Andy Trang

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.

Intraoperative neuromonitoring techniques in the surgical management of acoustic neuromas

Unfavorable outcomes such as facial paralysis and deafness were once unfortunate probable complications following resection of acoustic neuromas. However, the implementation of intraoperative neuromonitoring during acoustic neuroma surgery has demonstrated placing more emphasis on quality of life and preserving neurological function. A modern review demonstrates a great degree of recent success in this regard. In facial nerve monitoring, the use of modern electromyography along with improvements in microneurosurgery has significantly improved preservation. Recent studies have evaluated the use of video monitoring as an adjunctive tool to further improve outcomes for patients undergoing surgery. Vestibulocochlear nerve monitoring has also been extensively studied, with the most popular techniques including brainstem auditory evoked potential monitoring, electrocochleography, and direct compound nerve action potential monitoring. Among them, direct recording remains the most promising and preferred monitoring method for functional acoustic preservation. However, when compared with postoperative facial nerve function, the hearing preservation is only maintained at a lower rate. Here, the authors analyze the major intraoperative neuromonitoring techniques available for acoustic neuroma resection.

Chromosomal alterations, prognostic factors, and targeted molecular therapies for malignant meningiomas

Meningiomas are the second most common intracranial neoplasm in adults and originate from arachnoidal cap cells. Malignant meningiomas are resistant to conventional treatments such as surgery, chemotherapy, and radiotherapy. Unlike benign meningiomas, atypical and anaplastic tumors generally display more complex karyotypes associated with aggressive behavior. While these chromosomal anomalies are associated with greater malignancy in meningiomas, the specific genes involved remain unknown. Malignant meningiomas are characterized by increased tumor aggressiveness, rapid recurrence, local invasion, atypical histological appearance, and a high mitotic index. Potential prognostic factors include extent of resection, treatment with radiotherapy or stereotactic radiosurgery, Ki-67/MIB-1 labeling index, p53 overexpression, percentage of tumor cells in the S-phase, telomerase activity, and numerous genetic expression profiles. A greater understanding of prognostic factors and molecular markers involved in critical signaling pathways may aid in the identification of novel therapeutic targets. As such, further studies are needed to establish reliable prognostic factors and develop more effective treatments for malignant meningiomas.

Characteristics and Management of Superior Semicircular Canal Dehiscence

Objectives To review the characteristic symptoms of superior semicircular canal dehiscence, testing and imaging of the disease, and the current treatment and surgical options. Results and Conclusions Symptoms of superior semicircular canal dehiscence (SSCD) include autophony, inner ear conductive hearing loss, Hennebert sign, and sound-induced episodic vertigo and disequilibrium (Tullio phenomenon), among others. Potential etiologies noted for canal dehiscence include possible developmental abnormalities, congenital defects, chronic otitis media with cholesteatoma, fibrous dysplasia, and high-riding jugular bulb. Computed tomography (CT), vestibular evoked myogenic potentials, Valsalva maneuvers, and certain auditory testing may prove useful in the detection and evaluation of dehiscence syndrome. Multislice temporal bone CT examinations are normally performed with fine-cut (0.5- to 0.6-mm) collimation reformatted to the plane of the superior canal such that images are parallel and orthogonal to the plane. For the successful alleviation of auditory and vestibular symptoms, a bony dehiscence can be surgically resurfaced, plugged, or capped through a middle fossa craniotomy or the transmastoid approach. SSCD should only be surgically treated in patients who exhibit clinical manifestations.

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.

Genetic expression profiles of adult and pediatric ependymomas: Molecular pathways, prognostic indicators, and therapeutic targets

Ependymomas are tumors that can present within either the intracranial or spinal regions. While 90% of all pediatric ependymomas are intracranial, spinal cord ependymomas are more commonly found in patients 20-40 years old. Treatment for spinal lesions has achieved local control rates up to 100% following gross total resection, while pediatric intracranial tumors have 40-60% mortality. Given the inability to effectively treat ependymomas with current standard practices, researchers have focused their efforts on evaluating chromosomal alterations, genetic expression profiles, epigenetic events, and molecular pathways. While these studies have provided critical insight into the potential mechanisms underlying ependymoma pathogenesis, understanding of the intricate interplay between the various pathways involved in tumor initiation, development, and progression will require deeper investigation. However, several potential prognostic markers and therapeutic targets have been identified, providing key areas of focus for future research. The utilization of unique genetic expression profiles based upon patient age, tumor location, tumor grade, and subtype has revealed a multitude of findings warranting further study. Inspection of various molecular pathways associated with ependymomas may establish the foundation for developing novel therapies capable of achieving significant clinical improvements with individualized regimens specifically designed for personalized treatment strategies.

Chromosomal anomalies and prognostic markers for intracranial and spinal ependymomas

Ependymomas are neoplasms that can occur anywhere along the craniospinal axis. They are the third most common brain tumor in children, representing 10% of pediatric intracranial tumors, 4% of adult brain tumors, and 15% of all spinal cord tumors. As the heterogeneity of ependymomas has severely limited the prognostic value of the World Health Organization grading system, numerous studies have focused on genetic alterations as a potential basis for classification and prognosis. However, this endeavor has proven difficult due to variations of findings depending on tumor location, tumor grade, and patient age. While many have evaluated chromosomal abnormalities for ependymomas as a whole group, others have concentrated their efforts on specific subsets of populations. Here, we review modern findings of chromosomal analyses, their relationships with various genes, and their prognostic implications for intracranial and spinal cord ependymomas.

An analysis of intracranial epidermoid tumors with malignant transformation: treatment and outcomes

OBJECTIVE While typically benign, epidermoid tumors upon rare occasion can undergo malignant transformation, which carries a poor prognosis. Here, we reviewed treatment strategies and analyzed outcomes for every case of malignant epidermoid tumor reported since its original description in 1912. METHODS A comprehensive literature review identified all reported cases of malignant transformation of intracranial epidermoid tumor. Treatments were categorized as follows: palliative management, stereotactic radiosurgery (SRS), chemotherapy, and surgery plus multiple (2+) adjuvant therapies. Survival data of these groups were compared to treatment outcomes for patients receiving only surgical resection, as reported in our previous study. RESULTS We identified 58 cases of intracranial epidermoid tumor with malignant degeneration. Average survival regardless of therapy was 11.8 months. Mean survival outcomes for groups treated with palliative management, chemotherapy, SRS, and multiple postoperative adjuvant therapies were 5.3 months, 25.7 months, 29.2 months, and 36.3 months, respectively. Outcomes for the groups including SRS, chemotherapy, and multiple post-operative adjuvant therapies were statistically significant compared to surgical resection alone. CONCLUSION While there remains a lack of consensus regarding the best approach to the management of patients with malignant epidermoid tumors, our systematic analysis characterizes and confirms the added benefit of SRS, chemotherapy, and multimodal adjuvant therapies.

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.

198 An Antigen Vault Nanoparticle Vaccine Can Effectively Stimulate Dendritic Cells and Activate a Specific T cell Immune Response

be able to distinguish pertinent readmissions. Readmissions for reasons unrelated to the index spine surgery obscure the definition of a spine-related episode of care. Our modified algorithm for readmission evaluates not only hospital re-entry, but also incorporates a diagnosis code that indicates a spine-related complication and thus avoids the 25% overestimate by the UHC algorithm. As institutions consider accountable care models it will be important to define episodes of care that accurately portray and benchmark readmission rates.