Nolan Ung

Utilizing virtual and augmented reality for educational and clinical enhancements in neurosurgery

Neurosurgery has undergone a technological revolution over the past several decades, from trephination to image-guided navigation. Advancements in virtual reality (VR) and augmented reality (AR) represent some of the newest modalities being integrated into neurosurgical practice and resident education. In this review, we present a historical perspective of the development of VR and AR technologies, analyze its current uses, and discuss its emerging applications in the field of neurosurgery.

The role of regulatory T-cells in glioma immunology.

Despite recent advances in treatment, the prognosis for glioblastoma multiforme (GBM) remains poor. The lack of response to treatment in GBM patients may be attributed to the immunosuppressed microenvironment that is characteristic of invasive glioma. Regulatory T-cells (Tregs) are immunosuppressive T-cells that normally prevent autoimmunity when the human immune response is evoked; however, there have been strong correlations between glioma-induced immunosuppression and Tregs. In fact, induction of Treg activity has been correlated with glioma development in both murine models and patients. While the exact mechanisms by which regulatory T-cells function require further elucidation, various cytokines such as interleukin-10 (IL-10) and transforming growth factor-β (TFG-β) have been implicated in these processes and are currently under investigation. In addition, hypoxia is characteristic of tumor development and is also correlated with downstream induction of Tregs. Due to the poor prognosis associated with immunosuppression in glioma patients, Tregs remain a promising area for immunotherapeutic research.

Predictors of recurrence following resection of intracranial chordomas

Management of intracranial chordomas remains challenging, despite improvements in microsurgical techniques and radiotherapy. Here, we analyzed the prognostic factors associated with improved rates of tumor control in patients with intracranial chordomas, who received either gross (GTR) or subtotal resections (STR). A retrospective review was performed to identify all patients who were undergoing resection of their intracranial chordomas at the Ronald Reagan University of California Los Angeles Medical Center from 1990 to 2011. In total, 57 patients undergoing 81 resections were included. There were 24 females and 33 males with a mean age of 44.6 years, and the mean tumor diameter was 3.36 cm. The extent of resection was not associated with recurrence. For all 81 operations, the 1 and 5 year progression free survival (PFS) was 87.5 and 40.4%, and 88.0 and 33.6% for STR and GTR, respectively (p=0.90). Adjuvant radiotherapy was associated with improved rates of PFS (hazard ratio [HR] 0.20; p=0.009). Additionally, age >45 years (HR 5.88; p=0.01) and the presence of visual deficits (HR 7.59; p=0.03) were associated with worse rates of tumor control. Tumor size, sex, tumor histology, and recurrent tumors were not predictors of recurrence. Younger age, lack of visual symptoms on presentation and adjuvant radiotherapy were associated with improved rates of tumor control following surgery. However, GTR and STR produced comparable rates of tumor control. The surgical management of intracranial chordomas should take a conservative approach, with the aim of maximal but safe cytoreductive resection with adjuvant radiation therapy, and a major focus on quality of life.

Transferrin receptors and glioblastoma multiforme: Current findings and potential for treatment

The current standard treatment for glioblastoma multiforme (GBM) is surgery followed by chemotherapy and external radiation. Even with the standard treatment, the 2 year survival rate for GBM is less than 20%, making research for alternative treatments necessary. Transferrin receptor 1 (TfR1) controls the rate of cellular iron uptake by tuning the amount of iron delivered to the cells to meet metabolic needs. Kawabata et al. (J Biol Chem 1999;274:20826-32) cloned a second TfR molecule known as transferrin receptor 2 (TfR2) in 1999. Multiple experimental studies have documented increased expression of TfR1 on both proliferating cells and cells that have undergone malignant transformation. Calzolari et al. concluded that TfR2 is frequently expressed in human cell lines in 2007 (Blood Cells Mol Dis 2007;39:82-91) and in GBM in particular in 2010 (Transl Oncol 2010;3:123-34). In GBM, a highly significant correlation (p<0.0001) was found between the expression level of TfR2 and overall survival, showing that higher levels of TfR2 expression were associated with an overall longer survival. The data on which of the two transferrin receptors is the better target is also unclear and should be studied. The transferrin pathway may be a promising target, but more research should be completed on the antigenicity to discern the viability of it as an immunotherapy target.

Clinical outcomes of middle fossa craniotomy for superior semicircular canal dehiscence repair

OBJECTIVE Superior semicircular canal dehiscence (SSCD) is a rare disorder characterized by the formation of a third opening in the inner ear between the superior semicircular canal and the middle cranial fossa. Aberrant communication through this opening causes a syndrome of hearing loss, pulsatile tinnitus, disequilibrium, and autophony. This study analyzed the clinical outcomes of a single-institution series of patients with SSCD undergoing surgical repair by the same otolaryngologist and neurosurgeon. METHODS All patients who underwent SSCD repair at the University of California, Los Angeles, between March 2011 and November 2014 were included. All patients had their SSCD repaired via middle fossa craniotomy by the same otolaryngologist and neurosurgeon. Outcomes were analyzed with Fishers exact test. RESULTS A total of 18 patients with a mean age of 56.2 years (range 27-84 years) and an average follow-up of 5.0 months (range 0.2-21.8 months) underwent 21 cases of SSCD repair. Following treatment, all patients (100%) reported resolution in ≥ 1 symptom associated with SSCD. Autophony (p = 0.0005), tinnitus (p = 0.0059), and sound- and/or pressure-induced dizziness (p = 0.0437) showed significant symptomatic resolution. Following treatment, 29% (2/7) of patients developed imbalance, 20% (1/5) of patients developed sound- and/or pressure-induced dizziness, and 18% (2/11) of patients developed aural fullness. Among patients with improved symptoms following surgical repair, none reported recurrence of symptoms at subsequent follow-up visits. CONCLUSIONS SSCD remains an underdiagnosed and undertreated condition. Surgical repair of SSCD using a middle fossa craniotomy is associated with a high rate of symptom resolution. Continued investigation using a larger patient cohort and longer-term follow-up could further demonstrate the effectiveness of using middle fossa craniotomy for SSCD repair.

Clinical Manifestations of Central Neurocytoma

Central neurocytomas (CNs) are rare central nervous system tumors that occur in the lateral ventricles. They are prevalent in young adults and are typically benign with excellent prognosis following surgical resection. Because of the rarity of the disease and its similar features with more common tumors, misdiagnosis becomes an issue. Optimal treatment is achieved only when the correct tumor types are distinguished. Typical clinical manifestations include symptoms of increased intracranial pressure, although no clinical feature is pathognomonic to CN. Radiologic imaging, histology, magnetic resonance spectroscopy, and immunohistochemistry must be used to elucidate tumor characteristics and properly diagnose CN.

Nanotechnology to augment immunotherapy for the treatment of glioblastoma multiforme

Glioblastoma multiforme (GBM) is characterized as one of the most common and most deadly malignant primary brain tumors. Current treatment modalities include the use of surgical resection and adjuvant chemotherapy and radiation therapy, though survival is still limited. Because of this, new treatment strategies are needed to improve overall survival. Immunotherapy has emerged as a potential treatment, but still possesses certain limitations to have a substantial clinical effect. In addition, nanotechnology has emerged as potent treatment effectors that have been shown to augment the effects of therapies including chemotherapy, gene therapy, and more. Nanoparticles possess a novel approach due to the myriad of functional groups that can create targeted treatments, though further optimization is still required. In this review, the authors will present the current uses and abilities of nanotechnology and its implication for use with immunotherapy in the treatment of GBM.

Laser neurosurgery: A systematic analysis of magnetic resonance-guided laser interstitial thermal therapies

Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a novel minimally invasive modality that uses heat from laser probes to destroy tissue. Advances in probe design, cooling mechanisms, and real-time MR thermography have increased laser utilization in neurosurgery. The authors perform a systematic analysis of two commercially available MRgLITT systems used in neurosurgery: the Visualase® thermal therapy and NeuroBlate® Systems. Data extraction was performed in a blinded fashion. Twenty-two articles were included in the quantitative synthesis. A total of 223 patients were identified with the majority having undergone treatment with Visualase (n=154, 69%). Epilepsy was the most common indication for Visualase therapy (n=8 studies, 47%). Brain mass was the most common indication for NeuroBlate therapy (n=3 studies, 60%). There were no significant differences, except in age, wherein the NeuroBlate group was nearly twice as old as the Visualase group (p<0.001). Frame, total complications, and length-of-stay (LOS) were non-significant when adjusted for age and number of patients. Laser neurosurgery has evolved over recent decades. Clinical indications are currently being defined and will continue to emerge as laser technologies become more sophisticated. Head-to-head comparison of these systems was difficult given the variance in indications (and therefore patient population) and disparate literature.

Adjuvant Stereotactic Radiosurgery and Radiation Therapy for the Treatment of Intracranial Chordomas.

Objective Chordomas are locally aggressive, highly recurrent tumors requiring adjuvant radiotherapy following resection for successful management. We retrospectively reviewed patients treated for intracranial chordomas with adjuvant stereotactic radiosurgery (SRS) and stereotactic radiation therapy (SRT). Methods A total of 57 patients underwent 83 treatments at the UCLA Medical Center between February 1990 and August 2011. Mean follow-up was 57.8 months. Mean tumor diameter was 3.36 cm. Overall, 8 and 34 patients received adjuvant SRS and SRT, and the mean maximal dose of radiation therapy was 1783.3 cGy and 6339 cGy, respectively. Results Overall rate of recurrence was 51.8%, and 1- and 5-year progression-free survival (PFS) was 88.2% and 35.2%, respectively. Gross total resection was achieved in 30.9% of patients. Adjuvant radiotherapy improved outcomes following subtotal resection (5-year PFS 62.5% versus 20.1%; p = 0.036). SRS and SRT produced comparable rates of tumor control (p = 0.28). Higher dose SRT (> 6,000 cGy) (p = 0.013) and younger age (< 45 years) (p = 0.03) was associated with improved rates of tumor control. Conclusion Adjuvant radiotherapy is critical following subtotal resection of intracranial chordomas. Adjuvant SRT and SRS were safe and improved PFS following subtotal resection. Higher total doses of SRT and younger patient age were associated with improved rates of tumor control.

Characteristics and treatments of large cystic brain metastasis: radiosurgery and stereotactic aspiration.

Brain metastasis represents one of the most common causes of intracranial tumors in adults, and the incidence of brain metastasis continues to rise due to the increasing survival of cancer patients. Yet, the development of cystic brain metastasis remains a relatively rare occurrence. In this review, we describe the characteristics of cystic brain metastasis and evaluate the combined use of stereotactic aspiration and radiosurgery in treating large cystic brain metastasis. The results of several studies show that stereotactic radiosurgery produces comparable local tumor control and survival rates as other surgery protocols. When the size of the tumor interferes with radiosurgery, stereotactic aspiration of the metastasis should be considered to reduce the target volume as well as decreasing the chance of radiation induced necrosis and providing symptomatic relief from mass effect. The combined use of stereotactic aspiration and radiosurgery has strong implications in improving patient outcomes.