Endoscopic transorbital extradural anterior clinoidectomy: A stepwise surgical technique and case series study [SevEN-013].

Background: Anterior clinoidectomy is an important procedure for approaching the central skull base lesions. However, anterior clinoidectomy through the endoscopic transorbital approach (ETOA) still has limitations due to technical difficulties and the structural complexity of the anterior clinoid process (ACP). Therefore, the authors designed a stepwise surgical technique of extradural anterior clinoidectomy through the ETOA. The purpose of this study was to evaluate the feasibility of this technique. Methods: Anatomical dissections were performed in 6 cadaveric specimens using a neuroendoscope and neuro-navigation system. The extradural anterior clinoidectomy through the ETOA was performed stepwise, and based on the results, this surgical technique was performed in the 7 clinical cases to evaluate its safety and efficiency. Results: Endoscopic extradural anterior clinoidectomy was successfully performed in all cadaveric specimens and patients using the proposed technique. This 5-step technique enabled detachment of the lesser wing of sphenoid bone from the ACP, safe unroofing of the optic canal, and resection of the optic strut without injuring the optic nerve and internal carotid artery. Since the sequential resection of the 3 supporting roots of the ACP was accomplished safely, anterior clinoidectomy was then successfully performed in all clinical cases. Furthermore, no complications related to the anterior clinoidectomy occurred in any clinical case. Conclusion: We designed a stepwise surgical technique that allows safe and efficient anterior clinoidectomy through the ETOA. Using this technique, extradural anterior clinoidectomy can be accomplished under direct endoscopic visualization with low morbidity. Since this technique is applicable to the central skull base surgery where anterior clinoidectomy is necessary, it expands the application of the ETOA.

Iron commensalism of mesenchymal glioblastoma promotes ferroptosis susceptibility upon dopamine treatment.

The heterogeneity of glioblastoma multiforme (GBM) leads to poor patient prognosis. Here, we aim to investigate the mechanism through which GBM heterogeneity is coordinated to promote tumor progression. We find that proneural (PN)-GBM stem cells (GSCs) secreted dopamine (DA) and transferrin (TF), inducing the proliferation of mesenchymal (MES)-GSCs and enhancing their susceptibility toward ferroptosis. PN-GSC-derived TF stimulates MES-GSC proliferation in an iron-dependent manner. DA acts in an autocrine on PN-GSC growth in a DA receptor D1-dependent manner, while in a paracrine it induces TF receptor 1 expression in MES-GSCs to assist iron uptake and thus enhance ferroptotic vulnerability. Analysis of public datasets reveals worse prognosis of patients with heterogeneous GBM with high iron uptake than those with other GBM subtypes. Collectively, the findings here provide evidence of commensalism symbiosis that causes MES-GSCs to become iron-addicted, which in turn provides a rationale for targeting ferroptosis to treat resistant MES GBM.

Pedicled frontal periosteal rescue flap via eyebrow incision for skull base reconstruction (SevEN-002).

PURPOSE: Cerebrospinal fluid (CSF) leakage is one of the major complications after endoscopic endonasal surgery. The reconstructive nasoseptal flap is widely used to repair CSF leakage. However, it could not be utilized in all cases; thus, there was a need for an alternative. We developed a pericranial rescue flap that could cover both sellar and anterior skull base defects via the endonasal approach. A modified surgical technique that did not violate the frontal sinus and cause cosmetic problems was designed using the pericranial rescue flap. METHODS: We performed 12 cadaveric dissections to investigate the applicability of the lateral pericranial rescue flap. An incision was made, extending from the middle to the lateral part of the eyebrow. The pericranium layer was dissected away from the galea layer, from the supraorbital region towards the frontoparietal region. With endoscopic assistance, the periosteal flap was raised, the flap base was the pericranium layer at the eyebrow incision. After a burr-hole was made in the supraorbital bone, the pericranial flap was inserted via the intradural or extradural pathway. RESULTS: The mean size of the pericranial flap was 11.5 cm × 3.2 cm. It was large enough to cross the midline and cover the dural defects of the anterior skull base, including the sellar region. CONCLUSION: We demonstrated a modified endoscopic technique to repair the anterior skull base defects. This minimally invasive pericranial flap may resolve neurosurgical complications, such as CSF leakage.

Surgical Outcomes of Sphenoid Wing Meningioma with Periorbital Invasion.

OBJECTIVE: The aim of this study was to evaluate the clinical outcome of sphenoid wing meningioma with periorbital invasion (PI) after operation. METHODS: Sixty one patients with sphenoid wing meningioma were enrolled in this study. Their clinical conditions were monitored after the operation and followed up more than 5 years at the outpatient clinic of a single institution. Clinical and radiologic information of the patients were all recorded including the following parameters : presence of PI, presence of peri-tumor structure invasion, pathologic grade, extents of resection, presence of hyperostosis, exophthalmos index (EI), and surgical complications. We compared the above clinical parameters of the patients with sphenoid wing meningioma in the presence or absence of PI (non-PI), then linked the analyzed data with the clinical outcome of the patients. RESULTS: Of 61 cases, there were 14 PI and 47 non-PI patients. PI group showed a significantly higher score of EI (1.37±0.24 vs. 1.00±0.01, p<0.001), more frequent presence of hyperostosis (85.7% vs. 14.3%, p<0.001), and lower rate of gross total resection (GTR) (35.7% vs. 68.1%, p=0.032). The lower score of pre-operative EI, the absence of both PI and hyperostosis, smaller tumor size, and the performance of GTR were associated with lower recurrence rates in the univariate analysis. However, in the multivariate analysis, the performance of GTR was the only significant factor to determine the recurrence rate (p=0.043). The incidences of surgical complications were not statistically different between the subtotal resection (STR) and GTR groups, but it was strongly associated tumor size (p=0.017). CONCLUSION: The GTR group showed lower recurrence rate than the STR group without differences in the surgical complications. Therefore, the GTR is strongly recommended to treat sphenoid wing meningioma with PI for the better clinical outcome.

Missed Skeletal Trauma Detected by Whole Body Bone Scan in Patients with Traumatic Brain Injury.

OBJECTIVE: Unclear mental state is one of the major factors contributing to diagnostic failure of occult skeletal trauma in patients with traumatic brain injury (TBI). The aim of this study was to evaluate the overlooked co-occurring skeletal trauma through whole body bone scan (WBBS) in TBI. METHODS: A retrospective study of 547 TBI patients admitted between 2015 and 2017 was performed to investigate their cooccurring skeletal injuries detected by WBBS. The patients were divided into three groups based on the timing of suspecting skeletal trauma confirmed : 1) before WBBS (pre-WBBS); 2) after the routine WBBS (post-WBBS) with good mental state and no initial musculoskeletal complaints; and 3) after the routine WBBS with poor mental state (poor MS). The skeletal trauma detected by WBBS was classified into six skeletal categories : spine, upper and lower extremities, pelvis, chest wall, and clavicles. The skeletal injuries identified by WBBS were confirmed to be simple contusion or fractures by other imaging modalities such as X-ray or computed tomography (CT) scans. Of the six categorizations of skeletal trauma detected as hot uptake lesions in WBBS, the lesions of spine, upper and lower extremities were further statistically analyzed to calculate the incidence rates of actual fractures (AF) and actual surgery (AS) cases over the total number of hot uptake lesions in WBBS. RESULTS: Of 547 patients with TBI, 112 patients (20.4 %) were presented with TBI alone. Four hundred and thirty-five patients with TBI had co-occurring skeletal injuries confirmed by WBBS. The incidences were as follows : chest wall (27.4%), spine (22.9%), lower extremities (20.2%), upper extremities (13.5%), pelvis (9.4%), and clavicles (6.3%). It is notable that relatively larger number of positive hot uptakes were observed in the groups of post-WBBS and poor MS. The percentage of post-WBBS group over the total hot uptake lesions in upper and lower extremities, and spines were 51.0%, 43.8%, and 41.7%, respectively, while their percentages of AS were 2.73%, 1.1%, and 0%, respectively. The percentages of poor MS group in the upper and lower extremities, and spines were 10.4%, 17.4%, and 7.8%, respectively, while their percentages of AS were 26.7%, 14.2%, and 11.1%, respectively. There was a statistical difference in the percentage of AS between the groups of post-WBBS and poor MS (p=0.000). CONCLUSION: WBBS is a potential diagnostic tool in understanding the skeletal conditions of patients with head injuries which may be undetected during the initial assessment.

The need for a rapid transfer to a hybrid operating theatre: Do we lose benefit with poor efficiency?

PURPOSE: Recent studies on hybrid operating rooms (ORs) have mainly reported their applications in orthopaedic surgery and interventional radiology (IR); there are few studies assessing severely injured patients who underwent IR or surgery in hybrid ORs for haemostasis. Therefore, this study aimed to evaluate our early experience with the use of hybrid OR to control haemorrhage in severe trauma patients. METHODS: Medical charts of patients who underwent an emergency surgery or IR for haemostasis were analysed retrospectively between January and December 2015. RESULTS: Of the 95 patients directly transported to the general or hybrid OR, 69 (73%) were transported to the non-hybrid OR and underwent emergency surgeries, whereas 26 (27%) were transported to the hybrid OR and underwent emergency IR or surgery on-site. Patients transported to the hybrid OR had a higher median Injury Severity Score (median: 29, interquartile range[IQR]: 21-36.5 vs median: 21, IQR: 16-27) and lower median initial systolic blood pressure (median: 96, IQR: 82.75-128.75 vs median: 114, IQR: 95-151.5) than those transported to the non-hybrid OR. The median time from the emergency room (ER) arrival to the start of the emergency procedure in the hybrid OR group was similar with that in the non-hybrid OR group (median: 80, IQR: 62.75-91.5 vs median: 75, IQR: 56.5-99). Seven patients underwent IR and surgery concurrently in the hybrid OR because of a haemodynamically unstable pelvic fracture, severe liver injury, and severe brain haemorrhage. The median time from the ER arrival to the start of the haemostatic procedure or operation was 64(43-97) minutes. CONCLUSIONS: Although the hybrid OR may be used for haemostasis in severely injured patients, the long median time from ER arrival to the start of a haemostatic procedure in hybrid OR indicates the need for a new workflow to reduce this time and to facilitate hybrid OR use.

Peroxisome proliferator-activated receptor gamma as a theragnostic target for mesenchymal-type glioblastoma patients.

Glioblastomas (GBMs) are characterized by four subtypes, proneural (PN), neural, classical, and mesenchymal (MES) GBMs, and they all have distinct activated signaling pathways. Among the subtypes, PN and MES GBMs show mutually exclusive genetic signatures, and the MES phenotype is, in general, believed to be associated with more aggressive features of GBM: tumor recurrence and drug resistance. Therefore, targeting MES GBMs would improve the overall prognosis of patients with fatal tumors. In this study, we propose peroxisome proliferator-activated receptor gamma (PPARγ) as a potential diagnostic and prognostic biomarker as well as therapeutic target for MES GBM; we used multiple approaches to assess PPARγ, including biostatistics analysis and assessment of preclinical studies. First, we found that PPARγ was exclusively expressed in MES glioblastoma stem cells (GSCs), and ligand activation of endogenous PPARγ suppressed cell growth and stemness in MES GSCs. Further in vivo studies involving orthotopic and heterotopic xenograft mouse models confirmed the therapeutic efficacy of targeting PPARγ; compared to control mice, those that received ligand treatment exhibited longer survival as well as decreased tumor burden. Mechanistically, PPARγ activation suppressed proneural-mesenchymal transition (PMT) by inhibiting the STAT3 signaling pathway. Biostatistical analysis using The Cancer Genomics Atlas (TCGA, n = 206) and REMBRANDT (n = 329) revealed that PPARγ upregulation is linked to poor overall survival and disease-free survival of GBM patients. Analysis was performed on prospective (n = 2) and retrospective (n = 6) GBM patient tissues, and we finally confirmed that PPARγ expression was distinctly upregulated in MES GBM. Collectively, this study provides insight into PPARγ as a potential therapeutic target for patients with MES GBM.

Selection of endoscopic or transcranial surgery for tuberculum sellae meningiomas according to specific anatomical features: a retrospective multicenter analysis (KOSEN-002).

OBJECTIVE: The endoscopic endonasal approach (EEA) and the transcranial approach (TCA) are good options for the treatment of tuberculum sellae (TS) meningiomas. The objective of this study was to identify the key anatomical features in TS meningiomas and compare the two surgical approaches. METHODS: The authors retrospectively reviewed clinical data in 178 patients with TS meningiomas treated at 3 institutions between January 2010 and July 2016. Patients with tumors encasing the internal carotid artery or anterior cerebral artery or involving the anterior clinoid process or cavernous sinus were excluded. Tumors were classified as high-lying or low-lying based on their location, and involvement of the optic canal was evaluated. The surgical outcomes of EEA and TCA were analyzed according to the relevant anatomical features. RESULTS: During the study period, 84 patients underwent EEA and 94 patients underwent TCA. Based on preoperative MR images, 43 (24.2%) meningiomas were classified as high-lying tumors, 126 (70.8%) as low-lying, and 9 (5.0%) as nonspecific. Gross-total resection (GTR) was performed in 145 patients (81.5%); the GTR rate did not differ significantly between the EEA and TCA groups. Of 157 patients with preoperative visual disturbance, 140 had improved or stable vision postoperatively. However, 17 patients (9.6%) experienced some visual deterioration after surgery. The TCA group had a worse visual outcome than the EEA group in patients with preoperative optic canal involvement (77.6% vs 93.2%, p = 0.019), whereas there was no significant difference in visual outcome based on whether tumors were high-lying or low-lying. CONCLUSIONS: The results of this study support EEA over TCA, at least with respect to visual improvement with acceptable complications, although TCA is still an effective approach for TS meningioma.

Clinical Analysis of Delayed Surgical Epidural Hematoma.

OBJECTIVE: A small epidural hematoma (EDH) that has been diagnosed to be nonsurgical by initial brain computed tomography (CT) can increase in size and need surgical removal, resulting in a poor prognosis. However, there have been few studies, which focused delayed operated EDH. Therefore, we analyzed the clinical factors to determine the predicting factors of delayed operated EDH. METHODS: Between January 2011 and January 2014, 90 patients, who were admitted due to EDH, were enrolled in this study. None of the patients were indicated for operation initially. Based on the presence of surgery, we classified the patients into a delayed-surgery group (DG) and a non-surgical group (NG). Additionally, we analyzed them according to the following: time interval between the trauma and the initial CT, gender, age, medical history, drinking, change of mean arterial pressure (MAP), volume of EDH and other traumatic brain lesion. RESULTS: Among the 90 patients, the DG was 19 patients. Compared with NG, the DG revealed increased MAP, less presence of drinking, and a short time interval (DG vs. NG: +9.684 mm Hg vs. -0.428 mm Hg, 5.26% vs. 29.58%, 1.802 hours vs. 5.707 hours, respectively, p<0.05). Analyzing the time interval with receiver operating characteristic, there was 88.2% sensitivity and 68.3% specificity at the 2.05-hour cut-off value (area under the curve=0.854). CONCLUSION: According to our results, the time interval between the trauma and the initial CT along with blood pressure change are potential predicting factors in the cases of delayed operation of EDH.

Middle Meningeal Artery Embolization in Recurrent Chronic Subdural Hematoma Combined with Arachnoid Cyst.

Chronic subdural hematoma (CSDH) is a collection of old blood and its breakdown products between the surface of the brain parenchyma and the outermost layer called the dura. The most common treatment option for primary CSDH is burr-hole trephination; however, the treatment method for recurrent CSDH is still widely debated. An arachnoid cyst (AC) is a sac filled with cerebrospinal fluid located between the brain or spinal cord and the arachnoid membrane, which is one of the three meninges covering the brain or spinal cord. Although it is rare, the cyst is associated with CSDH in juveniles, and the recurrence rate of CSDH increases in such cases. Much of the literature has supported the preventive role of middle meningeal artery (MMA) embolization in recurrent CSDH. We report a 13-year-old male patient with recurrent CSDH and AC where the early intervention of MMA embolization was proven effective in preventing the further recurrence of CSDH.