Marenco-Hillembrand, Lina

Abstract INTRODUCTION Lung cancer is the most common tumor to metastasize to the brain, as 40% of patients develop brain metastasis (BM). Once diagnosed, survival is only 6.5-10 months. A potential target to prevent BM is circulating tumor cells (CTCs). The mechanisms that mediate a CTCs adaptation to the harsh environment of circulation and BM have not been elucidated. We have demonstrated that primary lung cancer cells (LCCs) subjected to circulation have increased migration across brain endothelial cell monolayers, increased side population, and decrease survival in rodents when injected intracardially vs plated controls. METHODS We engineered a microfluidic device capable of subjecting tumor cells to prolonged circulatory shear stress (CSS) that allows the isolation/modeling of CTC-like cells. Primary LCCs (A549, H1563) were subjected to circulation, suspension, or plated (2D) for 72h as controls. At this time point, LCCs were collected, and total mRNA was extracted. Samples were submitted for RNA sequencing. Weighted gene co-expression network analysis (WCGNA) and Ingenuity Pathway Analysis were performed. (FC >2 and p-value <0.05). RESULTS Transcriptomic analysis indicates that cells subjected to CSS activate specific gene networks involved in cell survival, migration, invasion, adhesion of tumor cells, and cytoskeletal reorganization (z-score: >2, p-value: 0.05). Canonical pathways in CTCs included ILK-signaling and Xenobiotic Metabolism. LCCs exposed to CSS had increased expression of multidrug resistance pumps ABCC2, ABCF2 (P:<0.001), and side population on flow cytometry (P: <0.05). The top differentially expressed genes in CTC-like cells (MMP1, ANGPTL4, and CEMIP) were involved in the invasion, angiogenesis, and pre-metastatic niche (PMN) formation of BM. CONCLUSION LCCs that survive CSS have increased expression of genes associated with migration, invasion, and chemoresistance compared to 2D controls. Targeting genes in CTCs that mediate survival and preparation of the PMN may be useful in preventing BM.

In recent years, the endoscopic endonasal approach (EEA) for craniopharyngiomas has proven to be a safe option for extensive tumor resection, with minimal or no manipulation of the optic nerves and excellent visualization of the superior hypophyseal branches when compared to the Transcranial Approach (TCA). However, there is an ongoing debate regarding the criteria for selecting different approaches. To explore the current results of EEA and discuss its role in the management of craniopharyngiomas, we performed MEDLINE, Embase, and LILACS searches from 2012 to 2022. Baseline characteristics, the extent of resection, and clinical outcomes were evaluated. Statistical analysis was performed through an X2 and Fisher exact test, and a comparison between quantitative variables through a Kruskal–Wallis and verified with post hoc Bonferroni. The tumor volume was similar in both groups (EEA 11.92 cm3, -TCA 13.23 cm3). The mean follow-up in months was 39.9 for EEA and 43.94 for TCA, p = 0.76). The EEA group presented a higher visual improvement rate (41.96% vs. 25% for TCA, p < 0.0001, OR 7.7). Permanent DI was less frequent with EEA (29.20% vs. 67.40% for TCA, p < 0.0001, OR 0.2). CSF Leaks occurred more frequently with EEA (9.94% vs. 0.70% for TCA, p < 0.0001, OR 15.8). Recurrence rates were lower in the EEA group (EEA 15.50% vs. for TCA 21.20%, p = 0.04, OR 0.7). Our results demonstrate that, in selected cases, EEA for resection of craniopharyngiomas is associated with better results regarding visual preservation and extent of tumor resection. Postoperative CSF leak rates associated with EEA have improved compared to the historical series. The decision-making process should consider each person’s characteristics; however, it is noticeable that recent data regarding EEA justify its widespread application as a first-line approach in centers of excellence for skull base surgery.

Leptomeningeal carcinomatosis (LMC) is a fatal but uncommon complication occurring in 5–15% of patients with stage IV cancer. Current treatment options are ineffective at managing leptomeningeal spread, with a median overall survival (mOS) of 2–6 months. We aimed to conduct a systematic review of the literature to identify past and future therapies for LMC from solid tumors. Forty-three clinical trials (CTs) published between 1982–2022 were identified. Of these, 35 (81.4%) were non-randomized CTs and 8 (18.6%) were randomized CTs. The majority consisted of phase I (16.3%) and phase II CTs (65.1%). Trials enrolled patients with LMC from various primary histology (n = 23, 57.5%), with one CT evaluating LCM from melanoma (2.4%). A total of 21 trials evaluated a single modality treatment. Among CTs, 23.7% closed due to low accrual. Intraventricular (ITV)/intrathecal (IT) drug delivery was the most common route of administration (n = 22, 51.2%) vs. systemic drug delivery (n = 13, 30.3%). Two clinical trials evaluated the use of craniospinal irradiation for LMC with favorable results. LMC continues to carry a dismal prognosis, and over the years, increments in survival have remained stagnant. A paradigm shift towards targeted systemic therapy with continued standardization of efficacy endpoints will help to shed light on promising treatments.

Abstract Introduction/Purpose: There is a general lack of consensus onboth the anatomic definition and function of Broca’s area. Given the belief that this region plays a critical role in expressive language, resective surgery is often avoided topreserve function. However, the putative role of Broca’s area in speech production has been recently challenged.The current study aims to investigatethe feasibilityof glioma resection and neurological outcomes in “Broca’s area” in 15 patients.Methods: We report a feasibility study describing the resection of gliomas within the IFG. Awake brain surgery for resection with mapping and intraoperative neuropsychological evaluation was carried out in all individuals. Results: All included patientshad tumors located in traditional “Broca’s area” and eight patients (53.33%) had tumors that additionally extendedinto the insula and subinsular regions. During stimulation, positive speech-language sites within the IFG were identified in ten patients. Two patients (13.33%) experienced a declinein naming during intraoperative cognitive monitoring and thirteen (86.66%) had a stable performance throughout surgery. With all patients had recovery of language functions at a two-week follow up. Extent of resection was stratified in anatomical regions within the IFG, being the pOr the area with the greatest EOR (97.4%), followed by the pT (84.1%), pOp (83.8%), and vPMC (80%).Conclusion: The belief that Broca’s area is not safe to resect is challenged. Adequate mapping and careful patient selection allow maximum safe resection of tumors located in thetraditional “Broca’s area”,with low risk of postoperative morbidity.

AbstractBackground The primary goal of brain tumor surgery is maximal safe resection while avoiding iatrogenic injury. As surgical technology increases, it is becoming more possible to resect these lesions using minimally invasive approaches. While keyhole surgeries are being advocated, the lower limit of these approaches is unclear. Bur hole–based approaches may represent a standardized minimally invasive approach. The exoscope may provide increased visualization over standard microscopic visualization, making this approach possible. This approach has yet to be described strictly for intra-axial brain tumors.Material and Methods All patients who underwent a bur hole–based surgery of an intra-axial tumor with exoscopic visualization by the senior author from January 2018 to December 2019 were prospectively identified and patient information and outcomes were collected.Results Fifteen consecutive patients underwent surgical resection of an intrinsic brain tumor using a bur hole–based approach with exoscopic visualization. The average ± standard deviation age was 57.9 ± 24.2 years. The pathology was a metastatic brain tumor in eight patients (53%), low-grade glioma in four patients (27%), and high-grade glioma in three patients (20%). The average percent resection was 100 ± 1%, where 14 (93%) underwent gross total resection. Following surgery, the median (interquartile range) Karnofsky performance scale (KPS) score was 90 (90–90), where 11 (73%) and four patients (27%) had improved and stable KPS, respectively. Zero patients had complications. The average length of stay following surgery was 1.4 ± 0.5 days, where nine patients (60%) were discharged on postoperative day 1.Conclusion This study shows that intra-axial tumors can be resected through a bur hole–based approach with exoscopic visualization with extensive resection, minimal morbidity, and early discharge rates.

Basilar invagination is a challenging dilemma that neurosurgeons may face. Herein, we present a case of a 65-year-old female with a history of rheumatoid arthritis and status post a previous C4–7 ACDF who presented to our clinic with progressive weakness in her bilateral upper and lower extremities. Imaging revealed basilar invagination. She underwent an endoscopic endonasal odontoidectomy followed by an occiput–C6 fusion. We present the endonasal portion of the procedure and have highlighted the technical nuances of this approach. Our goal is to provide better insight into this surgical strategy when dealing with basilar invagination. The video can be found here: https://youtu.be/aeMbvI_zYQA

Abstract INTRODUCTION The management of glioblastoma (GBM) has changed over time and varies based on geographic location. Despite its universally fatal prognoses, it is unclear if GBM outcomes have changed over time, if they vary by geographic location, and differ based on type of intervention. As a result, we conducted a systematic review of the literature to identify the average survival differences of GBM patients across time, between different continents, and among various treatments. METHODS The systematic review of PubMed included glioblastoma, GBM, and survival. Inclusion criteria consisted of full-text titles with human subjects, GBM/Grade IV astrocytoma, age >18 years old, and with available survival data. RESULTS 9,162 articles were screened for survival data, 1728 were eligible, 405 complied with the inclusion criteria. Of the 405 studies, 179 (44.2%) were conducted in Europe, 151 (37.3%) in the Americas, 61 (15.1%) in Asia, 9 (2.2%) in Oceania, and 1 (0.2%) in Africa. Leading countries are the United States (33.1%), Germany (12.3%), and Italy (11.1%). Asia had the highest median survival (14.9 months), followed by Europe (13.2 months), and the United States (12.9 months) (P=0.003). Regarding treatment, survival was significantly higher after the introduction of the Stupp protocol (P< 0.001). Post-Stupp Studies had longer survival estimates (15.3 months, range: 3.8–29.6) than Pre-Stupp Studies (12.2 months, range: 2.3–28). In the included clinical trials (182), radiation (43.4%), temozolomide (25.3%), or other chemotherapies (24.2%) were the most common interventions. Clinical trial median survival estimates were significantly higher than all other studies (P< 0.017). Bevacizumab (19.3 months) and Temozolomide (15.9 months) had the longest recorded median survival estimates; while radiation (14 months), other chemotherapies, and carmustine (13.2 months) had the shortest (P=0.009). CONCLUSION This epidemiological study describes the current global state of GBM. Important differences regarding survival and treatment of patients with GBM were found.

Intracerebral haemorrhage (ICH) describes haemorrhage into the brain parenchyma that may result in a decline of the patient’s neurological function. ICH is a common cause of morbidity and mortality worldwide. Aggressive surgical treatment for ICH has remained controversial as clinical trials have failed to demonstrate substantial improvement in patient outcome and mortality. Recently, promising mechanical and pharmacological minimally invasive surgery (MIS) techniques for the treatment of ICH have been described. MIS was designed with the objective of reducing morbidity due to complications of surgical manipulation. Mechanical MIS includes the use of tubular retractors and small diameter instruments for ICH removal. Pharmacological methods consist of catheter placement inside the haematoma cavity for the passive drainage of the haematoma over the course of several days. One of the most favourable approaches for MIS is the use of natural corridors for reaching the lesion, such as the transsulcal parafascicular approach. This approach provides an anatomical dissection of the subjacent white matter tracts, causing the least amount of damage while evacuating the haematoma. A detailed description of the currently known MIS techniques and devices is presented in this review. Special attention is given to the transsulcal parafascicular approach, which has particular benefits to provide a less traumatic MIS with promising overall patient outcome.