Angioleiomyoma in the Orbital Apex: A Case Report

A 56-year woman presented eyeball pain and blurred vision. MRI revealed a small well-delineated solid tumor in the apex of right orbit with optic nerve compression. Intraoperatively, the tumor was found very fibrous, hypervascular and adhesive to surrounding structures. The tumor was completely removed with the combination of endoscopic and microscopic technique. Patient experienced transient oculomotor nerve palsy, which completely recovered 3 months after surgery. Herein we report a rare case of angioleiomyoma in the orbital apex.ope

Anterior skull base reconstruction using nasoseptal flap: cadaveric feasibility study and clinical implication [SevEN-001]

Background: Pedicled nasoseptal flap (PNSF) has significantly improved the surgical outcomes of endoscopic endonasal approach (EEAs) by reducing cerebrospinal fluid (CSF) leakage. The purpose of this study is to assess the feasibility of using a PNSF for anterior skull base (ASB) reconstruction and to describe a method to compensate for a short flap based on our results. Methods: In this cadaveric study, ASB dissection without sphenoidotomy was performed using 10 formalin-fixed and 5 fresh adult cadaver specimens, and the sufficiency of the PNSF to cover the ASB was assessed. After the sphenoidotomy, the length by which the PNSF fell short in providing coverage at the posterior wall of the frontal sinus (CPFS), and the extent of the anterior coverage from the limbus (CL) of the sphenoid bone was measured. Results: Without sphenoidotomy, the mean length of the remaining PNSF after the coverage of the posterior wall of the frontal sinus was 0.67 cm. After sphenoidotomy, the PNSF fell short by a mean length of 2.10 cm, in providing CPFS. The CL was 1.86 cm. Based on these findings, defects resulting from an endoscopic resection of ASB tumors were reconstructed using PNSF without total sphenoidotomy in 3 patients. There were no postoperative CSF leaks or complications. Conclusions: The use of PNSF for ASB reconstruction may be insufficient to cover the entire ASB defect after removal of large lesions which need total sphenoidotomy. When possible, by leaving some portion of the anterior sphenoid wall for supporting the PNSF, successful ASB reconstruction could be achieved in endoscopic resection of ASB tumors. Additional methods might be needed in some cases of large ASB lesions wherein the anterior sphenoid wall should be removed totally and the ASB defect is too large.ope

Glioblastoma Cellular Origin and the Firework Pattern of Cancer Genesis from the Subventricular Zone

Glioblastoma (GBM) is a disease without any definite cure. Numerous approaches have been tested in efforts to conquer this brain disease, but patients invariably experience recurrence or develop resistance to treatment. New surgical tools, carefully chosen samples, and experimental methods are enabling discoveries at single-cell resolution. The present article reviews the cell-of-origin of isocitrate dehydrogenase (IDH)-wildtype GBM, beginning with the historical background for focusing on cellular origin and introducing the cancer genesis patterned on firework. The authors also review mutations associated with the senescence process in cells of the subventricular zone (SVZ), and biological validation of somatic mutations in a mouse SVZ model. Understanding GBM would facilitate research on the origin of other cancers and may catalyze the development of new management approaches or treatments against IDH-wildtype GBM.ope

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.ope

Radiation Therapy for Recurrent or Residual Pituitary Macroadenoma Invading Extrasellar Structures

Purpose: This study aimed to evaluate the efficacy of radiation therapy (RT) for recurrent or residual pituitary macroadenoma (PMA) invading extrasellar regions. Materials and methods: Patients from 2000 to 2020 who received RT with conventional fractionation for recurrent or residual PMA were included. The patients were divided according to the type of tumor [functioning (fx) or non-fx] and the aim of RT (salvage RT alone, immediate postoperative RT, delayed postoperative RT). Local and biochemical failure-free rates (FFR) were calculated using the Kaplan-Meier method. Results: With a median follow up of 82 months (IQR; 42-132 months), 36 patients treated with conventional RT (total 45-54 Gy in 1.8 or 2 Gy per fraction) for recurrent or residual PMA were analyzed. The 10-year local FFRs after RT for non-fx and fx tumor were 100% and 74.4%, respectively (p=0.047). In the immediate postoperative RT group, the 10-year local FFR was 100%, which was higher than the 90% FFR for salvage RT alone or 80% FFR for the delayed postoperative RT group (overall p=0.043, immediate vs. salvage; p=0.312, immediate vs. delayed; p=0.072). The local FFR was compared according to size of tumor with a cut-off value of 4 cm, and there was no significant difference (10-year local FFR 100% vs. 84.7% for >4 cm vs. <4 cm, p=0.320). The extents of extrasellar region invasion were not predictive of local failure after RT. We found no grade ≥3 acute toxicities or newly developed visual impairments as a late toxicity of RT. Conclusion: Conventional RT is safe and effective for the local control of recurrent or residual PMA. Our data suggest that immediate postoperative RT can be beneficial in recurrent or residual PMA, although further studies to evaluate risk factors of treatment failure in terms of treatment and disease characteristics are required.ope

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.ope

Clinical Significance of Radical Surgery in the Treatment of Silent Corticotroph Adenoma

OBJECTIVE: Silent corticotroph adenomas (SCA) are endocrine-inactive pituitary adenomas with positive immunohistochemistry staining for adrenocorticotropic hormone (ACTH). We investigated whether SCA-associated clinical profiles were more aggressive than hormonally negative adenomas (HNA). METHODS: Among 627 patients with pathologically proven endocrine-inactive pituitary adenomas between 2004 and 2013, positive immunohistochemistry revealed 55 SCAs and 411 HNAs. Surgical outcomes and radiological and endocrinological characteristics were compared. RESULTS: Strong female predominance was observed in the SCA group (p<0.001). Cavernous sinus invasion was identified in 22 (40%) SCA patients and 72 (17.6%) HNA patients (p<0.001). There were no differences in ACTH or cortisol levels between the two groups. The incidence of preoperative hypopituitarism and postoperative hormonal outcome did not differ between two groups. Total resection was achieved in 35 patients (63.7%) with SCA and 332 patients (80.8%) with HNA (p=0.007). When tumors were completely removed, recurrence rates were not statistically different between two groups (p=0.60). When complete resection was not achieved, tumors regrew from these remnants in seven patients (35.0%) with SCA and 12 patients (15.2%) with HNA (p=0.05). CONCLUSION: Total surgical resection for SCA is often challenging as these tumors frequently invade a cavernous sinus. Early remnant tumor intervention is justified, because untreated residual pituitary tumors regrow when patients were followed up for a long time. Prophylactic radiotherapy is not warranted for completely resected SCAs as tumor recurrence is uncommon.ope

A lignan from Alnus japonica inhibits glioblastoma tumorspheres by suppression of FOXM1

Forkhead Box M1 (FOXM1) is known to regulate cell proliferation, apoptosis and tumorigenesis. The lignan, (-)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol (DFS), from Alnus japonica has shown anti-cancer effects against colon cancer cells by suppressing FOXM1. The present study hypothesized that DFS can have anti-cancer effects against glioblastoma (GBM) tumorspheres (TSs). Immunoprecipitation and luciferase reporter assays were performed to evaluate the ability of DFS to suppress nuclear translocation of β-catenin through β-catenin/FOXM1 binding. DFS-pretreated GBM TSs were evaluated to assess the ability of DFS to inhibit GBM TSs and their transcriptional profiles. The in vivo efficacy was examined in orthotopic xenograft models of GBM. Expression of FOXM1 was higher in GBM than in normal tissues. DFS-induced FOXM1 protein degradation blocked β-catenin translocation into the nucleus and consequently suppressed downstream target genes of FOXM1 pathways. DFS inhibited cell viability and ATP levels, while increasing apoptosis, and it reduced tumorsphere formation and the invasiveness of GBM TSs. And DFS reduced the activities of transcription factors related to tumorigenesis, stemness, and invasiveness. DFS significantly inhibited tumor growth and prolonged the survival rate of mice in orthotopic xenograft models of GBM. It suggests that DFS inhibits the proliferation of GBM TSs by suppressing FOXM1. DFS may be a potential therapeutic agent to treat GBM.ope

Optimization of orbital retraction during endoscopic transorbital approach via quantitative measurement of the intraocular pressure - [SevEN 006]

Background: Increased use of the transorbital approach (TOA) warrants greater understanding of the risk of increased intraocular pressure (IOP) and intraorbital pressure (IORP) due to orbital compression. We aimed to investigate the changes in IOP and IORP in response to orbital retraction in TOA and establish a method for the continuous measurement of intraoperative IORP. Methods: We assessed nine patients who underwent TOA surgery from January 2017 to December 2019, in addition to five cadavers. IORP and IOP were measured using a cannula needle monitor, tonometer, cuff manometer, and micro strain gauge monitor. Results: In all nine clinical cases and five cadavers, increased physical compression of the orbit increased the IOP and IORP in a curvilinear pattern. In clinical cases, when the orbit was compressed 1.5 cm from the lateral margin in the sagittal plane, the mean IOP and IORP were 25.4 ± 5.2 mmHg and 14 ± 9.2 mmH2O, respectively. The IORP satisfactorily reflected the IOP (Pearson correlation coefficient = 0.824, p < 0.001). Conclusion: We measured IOP and IORP simultaneously during orbital compression to gain basic information on pressure changes. In clinical cases, the change in the IOP could be conveniently and noninvasively monitored using continuous IORP measurements.ope

Associations of GNAS Mutations with Surgical Outcomes in Patients with Growth Hormone-Secreting Pituitary Adenoma

Background: The guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics. Methods: We studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor. Results: GNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively). Conclusion: GNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.ope