Natural language processing to predict isocitrate dehydrogenase genotype in diffuse glioma using MR radiology reports.

OBJECTIVES: To evaluate the performance of natural language processing (NLP) models to predict isocitrate dehydrogenase (IDH) mutation status in diffuse glioma using routine MR radiology reports. MATERIALS AND METHODS: This retrospective, multi-center study included consecutive patients with diffuse glioma with known IDH mutation status from May 2009 to November 2021 whose initial MR radiology report was available prior to pathologic diagnosis. Five NLP models (long short-term memory [LSTM], bidirectional LSTM, bidirectional encoder representations from transformers [BERT], BERT graph convolutional network [GCN], BioBERT) were trained, and area under the receiver operating characteristic curve (AUC) was assessed to validate prediction of IDH mutation status in the internal and external validation sets. The performance of the best performing NLP model was compared with that of the human readers. RESULTS: A total of 1427 patients (mean age ± standard deviation, 54 ± 15; 779 men, 54.6%) with 720 patients in the training set, 180 patients in the internal validation set, and 527 patients in the external validation set were included. In the external validation set, BERT GCN showed the highest performance (AUC 0.85, 95% CI 0.81-0.89) in predicting IDH mutation status, which was higher than LSTM (AUC 0.77, 95% CI 0.72-0.81; p = .003) and BioBERT (AUC 0.81, 95% CI 0.76-0.85; p = .03). This was higher than that of a neuroradiologist (AUC 0.80, 95% CI 0.76-0.84; p = .005) and a neurosurgeon (AUC 0.79, 95% CI 0.76-0.84; p = .04). CONCLUSION: BERT GCN was externally validated to predict IDH mutation status in patients with diffuse glioma using routine MR radiology reports with superior or at least comparable performance to human reader. CLINICAL RELEVANCE STATEMENT: Natural language processing may be used to extract relevant information from routine radiology reports to predict cancer genotype and provide prognostic information that may aid in guiding treatment strategy and enabling personalized medicine. KEY POINTS: • A transformer-based natural language processing (NLP) model predicted isocitrate dehydrogenase mutation status in diffuse glioma with an AUC of 0.85 in the external validation set. • The best NLP models were superior or at least comparable to human readers in both internal and external validation sets. • Transformer-based models showed higher performance than conventional NLP model such as long short-term memory.

Etomoxir, a carnitine palmitoyltransferase 1 inhibitor, combined with temozolomide reduces stemness and invasiveness in patient-derived glioblastoma tumorspheres.

INTRODUCTION: The importance of fatty acid oxidation (FAO) in the bioenergetics of glioblastoma (GBM) is being realized. Etomoxir (ETO), a carnitine palmitoyltransferase 1 (CPT1) inhibitor exerts cytotoxic effects in GBM, which involve interrupting the FAO pathway. We hypothesized that FAO inhibition could affect the outcomes of current standard temozolomide (TMZ) chemotherapy against GBM. METHODS: The FAO-related gene expression was compared between GBM and the tumor-free cortex. Using four different GBM tumorspheres (TSs), the effects of ETO and/or TMZ was analyzed on cell viability, tricarboxylate (TCA) cycle intermediates and adenosine triphosphate (ATP) production to assess metabolic changes. Alterations in tumor stemness, invasiveness, and associated transcriptional changes were also measured. Mouse orthotopic xenograft model was used to elucidate the combinatory effect of TMZ and ETO. RESULTS: GBM tissues exhibited overexpression of FAO-related genes, especially CPT1A, compared to the tumor-free cortex. The combined use of ETO and TMZ further inhibited TCA cycle and ATP production than single uses. This combination treatment showed superior suppression effects compared to treatment with individual agents on the viability, stemness, and invasiveness of GBM TSs, as well as better downregulation of FAO-related gene expression. The results of in vivo study showed prolonged survival outcomes in the combination treatment group. CONCLUSION: ETO, an FAO inhibitor, causes a lethal energy reduction in the GBM TSs. When used in combination with TMZ, ETO effectively reduces GBM cell stemness and invasiveness and further improves survival. These results suggest a potential novel treatment option for GBM.

Endoscopic transorbital approach to the cavernous sinus: Cadaveric anatomy study and clinical application (‡SevEN-009).

Objective: Cavernous sinus (CS) invasion is frequently encountered in the management of skull base tumors. Surgical treatment of tumors in the CS is technically demanding, and selection of an optimal surgical approach is critical for maximal tumor removal and patient safety. We aimed to evaluate the feasibility of an endoscopic transorbital approach (ETOA) to the CS based on a cadaveric study. Methods: Five cadaveric heads were used for dissection under the ETOA in the comparison with the endoscopic endonasal approach (EEA) and the microscopic transcranial approach (TCA). The CS was exposed, accessed, and explored, first using the ETOA, followed by the EEA and TCA. A dedicated endoscopic system aided by neuronavigation guidance was used for the procedures. During the ETOA, neurovascular structures inside the CS were approached through different surgical triangles. Results: After completing the ETOA with interdural dissection, the lateral wall of the CS was fully exposed. The lateral and posterior compartments of the CS, of which accessibility is greatly limited under the EEA, were effectively approached and explored under the ETOA. The anteromedial triangle was the largest window via which most of the lateral compartment was freely approached. The internal carotid artery and abducens nerve were also observed through the anteromedial triangle and just behind V1. During the ETOA, the approaching view through the supratrochlear and infratrochlear triangles was more directed towards the posterior compartment. After validation of the feasibility and safety based on the cadaveric study, ETOA was successfully performed in a patient with a pituitary adenoma with extensive CS invasion. Conclusions: Based on the cadaveric study, we demonstrated that the lateral CS wall was reliably accessed under the ETOA. The lateral and posterior compartments of the CS were effectively explored via surgical triangles under the ETOA. ETOA provides a unique and valuable surgical route to the CS with a promising synergy when used with EEA and TCA. Our experience with a clinical case convinces us of the efficacy of the ETOA during surgical management of skull base tumors with CS-invasion.

Extended endoscopic transorbital approach with superior-lateral orbital rim osteotomy: cadaveric feasibility study and clinical implications (SevEN-007).

OBJECTIVE: The endoscopic transorbital approach (ETOA) has been developed, permitting a new surgical corridor. Due to the vertical limitation of the ETOA, some lesions of the anterior cranial fossa are difficult to access. The ETOA with superior-lateral orbital rim (SLOR) osteotomy can achieve surgical freedom of vertical as well as horizontal movement. The purpose of this study was to confirm the feasibility of the ETOA with SLOR osteotomy. METHODS: Anatomical dissections were performed in 5 cadaveric heads with a neuroendoscope and neuronavigation system. ETOA with SLOR osteotomy was performed on one side of the head, and ETOA with lateral orbital rim (LOR) osteotomy was performed on the other side. After analysis of the results of the cadaveric study, the ETOA with SLOR osteotomy was applied in 6 clinical cases. RESULTS: The horizontal and vertical movement range through ETOA with SLOR osteotomy (43.8° ± 7.49° and 36.1° ± 3.32°, respectively) was improved over ETOA with LOR osteotomy (31.8° ± 5.49° and 23.3° ± 1.34°, respectively) (p < 0.01). Surgical freedom through ETOA with SLOR osteotomy (6025.1 ± 220.1 mm3) was increased relative to ETOA with LOR osteotomy (4191.3 ± 57.2 mm3) (p < 0.01); these values are expressed as the mean ± SD. Access levels of ETOA with SLOR osteotomy were comfortable, including anterior skull base lesion and superior orbital area. The view range of the endoscope for anterior skull base lesions was increased through ETOA with SLOR osteotomy. After SLOR osteotomy, the space for moving surgical instruments and the endoscope was widened. Anterior clinoidectomy could be achieved successfully using ETOA with SLOR osteotomy. The authors performed ETOA with SLOR osteotomy in 6 cases of brain tumor. In all 6 cases, complete removal of the tumor was successfully accomplished. In the 3 cases of anterior clinoidal meningioma, anterior clinoidectomy was performed easily and safely, and manipulation of the extended dural margin and origin dura mater was possible. There was no complication related to this approach. CONCLUSIONS: The authors evaluated the clinical feasibility of ETOA with SLOR osteotomy based on a cadaveric study. ETOA with SLOR osteotomy could be applied to more diverse disease groups that do not permit conventional ETOA or to cases in which surgical application is challenging. ETOA with SLOR osteotomy might serve as an opportunity to broaden the indication for the ETOA.

Endoscopic Transorbital Approach to Mesial Temporal Lobe for Intra-Axial Lesions: Cadaveric Study and Case Series (SevEN-008).

BACKGROUND: Endoscopic transorbital approach (ETOA) has been proposed as a minimally invasive technique for the treatment of skull base lesions located around mesial temporal lobe (MTL), mostly extra-axial pathology. OBJECTIVE: To explore the feasibility of ETOA in accessing intraparenchymal MTL with cadaveric specimens and describe our initial clinical experience of ETOA for intra-axial lesions in MTL. METHODS: Anatomic dissections were performed in 4 adult cadaveric heads using a 0° endoscope. First, a stepwise anatomical investigation of ETOA to intraparenchymal MTL was explored. Then, ETOA was applied clinically for 7 patients with intra-axial lesions in MTL, predominantly high-grade gliomas (HGGs) and low-grade gliomas (LGGs). RESULTS: The extradural stage of ETOA entailed a superior eyelid incision followed by orbital retraction, drilling of orbital roof, greater and lesser wing of sphenoid bone, and cutting of the meningo-orbital band. For the intradural stage, the brain tissue medial to the occipito-temporal gyrus was aspirated until the temporal horn was opened. The structures of MTL could be aspirated selectively in a subpial manner without injury to the neurovascular structures of the ambient and sylvian cisterns, and the lateral neocortex. After cadaveric validation, ETOA was successfully performed for 4 patients with HGGs and 3 patients with LGGs. Gross total resection was achieved in 6 patients (85.7%) without significant surgical morbidities including visual field deficits. CONCLUSION: ETOA provides a logical line of access for intra-axial lesions in MTL. The safe and natural surgical trajectory of ETOA can spare brain retraction, neurovascular injury, and disruption of the lateral neocortex.

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.

Revisiting the Role of Insulin-like Growth Factor-1 Measurement After Surgical Treatment of Acromegaly.

CONTEXT: In the management of growth hormone (GH)-secreting pituitary adenomas, the oral glucose tolerance test (OGTT) has been the gold standard not only for diagnoses but also for the determination of biochemical remission. Insulin-like growth factor-1 (IGF-1) is an essential biomarker, although it should be adjusted for both age and sex. OBJECTIVE: We evaluated whether IGF-1 levels could serve as a reliable alternative to an OGTT for disease monitoring after the surgical treatment of acromegaly. We retrospectively reviewed the medical records of 320 patients who underwent surgical resection of their GH-secreting pituitary tumors at the Severance hospital. Receiver operator characteristic (ROC) analyses were performed to validate the accuracy of IGF-1 levels for the assessment of remission. In addition, regression analyses were performed to identify factors associated with discrepancy between OGTT and IGF-1 levels. RESULTS: Except for 1 week after surgery, ROC analyses showed an area under the curve of greater than 0.8 for IGF-1 at all time points. Of 320 patients, 270 achieved endocrine remission after surgery alone. Among these patients, IGF-1 levels were normalized in 250 patients. The mean duration from surgery to IGF-1 normalization was 4.7 months. Regression analyses demonstrated that risk of failed IGF-1 normalization was increased by 3.1-fold when the tumor invaded the cavernous sinus and increased by 9.0-fold in patients with incomplete tumor removal. CONCLUSION: IGF-1 level is a reliable alternative to OGTT and plays a valuable role in monitoring acromegaly status.

The underestimated incidence of an orbital angioleiomyoma is possibly associated with an orbital cavernous hemangioma: illustrative case.

BACKGROUND: Orbital angioleiomyoma is generally considered a rare tumor; approximately 40 cases have been reported. However, after their experience with 6 consecutive cases in their single institution during 3 years, the authors speculate that the incidence of orbital angioleiomyomas is possibly underestimated. OBSERVATIONS: A 34-year-old female presented with progressive exophthalmos of 2 years' duration. Orbital computed tomography and magnetic resonance imaging revealed a well-circumscribed orbital tumor with partial and heterogeneous gadolinium enhancement. Technetium-99m red blood cell single-photon emission computed tomography showed positive perfusion in the late blood-pool phase, which was exactly consistent with the finding of a cavernous hemangioma. Under the impression of a cavernous hemangioma, the authors accessed the mass with an endoscopic endonasal approach and completely removed it without neurological deficit. Pathological examination revealed that the final diagnosis was an angioleiomyoma with positive immunostaining results for smooth muscle actin (SMA). LESSONS: The incidence of orbital angioleiomyomas may not be very low, as these lesions have possibly been misdiagnosed as orbital cavernous hemangiomas because of their histological similarity. Preoperative presumption and differentiation from cavernous hemangiomas are very challenging because of the rarity of orbital angioleiomyoma and similar radiological findings. SMA immunostaining may be critical to differentiate orbital angioleiomyomas from cavernous hemangiomas.