Proteomic analysis predicts anti-angiogenic resistance in recurred glioblastoma.

BACKGROUND: Recurrence is common in glioblastoma multiforme (GBM) because of the infiltrative, residual cells in the tumor margin. Standard therapy for GBM consists of surgical resection followed by chemotherapy and radiotherapy, but the median survival of GBM patients remains poor (~ 1.5 years). For recurrent GBM, anti-angiogenic treatment is one of the common treatment approaches. However, current anti-angiogenic treatment modalities are not satisfactory because of the resistance to anti-angiogenic agents in some patients. Therefore, we sought to identify novel prognostic biomarkers that can predict the therapeutic response to anti-angiogenic agents in patients with recurrent glioblastoma. METHODS: We selected patients with recurrent GBM who were treated with anti-angiogenic agents and classified them into responders and non-responders to anti-angiogenic therapy. Then, we performed proteomic analysis using liquid-chromatography mass spectrometry (LC-MS) with formalin-fixed paraffin-embedded (FFPE) tissues obtained from surgical specimens. We conducted a gene-ontology (GO) analysis based on protein abundance in the responder and non-responder groups. Based on the LC-MS and GO analysis results, we identified potential predictive biomarkers for anti-angiogenic therapy and validated them in recurrent glioblastoma patients. RESULTS: In the mass spectrometry-based approach, 4957 unique proteins were quantified with high confidence across clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic patterns (n = 269 proteins) between responders and non-responders. The GO term enrichment analysis revealed a cluster of genes related to immune cell-related pathways (e.g., TMEM173, FADD, CD99) in the responder group, whereas the non-responder group had a high expression of genes related to nuclear replisome (POLD) and damaged DNA binding (ERCC2). Immunohistochemistry of these biomarkers showed that the expression levels of TMEM173 and FADD were significantly associated with the overall survival and progression-free survival of patients with recurrent GBM. CONCLUSIONS: The candidate biomarkers identified in our protein analysis may be useful for predicting the clinical response to anti-angiogenic agents in patients with recurred GBM.

Defining subventricular zone involvement to predict the survival of patients in isocitrate dehydrogenase-wild type glioblastoma: validation in a prospective registry.

OBJECTIVES: The prognostic value of subventricular zone distance (SVD) is unclear because of different definitions and lack of evaluation of clinical survival models. The aim of this study was to define SVD and evaluate its prognostic value in a survival nomogram for glioblastoma. METHODS: This retrospective study included 158 (SVD biomarker) from historical glioblastoma patients and 187 (survival modeling) with IDH-wild type glioblastoma from a prospective registry (NCT02619890). SVD was assessed by two radiologists: definition 1, the distance between the tumor edge to subventricular zone (SVZ); definition 2, the distance between the tumor centroid to SVZ; definition 3, enhancement at the ventricular wall. The associations between SVD and overall survival (OS) were evaluated using multivariable Cox proportional hazards regression analysis. Performance of an updated SVD survival model was compared with that of the Radiation Therapy Oncology Group (RTOG) 0525 nomogram. RESULTS: SVD according to both definition 1 (hazard ratio [HR]: 0.97, 95% CI: 0.94-0.99; p = .011) and definition 2 (HR: 0.96, 0.94-0.98, p < .001) was adversely associated with OS. Definition 1 was adversely associated with PFS (HR: 0.96, 0.94-0.99, p = .008) and showed the highest reproducibility (intraclass correlation coefficient, 0.90). The SVD-updated model showed similar to better performance than the RTOG model for predicting OS of up to 3 years (AUC: 0.735-0.738 vs. 0.687-0.708), with higher time-dependent specificity for 1-year (89.9% vs. 70.6%) and 3-year OS (93.3% vs. 80.0%). CONCLUSION: SVZ distance is an independent adverse prognostic factor in patients with IDH-wild type glioblastoma. Updating the survival model with SVZ provides better time-dependent specificity and reproducibility. KEY POINTS: • Subventricular zone distance (SVD) measurement from tumor edge showed high reproducibility. • Longer SVD was independently associated with longer overall survival. • Adding SVD improved time-dependent specificity for survival model in a prospective registry.

Prediction of pseudoprogression in post-treatment glioblastoma using dynamic susceptibility contrast-derived oxygenation and microvascular transit time heterogeneity measures.

OBJECTIVES: To evaluate the added value of MR dynamic susceptibility contrast (DSC)-perfusion-weighted imaging (PWI)-derived tumour microvascular and oxygenation information with cerebral blood volume (CBV) to distinguish pseudoprogression from true progression (TP) in post-treatment glioblastoma. METHODS: This retrospective single-institution study included patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma and a newly developed or enlarging measurable contrast-enhancing mass within 12 weeks after concurrent chemoradiotherapy. CBV, capillary transit time heterogeneity (CTH), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) were obtained from DSC-PWI. Predictors were selected using univariable logistic regression, and performance was measured with adjusted diagnostic odds with tumour volume and area under the curve (AUC) of receiver operating characteristics analysis. RESULTS: A total of 103 patients were included (mean age, 59.6 years; 59 women), with 67 cases of TP and 36 cases of pseudoprogression. Pseudoprogression exhibited higher CTH (4.0 vs. 3.4, p = .019) and higher OEF (12.7 vs. 10.7, p = .014) than TP, but a similar CBV (1.48 vs. 1.53, p = .13) and CMRO2 (7.7 vs. 7.3s, p = .598). Independent of tumour volume, both high CTH (adjusted odds ratio [OR] 1.52; 95% confidence interval [CI]: 1.11-2.09, p = .009) and high OEF (adjusted OR 1.17; 95% CI:1.03-1.33, p = .016) were predictors of pseudoprogression. The combination of CTH, OEF, and CBV yielded higher diagnostic performance (AUC 0.71) than CBV alone (AUC 0.65). CONCLUSION: High intratumoural capillary transit heterogeneity and high oxygen extraction fraction derived from DSC-PWI have enhanced the diagnostic value of CBV in pseudoprogression of post-treatment IDH-wild type glioblastoma. CLINICAL RELEVANCE STATEMENT: In the early post-treatment stage of glioblastoma, pseudoprogression exhibited both high oxygen extraction fraction and high capillary transit heterogeneity and these dynamic susceptibility contrast-perfusion weighted imaging derived parameters have added value in cerebral blood volume-based noninvasive differentiation of pseudoprogression from true progression. KEY POINTS: • Capillary transit time heterogeneity and oxygen extraction fraction can be measured noninvasively through processing of dynamic susceptibility contrast imaging. • Pseudoprogression exhibited higher capillary transit time heterogeneity and higher oxygen extraction fraction than true progression. • A combination of cerebral blood volume, capillary transit time heterogeneity, and oxygen extraction fraction yielded the highest diagnostic performance (area under the curve 0.71).

The role of apparent diffusion coefficient as a predictive factor for tumor recurrence in patients with cerebellopontine angle epidermoid tumor.

Intracranial epidermoid tumors are slowly growing benign tumors, but due to adjacent critical neurovascular structures, surgical resection is challenging, with the risk of recurrence. The apparent diffusion coefficient (ADC) has been used to evaluate the characteristics of brain tumors, but its utility for intracranial epidermoid tumors has not been specifically explored. This study analyzed the utility of preoperative ADC values in predicting tumor recurrence for patients with intracranial epidermoid tumors. Between 2008 and 2019, 21 patients underwent surgery for cerebellopontine angle (CPA) epidermoid tumor, and their preoperative ADC data were analyzed. The patients were divided into two groups: the recurrence group, defined by regrowth of the remnant tumor or newly developed mass after gross total resection on magnetic resonance imaging (MRI); and the stable group, defined by the absence of growth or evidence of tumor on MRI. Receiver operating characteristic (ROC) analysis was used to obtain the ADC cutoff values for predicting tumor recurrence. The prognostic value of the ADC was assessed using Kaplan-Meier curves. The minimum ADC values were significantly lower in the recurrence group than in the stable tumor group (P = 0.020). ROC analysis showed that a minimum ADC value lower than 804.5 × 10-6 mm2/s could be used to predict higher recurrence risk of CPA epidermoid tumors. Non-total resection and mean and minimum ADC values lower than the respective cutoffs were negative predictors of recurrence-free survival. Minimum ADC values could be useful in predicting the recurrence of CPA epidermoid tumors.

Factors Associated With Abducens Nerve Palsy in Patients Undergoing Surgery for Petroclival Meningiomas.

BACKGROUND: During the surgical resection of petroclival meningiomas, preserving the cranial nerves is crucial. The abducens nerve is particularly vulnerable during surgery. However, the preoperative risk factors and postoperative prognosis of abducens nerve palsy (ANP) are poorly understood. METHODS: We retrospectively analyzed 70 patients who underwent surgery for petroclival meningiomas between May 2010 and December 2019, divided into gross-total resection (GTR) and subtotal resection (STR) groups. The relationship of preoperative clinical factors with the incidence and recovery of postoperative ANP was analyzed. RESULTS: Postoperative ANP was observed in 23 patients (32.9%). Multivariable logistic regression revealed that the tumor-to-cerebellar peduncle T2 imaging intensity index (TCTI) (P < 0.001) and internal auditory canal invasion (P = 0.033) contributed to postoperative ANP. GTR was achieved in 37 patients (52.9%), and 10 (27.0%) of them showed ANP. STR was achieved in 33 patients (47.1%), and 13 (39.4%) of them showed ANP. Recovery from ANP took a median of 6.6 months (range, 4.5-20.3 months). At 6 months after the operation, recovery of the abducens nerve function was observed in 16 patients (69.0%); of whom, 4 (40.0%) were in the GTR group and 12 (92.3%) were in the STR group (P = 0.025). CONCLUSIONS: TCTI and internal auditory canal invasion were the risk factors for postoperative ANP. Although intentional STR did not prevent ANP immediately after the operation, recovery of the abducens nerve function after surgery was observed more frequently in the STR group than in the GTR group.

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.

Sphero-Conical Modeling for the Estimation of Very Long Baseline Interferometry Invariant Point.

A geodetic reference frame is a fundamental element in geoinformation fields such as autonomous navigation and digital twins. The international terrestrial reference frame is established and maintained using several space-geodetic techniques, including very long baseline interferometry (VLBI) and satellite laser ranging (SLR). For several decades, geodesists have been devoted to connecting these two sensors at a site (local tie). The reference point of the VLBI antenna and SLR telescope, called invariant point (IVP), should be precisely determined to connect these two solutions. We developed an innovative integrated model to estimate the IVP, which is composed of spherical and conical models, depending on the rotational axis. In this model, all target points in 3D spaces were directly connected to the IVP; thus, the stability and robustness of the system were secured. Furthermore, all inherent errors in the coordinates were predicted by applying the total least-squares approach.

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.

Virtual dissection of the real brain: integration of photographic 3D models into virtual reality and its effect on neurosurgical resident education.

OBJECTIVE: Virtual reality (VR) is increasingly being used for education and surgical simulation in neurosurgery. So far, the 3D sources for VR simulation have been derived from medical images, which lack real color. The authors made photographic 3D models from dissected cadavers and integrated them into the VR platform. This study aimed to introduce a method of developing a photograph-integrated VR and to evaluate the educational effect of these models. METHODS: A silicone-injected cadaver head was prepared. A CT scan of the specimen was taken, and the soft tissue and skull were segmented to 3D objects. The cadaver was dissected layer by layer, and each layer was 3D scanned by a photogrammetric method. The objects were imported to a free VR application and layered. Using the head-mounted display and controllers, the various neurosurgical approaches were demonstrated to neurosurgical residents. After performing hands-on virtual surgery with photographic 3D models, a feedback survey was collected from 31 participants. RESULTS: Photographic 3D models were seamlessly integrated into the VR platform. Various skull base approaches were successfully performed with photograph-integrated VR. During virtual dissection, the landmark anatomical structures were identified based on their color and shape. Respondents rated a higher score for photographic 3D models than for conventional 3D models (4.3 ± 0.8 vs 3.2 ± 1.1, respectively; p = 0.001). They responded that performing virtual surgery with photographic 3D models would help to improve their surgical skills and to develop and study new surgical approaches. CONCLUSIONS: The authors introduced photographic 3D models to the virtual surgery platform for the first time. Integrating photographs with the 3D model and layering technique enhanced the educational effect of the 3D models. In the future, as computer technology advances, more realistic simulations will be possible.

Differences in surgical outcome between petroclival meningioma and anterior petrous meningioma.

BACKGROUND: Petroclival meningiomas (PC MNGs) and anterior petrous meningiomas (AP MNGs) have similar locations. However, these are different tumors clearly divided by the trigeminal nerve. There has never been a study on the comparison of the surgical outcomes of these two meningiomas. In this study, we compared and analyzed the surgical outcome of PC MNGs and AP MNGs. METHODS: The charts of 85 patients diagnosed with PC MNGs of AP MNGs who underwent surgical treatment were retrospectively reviewed. And we analyzed the characteristics of 49 PC MNGs (57.6%) and compared them with those of 36 AP MNGs. RESULTS: Preoperative brainstem edema was observed in 11 patients (22.4%) of the PC MNG group and 1 patient (2.8%) of the AP MNG group (p = 0.024). Total tumor removal was achieved in 21 patients (58.3%) of the AP MNG group, but only 17 patients (34.7%) of the PC MNG group were able to completely (p = 0.047). In addition, sixth cranial nerve palsy occurred in 17 patients (34.7%) of the PC MNG group and 4 patients (11.1%) of the AP MNG group (p = 0.025). CONCLUSIONS: In this study, we found that PC MNGs has a worse surgical outcome than AP MNGs, because PC MNGs were difficult to completely remove and were more likely to damage abducens nerve.

Clinical applications of the endoscopic transorbital approach for various lesions.

BACKGROUND: The endoscopic transorbital approach (ETOA) was recently added to the neurosurgical armamentarium. Although this approach could result in less injury to normal brain tissue, shorter operation times, and smaller scars, its clinical applications have not been fully investigated. We, therefore, sought to share our unique experiences of exploring the application of this approach in various diseases. METHODS: From June 2017 to March 2019, we conducted ETOAs via the superior eyelid crease in 22 patients for the treatment of lesions confined to the middle fossa with and without slight extension to the posterior fossa. These lesions included 5 gliomas, 11 meningiomas, 3 schwannomas, 1 lymphoma, 1 cavernous hemangioma in the orbital wall, and 1 hemangiopericytoma mimicking schwannoma. Perioperative radiologic findings and clinical outcomes were recorded. RESULTS: Gross total resection was accomplished in three (60%) patients with gliomas, nine (81.8%) with meningiomas, two (66.7%) with schwannomas, and one (33.3%) with another lesion. The mean bleeding count was 1051.4 ± 961.1 cc, and major complications were observed in only two (9.1%) cases (one major cerebral artery infarction and one reoperation due to a large amount of bleeding). A cerebrospinal fluid leak was reported in two (9.1%) patients, and transient eye movement palsy was noted in four (18.2%) patients without permanent disability. CONCLUSIONS: The endoscopic transorbital approach could be considered to be feasible for various lesions with different characteristics. After carefully considering the lesion anatomy, consistency, and vascular relationships, using this approach, we could achieve a satisfactory extent of resection without severe complications.

Validation and optimization of a web-based nomogram for predicting survival of patients with newly diagnosed glioblastoma.

PURPOSE: To optimize and validate a current (NRG [a newly constituted National Clinical Trials Network group through National Surgical Adjuvant Breast and Bowel Project [NSABP], the Radiation Therapy Oncology Group [RTOG] and the Gynecologic Oncology Group (GOG)]) nomogram for glioblastoma patients as part of continuous validation. METHODS: We identified patients newly diagnosed with glioblastoma who were treated with temozolomide-based chemoradiotherapy between 2006 and 2016 at three large-volume hospitals. The extent of resection was determined via postoperative MRI. The discrimination and calibration abilities of the prediction algorithm were assessed; if additional factors were identified as independent prognostic factors, updated models were developed using the data from two hospitals and were externally validated using the third hospital. Models were internally validated using cross-validation and bootstrapping. RESULTS: A total of 837 patients met the eligibility criteria. The median overall survival (OS) was 20.0 (95% CI 18.5-21.5) months. The original nomogram was able to estimate the 6­, 12-, and 24-month OS probabilities, but it slightly underestimated the OS values. In multivariable Cox regression analysis, MRI-defined total resection had a greater impact on OS than that shown by the original nomogram, and two additional factors-IDH1 mutation and tumor contacting subventricular zone-were newly identified as independent prognostic values. An updated nomogram incorporating these new variables outperformed the original nomogram (C-index at 6, 12, 24, and 36 months: 0.728, 0.688, 0.688, and 0.685, respectively) and was well calibrated. External validation using an independent cohort showed C­indices of 0.787, 0.751, 0.719, and 0.702 at 6, 12, 24, and 36 months, respectively, and was well calibrated. CONCLUSION: An updated and validated nomogram incorporating the contemporary parameters can estimate individual survival outcomes in patients with glioblastoma with better accuracy.

The timing of fusion surgery for clival chordoma with occipito-cervical joint instability: before or after tumor resection?

Clival chordoma with occipito-cervical (OC) joint invasion can result in preoperative and postoperative instability. The authors investigate the appropriate timing of OC fusion to prevent instability-, fusion-, and surgery time-related morbidity. Twenty-two consecutive patients underwent surgery for clival chordoma from December 2008 to September 2014. OC fusion was performed for patients with OC joint invasion and instability due to preoperative destruction of the occipital condyle or extensive postoperative condylectomy. The data in relation to OC joint instability, fusion, and surgery time were analyzed retrospectively and compared between OC fusion before and after tumor resection. Of the 22 patients, 8 with tumor invasion of the OC joint underwent OC fusion. OC fusion was performed after tumor resection in one-stage for four patients and before tumor resection in two-stage for four patients. There was OC joint instability from tumor destruction of the occipital condyle in seven patients (87.5%). Patients with OC fusion after tumor resection encountered complications such as surgery site wound dehiscence, encephalitis, and cardiac arrest with consequent mortality in one patient. These complications were avoided in subsequent patients where OC fusion was performed before tumor resection. There were no differences in the extent of tumor resection between OC fusion before and after tumor resection. Two-stage OC fusion before tumor resection can reduce instability-, fusion-, and surgery time-related morbidity and achieve feasible tumor resection when OC joint instability is expected. The extent of tumor invasion and brain stem compression should be considered when fusion precedes tumor resection.

Radiosurgery vs. microsurgery for newly diagnosed, small petroclival meningiomas with trigeminal neuralgia.

Trigeminal neuralgia (TN) is an excruciating pain that can occur with petroclival meningiomas (PCMs). Gamma knife radiosurgery (GKRS) is an appealing option for small PCMs, but the role of microsurgery (MS) compared to GKRS is not well defined for small PCMs with regard to TN relief. From January 2009 to September 2019, 70 consecutive patients were treated by GKRS or MS for newly diagnosed, small (< 3.5 cm) PCMs with TN. GKRS or MS were performed for 35 patients each. The surgical outcome and TN control according to Barrow Neurological Institute (BNI) score were retrospectively analyzed and compared between GKRS and MS. The predominant origin of PCMs was upper clival (49%) with trigeminal nerve compression at the medial dorsal root entry zone. Tumor control rates were equally 94% with GKRS or MS for a mean tumor size and volume of 2.3 cm and 5.3 cm3, respectively. The preoperative BNI scores were mostly II (40%) and IV (37%) with GKRS and MS, respectively. TN relief without medications (BNI scores I and II) was achieved in 13 of 35 patients (37%) with GKRS and 32 of 35 patients (91%) with MS during a mean follow-up of 50.5 months. The most common complications after GKRS and MS were dysesthesia (23%) and diplopia (9%), respectively. MS could be more effective than GKRS in providing prompt, medication-free pain relief from TN for small PCMs. The risks of MS have to be considered carefully in experienced hands, especially for small PCMs.

Lateral supraorbital versus pterional approach for parachiasmal meningiomas: surgical indications and esthetic benefits.

The lateral supraorbital (LSO) approach is a minimally invasive modification of the pterional approach. The authors assess the surgical indications and esthetic benefits of the LSO approach in comparison with the pterional approach for parachiasmal meningiomas. From April 2013 to May 2017, a total of 64 patients underwent surgery for parachiasmal meningiomas. Among them, tumor resection was performed with the LSO approach for 34 patients and pterional approach for 30 patients. A retrospective analysis was done on tumor characteristics, surgical outcome, approach-related morbidity, and esthetic outcome between the two approaches. Gross total resection was achieved in 33 of 34 patients (97.1%) with the LSO approach. There were no differences in tumor size, origin, consistency, internal carotid artery encasement, cranial nerve adhesion, and optic canal invasion between the two approaches. The most common tumor origin was the tuberculum sellae for both the LSO and pterional approaches. For tumors with preoperative visual compromise, immediate visual outcome improved or remained stable in 76% and 80.9% with the LSO and pterional approaches, respectively. Surgery time, surgical bleeding, hospital length of stay, and esthetic outcome were significantly shorter and superior with the LSO approach. There were no differences in surgical morbidity and brain retraction injury between the two approaches. The LSO approach can provide a safe, rapid, and minimally invasive exposure for parachiasmal meningiomas compared with the pterional approach. Surgeons must consider tumor size, origin, and extent in determining the resectability of the tumor rather than the extent of exposure.

Biportal endoscopic transorbital approach: a quantitative anatomical study and clinical application.

BACKGROUND: We devised a biportal endoscopic transorbital approach (BiETOA) to gain surgical freedom by making a port for the endoscope and investigated the benefits and limitations of BiETOA. METHODS: A cylindrical port was designed and 3-D printed using biocompatible material. The port was inserted through a keyhole between the superolateral side of the orbital rim and the temporal muscle. An endoscope was inserted through the port, and other instruments were inserted through the conventional transorbital route. BiETOA was used to dissect eight cadaveric heads, and the angle of attack and surgical freedom were assessed. RESULTS: The mean maximal angle of attack was significantly different in BiETOA and endoscopic transorbital approach (ETOA) (P < 0.01) but not in BiETOA and ETOA lateral orbital rim (LOR) osteotomy (P = 0.207, P = 0.21). The mean surgical freedom was significantly different in BiETOA and ETOA (P < 0.01) and in BiETOA and ETOA LOR osteotomy (P < 0.01). In the clinical cases, tumors were removed successfully without any complications. CONCLUSIONS: BiETOA provided increased surgical freedom and better visibility of deep target lesion and resulted in good surgical and cosmetic outcomes.

Impact of adjuvant treatments on survival in Korean patients with WHO grade II gliomas: KNOG 15-02 and KROG 16-04 intergroup study.

INTRODUCTION: Optimal treatment strategies for low-grade glioma (LGG) remain controversial. We analyzed treatment outcomes and evaluated prognostic factors of adult LGG patients in Korea. METHODS: We reviewed the medical records of 555 patients diagnosed with WHO grade II LGG (astrocytoma 37.8%, oligoastrocytoma 15.3%, and oligodendroglioma 46.8%) at 14 institutions between 2000 and 2010. Primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS). Propensity-score matching (PSM) analyses were performed to correct imbalances in patient/tumor characteristics among adjuvant treatment groups. RESULTS: The median follow-up time was 83.4 months, and the 5-year PFS and OS rates were 52.2% and 83.0%, respectively. Male, older age, poorer performance status, multiple lobe involvement, and astrocytoma histology were associated with poorer survival. Among the treatment factors, gross total resection (GTR) was associated with better PFS and OS, and adjuvant chemotherapy with improved PFS. Interestingly, adjuvant radiotherapy (RT) did not improve PFS; rather, it was related with poorer OS. Regarding patient/tumor characteristics, the RT group had poorer characteristics than the non-RT group. After PSM, we detected a tendency for improved PFS in the matched RT group, and no significant difference in OS compared with the matched non-RT group. CONCLUSIONS: The achievement of GTR is important to improve survival in LGG patients. Adjuvant chemotherapy may enhance PFS, but adjuvant RT did not improve survival outcomes. After PSM, we observed potential impacts of adjuvant RT on PFS. Our results may reflect real-world practice and consequently may help to optimize treatment strategies for LGG.

Multi-institutional study of treatment patterns in Korean patients with WHO grade II gliomas: KNOG 15-02 and KROG 16-04 intergroup study.

INTRODUCTION: We performed this study to identify the treatment patterns of patients with low-grade gliomas (LGG) in Korea. METHODS: A total of 555 patients diagnosed as WHO grade II gliomas between 2000 and 2010 at 14 Korean institutions were included. The patients were divided into four adjuvant treatment groups: adjuvant fractionated radiotherapy (RT, N = 204), adjuvant chemotherapy (N = 20), adjuvant fractionated RT and chemotherapy (N = 65), and non-adjuvant treatment (N = 266) groups. We examined differences among the groups and validated patient/tumor characteristics associated with the adjuvant treatments. RESULTS: Astrocytoma was diagnosed in 210 patients (38%), oligoastrocytoma in 85 patients (15%), and oligodendroglioma in 260 patients (47%). Gross total resection was performed in 200 patients (36%), subtotal resection in 153 (28%), partial resection in 71 patients (13%), and biopsy in 131 patients (24%). RT was most commonly applied as an adjuvant treatment. The use of chemotherapy with or without RT decreased after 2008 (from 38 to 4%). The major chemotherapeutic regimen was procarbazine, lomustine, and vincristine (PCV); however, the proportion of temozolomide increased since 2005 (up to 69%). Patient/tumor characteristics related with RT were male gender, non-seizure, multiple lobes involvement, and non-gross total resection. Chemotherapy was associated with non-gross total resection and non-astrocytoma. CONCLUSIONS: A preference for RT and increased use of temozolomide was evident in the treatment pattern of LGG. The extent of resection was associated with a decision to perform RT and chemotherapy. To establish a robust guideline for LGG, further studies including molecular information are needed.

Radiographic and microsurgical characteristics of proximal (A1) segment aneurysms of the anterior cerebral artery.

BACKGROUND: Proximal A1 segment aneurysms of the anterior cerebral artery (ACA) radiologically resemble internal carotid artery bifurcation (ICBIF) aneurysms because of their anatomical proximity. However, proximal A1 aneurysms exhibit distinguishing features, relative to ICBIF aneurysms. We report our experience of managing proximal A1 aneurysms, then compare them to ICBIF aneurysms. METHODS: Among 2191 aneurysms treated between 2000 and 2016 in a single institution, we retrospectively reviewed 100 cases categorized as ICBIF or A1 aneurysms. We included aneurysms originating from the ICBIF and ACA, proximal to the anterior communicating artery (A1 segment) and divided them into two groups: proximal A1 (n = 32) and ICBIF (n = 50). If any portion of the aneurysm involved the ICBIF, it was classified as ICBIF. Aneurysms wholly located in the A1 segment were classified as proximal A1. Patient factors and angiographic factors were evaluated and compared. RESULTS: The proximal A1 group exhibited differences in aneurysm size (p = 0.013), posterior aneurysm direction (p = 0.001), and A1 perforators as incorporating vessels (p = 0.001). The proximal A1 group tended to rupture more frequently when the aneurysm was smaller (p = 0.046). One case of morbidity occurred in the proximal A1 group. CONCLUSION: Compared to ICBIF aneurysms, proximal A1 aneurysms were smaller and directed posteriorly, with incorporating perforators. Because of these characteristics, it may be difficult to perform clipping with 360° view in microsurgical field. Therefore, when planning to treat proximal A1 aneurysms, different treatment strategies may be necessary, relative to those used for ICBIF aneurysms.

Poorly differentiated chordoma with loss of SMARCB1/INI1 expression in pediatric patients: A report of two cases and review of the literature.

Identification of loss of SMARCB1/INI1 expression in poorly differentiated (PD) chordoma in pediatric patients suggests that PD chordoma is an entity molecularly distinct from conventional chordoma or atypical teratoid/rhabdoid tumor, which is also characterized by loss of SMARCB1/INI1 expression by inactivating mutation of the SMARCB1/INI gene. So far, around 20 cases of pediatric PD chordoma with loss of SMARCB1/INI1 expression have been reported. Here, we report two cases of pediatric PD chordoma with loss of SMARCB1/INI1 expression, which is very rare among the pediatric chordoma types. Both patients presented clival masses on preoperative MRI. Histologically, both tumors had nonclassic histologic features for conventional chordoma: sheets of large epithelioid to spindle cells with vesicular nuclei and prominent nucleoli. Both cases revealed nuclear expression of brachyury, loss of SMARCB1/INI1 expression and lack of embryonal, neuroectodermal, or epithelial component. One case showed heterozygous loss of EWSR1 gene by break-apart fluorescence in situ hybridization that reflected loss of SMARCB1/INI1 gene. Based on the clival location and histologic findings along with the loss of SMARCB1/INI1 expression and positivity for nuclear brachyury staining, the final pathologic diagnosis for both cases was PD chordoma.