis enrolling 384 (experimental dataset) and 100 (external validation dataset) awake surgeries. RESULTS: In the experimental data set, an insufficient intraoperative cooperation occurred in 20/384 patients (5.2%), leading to awake surgery failure in 3/384 patients (ie, no resection, 0.8%), and precluded the achievement of the function-based resection in 17/384 patients (ie, resection limitation, 4.4%). The insufficient intraoperative cooperation significantly reduced the resection rates (55.0% vs 94.0%, P < .001) and precluded a supratotal resection (0% vs 11.3%, P = .017). Seventy years or older, uncontrolled epileptic seizures, previous oncological treatment, hyperperfusion on MRI, and mass effect on midline were independent predictors of insufficient cooperation during awake surgery ( P < .05). An Awake Surgery Insufficient Cooperation score was then assessed: 96.9% of patients (n = 343/354) with a score ≤2 presented a good intraoperative cooperation, while only 70.0% of patients (n = 21/30) with a score >2 presented a good intraoperative cooperation. In the experimental data set, similar date were found: 98.9% of patients (n = 98/99) with a score ≤2 presented a good cooperation, while 0% of patients (n = 0/1) with a score >2 presented a good cooperation. CONCLUSION: Function-based resection under awake conditions can be safely performed with a low rate of insufficient patient intraoperative cooperation. The risk can be assessed preoperatively by a careful patient selection.

An extracranial CNS presentation of the emerging "intracranial" mesenchymal tumor, FET: CREB-fusion positive.

A novel histomolecular tumor, the "intracranial mesenchymal tumor (IMT), FET::CREB fusion-positive", has recently been identified and added to the 2021 World Health Organization Classification of Tumors of the Central Nervous System. One of the essential diagnostic criteria defined in this classification is the intracranial location of the tumor. Herein, we report a spinal case of IMT with a classical EWSR1::CREM fusion. We compare its clinical, histopathological, immunophenotypical, genetic and epigenetic features with those previously described in IMT, FET::CREB fusion-positive. The current case presented histopathological (epithelioid morphology with mucin-rich stroma, and expression of EMA and desmin), radiological (an extraparenchymal lobulated mass without dural tail), genetic (fusion implicating the EWSR1 and CREM genes), and epigenetic (DNA-methylation profiling) similarities to previously reported cases. This case constitutes the third "extracranial" observation of an IMT. Our results added data suggesting that the terminology "IMT, FET::CREB fusion-positive" is provisional and that further series of cases are needed to better characterize them.

Accuracy and safety of 101 consecutives neurosurgical procedures for newly diagnosed central nervous system lymphomas: a single-institution experience.

INTRODUCTION: Brain surgery is required to ascertain the diagnosis of central nervous system lymphoma. We assessed the diagnostic yield and safety of the surgical procedures, the predictors of postoperative morbidity, and of overall survival. METHODS: Observational single-institution retrospective cohort study (1992-2020) of 101 consecutive adult patients who underwent stereotactic biopsy, open biopsy, or resection for a newly diagnosed central nervous system lymphoma. RESULTS: The diagnostic yield was 100% despite preoperative steroid administration in 48/101 cases (47.5%). A preoperative Karnofsky Performance Status score less than 70 (p = 0.006) was an independent predictor of a new postoperative focal neurological deficit (7/101 cases, 6.9%). A previous history of hematological malignancy (p = 0.049), age 65 years or more (p = 0.031), and new postoperative neurological deficit (p < 0.001) were independent predictors of a Karnofsky Performance Status score decrease 20 points or more postoperatively (13/101 cases, 12.9%). A previous history of hematological malignancy (p = 0.034), and preoperative Karnofsky Performance Status score less than 70 (p = 0.024) were independent predictors of postoperative hemorrhage (13/101 cases, 12.9%). A preoperative Karnofsky Performance Status score less than 70 (p = 0.019), and a previous history of hematological malignancy (p = 0.014) were independent predictors of death during hospital stay (8/101 cases, 7.9%). In the 82 immunocompetent patients harboring a primary central nervous system lymphoma, age 65 years or more (p = 0.044), and time to hematological treatment more than 21 days (p = 0.008), were independent predictors of a shorter overall survival. A dedicated hematological treatment (p < 0.001) was an independent predictor of a longer overall survival. CONCLUSION: Brain biopsy is feasible with low morbidity for central nervous system lymphomas. Postoperatively, patients should be promptly referred for hematological treatment initiation.

An integrative histopathological and epigenetic characterization of primary intracranial mesenchymal tumors, FET:CREB-fused broadening the spectrum of tumor entities in comparison with their soft tissue counterparts.

FET:CREB fusions have been described in a variety of tumors from various phenotypes. Recently, these fusion transcripts were reported in intracranial tumors, variably named intracranial mesenchymal myxoid tumors or angiomatoid fibrous histiocytomas. Controversy remains concerning the terminology for these tumors. Here, we report 11 cases of central nervous system mesenchymal tumors with proven FET:CREB fusion. Most DNA methylation profiles were not classifiable using the Heidelberg Brain Tumor or Sarcoma Classifier (v11b4/v12.2). However, by using unsupervised t-SNE and hierarchical clustering analyses, six of the cases constituted a distinct cluster. The remaining four tumors showed no obvious relation to any of the other referenced classes but were close to the clusters of extra-CNS angiomatoid fibrous histiocytomas (n = 1), clear cell sarcomas (n = 1), or solitary fibrous tumors (n = 2). Our findings confirm that intracranial FET:CREB-fused tumors do not represent a single molecular tumor entity, although most samples clustered close to each other, indicating the existence of a distinct epigenetic group that could potentially be partially masked by the low number of cases included. Further analyses are needed to characterize intracranial FET:CREB fused-defined tumors in more detail.

Discriminating surgical bed cysts from bacterial brain abscesses after Carmustine wafer implantation in newly diagnosed IDH-wildtype glioblastomas.

Carmustine wafers can be implanted in the surgical bed of high-grade gliomas, which can induce surgical bed cyst formation, leading to clinically relevant mass effect. An observational retrospective monocentric study was conducted including 122 consecutive adult patients with a newly diagnosed supratentorial glioblastoma who underwent a surgical resection with Carmustine wafer implantation as first line treatment (2005-2018). Twenty-two patients (18.0%) developed a postoperative contrast-enhancing cyst within the surgical bed: 16 surgical bed cysts and six bacterial abscesses. All patients with a surgical bed cyst were managed conservatively, all resolved on imaging follow-up, and no patient stopped the radiochemotherapy. Independent risk factors of formation of a postoperative surgical bed cyst were age ≥ 60 years (p = 0.019), number of Carmustine wafers implanted ≥ 8 (p = 0.040), and partial resection (p = 0.025). Compared to surgical bed cysts, the occurrence of a postoperative bacterial abscess requiring surgical management was associated more frequently with a shorter time to diagnosis from surgery (p = 0.009), new neurological deficit (p < 0.001), fever (p < 0.001), residual air in the cyst (p = 0.018), a cyst diameter greater than that of the initial tumor (p = 0.027), and increased mass effect and brain edema compared to early postoperative MRI (p = 0.024). Contrast enhancement (p = 0.473) and diffusion signal abnormalities (p = 0.471) did not differ between postoperative bacterial abscesses and surgical bed cysts. Clinical and imaging findings help discriminate between surgical bed cysts and bacterial abscesses following Carmustine wafer implantation. Surgical bed cysts can be managed conservatively. Individual risk factors will help tailor their steroid therapy and imaging follow-up.

Supratentorial non-RELA, ZFTA-fused ependymomas: a comprehensive phenotype genotype correlation highlighting the number of zinc fingers in ZFTA-NCOA1/2 fusions.

The cIMPACT-NOW Update 7 has replaced the WHO nosology of "ependymoma, RELA fusion positive" by "Supratentorial-ependymoma, C11orf95-fusion positive". This modification reinforces the idea that supratentorial-ependymomas exhibiting fusion that implicates the C11orf95 (now called ZFTA) gene with or without the RELA gene, represent the same histomolecular entity. A hot off the press molecular study has identified distinct clusters of the DNA methylation class of ZFTA fusion-positive tumors. Interestingly, clusters 2 and 4 comprised tumors of different morphologies, with various ZFTA fusions without involvement of RELA. In this paper, we present a detailed series of thirteen cases of non-RELA ZFTA-fused supratentorial tumors with extensive clinical, radiological, histopathological, immunohistochemical, genetic and epigenetic (DNA methylation profiling) characterization. Contrary to the age of onset and MRI aspects similar to RELA fusion-positive EPN, we noted significant histopathological heterogeneity (pleomorphic xanthoastrocytoma-like, astroblastoma-like, ependymoma-like, and even sarcoma-like patterns) in this cohort. Immunophenotypically, these NFκB immunonegative tumors expressed GFAP variably, but EMA constantly and L1CAM frequently. Different gene partners were fused with ZFTA: NCOA1/2, MAML2 and for the first time MN1. These tumors had epigenetic homologies within the DNA methylation class of ependymomas-RELA and were classified as satellite clusters 2 and 4. Cluster 2 (n = 9) corresponded to tumors with classic ependymal histological features (n = 4) but also had astroblastic features (n = 5). Various types of ZFTA fusions were associated with cluster 2, but as in the original report, ZFTA:MAML2 fusion was frequent. Cluster 4 was enriched with sarcoma-like tumors. Moreover, we reported a novel anatomy of three ZFTA:NCOA1/2 fusions with only 1 ZFTA zinc finger domain in the putative fusion protein, whereas all previously reported non-RELA ZFTA fusions have 4 ZFTA zinc fingers. All three cases presented a sarcoma-like morphology. This genotype/phenotype association requires further studies for confirmation. Our series is the first to extensively characterize this new subset of supratentorial ZFTA-fused ependymomas and highlights the usefulness of ZFTA FISH analysis to confirm the existence of a rearrangement without RELA abnormality.

Feasibility, Safety and Impact on Overall Survival of Awake Resection for Newly Diagnosed Supratentorial IDH-Wildtype Glioblastomas in Adults.

BACKGROUND: Although awake resection using intraoperative cortico-subcortical functional brain mapping is the benchmark technique for diffuse gliomas within eloquent brain areas, it is still rarely proposed for IDH-wildtype glioblastomas. We have assessed the feasibility, safety, and efficacy of awake resection for IDH-wildtype glioblastomas. METHODS: Observational single-institution cohort (2012-2018) of 453 adult patients harboring supratentorial IDH-wildtype glioblastomas who benefited from awake resection, from asleep resection, or from a biopsy. Case matching (1:1) criteria between the awake group and asleep group: gender, age, RTOG-RPA class, tumor side, location and volume and neurosurgeon experience. RESULTS: In patients in the awake resection subgroup (n = 42), supratotal resections were more frequent (21.4% vs. 3.1%, p < 0.0001) while partial resections were less frequent (21.4% vs. 40.1%, p < 0.0001) compared to the asleep (n = 222) resection subgroup. In multivariable analyses, postoperative standard radiochemistry (aHR = 0.04, p < 0.0001), supratotal resection (aHR = 0.27, p = 0.0021), total resection (aHR = 0.43, p < 0.0001), KPS score > 70 (HR = 0.66, p = 0.0013), MGMT promoter methylation (HR = 0.55, p = 0.0031), and awake surgery (HR = 0.54, p = 0.0156) were independent predictors of overall survival. After case matching, a longer overall survival was found for awake resection (HR = 0.47, p = 0.0103). CONCLUSIONS: Awake resection is safe, allows larger resections than asleep surgery, and positively impacts overall survival of IDH-wildtype glioblastoma in selected adult patients.

Automated end-to-side anastomosis to the middle cerebral artery with C-Port xA: A feasibility study on human cadavers.

BACKGROUND: Anastomosis to the superficial temporal artery is suitable in patients with functional and structural impairment of the middle cerebral artery (i.e., complex aneurysms and skull base tumors), as either definitive treatment or an additional safety measure. A shorter occlusion time or a non-occlusive technique is expected to reduce the risk of cerebral ischemia following the procedure. In this cadaver study, we assessed the fitness of C-Port xA(®) device for use in superficial temporal artery (STA)-middle cerebral artery (MCA) bypass. MATERIALS AND METHODS: Seven fixed human head specimens were prepared through eight pterional craniotomies. The superficial temporal artery was dissected and the sylvian fissure was opened to access the MCA. The C-Port xA was tested on each of the eight exposures. We recorded the lengths of both donor and recipient vessel, the durations of the procedure and the craniotomy, and sylvian scissure opening sizes. The bypass was then assessed by pressure injection of methylene blue in the donor vessel. RESULTS: C-Port xA-assisted STA-MCA anastomosis was successfully accomplished in seven dissections. A minimum STA length of 7 cm, a sylvian scissure opening larger than 5 cm, and a craniotomy size of at least 6 × 6 cm appeared to be the requisites for a safe maneuverability of the device. The MCA occlusion time lasted in all cases less than 4.5 min, and we observed a clear improvement in time performance with growing experience. CONCLUSIONS: The results suggest that the C-Port xA device is suitable for STA-MCA bypass. We experienced a shorter occlusion time and a shorter learning curve compared to conventional techniques. Further miniaturization and special adaptation of this device may allow a future application even to deeper intracranial vessels. Clinical trials will have to assess the long-term results and benefits of this minimal occlusive technique.

Subarachnoid hemorrhage and negative angiography: clinical course and long-term follow-up.

The aim of this study was to investigate the long-term natural history of nontraumatic angiogram-negative subarachnoid hemorrhage with typical pretruncal (P-SAH) and diffuse (D-SAH) pattern of hemorrhage. A retrospective review of 102 patients who experienced angiographically negative SAH at our institution was undertaken (11.6% of 882 spontaneous SAH). Follow-ups were obtained at 7.9 to 16 years. In the D-SAH group, 11 patients (13.9%) out of 79 had an aneurysm, and four (5.1%) had rebleeding episodes. In the P-SAH group, the second angiography was negative in all of the 23 cases, and no rebleeding episodes were recorded. The long-term follow-up confirms that P-SAH is a benign disease. A second angiography could not be necessary. D-SAH is probably due to an aneurysm that thrombose early after the bleeding. At short-term follow-up, the sack could frequently recanalize and rebleed, whereas a late follow-up shows that rebleeding is very rare.

Interleukin-1 cluster gene polymorphisms and aneurysmal subarachnoid hemorrhage.

BACKGROUND: Emerging data indicate that proinflammatory cytokines may be involved in the pathogenesis of intracranial aneurysms. Interleukin (IL)-1 is a proinflammatory cytokine that plays a pivotal role in both acute and chronic central nervous system injuries. OBJECTIVE: To investigate whether select polymorphisms in the IL-1alpha, IL-1beta, and IL-1 receptor antagonist genes are associated with both susceptibility to and clinical characteristics of subarachnoid hemorrhage due to intracranial aneurysm rupture. METHODS: Allelic and genotypic frequencies of the IL-1alpha (-889), IL-1beta (-511), and IL-1 receptor antagonist (VNTR) genes were determined in 215 patients and 155 healthy controls. Patient files were reviewed for the clinical characteristics at hospital admission and at 6-month follow-up. RESULTS: No association between aneurysmal subarachnoid hemorrhage susceptibility and the examined cytokine gene polymorphisms was found. Haplotype analysis did not show any significant difference between cases and controls. However, aneurysmal subarachnoid hemorrhage patients carrying the T/T genotype of the IL-1beta gene showed a significant (P = .034) increase in the Hunt and Hess scores at hospital admission and a significant (P = .026) reduction in 6-month Glasgow Outcome Scale scores. The remaining polymorphisms showed no effect on the clinical features examined. CONCLUSION: Our results do not support the hypothesis that genetic variation in select polymorphisms of the IL-1 cluster genes is associated with aneurysmal subarachnoid cerebral hemorrhage. However, the IL-1beta gene may modify disease severity and may be regarded as disease severity gene.