Handling Severe Intraoperative Hemorrhage and Avoiding Iatrogenic Stroke During Brain Tumor Surgery: Techniques for Prevention of Hemorrhagic and Ischemic Complications.

BACKGROUND: Nationwide databases show that iatrogenic stroke and postoperative hematoma are among the commonest complications in brain tumor surgery, with a 10-year incidence of 16.3/1000 and 10.3/1000, respectively. However, techniques for handling severe intraoperative hemorrhage and dissecting, preserving, or selectively obliterating vessels traversing the tumor are sparse in the literature. METHODS: Records of the senior author's intraoperative techniques during severe haemorrhage and vessel preservation were reviewed and analyzed. Intraoperative media demonstrations of key techniques were collected and edited. In parallel, a literature search investigating technique description in handling severe intraoperative hemorrhage and vessel preservation in tumor surgery was undertaken. Histologic, anesthetic, and pharmacologic prerequisites of significant hemorrhagic complications and hemostasis were analyzed. RESULTS: The senior author's techniques for arterial and venous skeletonization, temporary clipping with cognitive or motor mapping, and ION monitoring were categorized. Vessels interfacing with tumor are labeled intraoperatively as supplying/draining the tumor, or traversing en passant, while supplying/draining functional neural tissue. Intraoperative techniques of differentiation were analyzed and illustrated. Literature search found 2 vascular-related complication domains in tumor surgery: perioperative management of excessively vascular intraparenchymal tumors and lack of intraoperative techniques and decision processes for dissecting and preserving vessels interfacing or traversing tumors. CONCLUSIONS: Literature searches showed a dearth of complication-avoidance techniques in tumor-related iatrogenic stroke, despite its high prevalence. A detailed preoperative and intraoperative decision process was provided along with a series of case illustrations and intraoperative videos showing the techniques required to reduce intraoperative stroke and associated morbidity addressing a void in complication avoidance of tumor surgery.

Practical, Stereotactic, Low-Profile Technique for Transcortical/Transventricular Colloid Cyst Removal Independent of Ventricular Size: Technical Note and Analysis of Approaches.

BACKGROUND: In the presence of a dilated foramen of Monro, a transcortical, transforaminal approach is considered the safest and simplest approach for resection of colloid cysts. However, in the presence of small or normal frontal horns, numerous microsurgical approaches and, often complicated, variations have been described, invariably employing forms of stereotactic navigation. OBJECTIVE: To report an alternative, accurate, microsurgical stereotactic low-profile technique. METHODS: The small frontal horn is stereotactically targeted as previously described. Routine equipment is used to accurately create a novel, rigid, atraumatic surgical corridor. RESULTS: After a 7-mm corticotomy, a peel-away catheter carrying the AxiEM stylet engages the target set as the frontal horn. All joints of the endoscope holder are locked, allowing only catheter advancement (y axis) while lateral (x axis) or anteroposterior (z axis) movements are secure. Two, 7-mm retractor blades are inserted. The extremely consistent anatomy of the foramen of Monro allows en bloc microsurgical removal without unnecessary coagulation of cyst wall or choroid plexus. CONCLUSION: Despite a plethora of approaches to the rostral third ventricle, in the presence of normal or small frontal horns, including creation of transcallosal/interforniceal, suprachoroidal (or transchoroidal), and sub-choroidal, colloid cyst resection does not necessarily need to be convoluted. Technical nuances of an accurate, practical, minimally invasive technique are described.

Molecular landscapes of longitudinal NF2/22q and non-NF2/22q meningiomas show different life histories.

Recurrence is a major complication of some meningiomas. Although there were many studies on biomarkers associated with higher grades or increased aggressiveness, few studies specifically examined longitudinal samples of primary meningiomas and recurrences from the same patients for molecular life history. We studied 99 primary and recurrent meningiomas from 42 patients by FISH for 22q, 1q, 1p, 3p, 5q, 6q, 10p, 10q, 14q, 18q, CDKN2A/B homozygous deletion, ALT (Alternative Lengthening of Telomere), TERT re-arrangement, targeted sequencing and TERTp sequencing. Although NF2 mutation and 22q were well known to be aetiological events in meningiomas, we found that in these paired meningiomas, combining the two events resulted in an NF2/22q group (57 tumors from 25 patients) which were almost mutually exclusive with those cases without these two changes (42 tumors from 17 patients) for NF2/22q. No other molecular changes were totally unique to NF2/22q or non-NF2/22q tumors. For molecular evolution, NF2/22q meningiomas had higher cytogenetic abnormalities than non-NF2/22q meningiomas (p = 0.003). Most of the cytogenetic changes in NF2/22q meningiomas were present from the outset whereas for non-NF2/22q meningiomas, cytogenetic events were uncommon in the primary tumors and most were acquired in recurrences. For non-NF2/22q tumors, CDKN2A/B homozygous deletion, 1q gain, 18p loss, 3p loss, and ALT were preferentially found in recurrences. Mutations were largely conserved between primary and recurrent tumors. Phylogenetic trees showed 11/11 patients with multiple recurrent tumors had a conserved evolutionary pattern. We conclude that for molecular life history, NF2 and 22q should be regarded as a group. NF2/22q recurring meningiomas showed more cytogenetic abnormalities in the primary tumors, whereas non-NF2/22q meningiomas showed CDKN2A/B deletion and other cytogenetic abnormalities and ALT at recurrences. Although chromosome 1p loss is a known poor prognostic marker in meningiomas, it was also associated with a shorter TBR (time between resection) in this cohort (p = 0.002).

Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas.

WHO 2016 classified glioblastomas into IDH-mutant and IDH-wildtype with the former having a better prognosis but there was no study on IDH-mutant primary glioblastomas only, as previous series included secondary glioblastomas. We recruited a series of 67 IDH-mutant primary glioblastomas/astrocytoma IV without a prior low-grade astrocytoma and examined them using DNA-methylation profiling, targeted sequencing, RNA sequencing and TERT promoter sequencing, and correlated the molecular findings with clinical parameters. The median OS of 39.4 months of 64 cases and PFS of 25.9 months of 57 cases were better than the survival data of IDH-wildtype glioblastomas and IDH-mutant secondary glioblastomas retrieved from datasets. The molecular features often seen in glioblastomas, such as EGFR amplification, combined +7/-10, and TERT promoter mutations were only observed in 6/53 (11.3%), 4/53 (7.5%), and 2/67 (3.0%) cases, respectively, and gene fusions were found only in two cases. The main mechanism for telomere maintenance appeared to be alternative lengthening of telomeres as ATRX mutation was found in 34/53 (64.2%) cases. In t-SNE analyses of DNA-methylation profiles, with an exceptional of one case, a majority of our cases clustered to IDH-mutant high-grade astrocytoma subclass (40/53; 75.5%) and the rest to IDH-mutant astrocytoma subclass (12/53; 22.6%). The latter was also enriched with G-CIMP high cases (12/12; 100%). G-CIMP-high status and MGMT promoter methylation were independent good prognosticators for OS (p = 0.022 and p = 0.002, respectively) and TP53 mutation was an independent poor prognosticator (p = 0.013) when correlated with other clinical parameters. Homozygous deletion of CDKN2A/B was not correlated with OS (p = 0.197) and PFS (p = 0.278). PDGFRA amplification or mutation was found in 16/59 (27.1%) of cases and was correlated with G-CIMP-low status (p = 0.010). Aside from the three well-known pathways of pathogenesis in glioblastomas, chromatin modifying and mismatch repair pathways were common aberrations (88.7% and 20.8%, respectively), the former due to high frequency of ATRX involvement. We conclude that IDH-mutant primary glioblastomas have better prognosis than secondary glioblastomas and have major molecular differences from other commoner glioblastomas. G-CIMP subgroups, MGMT promoter methylation, and TP53 mutation are useful prognostic adjuncts.

Clinical and mutational profiles of adult medulloblastoma groups.

Adult medulloblastomas are clinically and molecularly understudied due to their rarity. We performed molecular grouping, targeted sequencing, and TERT promoter Sanger sequencing on a cohort of 99 adult medulloblastomas. SHH made up 50% of the cohort, whereas Group 3 (13%) was present in comparable proportion to WNT (19%) and Group 4 (18%). In contrast to paediatric medulloblastomas, molecular groups had no prognostic impact in our adult cohort (p = 0.877). Most frequently mutated genes were TERT (including promoter mutations, mutated in 36% cases), chromatin modifiers KMT2D (31%) and KMT2C (30%), TCF4 (31%), PTCH1 (27%) and DDX3X (24%). Adult WNT patients showed enrichment of TP53 mutations (6/15 WNT cases), and 3/6 TP53-mutant WNT tumours were of large cell/anaplastic histology. Adult SHH medulloblastomas had frequent upstream pathway alterations (PTCH1 and SMO mutations) and few downstream alterations (SUFU mutations, MYCN amplifications). TERT promoter mutations were found in 72% of adult SHH patients, and were restricted to this group. Adult Group 3 tumours lacked hallmark MYC amplifications, but had recurrent mutations in KBTBD4 and NOTCH1. Adult Group 4 tumours harboured recurrent mutations in TCF4 and chromatin modifier genes. Overall, amplifications of MYC and MYCN were rare (3%). Since molecular groups were not prognostic, alternative prognostic markers are needed for adult medulloblastoma. KMT2C mutations were frequently found across molecular groups and were associated with poor survival (p = 0.002). Multivariate analysis identified histological type (p = 0.026), metastasis (p = 0.031) and KMT2C mutational status (p = 0.046) as independent prognosticators in our cohort. In summary, we identified distinct clinical and mutational characteristics of adult medulloblastomas that will inform their risk stratification and treatment.