Gordon Li, MD

All Publications

• Publisher Correction: Notch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma. Nature communications Kahn, S. A., Wang, X., Nitta, R. T., Gholamin, S., Theruvath, J., Hutter, G., Azad, T. D., Wadi, L., Bolin, S., Ramaswamy, V., Esparza, R., Liu, K., Edwards, M., Swartling, F. J., Sahoo, D., Li, G., Wechsler-Reya, R. J., Reimand, J., Cho, Y., Taylor, M. D., Weissman, I. L., Mitra, S. S., Cheshier, S. H. 2018; 9 (1): 4651

  Abstract

  The original version of this Article omitted Suzana A. Kahn, Siddhartha S. Mitra & Samuel H. Cheshier as jointly supervising authors. This has now been corrected in both the PDF and HTML versions of the Article.

  View details for DOI 10.1038/s41467-018-07182-1

  View details for PubMedID 30389946

• How Intraoperative Tools and Techniques Have Changed the Approach to Brain Tumor Surgery. Current oncology reports Fatemi, P., Zhang, M., Miller, K. J., Robe, P., Li, G. 2018; 20 (11): 89

  Abstract

  PURPOSE OF REVIEW: Surgical treatment of brain tumors remains an integral part of a comprehensive treatment plan. Here, we review technological advances that have enhanced what surgeons are capable of doing within and outside the traditional operating room.RECENT FINDINGS: Extent of surgical resection has improved with the use of MRI and fluorescent dyes intraoperatively. Neurological injury during brain tumor surgery has decreased with appropriate use of neurophysiological monitoring. New operative scopes have enhanced ability of surgeons to visualize tissues during dissection. Laser interstitial therapy and radiation treatment have made possible the treatment of previously considered non-operable brain tumors in addition to replacing or serving as adjunct to surgical treatment of brain tumors. Surgery remains an important pillar in treatment of most brain tumors. Ongoing technological advances have augmented extent of what is possible in this realm.

  View details for DOI 10.1007/s11912-018-0723-9

  View details for PubMedID 30259202

• Developmental phosphoproteomics identifies the kinase CK2 as a driver of Hedgehog signaling and a therapeutic target in medulloblastoma. Science signaling Purzner, T., Purzner, J., Buckstaff, T., Cozza, G., Gholamin, S., Rusert, J. M., Hartl, T. A., Sanders, J., Conley, N., Ge, X., Langan, M., Ramaswamy, V., Ellis, L., Litzenburger, U., Bolin, S., Theruvath, J., Nitta, R., Qi, L., Li, X., Li, G., Taylor, M. D., Wechsler-Reya, R. J., Pinna, L. A., Cho, Y., Fuller, M. T., Elias, J. E., Scott, M. P. 2018; 11 (547)

  Abstract

  A major limitation of targeted cancer therapy is the rapid emergence of drug resistance, which often arises through mutations at or downstream of the drug target or through intrinsic resistance of subpopulations of tumor cells. Medulloblastoma (MB), the most common pediatric brain tumor, is no exception, and MBs that are driven by sonic hedgehog (SHH) signaling are particularly aggressive and drug-resistant. To find new drug targets and therapeutics for MB that may be less susceptible to common resistance mechanisms, we used a developmental phosphoproteomics approach in murine granule neuron precursors (GNPs), the developmental cell of origin of MB. The protein kinase CK2 emerged as a driver of hundreds of phosphorylation events during the proliferative, MB-like stage of GNP growth, including the phosphorylation of three of the eight proteins commonly amplified in MB. CK2 was critical to the stabilization and activity of the transcription factor GLI2, a late downstream effector in SHH signaling. CK2 inhibitors decreased the viability of primary SHH-type MB patient cells in culture and blocked the growth of murine MB tumors that were resistant to currently available Hh inhibitors, thereby extending the survival of tumor-bearing mice. Because of structural interactions, one CK2 inhibitor (CX-4945) inhibited both wild-type and mutant CK2, indicating that this drug may avoid at least one common mode of acquired resistance. These findings suggest that CK2 inhibitors may be effective for treating patients with MB and show how phosphoproteomics may be used to gain insight into developmental biology and pathology.

  View details for DOI 10.1126/scisignal.aau5147

  View details for PubMedID 30206138

• In Reply: The Use of Vancomycin Powder for Surgical Prophylaxis Following Craniotomy NEUROSURGERY Ho, A. L., Li, G. H. 2018; 82 (2): E71

  View details for DOI 10.1093/neuros/nyx537

  View details for Web of Science ID 000424225800017

  View details for PubMedID 29149292

• Osimertinib for EGFR-Mutant Lung Cancer with Brain Metastases: Results from a Single-Center Retrospective Study. The oncologist Xie, L., Nagpal, S., Wakelee, H. A., Li, G., Soltys, S. G., Neal, J. W. 2018

  Abstract

  Osimertinib is a third-generation tyrosine kinase inhibitor, initially approved for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) with T790M acquired resistance, and now approved in the first-line setting. However, data supporting the use of osimertinib in untreated brain metastases are limited, although it has established central nervous system (CNS) activity. Our study compares the clinical outcomes of patients experiencing progressing brain metastases treated with cranial irradiation and osimertinib with those treated with osimertinib alone.Forty patients who were treated with osimertinib at the Stanford Cancer Center from November 2015 to December 2016 were identified by searching an electronic medical record database. Eleven patients had progressing brain metastases and did not receive radiation (group A), 9 patients had progressing brain metastases and received radiation when starting osimertinib (group B), and 20 patients had stable brain metastases at the time of initiating osimertinib (group C). Patient and disease characteristics, radiographic responses, and survival outcomes were evaluated retrospectively for the three groups.The CNS response rate was 32.3%. Median time to treatment failure (TTF), overall progression-free survival (PFS), and overall survival (OS) were 10.0 months (95% confidence interval [CI], 4.5-11.8), 8.8 months (95% CI, 6.2-12.1), and 16.2 months, respectively. Median TTF was 15.1 months for group A (95% CI, 1.7-28.5), 7.7 months for group B (95% CI, 0-15.5), and 10.7 months for group C (95% CI, 9.0-12.5). The median PFS was 8.8 months for group A (95% CI, 4.3-13.4), not reached for group B, and 8.4 months for group C (95% CI, 5.6-11.1). The median OS was not reached for group A and C, and was 16.2 months for group B. There was no apparent difference in TTF, PFS, or OS between the three groups.Receiving radiation prior to starting osimertinib for patients with progressing brain metastases did not prolong TTF, PFS, or OS in our series. To minimize the risks of radiation-related toxicity, delaying radiation could be considered for some patients with EGFR-mutant NSCLC with brain metastases who initially respond to osimertinib in the second-line setting.Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor recently approved for the first-line treatment of EGFR-mutant non-small cell lung cancer. Although it appears to have central nervous system (CNS) activity, most clinical trials have excluded patients with untreated, progressing brain metastases. This study included patients with stable and progressing CNS metastases treated with osimertinib and found no apparent differences in median time to treatment failure, time to progression, and overall survival in patients who received osimertinib alone compared with those who received osimertinib and radiosurgery. This may support a clinician's decision to defer radiation for selected patients with untreated brain metastases who are candidates for osimertinib therapy.

  View details for DOI 10.1634/theoncologist.2018-0264

  View details for PubMedID 30126856

• First-in-human intraoperative near-infrared fluorescence imaging of glioblastoma using cetuximab-IRDye800. Journal of neuro-oncology Miller, S. E., Tummers, W. S., Teraphongphom, N., van den Berg, N. S., Hasan, A., Ertsey, R. D., Nagpal, S., Recht, L. D., Plowey, E. D., Vogel, H., Harsh, G. R., Grant, G. A., Li, G. H., Rosenthal, E. L. 2018

  Abstract

  Maximizing extent of surgical resection with the least morbidity remains critical for survival in glioblastoma patients, and we hypothesize that it can be improved by enhancements in intraoperative tumor detection. In a clinical study, we determined if therapeutic antibodies could be repurposed for intraoperative imaging during resection.Fluorescently labeled cetuximab-IRDye800 was systemically administered to three patients 2 days prior to surgery. Near-infrared fluorescence imaging of tumor and histologically negative peri-tumoral tissue was performed intraoperatively and ex vivo. Fluorescence was measured as mean fluorescence intensity (MFI), and tumor-to-background ratios (TBRs) were calculated by comparing MFIs of tumor and histologically uninvolved tissue.The mean TBR was significantly higher in tumor tissue of contrast-enhancing (CE) tumors on preoperative imaging (4.0 ± 0.5) compared to non-CE tumors (1.2 ± 0.3; p = 0.02). The TBR was higher at a 100 mg dose than at 50 mg (4.3 vs. 3.6). The smallest detectable tumor volume in a closed-field setting was 70 mg with 50 mg of dye and 10 mg with 100 mg. On sections of paraffin embedded tissues, fluorescence positively correlated with histological evidence of tumor. Sensitivity and specificity of tumor fluorescence for viable tumor detection was calculated and fluorescence was found to be highly sensitive (73.0% for 50 mg dose, 98.2% for 100 mg dose) and specific (66.3% for 50 mg dose, 69.8% for 100 mg dose) for viable tumor tissue in CE tumors while normal peri-tumoral tissue showed minimal fluorescence.This first-in-human study demonstrates the feasibility and safety of antibody based imaging for CE glioblastomas.

  View details for DOI 10.1007/s11060-018-2854-0

  View details for PubMedID 29623552

• Multiple Extradural Spinal Meningiomas in a Patient with Acquired Immunodeficiency Syndrome: Case Report and Literature Review. World neurosurgery Ghanchi, H., Hariri, O. R., Takayanagi, A., Li, G. 2018

  View details for DOI 10.1016/j.wneu.2018.06.162

  View details for PubMedID 29966786

• Notch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma. Nature communications Kahn, S. A., Wang, X., Nitta, R. T., Gholamin, S., Theruvath, J., Hutter, G., Azad, T. D., Wadi, L., Bolin, S., Ramaswamy, V., Esparza, R., Liu, K. W., Edwards, M., Swartling, F. J., Sahoo, D., Li, G., Wechsler-Reya, R. J., Reimand, J., Cho, Y. J., Taylor, M. D., Weissman, I. L., Mitra, S. S., Cheshier, S. H. 2018; 9 (1): 4121

  Abstract

  Medulloblastoma is the most common malignant brain tumor of childhood. Group 3 medulloblastoma, the most aggressive molecular subtype, frequently disseminates through the leptomeningeal cerebral spinal fluid (CSF) spaces in the brain and spinal cord. The mechanism of dissemination through the CSF remains poorly understood, and the molecular pathways involved in medulloblastoma metastasis and self-renewal are largely unknown. Here we show that NOTCH1 signaling pathway regulates both the initiation of metastasis and the self-renewal of medulloblastoma. We identify a mechanism in which NOTCH1 activates BMI1 through the activation of TWIST1. NOTCH1 expression and activity are directly related to medulloblastoma metastasis and decreased survival rate of tumor-bearing mice. Finally, medulloblastoma-bearing mice intrathecally treated with anti-NRR1, a NOTCH1 blocking antibody, present lower frequency of spinal metastasis and higher survival rate. These findings identify NOTCH1 as a pivotal driver of Group 3 medulloblastoma metastasis and self-renewal, supporting the development of therapies targeting this pathway.

  View details for DOI 10.1038/s41467-018-06564-9

  View details for PubMedID 30297829

• Quantification of Macrophages in High-Grade Gliomas by Using Ferumoxytol-enhanced MRI: A Pilot Study. Radiology Iv, M., Samghabadi, P., Holdsworth, S., Gentles, A., Rezaii, P., Harsh, G., Li, G., Thomas, R., Moseley, M., Daldrup-Link, H. E., Vogel, H., Wintermark, M., Cheshier, S., Yeom, K. W. 2018: 181204

  Abstract

  Purpose To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adults with high-grade gliomas. Materials and Methods In this prospective study, adults with high-grade gliomas were enrolled between July 2015 and July 2017. Each participant was administered intravenous ferumoxytol (5 mg/kg) and underwent 3.0-T MRI 24 hours later. Two sites in each tumor were selected for intraoperative sampling on the basis of the degree of ferumoxytol-induced signal change. Susceptibility and the relaxation rates R2* (1/T2*) and R2 (1/T2) were obtained by region-of-interest analysis by using the respective postprocessed maps. Each sample was stained with Prussian blue, CD68, CD163, and glial fibrillary acidic protein. Pearson correlation and linear mixed models were performed to assess the relationship between imaging measurements and number of 400× magnification high-power fields with iron-containing macrophages. Results Ten adults (four male participants [mean age, 65 years ± 9 {standard deviation}; age range, 57-74 years] and six female participants [mean age, 53 years ± 12 years; age range, 32-65 years]; mean age of all participants, 58 years ± 12 [age range, 32-74 years]) with high-grade gliomas were included. Significant positive correlations were found between susceptibility, R2*, and R2' and the number of high-power fields with CD163-positive (r range, 0.64-0.71; P < .01) and CD68-positive (r range, 0.55-0.57; P value range, .01-.02) iron-containing macrophages. No significant correlation was found between R2 and CD163-positive (r = 0.33; P = .16) and CD68-positive (r = 0.24; P = .32) iron-containing macrophages. Similar significance results were obtained with linear mixed models. At histopathologic analysis, iron particles were found only in macrophages; none was found in glial fibrillary acidic protein-positive tumor cells. Conclusion MRI measurements of susceptibility, R2*, and R2' (R2* - R2) obtained after ferumoxytol administration correlate with iron-containing macrophage concentration, and this shows their potential as quantitative imaging markers of macrophages in malignant gliomas. © RSNA, 2018 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2018181204

  View details for PubMedID 30398435

• Clinical factors associated with mortality within three months after radiosurgery of asymptomatic brain metastases from non-small cell lung cancer. Journal of neuro-oncology Kakusa, B., Han, S., Aggarwal, S., Liu, B., Li, G., Soltys, S., Hayden Gephart, M. 2018

  Abstract

  Routine brain MRI surveillance frequently diagnoses small, asymptomatic brain metastases from non-small cell lung cancer (NSCLC) that are effectively treated with stereotactic radiosurgery (SRS). A subset of patients, however, may die prior to the onset of symptoms. This study identifies clinical features that distinguish neurologically-asymptomatic NSCLC brain metastases patients that die prior to routine 3 month follow-up after SRS.Retrospective chart review from 2007 to 2017 identified 18 patients with neurologically-asymptomatic NSCLC brain metastases who died < 3 months after SRS. Twenty-eight additional patients meeting criteria and surviving > 6 months after SRS were identified. Clinical factors were examined to determine characteristics correlated with survival using cox proportional hazards and nominal logistic regression models. Logistic regression models using salient factors were trained with 10-fold cross-validation and compared to the graded prognostic assessment (GPA) and score index of radiosurgery (SIR) using the AUC from receiver operant characteristic curves.The median survival following SRS was 1.4 and 9.2 months for the < 3 months and > 6 months groups, respectively. Age, number of brain metastases, and Karnofsky performance status were associated with overall survival while gender and interval between primary cancer and first brain metastasis diagnoses were associated with < 3 months and > 6 months survival, respectively. Models using GPA and SIR performed poorly compared to preliminary metrics generated in this study for prognosis of both < 3 months and > 6 months survival.Physicians require data to provide high-value, cost-conscious health care. Clinical metrics can screen patients with asymptomatic NSCLC brain metastases likely to die prior to the standard screening interval and observation could be considered.

  View details for DOI 10.1007/s11060-018-03002-0

  View details for PubMedID 30460628

• Long-Term Update of Stereotactic Radiosurgery for Benign Spinal Tumors. Neurosurgery Chin, A. L., Fujimoto, D., Kumar, K. A., Tupper, L., Mansour, S., Chang, S. D., Adler, J. R., Gibbs, I. C., Hancock, S. L., Dodd, R., Li, G., Gephart, M. H., Ratliff, J. K., Tse, V., Usoz, M., Sachdev, S., Soltys, S. G. 2018

  Abstract

  Stereotactic radiosurgery (SRS) for benign intracranial tumors is an established standard of care. The widespread implementation of SRS for benign spinal tumors has been limited by lack of long-term data.To update our institutional experience of safety and efficacy outcomes after SRS for benign spinal tumors.We performed a retrospective cohort study of 120 patients with 149 benign spinal tumors (39 meningiomas, 26 neurofibromas, and 84 schwannomas) treated with SRS between 1999 and 2016, with follow-up magnetic resonance imaging available for review. The primary endpoint was the cumulative incidence of local failure (LF), with death as a competing risk. Secondary endpoints included tumor shrinkage, symptom response, toxicity, and secondary malignancy.Median follow-up was 49 mo (interquartile range: 25-103 mo, range: 3-216 mo), including 61 courses with >5 yr and 24 courses with >10 yr of follow-up. We observed 9 LF for a cumulative incidence of LF of 2%, 5%, and 12% at 3, 5, and 10 yr, respectively. Excluding 10 tumors that were previously irradiated or that arose within a previously irradiated field, the 3-, 5-, and 10-yr cumulative incidence rates of LF were 1%, 2%, and 8%, respectively. At last follow-up, 35% of all lesions had decreased in size. With a total of 776 patient-years of follow-up, no SRS-related secondary malignancies were observed.Comparable to SRS for benign intracranial tumors, SRS provides longer term local control of benign spinal tumors and is a standard-of-care alternative to surgical resection.

  View details for DOI 10.1093/neuros/nyy442

  View details for PubMedID 30445557

• Topical vancomycin surgical prophylaxis in pediatric open craniotomies: an institutional experience. Journal of neurosurgery. Pediatrics Ho, A. L., Cannon, J. G., Mohole, J., Pendharkar, A. V., Sussman, E. S., Li, G., Edwards, M. S., Cheshier, S. H., Grant, G. A. 2018: 1–6

  Abstract

  OBJECTIVE Topical antimicrobial compounds are safe and can reduce cost and complications associated with surgical site infections (SSIs). Topical vancomycin has been an effective tool for reducing SSIs following routine neurosurgical procedures in the spine and following adult craniotomies. However, widespread adoption within the pediatric neurosurgical community has not yet occurred, and there are no studies to report on the safety and efficacy of this intervention. The authors present the first institution-wide study of topical vancomycin following open craniotomy in the pediatric population. METHODS In this retrospective study the authors reviewed all open craniotomies performed over a period from 05/2014 to 12/2016 for topical vancomycin use, SSIs, and clinical variables associated with SSI. Topical vancomycin was utilized as an infection prophylaxis and was applied as a liquid solution following replacement of a bone flap or after dural closure when no bone flap was reapplied. RESULTS Overall, 466 consecutive open craniotomies were completed between 05/2014 and 12/2016, of which 43% utilized topical vancomycin. There was a 1.5% SSI rate in the nontopical cohort versus 0% in the topical vancomycin cohort (p = 0.045). The number needed to treat was 66. There were no significant differences in risk factors for SSI between cohorts. There were no complications associated with topical vancomycin use. CONCLUSIONS Routine topical vancomycin administration during closure of open craniotomies can be a safe and effective tool for reducing SSIs in the pediatric neurosurgical population.

  View details for DOI 10.3171/2018.5.PEDS17719

  View details for PubMedID 30141749

• Cranioplasty Complications and Costs: A National Population-Level Analysis Using the MarketScan Longitudinal Database. World neurosurgery Li, A., Azad, T. D., Veeravagu, A., Bhatti, I., Long, C., Ratliff, J. K., Li, G. 2017; 102: 209-220

  Abstract

  To characterize cranioplasty complications and costs at a population level using a longitudinal national claims database.We identified cranioplasty patients between 2007-2014 in the MarketScan national database. We evaluated age, autograft usage, cranioplasty size, and cranioplasty timing on postoperative outcomes. We further analyzed associated costs. A subset analysis of adult cranioplasty patients with emergent indications, including stroke and trauma, was also performed.We identified 8,275 patients (mean 44.0±20.0 years, 45.2% male) consisting of 13.8% pediatric (<18 years), 76.0% adults (18-64 years), and 10.2% elderly adults (>65 years). Overall complication rate was 36.6%, mortality rate 0.5%, and 30-day readmission rate 12.0%. Elderly patients had the highest complication rate (p<0.0001). Overall, large cranioplasties (>5 cm) saw higher complication rates than small cranioplasties (≤5 cm, p=0.047). In those with emergent indications only(N=1,282), size did not influence complications-though large cranioplasties showed higher infection risk (p=0.02). Overall, autograft use did not affect outcomes, but was associated with higher complication risk-including infections-in the subset with only emergent indications (p<0.001, p=0.001). Late (>90 days) cranioplasty timing had higher complication rates in both the overall cohort and subset with emergent indications (p<0.001, p<0.001). Index costs of care were mainly driven by hospital payments in both the overall cohort and those with emergent indications.We found a high complication rate associated with cranioplasty in the U.S.A. Older age, large cranioplasties, and delayed cranioplasties increased complication risk overall. Among those with only emergent indications, complications were associated with a delayed time to cranioplasty and autograft usage.

  View details for DOI 10.1016/j.wneu.2017.03.022

  View details for PubMedID 28315803

• Phase 1/2 Trial of 5-Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma: Health-Related Quality of Life Results. International journal of radiation oncology, biology, physics Pollom, E. L., Fujimoto, D., Wynne, J., Seiger, K., Modlin, L. A., Jacobs, L. R., Azoulay, M., von Eyben, R., Tupper, L., Gibbs, I. C., Hancock, S. L., Li, G., Chang, S. D., Adler, J. R., Harsh, G. R., Harraher, C., Nagpal, S., Thomas, R. P., Recht, L. D., Choi, C. Y., Soltys, S. G. 2017; 98 (1): 123-130

  Abstract

  We report a longitudinal assessment of health-related quality of life (HRQOL) in patients with glioblastoma (GBM) treated on a prospective dose escalation trial of 5-fraction stereotactic radiosurgery (25-40 Gy in 5 fractions) with concurrent and adjuvant temozolomide.HRQOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire core-30 (QLQ-C30) general, the EORTC quality of life questionnaire-brain cancer specific module (QLQ-BN20), and the M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Questionnaires were completed at baseline and at every follow-up visit after completion of radiosurgery. Changes from baseline for 9 predefined HRQOL measures (global quality of life, physical functioning, social functioning, emotional functioning, motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty) were calculated at every time point.With a median follow-up time of 10.4 months (range, 0.4-52 months), 139 total HRQOL questionnaires were completed by the 30 patients on trial. Compliance with HRQOL assessment was 76% at 12 months. Communication deficit significantly worsened over time, with a decline of 1.7 points per month (P=.008). No significant changes over time were detected in the other 8 scales of our primary analysis, including global quality of life. Although 8 patients (27%) experienced adverse radiation effects (ARE) on this dose escalation trial, it was not associated with a statistically significant decline in any of the primary HRQOL scales. Disease progression was associated with communication deficit, with patients experiencing an average worsening of 13.9 points per month after progression compared with 0.7 points per month before progression (P=.01).On this 5-fraction dose escalation protocol for newly diagnosed GBM, overall HRQOL remained stable and appears similar to historical controls of 30 fractions of radiation therapy. Tumor recurrence was associated with worsening communication deficit, and ARE did not correlate with a decline in HRQOL.

  View details for DOI 10.1016/j.ijrobp.2017.01.242

  View details for PubMedID 28586949

• History and current state of immunotherapy in glioma and brain metastasis THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY McGranahan, T., Li, G., Nagpal, S. 2017; 9 (5): 347-368

  Abstract

  Malignant brain tumors such as glioblastoma (GBM) and brain metastasis have poor prognosis despite conventional therapies. Successful use of vaccines and checkpoint inhibitors in systemic malignancy has increased the hope that immune therapies could improve survival in patients with brain tumors. Manipulating the immune system to fight malignancy has a long history of both modest breakthroughs and pitfalls that should be considered when applying the current immunotherapy approaches to patients with brain tumors. Therapeutic vaccine trials for GBM date back to the mid 1900s and have taken many forms; from irradiated tumor lysate to cell transfer therapies and peptide vaccines. These therapies were generally well tolerated without significant autoimmune toxicity, however also did not demonstrate significant clinical benefit. In contrast, the newer checkpoint inhibitors have demonstrated durable benefit in some metastatic malignancies, accompanied by significant autoimmune toxicity. While this toxicity was not unexpected, it exceeded what was predicted from pre-clinical studies and in many ways was similar to the prior trials of immunostimulants. This review will discuss the history of these studies and demonstrate that the future use of immune therapy for brain tumors will likely need a personalized approach that balances autoimmune toxicity with the opportunity for significant survival benefit.

  View details for DOI 10.1177/1758834017693750

  View details for Web of Science ID 000400896200004

  View details for PubMedID 28529551

  View details for PubMedCentralID PMC5424864

• The Use of Vancomycin Powder for Surgical Prophylaxis Following Craniotomy. Neurosurgery Ravikumar, V., Ho, A. L., Pendhakar, A. V., Sussman, E. S., Kwong-Hon Chow, K., Li, G. 2017; 80 (5): 754-758

  Abstract

  Intrawound vancomycin powder has been studied extensively in spinal fusion surgeries and been found to reduce rates of surgical site infections (SSIs) significantly. Despite its success in spinal surgeries, topical vancomycin has not been extensively studied with respect to cranial neurosurgery.To evaluate the efficacy of intrawound topical vancomycin for prevention of SSIs following open craniotomies.We retrospectively analyzed a large series of 350 patients from 2011 to 2015 in a pre/postintervention study of use of topical vancomycin to reduce postoperative craniotomy infection rates. We had a preintervention control group of 225 patients and a postintervention group of 125 patients that received intrawound topical vancomycin.Our preintervention incidence of SSI was 2.2% and this was significantly reduced to 0% following introduction of topical vancomycin ( P < .5). An ad hoc cost analysis suggested a cost savings of $59 965 with the use of topical vancomycin for craniotomies.Our study found a significant reduction in SSI rates after introduction of topical vancomycin. Thus, this simple intervention should be considered in all open craniotomy patients as both infection prophylaxis and a potential cost saving intervention.

  View details for DOI 10.1093/neuros/nyw127

  View details for PubMedID 28327930

• Stereotactic Radiosurgery and Hypofractionated Radiotherapy for Glioblastoma. Neurosurgery Shah, J. L., Li, G., Shaffer, J. L., Azoulay, M. I., Gibbs, I. C., Nagpal, S., Soltys, S. G. 2017

  Abstract

  Glioblastoma is the most common primary brain tumor in adults. Standard therapy depends on patient age and performance status but principally involves surgical resection followed by a 6-wk course of radiation therapy given concurrently with temozolomide chemotherapy. Despite such treatment, prognosis remains poor, with a median survival of 16 mo. Challenges in achieving local control, maintaining quality of life, and limiting toxicity plague treatment strategies for this disease. Radiotherapy dose intensification through hypofractionation and stereotactic radiosurgery is a promising strategy that has been explored to meet these challenges. We review the use of hypofractionated radiotherapy and stereotactic radiosurgery for patients with newly diagnosed and recurrent glioblastoma.

  View details for DOI 10.1093/neuros/nyx115

  View details for PubMedID 28605463

• Endoscopic vs. Microscopic Resection of Sellar Lesions-A Matched Analysis of Clinical and Socioeconomic Outcomes. Frontiers in surgery Azad, T. D., Lee, Y. J., Vail, D., Veeravagu, A., Hwang, P. H., Ratliff, J. K., Li, G. 2017; 4: 33

  Abstract

  Direct comparisons of microscopic and endoscopic resection of sellar lesions are scarce, with conflicting reports of cost and clinical outcome advantages.To determine if the proposed benefits of endoscopic resection are realized on a population level.We performed a matched cohort study of 9,670 adult patients in the MarketScan database who underwent either endoscopic or microscopic surgery for sellar lesions. Coarsened matching was applied to estimate the effects of surgical approach on complication rates, length of stay (LOS), costs, and likelihood of postoperative radiation.We found that LOS, readmission, and revision rates did not differ significantly between approaches. The overall complication rate was higher for endoscopy (47% compared to 39%, OR 1.37, 95% CI 1.22-1.53). Endoscopic approach was associated with greater risk of neurological complications (OR 1.32, 95% CI 1.11-1.55), diabetes insipidus (OR 1.65, 95% CI 1.37-2.00), and cerebrospinal fluid rhinorrhea (OR 1.83, 95% CI 1.07-3.13) compared to the microscopic approach. Although the total index payment was higher for patients receiving endoscopic resection ($32,959 compared to $29,977 for microscopic resection), there was no difference in long-term payments. Endoscopic surgery was associated with decreased likelihood of receiving post-resection stereotactic radiosurgery (OR 0.67, 95% CI 0.49-0.90) and intensity-modulated radiation therapy (OR 0.78, 95% CI 0.65-0.93).Our results suggest that the transition from a microscopic to endoscopic approach to sellar lesions must be subject to careful evaluation. Although there are evident advantages to transsphenoidal endoscopy, our analysis suggests that the benefits of the endoscopic approach are yet to be materialized.

  View details for DOI 10.3389/fsurg.2017.00033

  View details for PubMedID 28691009

  View details for PubMedCentralID PMC5479879

• Microsurgical vs. Endoscopic Excision of Colloid Cysts: An Analysis of Complications and Costs Using a Longitudinal Administrative Database. Frontiers in neurology Connolly, I. D., Johnson, E., Lamsam, L., Veeravagu, A., Ratliff, J., Li, G. 2017; 8: 259

  Abstract

  Open microsurgical and endoscopic approaches are the two main surgical options for excision of colloid cysts. Controversy remains as to which is superior. Previous studies consist of small cohort sizes. This topic has not been investigated using national administrative claims data which benefits from larger patient numbers.Current Procedural Terminology (CPT) and International Classification of Disease version 9 (ICD-9) coding at inpatient visit was used to select for index surgical procedures corresponding to microsurgical or endoscopic excision of colloid cysts. Comorbidities, costs, and complications were collected.We identified a total of 483 patients. In all, 240 were from the microsurgical cohort and 243 were from the endoscopic cohort. The two groups displayed similar demographic and comorbidity profiles. Thirty-day post-operative complications were also similar between groups with the exception of seizures and thirty-day readmissions, both higher in the open surgical cohort. The seizure rates were 14.7 and 5.4% in the microsurgical and endoscopic cohorts, respectively (p = 0.0011). The thirty-day readmission rates were 17.3 and 9.6% in the microsurgical and endoscopic cohorts, respectively (p = 0.0149). Index admission costs and 90-day post discharge payments were higher in patients receiving microsurgical excision.An analysis of administrative claims data revealed few differences in surgical complications following colloid cyst excision via microsurgical and endoscopic approaches. Post-operative seizures and thirty-day readmissions were seen at higher frequency in patients who underwent microsurgical resection. Despite similar complication profiles, patients undergoing microsurgical excision experienced higher index admission costs and 90-day aggregated costs suggesting that complications may have been more severe in this group.

  View details for DOI 10.3389/fneur.2017.00259

  View details for PubMedID 28649225

  View details for PubMedCentralID PMC5465269

• Neurosurgery concepts: Key perspectives on endoscopic versus microscopic resection for pituitary adenomas, surgical decision-making in tuberculum sellae meningiomas, optic nerve mobilization during resection of craniopharyngiomas, and evaluation of headache and quality of life after endoscopic transphenoidal surgery for pituitary adenomas. Surgical neurology international Germanwala, A. V., Hofler, R., Lagman, C., Chung, L. K., Khalessi, A. A., Zada, G., Smith, Z. A., Dahdaleh, N. S., Bohnen, A. M., Cho, J. M., Colen, C. B., Duckworth, E., Kan, P., Lam, S., Kim, C. Y., Li, G., Lim, M., Sherman, J. H., Wang, V. Y., Yang, I. 2017; 8: 52

  View details for DOI 10.4103/sni.sni_17_17

  View details for PubMedID 28480114

• Neurosurgery concepts: Key perspectives on imaging characteristics of spinal metastases, surgery for low back pain, anesthesia for disc surgery, and laminectomy versus laminectomy and fusion for lumbar spondylolisthesis. Surgical neurology international Lagman, C., Chung, L. K., Macyszyn, L., Choy, W., Smith, Z. A., Dahdaleh, N. S., Bohnen, A. M., Cho, J. M., Colen, C. B., Duckworth, E., Germanwala, A. V., Kan, P., Khalessi, A. A., Kim, C. Y., Lam, S., Li, G., Lim, M., Sherman, J. H., Wang, V. Y., Zada, G., Yang, I. 2017; 8: 9

  View details for DOI 10.4103/2152-7806.198736

  View details for PubMedID 28217388

• Comparison of porcine and bovine collagen dural substitutes in posterior fossa decompression for Chiari I malformation in adults. World neurosurgery Lee, C. K., Mokhtari, T., Connolly, I. D., Li, G., Shuer, L. M., Chang, S. D., Steinberg, G. K., Gephart, M. H. 2017

  Abstract

  Posterior fossa decompression surgeries for Chiari malformations are susceptible to post-operative complications such as pseudomeningocele, external cerebrospinal fluid (CSF) leak, and meningitis. Various dural substitutes have been employed to improve surgical outcomes.This study examined whether the collagen matrix dural substitute type correlated with the incidence of post-operative complications following posterior fossa decompression in adult patients with Chiari I malformations.A retrospective cohort study was conducted on 81 adult patients who underwent an elective decompressive surgery for treatment of symptomatic Chiari I malformations, with duraplasty involving a dural substitute derived from either bovine or porcine collagen matrix. Demographics and treatment characteristics were correlated with surgical outcomes.A total of 81 patients were included in the study. Compared to bovine dural substitute, porcine dural substitute was associated with a significantly higher risk of pseudomeningocele occurrence (OR 5.78, 95% CI 1.65-27.15; P = .01) and a higher overall complication rate (OR 3.70, 95% CI 1.23-12.71; P = .03) by univariate analysis. There was no significant difference in the rate of meningitis, repeat operations, or overall complication rate between the two dural substitutes. In addition, estimated blood loss was a significant risk factor for meningitis (P = .03). Multivariate analyses again demonstrated that porcine dural substitute was associated with pseudomeningocele occurrence, though the association with higher overall complication rate did not reach significance.Dural substitutes generated from porcine collagen, compared to those from bovine collagen, were associated with a higher likelihood of pseudomeningocele development in adult patients undergoing Chiari I malformation decompression and duraplasty.

  View details for DOI 10.1016/j.wneu.2017.08.061

  View details for PubMedID 28838875

• Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma. Cell reports Darmanis, S., Sloan, S. A., Croote, D., Mignardi, M., Chernikova, S., Samghababi, P., Zhang, Y., Neff, N., Kowarsky, M., Caneda, C., Li, G., Chang, S. D., Connolly, I. D., Li, Y., Barres, B. A., Gephart, M. H., Quake, S. R. 2017; 21 (5): 1399–1410

  Abstract

  Glioblastoma (GBM) is the most common primary brain cancer in adults and is notoriously difficult to treat because of its diffuse nature. We performed single-cell RNA sequencing (RNA-seq) on 3,589 cells in a cohort of four patients. We obtained cells from the tumor core as well as surrounding peripheral tissue. Our analysis revealed cellular variation in the tumor's genome and transcriptome. We were also able to identify infiltrating neoplastic cells in regions peripheral to the core lesions. Despite the existence of significant heterogeneity among neoplastic cells, we found that infiltrating GBM cells share a consistent gene signature between patients, suggesting a common mechanism of infiltration. Additionally, in investigating the immunological response to the tumors, we found transcriptionally distinct myeloid cell populations residing in the tumor core and the surrounding peritumoral space. Our data provide a detailed dissection of GBM cell types, revealing an abundance of information about tumor formation and migration.

  View details for DOI 10.1016/j.celrep.2017.10.030

  View details for PubMedID 29091775

• Imaging changes over 18 months following stereotactic radiosurgery for brain metastases: both late radiation necrosis and tumor progression can occur. Journal of neuro-oncology Fujimoto, D., von Eyben, R., Gibbs, I. C., Chang, S. D., Li, G., Harsh, G. R., Hancock, S., Fischbein, N., Soltys, S. G. 2017

  Abstract

  Following stereotactic radiosurgery (SRS) for brain metastases, the median time range to develop adverse radiation effect (ARE) or radiation necrosis is 7-11 months. Similarly, the risk of local tumor recurrence following SRS is < 5% after 18 months. With improvements in systemic therapy, patients are living longer and are at risk for both late (defined as > 18 months after SRS) tumor recurrence and late ARE, which have not previously been well described. An IRB-approved, retrospective review identified patients treated with SRS who developed new MRI contrast enhancement > 18 months following SRS. ARE was defined as stabilization/shrinkage of the lesion over time or pathologic confirmation of necrosis, without tumor. Local failure (LF) was defined as continued enlargement of the lesion over time or pathologic confirmation of tumor. We identified 16 patients, with a median follow-up of 48.2 months and median overall survival of 73.0 months, who had 19 metastases with late imaging changes occurring a median of 32.9 months (range 18.5-63.2 months) after SRS. Following SRS, 12 lesions had late ARE at a median of 33.2 months and 7 lesions had late LF occurring a median of 23.6 months. As patients with cancer live longer and as SRS is increasingly utilized for treatment of brain metastases, the incidence of these previously rare imaging changes is likely to increase. Clinicians should be aware of these late events, with ARE occurring up to 5.3 years and local failure up to 3.8 years following SRS in our cohort.

  View details for DOI 10.1007/s11060-017-2647-x

  View details for PubMedID 29098569

• Magnetic Resonance-Guided Laser-Induced Thermal Therapy for Recurrent Brain Metastases in the Motor Strip After Stereotactic Radiosurgery. Cureus Iyer, A., Halpern, C. H., Grant, G. A., Deb, S., Li, G. H. 2016; 8 (12)

  Abstract

  The authors report a challenging case of a brain metastasis located in the motor cortex, which was not responsive to radiosurgery. Use of a novel technique, magnetic resonance-guided laser-induced thermotherapy (MRgLITT), resulted in the complete obliteration of the lesion without adverse effects or evidence of tumor recurrence at follow-up. This case illustrates that MRgLITT may provide a viable alternative for patients with brain metastases refractory to radiosurgery or in deep locations, where both stereotactic radiosurgery (SRS) and surgical resection may be ineffective.

  View details for DOI 10.7759/cureus.919

  View details for PubMedID 28083463

  View details for PubMedCentralID PMC5218883

• Frameless, electromagnetic image-guided ventriculostomy for ventriculoperitoneal shunt and Ommaya reservoir placement CLINICAL NEUROLOGY AND NEUROSURGERY Xu, L. W., Sussman, E. S., Li, G. 2016; 147: 46-52

  Abstract

  Catheter ventriculostomy is a common neurosurgical procedure for placement of Ommaya reservoirs or ventriculo-peritoneal shunts (VPS). Malpositioning or multiple attempts at catheter placement may lead to complications such as hemorrhage, mechanical obstruction, or tissue injury. Traditional navigation systems to guide placement require head fixation, which can lead to additional risks of pin placement as well as inconvenience, particularly with regard to patient positioning. Here we report our experience using frameless, electromagnetic (EM) image-guidance as a fast and low risk method of ensuring accurate ventriculostomy catheter placement.51 consecutive patients with frameless, EM image-guided Ommaya or VPS placement from 2011 to 2015.We retrospectively reviewed patient charts and recorded case duration and patient post-operative outcomes.Twenty-four (24) patients received Ommayas and 27 received VPS. Average time of operative room set up was 48min. Average case duration was 35min for Ommaya cases and 61min for VPS cases. All catheters were placed with one pass. One patient required revision surgery for obstruction or misplacement. No clinically significant hemorrhages occurred postoperatively.Ventriculostomy with EM image-guidance is a safe and efficient way to ensure proper catheter placement and minimize patient complications.

  View details for DOI 10.1016/j.clineuro.2016.05.024

  View details for Web of Science ID 000381240800009

  View details for PubMedID 27290637

• Glioblastoma Multiforme Recurrence: An Exploratory Study of (18)F FPPRGD2 PET/CT. Radiology Iagaru, A., Mosci, C., Mittra, E., Zaharchuk, G., Fischbein, N., Harsh, G., Li, G., Nagpal, S., Recht, L., Gambhir, S. S. 2016; 280 (1): 328-?

  View details for DOI 10.1148/radiol.2016164020

  View details for PubMedID 27322985

• Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery SEMINARS IN RADIATION ONCOLOGY Hiniker, S. M., Modlin, L. A., Choi, C. Y., Atalar, B., Seiger, K., Binkley, M. S., Harris, J. P., Liao, Y. J., Fischbein, N., Wang, L., Ho, A., Lo, A., Chang, S. D., Harsh, G. R., Gibbs, I. C., Hancock, S. L., Li, G., Adler, J. R., Soltys, S. G. 2016; 26 (2): 97-104

  Abstract

  Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using α/β = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12Gy in 1 fraction from QUANTEC, 19.5Gy in 3 fractions from Timmerman 2008, and 25Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus.

  View details for DOI 10.1016/j.semradonc.2015.11.008

  View details for Web of Science ID 000373242700003

• Endovascular therapies for malignant gliomas: Challenges and the future JOURNAL OF CLINICAL NEUROSCIENCE Su, Y. S., Ali, R., Feroze, A. H., Li, G., Lawton, M. T., Choudhri, O. 2016; 26: 26-32

  Abstract

  Malignant gliomas are very difficult tumors to treat, with few effective therapies, early progression and high rates of recurrence. Here we review the literature on malignant gliomas treated with endovascular therapy. Endovascular therapy for malignant gliomas falls into one of three categories: (1) neoadjuvant embolization and devascularization; (2) direct intra-arterial drug delivery; and (3) disruption of the blood-brain barrier for improved intra-arterial drug delivery. There is a range of therapeutic benefits based on the endovascular intervention used. Challenges remain for those who aim to treat malignant gliomas with an endovascular approach. Specifically, embolization is difficult to accomplish in the small vessels that feed into malignant gliomas, and intra-arterial chemotherapy has yet to prove itself better than traditional intravenous chemotherapy. However, there exists promise in the therapeutic potential of intra-arterial chemotherapy paired with disruption of the blood-brain barrier at tumor-specific sites, and as such, continued research to optimize this approach is expected to yield benefit for patients with malignant gliomas.

  View details for DOI 10.1016/j.jocn.2015.10.019

  View details for Web of Science ID 000372384600005

• New tools for studying microglia in the mouse and human CNS. Proceedings of the National Academy of Sciences of the United States of America Bennett, M. L., Bennett, F. C., Liddelow, S. A., Ajami, B., Zamanian, J. L., Fernhoff, N. B., Mulinyawe, S. B., Bohlen, C. J., Adil, A., Tucker, A., Weissman, I. L., Chang, E. F., Li, G., Grant, G. A., Hayden Gephart, M. G., Barres, B. A. 2016; 113 (12): E1738-46

  Abstract

  The specific function of microglia, the tissue resident macrophages of the brain and spinal cord, has been difficult to ascertain because of a lack of tools to distinguish microglia from other immune cells, thereby limiting specific immunostaining, purification, and manipulation. Because of their unique developmental origins and predicted functions, the distinction of microglia from other myeloid cells is critically important for understanding brain development and disease; better tools would greatly facilitate studies of microglia function in the developing, adult, and injured CNS. Here, we identify transmembrane protein 119 (Tmem119), a cell-surface protein of unknown function, as a highly expressed microglia-specific marker in both mouse and human. We developed monoclonal antibodies to its intracellular and extracellular domains that enable the immunostaining of microglia in histological sections in healthy and diseased brains, as well as isolation of pure nonactivated microglia by FACS. Using our antibodies, we provide, to our knowledge, the first RNAseq profiles of highly pure mouse microglia during development and after an immune challenge. We used these to demonstrate that mouse microglia mature by the second postnatal week and to predict novel microglial functions. Together, we anticipate these resources will be valuable for the future study and understanding of microglia in health and disease.

  View details for DOI 10.1073/pnas.1525528113

  View details for PubMedID 26884166

  View details for PubMedCentralID PMC4812770

• Intracranial Dislocation of the Mandibular Condyle: A Case Report and Literature Review WORLD NEUROSURGERY Zhang, M., Alexander, A. L., Most, S. P., Li, G., Harris, O. A. 2016; 86

  View details for DOI 10.1016/j.wneu.2015.09.007

  View details for Web of Science ID 000369625300100

  View details for PubMedID 26365884

• Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse NEURON Zhang, Y., Sloan, S. A., Clarke, L. E., Caneda, C., Plaza, C. A., Blumenthal, P. D., Vogel, H., Steinberg, G. K., Edwards, M. S., Li, G., Duncan, J. A., Cheshier, S. H., Shuer, L. M., Chang, E. F., Grant, G. A., Gephart, M. G., Barres, B. A. 2016; 89 (1): 37-53

  Abstract

  The functional and molecular similarities and distinctions between human and murine astrocytes are poorly understood. Here, we report the development of an immunopanning method to acutely purify astrocytes from fetal, juvenile, and adult human brains and to maintain these cells in serum-free cultures. We found that human astrocytes have abilities similar to those of murine astrocytes in promoting neuronal survival, inducing functional synapse formation, and engulfing synaptosomes. In contrast to existing observations in mice, we found that mature human astrocytes respond robustly to glutamate. Next, we performed RNA sequencing of healthy human astrocytes along with astrocytes from epileptic and tumor foci and compared these to human neurons, oligodendrocytes, microglia, and endothelial cells (available at http://www.brainrnaseq.org). With these profiles, we identified novel human-specific astrocyte genes and discovered a transcriptome-wide transformation between astrocyte precursor cells and mature post-mitotic astrocytes. These data represent some of the first cell-type-specific molecular profiles of the healthy and diseased human brain.

  View details for DOI 10.1016/j.neuron.2015.11.013

  View details for Web of Science ID 000373564300006

  View details for PubMedID 26687838

  View details for PubMedCentralID PMC4707064

• Immune Evasion Strategies of Glioblastoma. Frontiers in surgery Razavi, S., Lee, K. E., Jin, B. E., Aujla, P. S., Gholamin, S., Li, G. 2016; 3: 11-?

  Abstract

  Glioblastoma (GBM) is the most devastating brain tumor, with associated poor prognosis. Despite advances in surgery and chemoradiation, the survival of afflicted patients has not improved significantly in the past three decades. Immunotherapy has been heralded as a promising approach in treatment of various cancers; however, the immune privileged environment of the brain usually curbs the optimal expected response in central nervous system malignancies. In addition, GBM cells create an immunosuppressive microenvironment and employ various methods to escape immune surveillance. The purpose of this review is to highlight the strategies by which GBM cells evade the host immune system. Further understanding of these strategies and the biology of this tumor will pave the way for developing novel immunotherapeutic approaches for treatment of GBM.

  View details for DOI 10.3389/fsurg.2016.00011

  View details for PubMedID 26973839

• Key perspectives on auditory outcomes following radiosurgery for vestibular schwannoma, tumor treating fields for glioblastoma, and a proposed myelopathy score for cervical decompression surgery, intracranial pressure monitoring in diffuse traumatic brain injury. Surgical neurology international Sherman, J. H., Li, G., Cho, J. M., Choy, W., Yang, I., Smith, Z. A. 2016; 7 (Suppl 27): S725–S728

  View details for DOI 10.4103/2152-7806.192512

  View details for PubMedID 27857864

• Craniotomy for Resection of Meningioma: An Age-Stratified Analysis of the MarketScan Longitudinal Database WORLD NEUROSURGERY Connolly, I. D., Cole, T., Veeravagu, A., Popat, R., Ratliff, J., Li, G. 2015; 84 (6): 1864-1870

  Abstract

  We sought to describe complications after resection for meningioma with the use of longitudinal administrative data, which our group has shown recently to be superior to nonlongitudinal administrative data.We identified patients who underwent resection for meningioma between 2010 and 2012 in the Thomson Reuters MarketScan database. Current Procedural Terminology coding at inpatient visit was used to select for meningioma resection procedure. Comorbidities and complications were obtained by use of the International Classification of Diseases, Ninth Revision or Current Procedural Terminology coding. Associations between complications and demographic and clinical factors were evaluated with logistic regression.We identified a total of 2216 patients. Approximately 41% developed 1 or more perioperative complications. Approximately 15% were readmitted within 30 days of their procedure. The most frequent complications that occurred in our cohort were new postoperative seizures (11.8%), postoperative dysrhythmia (7.9%), intracranial hemorrhage (5.9%), and cerebral artery occlusion (5.4%). General neurosurgical complications and general neurologic complications occurred in 4.4% and 16.1% of patients, respectively. Nearly 55% of elderly patients (≥ 70 years) developed 1 or more perioperative complication (vs. 39% of nonelderly patients). After we adjusted for comorbidities, elderly status and male sex were found to be significantly associated with increased odds for a variety of complications.In this study, we report complication rates in patients undergoing resection for meningioma. Because of the longitudinal nature of the MarketScan database, we were able to capture a wide array of specific postoperative complications associated with meningioma resection procedures. Care should be taken in the selection of candidates for meningioma resection.

  View details for DOI 10.1016/j.wneu.2015.08.018

  View details for Web of Science ID 000366286300065

  View details for PubMedID 26318633

• Glioblastoma Multiforme Recurrence: An Exploratory Study of F-18 FPPRGD(2) PET/CT1 RADIOLOGY Iagaru, A., Mosci, C., Mittra, E., Zaharchuk, G., Fischbein, N., Harsh, G., Li, G., Nagpal, S., Recht, L., Gambhir, S. S. 2015; 277 (2): 497-506

  Abstract

  Purpose To prospectively evaluate fluorine 18 ((18)F) 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) (FPPRGD2) positron emission tomography (PET) in patients with glioblastoma multiforme (GBM). Materials and Methods The institutional review board approved this HIPAA-compliant protocol. Written informed consent was obtained from each patient. (18)F FPPRGD2 uptake was measured semiquantitatively in the form of maximum standardized uptake values (SUVmax) and uptake volumes before and after treatment with bevacizumab. Vital signs and laboratory results were collected before, during, and after the examinations. A nonparametric version of multivariate analysis of variance was used to assess safety outcome measures simultaneously across time points. A paired two-sample t test was performed to compare SUVmax. Results A total of 17 participants (eight men, nine women; age range, 25-65 years) were enrolled prospectively. (18)F FPPRGD2 PET/computed tomography (CT), (18)F fluorodeoxyglucose (FDG) PET/CT, and brain magnetic resonance (MR) imaging were performed within 3 weeks, prior to the start of bevacizumab therapy. In eight of the 17 patients (47%), (18)F FPPRGD2 PET/CT was repeated 1 week after the start of bevacizumab therapy; six patients (35%) underwent (18)F FPPRGD2 PET/CT a third time 6 weeks after starting bevacizumab therapy. There were no changes in vital signs, electrocardiographic findings, or laboratory values that qualified as adverse events. One patient (6%) had recurrent GBM identified only on (18)F FPPRGD2 PET images, and subsequent MR images enabled confirmation of recurrence. Of the 17 patients, 14 (82%) had recurrent GBM identified on (18)F FPPRGD2 PET and brain MR images, while (18)F FDG PET enabled identification of recurrence in 13 (76%) patients. Two patients (12%) had no recurrent GBM. Conclusion (18)F FPPRGD2 is a safe PET radiopharmaceutical that has increased uptake in GBM lesions. Larger cohorts are required to confirm these preliminary findings. (©) RSNA, 2015 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2015141550

  View details for Web of Science ID 000368435100026

• Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Shultz, D. B., Modlin, L. A., Jayachandran, P., von Eyben, R., Gibbs, I. C., Choi, C. Y., Chang, S. D., Harsh, G. R., Li, G., Adler, J. R., Hancock, S. L., Soltys, S. G. 2015; 92 (5): 993-999

  Abstract

  To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS).We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS.Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the time of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites.Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.

  View details for DOI 10.1016/j.ijrobp.2015.04.036

  View details for Web of Science ID 000357900600018

  View details for PubMedID 26194677

• Casein kinase 2a regulates glioblastoma brain tumor-initiating cell growth through the ß-catenin pathway. Oncogene Nitta, R. T., Gholamin, S., Feroze, A. H., Agarwal, M., Cheshier, S. H., Mitra, S. S., Li, G. 2015; 34 (28): 3688-3699

  Abstract

  Glioblastoma (GBM) is the most common and fatal primary brain tumor in humans, and it is essential that new and better therapies are developed to treat this disease. Previous research suggests that casein kinase 2 (CK2) may be a promising therapeutic target for GBMs. CK2 has enhanced expression or activity in numerous cancers, including GBM, and it has been demonstrated that inhibitors of CK2 regressed tumor growth in GBM xenograft mouse models. Our studies demonstrate that the CK2 subunit, CK2α, is overexpressed in and has an important role in regulating brain tumor-initiating cells (BTIC) in GBM. Initial studies showed that two GBM cell lines (U87-MG and U138) transduced with CK2α had enhanced proliferation and anchorage-independent growth. Inhibition of CKα using siRNA or small-molecule inhibitors (TBBz, CX-4945) reduced cell growth, decreased tumor size, and increased survival rates in GBM xenograft mouse models. We also verified that inhibition of CK2α decreased the activity of a well-known GBM-initiating cell regulator, β-catenin. Loss of CK2α decreased two β-catenin-regulated genes that are involved in GBM-initiating cell growth, OCT4 and NANOG. To determine the importance of CK2α in GBM stem cell maintenance, we reduced CK2α activity in primary GBM samples and tumor spheres derived from GBM patients. We discovered that loss of CK2α activity reduced the sphere-forming capacity of BTIC and decreased numerous GBM stem cell markers, including CD133, CD90, CD49f and A2B5. Our study suggests that CK2α is involved in GBM tumorigenesis by maintaining BTIC through the regulation of β-catenin.Oncogene advance online publication, 22 September 2014; doi:10.1038/onc.2014.299.

  View details for DOI 10.1038/onc.2014.299

  View details for PubMedID 25241897

• Glioblastoma antigen discovery--foundations for immunotherapy. Journal of neuro-oncology Azad, T. D., Razavi, S., Jin, B., Lee, K., Li, G. 2015; 123 (3): 347-358

  Abstract

  Prognosis for patients with glioblastoma (GBM), the most common high-grade primary central nervous system (CNS) tumor, remains discouraging despite multiple discoveries and clinical advances. Immunotherapy has emerged as a promising approach to GBM therapy as the idea the human CNS is immunoprivileged is being challenged. Early clinical studies of vaccine-based approaches have been encouraging, but further investigation is required before these therapies become clinically meaningful. A key challenge in immunotherapy involves identification of target antigens that are specific and sensitive for GBM. Here we discuss tumor-associated antigens that have been targeted for GBM therapy, strategies for discovery of novel antigens, and the theory of epitope spreading as it applies to GBM immunotherapy.

  View details for DOI 10.1007/s11060-015-1836-8

  View details for PubMedID 26045361

• Combining immunotherapy with radiation for the treatment of glioblastoma. Journal of neuro-oncology Chow, K. K., Hara, W., Lim, M., Li, G. 2015; 123 (3): 459-464

  Abstract

  Glioblastoma is a devastating cancer with universally poor outcomes in spite of current standard multimodal therapy. Immunotherapy is an attractive new treatment modality given its potential for exquisite specificity and its favorable side effect profile; however, clinical trials of immunotherapy in GBM have thus far shown modest benefit. Optimally combining radiation with immunotherapy may be the key to unlocking the potential of both therapies given the evidence that radiation can enhance anti-tumor immunity. Here we review this evidence and discuss considerations for combined therapy.

  View details for DOI 10.1007/s11060-015-1762-9

  View details for PubMedID 25877468

• Phase II pilot study of single-agent etirinotecan pegol (NKTR-102) in bevacizumab-resistant high grade glioma JOURNAL OF NEURO-ONCOLOGY Nagpal, S., Recht, C. K., Bertrand, S., Thomas, R. P., Ajlan, A., Pena, J., Gershon, M., Coffey, G., Kunz, P. L., Li, G., Recht, L. D. 2015; 123 (2): 277-282

  Abstract

  Patients with recurrence of high-grade glioma (HGG) after bevacizumab (BEV) have an extremely poor prognosis. Etirinotecan pegol (EP) is the first long-acting topoisomerase-I inhibitor designed to concentrate in and provide continuous tumor exposure throughout the entire chemotherapy cycle. Here we report results of a Phase 2, single arm, open-label trial evaluating EP in HGG patients who progressed after BEV. Patients age >18 with histologically proven anaplastic astrocytoma or glioblastoma (GB) who previously received standard chemo-radiation and recurred after BEV were eligible. A predicted life expectancy >6 weeks and KPS ≥ 50 were required. The primary endpoint was PFS at 6-weeks. Secondary endpoint was overall survival from first EP infusion. Response was assessed by RANO criteria. Single agent EP was administered IV every 3 weeks at 145 mg/m2. Patients did not receive BEV while on EP. 20 patients (90 % GB) were enrolled with a median age of 50 and median KPS of 70. Three patients with GB (16.7 % of GB) had partial MRI responses. 6-week PFS was 55 %. Median and 6-month PFS were 2.2 months (95 % CI 1.4-3.4 months) and 11.2 % (95 % CI 1.9-28.9 %) respectively. Median overall survival from first EP infusion was 4.5 months (95 % CI 2.4-5.9). Only one patient had grade 3 toxicity (diarrhea with dehydration) attributable to EP. Hematologic toxicity was mild. Three patients had confirmed partial responses according to RANO criteria. These clinical data combined with a favorable safety profile warrant further clinical investigation of this agent in HGG.

  View details for DOI 10.1007/s11060-015-1795-0

  View details for Web of Science ID 000355632800010

  View details for PubMedID 25935109

• gamma-Glutamyl transferase 7 is a novel regulator of glioblastoma growth BMC CANCER Bui, T. T., Nitta, R. T., Kahn, S. A., Razavi, S., Agarwal, M., Aujla, P., Gholamin, S., Recht, L., Li, G. 2015; 15

  View details for DOI 10.1186/s12885-015-1232-y

  View details for Web of Science ID 000352602800001

  View details for PubMedID 25884624

• Dual-trajectory Approach for Simultaneous Cyst Fenestration and Endoscopic Third Ventriculostomy for Treatment of a Complex Third Ventricular Arachnoid Cyst. Cureus Ho, A. L., Pendharkar, A. V., Sussman, E. S., Ravikumar, V. K., Li, G. H. 2015; 7 (3)

  Abstract

  We present a case of a multiloculated third ventricular arachnoid cyst to describe a novel technique for definitive management of these lesions via direct endoscopic fenestration and CSF diversion utilizing separate trajectories that offers superior visualization and avoids forniceal injury.We present a case of a 33-year-old woman with progressive headache and worsened vision, a known history of a multiloculated third-ventricular arachnoid cyst, and imaging findings consistent with cyst expansion and worsened obstructive hydrocephalus. We then describe the dual-trajectory approach for simultaneous cyst fenestration and endoscopic third ventriculostomy that ultimately resulted in successful treatment of her cyst and hydrocephalus.Dual-trajectory endoscopic approach utilizing double burr holes should be considered when addressing lesions of the third ventricle causing obstructive hydrocephalus.

  View details for DOI 10.7759/cureus.253

  View details for PubMedID 26180677

• Preoperative endovascular embolization of meningiomas: update on therapeutic options NEUROSURGICAL FOCUS Shah, A., Choudhri, O., Jung, H., Li, G. 2015; 38 (3)

  Abstract

  In this review paper the authors analyze new therapeutic options for the embolization of meningiomas, as well as the future of meningioma treatment through recent relevant cohorts and articles. They investigate various embolic materials, types of meningiomas amenable to embolization, imaging techniques, and potential imaging biomarkers that could aid in the delivery of embolic materials. They also analyze perfusion status, complications, and new technical aspects of endovascular preoperative embolization of meningiomas. A literature search was performed in PubMed using the terms "meningioma" and "embolization" to investigate recent therapeutic options involving embolization in the treatment of meningioma. The authors looked at various cohorts, complications, materials, and timings of meningioma treatment. Liquid embolic materials are preferable to particle agents because particle embolization carries a higher risk of hemorrhage. Liquid agents maximize the effect of devascularization because of deeper penetration into the trunk and distal tumor vessels. The 3 main imaging techniques, MRI, CT, and angiography, can all be used in a complementary fashion to aid in analyzing and treating meningiomas. Intraarterial perfusion MRI and a new imaging modality for identifying biomarkers, susceptibility-weighted principles of echo shifting with a train of observations (SW-PRESTO), can relay information about perfusion status and degrees of ischemia in embolized meningiomas, and they could be very useful in the realm of therapeutics with embolic material delivery. Direct puncture is yet another therapeutic technique that would allow for more accurate embolization and less blood loss during resection.

  View details for DOI 10.3171/2014.12.FOCUS14728

  View details for Web of Science ID 000350422600005

  View details for PubMedID 25727229

• The Combined Subtemporal-Transfacial Approach for the Resection of Juvenile Nasopharyngeal Angiofibromas With Intracranial Extension OTOLOGY & NEUROTOLOGY Kumar, A. R., Nayak, J. V., Janisiewicz, A. M., Li, G., Oghalai, J. S. 2015; 36 (1): 151-155

  Abstract

  Stage IVb juvenile nasopharyngeal angiofibromas (JNAs) are frequently regarded as unresectable because of their intracranial extension and cavernous sinus invasion. Although radiation has been described to control these tumors, it can leave the adolescent with long-lasting sequelae. Herein, we describe an alternative treatment strategy based on a combined subtemporal-transfacial surgical approach that permits the successful management of advanced stage JNAs by divorcing the intracranial vascular supply to these massive lesions.Four male patients were identified with Andrew's Stage IVB JNAs.All patients were treated by surgical resection using a combined subtemporal-transfacial surgical approach.Parameters assessed included tumor extent, number and types of surgical procedures, extent of resections, complications, and recurrence rate.Near-total tumor resections were achieved in all patients. No cerebrospinal fluid leak or cranial neuropathies were noted. All but one patient had local recurrences, and these could be managed with repetitive endoscopic debridement. No patient required adjuvant radiation treatment to control advanced disease.With the use of modern skull base surgical techniques, coordinated interdisciplinary care, and safe, near-total removal of the tumor mass, adolescent males with advanced JNAs may be spared the long-term morbidities associated with using radiation to treat these benign but aggressive lesions.

  View details for Web of Science ID 000346368200030

  View details for PubMedID 25036780

• Retrosigmoid Versus Translabyrinthine Approach for Acoustic Neuroma Resection: An Assessment of Complications and Payments in a Longitudinal Administrative Database. Cure¯us Cole, T., Veeravagu, A., Zhang, M., Azad, T., Swinney, C., Li, G. H., Ratliff, J. K., Giannotta, S. L. 2015; 7 (10)

  Abstract

  Object Retrosigmoid (RS) and translabyrinthine (TL) surgery remain essential treatment approaches for symptomatic or enlarging acoustic neuromas (ANs). We compared nationwide complication rates and payments, independent of tumor characteristics, for these two strategies. Methods We identified 346 and 130 patients who underwent RS and TL approaches, respectively, for AN resection in the 2010-2012 MarketScan database, which characterizes primarily privately-insured patients from multiple institutions nationwide. Results Although we found no difference in 30-day general neurological or neurosurgical complication rates, in TL procedures there was a decreased risk for postoperative cranial nerve (CN) VII injury (20.2% vs 10.0%, CI 0.23-0.82), dysphagia (10.4% vs 3.1%, CI 0.10-0.78), and dysrhythmia (8.4% vs 2.3%, CI 0.08-0.86). Overall, there was no difference in surgical repair rates of CSF leak; however, intraoperative fat grafting was significantly higher in TL approaches (19.8% vs 60.2%, CI 3.95-9.43). In patients receiving grafts, there was a trend towards a higher repair rate after RS approach, while in those without grafts, there was a trend towards a higher repair rate after TL approach. Median total payments were $16,856 higher after RS approaches ($67,774 vs $50,918, p < 0.0001), without differences in physician or 90-day postoperative payments. Conclusions  Using a nationwide longitudinal database, we observed that the TL, compared to RS, approach for AN resection experienced lower risks of CN VII injury, dysphagia, and dysrhythmia. There was no significant difference in CSF leak repair rates. The payments for RS procedures exceed payments for TL procedures by approximately $17,000. Data from additional years and non-private sources will further clarify these trends.

  View details for DOI 10.7759/cureus.369

  View details for PubMedID 26623224

  View details for PubMedCentralID PMC4659577

• Key perspectives on donepezil following brain irradiation, sacroiliac joint fusion, indocyanine green fluorescence endoscope in endonasal transsphenoidal surgery, postconcussion syndrome in young athletes. Surgical neurology international Li, G., Dahdaleh, N. S., Germanwala, A. V., Lam, S., Choy, W., Smith, Z. A., Yang, I. 2015; 6 (Suppl 26): S647–50

  View details for DOI 10.4103/2152-7806.171220

  View details for PubMedID 26713171

• 107 ReACT: Overall Survival From a Randomized Phase II Study of Rindopepimut (CDX-110) Plus Bevacizumab in Relapsed Glioblastoma. Neurosurgery Reardon, D. A., Schuster, J. M., Tran, D. D., Fink, K. L., Nabors, L. B., Li, G., Bota, D. A., Lukas, R. V., Desjardins, A., Ashby, L. S., Duic, J. P., Mrugala, M. M., Werner, A., Hawthorne, T., He, Y., Green, J., Yellin, M. J., Turner, C. D., Davis, T. A., Sampson, J. H. 2015; 62 Suppl 1, CLINICAL NEUROSURGERY: 198–99

  Abstract

  EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine rindopepimut consists of a peptide sequence unique to EGFRvIII conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with granulocyte macrophage colony-stimulating factor. Three phase II studies in newly diagnosed, resected, EGFRvIII+ GB demonstrated encouraging progression-free survival (PFS), overall survival (OS), and safety profile. Compassionate-use experience suggests that rindopepimut may also provide benefit in relapsed GB, particularly with agents such as bevacizumab (BV).In the Phase II "ReACT" study, BV-naïve patients in 1st or 2nd relapse with EGFRvIII+ GB were randomly assigned 1:1 to BV plus double-blinded injection of rindopepimut or control (KLH).6-month PFS (PFS6; primary), objective response rate (ORR), PFS, OS, and safety.Accrual is complete (n = 72); study follow-up continues (n = 30). Primary rindopepimut toxicity is grade 1 to 2 injection site reaction. For rindopepimut + BV vs KLH + BV (per investigator; RANO criteria): PFS6 = 27% (9/33) vs 11% (4/35) (P = .048, 1-side χ test); ORR = 24% (7/29) vs 17% (5/30). Central PFS/ORR assessment is underway. Median (95% CI) OS = 12.0 (9.7, -) vs 8.8 (6.8, 11.4) months (HR = 0.47 [0.25, 0.91]; P = .0208), with 8 vs 4 patients progression-free. OS analyses favor rindopepimut including when adjusted for various prognostic factors. Rindopepimut induced robust anti-EGFRvIII titers (1:12800-1:6553600) in 80% of patients. Rapid titer generation was associated with prolonged OS (HR = 0.47 [0.18, 1.27]; P = .128) within the rindopepimut arm, and was most frequent in patients with KPS ≥ 90 (odds ratio = 9.75; P = .007). Evaluation of humoral response quality and HLA typing vs outcome are underway. In an additional cohort of BV-exposed patients (n = 53), four patients experienced objective tumor response.These near-final data show that rindopepimut induces potent EGFRvIII-specific immune response and tumor regression, and appears to significantly prolong survival when administered with BV in patients with relapsed GB.

  View details for DOI 10.1227/01.neu.0000467069.86811.3f

  View details for PubMedID 26181953

• Neurosurgery Concepts: Key perspectives on Traumatic Brain Injury, New Treatments for Glioblastoma, Hemicraniectomy for Extensive Middle-Cerebral-Artery Stroke, Minimally Invasive Spine Surgery and Lumbar Epidural Injections for Radiculopathy. Surgical neurology international Cho, J. M., Colen, C. B., Li, G., Wang, V. Y., Dahdaleh, N., Choy, W., Yang, I., Smith, Z. A. 2015; 6: 98

  View details for DOI 10.4103/2152-7806.158374

  View details for PubMedID 26110080

• Neurosurgery concepts: Key perspectives on dendritic cell vaccines, metastatic tumor treatment, and radiosurgery. Surgical neurology international Li, G., Sherman, J. H., Cho, J. M., Lim, M., Khalessi, A. A., Colen, C. B., Kim, C. Y., Wang, V. Y., Zada, G., Smith, Z. A., Yang, I. 2015; 6: 6

  Abstract

  This is a laboratory study to investigate the effect of adding brain-derived-neurotrophic factor (BDNF) in a poly (N-isopropylacrylamide-g-poly (ethylene glycol) scaffold and its effect on spinal cord injury in a rat model.This is a laboratory investigation of a spinal cord injury in a rat model. A dorsolateral funiculotomy was used to disrupt the dorsolateral funiculus and rubrospinal tract. Animals were then injected with either the scaffold polymer or scaffold polymer with BDNF. Postoperatively, motor functions were assessed with single pellet reach to grasp task, stair case reaching task and cylinder task. Histological study was also performed to look at extent of glial scar and axonal growth.Animals received BDNF containing polymer had an increased recovery rate of fine motor function of forelimb, as assessed by stair case reaching task and single pellet reach to grasp task compared with control animals that received the polymer only. There is no significant difference in the glial scar formation. BDNF treated animals also had increased axon growth including increase in the number and length of the rubrospinal tract axons.BDNF delivered via a scaffold polymer results in increased recovery rate in forelimb motor function in an experimental model of spinal cord injury, possibly through a promotion of growth of axons of the rubrospinal tract.

  View details for DOI 10.4103/2152-7806.149389

  View details for PubMedID 25657859

• Intracranial fat migration: A newly described complication of autologous fat repair of a cerebrospinal fluid leak following supracerebellar infratentorial approach. International journal of surgery case reports Ludwig, C. A., Aujla, P., Moreno, M., Veeravagu, A., Li, G. 2015; 7C: 1-5

  Abstract

  Intracranial fat migration following autologous fat graft and placement of a lumbar drain for cerebrospinal fluid leak after pineal cyst resection surgery has not been previously reported.The authors present a case of a 39-year-old male with a history of headaches who presented for removal of a pineal cyst from the pineal region. He subsequently experienced cerebrospinal fluid leak and postoperative Escherichia coli (E. Coli) wound infection, and meningitis, which were treated initially with wound washout and antibiotics in addition to bone removal and primary repair with primary suture-closure of the durotomy. A lumbar drain was left in place. The cerebrospinal fluid leak returned two weeks following removal of the lumbar drain; therefore, autologous fat graft repair and lumbar drain placement were performed. Three days later, the patient began experiencing right homonymous hemianopia and was found via computed tomography and magnetic resonance imaging to have autologous fat in the infra‑ and supratentorial space, including intraparenchymal and subarachnoid spread. Symptoms began to resolve with supportive care over 48 hours and had almost fully resolved within one week.This is the first known report of a patient with an autologous fat graft entering the subarachnoid space, intraparenchymal space, and ventricles following fat graft and lumbar drainage.This case highlights the importance of monitoring for complications of lumbar drain placement.

  View details for DOI 10.1016/j.ijscr.2014.12.008

  View details for PubMedID 25557086

• Atypical and rare variants of central neurocytomas. Neurosurgery clinics of North America Choudhri, O., Razavi, S., Vogel, H., Li, G. 2015; 26 (1): 91-98

  Abstract

  This article reviews the variation in imaging, histopathology, clinical course, and management seen with central neurocytomas (CNs). CNs have often been misdiagnosed as oligodendrogliomas and ependymomas; however, synaptophysin positivity can correctly diagnose these neurocytic neoplasms. Atypical CNs, an important variant first described in 1997, are marked by increased proliferative potential and associated with worse clinical outcomes in terms of long-term survival and local tumor control. Complete surgical resection is the cornerstone of therapy, and postoperative radiation is recommended in the setting of residual disease. Other less aggressive variants of central neurocytomas, including liponeurocytomas, ganglioneurocytomas, and pigmented neurocytomas, are also discussed.

  View details for DOI 10.1016/j.nec.2014.09.003

  View details for PubMedID 25432187

• Atypical and Rare Variants of Central Neurocytomas NEUROSURGERY CLINICS OF NORTH AMERICA Choudhri, O., Razavi, S., Vogel, H., Li, G. 2015; 26 (1): 91-?

  View details for DOI 10.1016/j.nec.2014.09.003

  View details for Web of Science ID 000346620900012

  View details for PubMedID 25432187

• Neurosurgery Concepts: Key perspectives on quality of life in children with spina bifida, cilengitide for the treatment of newly diagnosed glioblastoma, surgery and stereotactic radiosurgery in the management of intracranial metastasis, Gamma Knife radiosurgery in patients with Neurofibromatosis Type 2, patient misconceptions on the diagnosis and treatment of lumbar spondylosis. Surgical neurology international Lam, S., Li, G., Zada, G., Pelargos, P., Choy, W., Yang, I., Smith, Z. A. 2015; 6: 110

  View details for DOI 10.4103/2152-7806.159075

  View details for PubMedID 26167362

• The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy CANCERS Patel, M. A., Kim, J. E., Ruzevick, J., Li, G., Lim, M. 2014; 6 (4): 1953-1985

  Abstract

  The current standard of care for glioblastoma (GBM) is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ). As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC) vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII) vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care.

  View details for DOI 10.3390/cancers6041953

  View details for Web of Science ID 000209950800005

• Targeting a Glioblastoma Cancer Stem-Cell Population Defined by EGF Receptor Variant III. Cancer research Emlet, D. R., Gupta, P., Holgado-Madruga, M., Del Vecchio, C. A., Mitra, S. S., Han, S., Li, G., Jensen, K. C., Vogel, H., Xu, L. W., Skirboll, S. S., Wong, A. J. 2014; 74 (4): 1238-1249

  Abstract

  The relationship between mutated proteins and the cancer stem cell population is unclear. Glioblastoma tumors frequently express EGFRvIII, an EGFR variant that arises via gene rearrangement and amplification. However, expression of EGFRvIII is restricted despite the prevalence of the alteration. Here we show that EGFRvIII is highly co-expressed with CD133 and that EGFRvIII+/CD133+ defines the population of cancer stem cells with the highest degree of self-renewal and tumor initiating ability. EGFRvIII+ cells are associated with other stem/progenitor markers while markers of differentiation are found in EGFRvIII- cells. EGFRvIII expression is lost in standard cell culture but its expression is maintained in tumor sphere culture, and cultured cells also retain the EGFRvIII+/CD133+ co-expression and self-renewal and tumor initiating abilities. Elimination of the EGFRvIII+/CD133+ population using a bispecific antibody reduced tumorigenicity of implanted tumor cells better than any reagent directed against a single epitope. This work demonstrates that a mutated oncogene can have CSC specific expression and be used to specifically target this population.

  View details for DOI 10.1158/0008-5472.CAN-13-1407

  View details for PubMedID 24366881

• Pilocytic astrocytoma with IDH1 mutation in the cerebellum of an elderly patient. Clinical neuropathology Medress, Z. A., Xu, L. W., Ziskin, J. L., Lefterova, M., Vogel, H., Li, G. 2014

  View details for DOI 10.5414/NP300810

  View details for PubMedID 25295857

• The future of glioblastoma therapy: synergism of standard of care and immunotherapy. Cancers Patel, M. A., Kim, J. E., Ruzevick, J., Li, G., Lim, M. 2014; 6 (4): 1953-1985

  Abstract

  The current standard of care for glioblastoma (GBM) is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ). As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC) vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII) vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care.

  View details for DOI 10.3390/cancers6041953

  View details for PubMedID 25268164

• Current Vaccine Trials in Glioblastoma: A Review JOURNAL OF IMMUNOLOGY RESEARCH Xu, L., Chow, K. K., Lim, M., Li, G. 2014

  Abstract

  Glioblastoma (GBM) is the most common primary brain tumor, and despite aggressive therapy with surgery, radiation, and chemotherapy, average survival remains at about 1.5 years. The highly infiltrative and invasive nature of GBM requires that alternative treatments for this disease be widespread and targeted to tumor cells. Immunotherapy in the form of tumor vaccines has the potential to meet this need. Vaccines against GBM hold the promise of triggering specific and systemic antitumor immune responses that may be the key to eradicating this unrelenting cancer. In this review, we will discuss past and present clinical trials of various GBM vaccines and their potential impact on the future care of GBM patients. There have been many promising phase I and phase II GBM vaccine studies that have led to ongoing and upcoming phase III trials. If the results of these randomized trials show a survival benefit, immunotherapy will become a standard part of the treatment of this devastating disease.

  View details for DOI 10.1155/2014/796856

  View details for Web of Science ID 000334230200001

  View details for PubMedID 24804271

  View details for PubMedCentralID PMC3996322

• Casein Kinase 2: a novel player in glioblastoma therapy and cancer stem cells. Journal of molecular and genetic medicine : an international journal of biomedical research Agarwal, M., Nitta, R. T., Li, G. 2013; 8 (1)

  Abstract

  Casein kinase 2 (CK2) is an oncogenic protein kinase which contributes to tumor development, proliferation, and suppression of apoptosis in multiple cancer types. The mechanism by which CK2 expression and activity leads to tumorigenesis in glioblastoma (GBM), a stage IV primary brain tumor, is being studied. Recent studies demonstrate that CK2 plays an important role in GBM formation and growth through the inhibition of tumor suppressors and activation of oncogenes. In addition, intriguing new reports indicate that CK2 may regulate GBM formation in a novel manner; CK2 may play a critical role in cancer stem cell (CSC) maintenance. Since glial CSCs have the ability to self-renew and initiate tumor growth, new treatments which target these CSCs are needed to treat this fatal disease. Inhibition of CK2 is potentially a novel method to inhibit GBM growth and reoccurrence by targeting the glial CSCs. A new, orally available, selective CK2 inhibitor, CX-4945 has had promising results when tested in cancer cell lines, in vivo xenograft models, and human clinical trials. The development of CK2 targeted inhibitors, starting with CX-4945, may lead to a new class of more effective cancer therapies.

  View details for PubMedID 25264454

• Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Atalar, B., Modlin, L. A., Choi, C. Y., Adler, J. R., Gibbs, I. C., Chang, S. D., Harsh, G. R., Li, G., Nagpal, S., Hanlon, A., Soltys, S. G. 2013; 87 (4): 713-718

  Abstract

  We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients.We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other).With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004).In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

  View details for DOI 10.1016/j.ijrobp.2013.07.034

  View details for Web of Science ID 000325763300022

  View details for PubMedID 24054875

• Multi-institutional validation of a preoperative scoring system which predicts survival for patients with glioblastoma. Journal of clinical neuroscience Chaichana, K. L., Pendleton, C., Chambless, L., Camara-Quintana, J., Nathan, J. K., Hassam-Malani, L., Li, G., Harsh, G. R., Thompson, R. C., Lim, M., Quinones-Hinojosa, A. 2013; 20 (10): 1422-1426

  Abstract

  Glioblastoma is the most common and aggressive type of primary brain tumor in adults. Average survival is approximately 1 year, but individual survival is heterogeneous. Using a single institutional experience, we have previously identified preoperative factors associated with survival and devised a prognostic scoring system based on these factors. The aims of the present study are to validate these preoperative factors and verify the efficacy of this scoring system using a multi-institutional cohort. Of the 334 patients in this study from three different institutions, the preoperative factors found to be negatively associated with survival in a Cox analysis were age >60 years (p<0.0001), Karnofsky Performance Scale score ≤80 (p=0.03), motor deficit (p=0.02), language deficit (p=0.04), and periventricular tumor location (p=0.04). Patients possessing 0-1, 2, 3, and 4-5 of these variables were assigned a preoperative grade of 1, 2, 3, and 4, respectively. Patients with a preoperative grade of 1, 2, 3, and 4 had a median survival of 17.9, 12.3, 10, and 7.5 months, respectively. Survival of each of these grades was statistically significant (p<0.05) in log-rank analysis. This grading system, based only on preoperative variables, may provide patients and physicians with prognostic information that may guide medical and surgical therapy before any intervention is pursued.

  View details for DOI 10.1016/j.jocn.2013.02.007

  View details for PubMedID 23928040

• The invasive nature of glioblastoma. World neurosurgery Nitta, R. T., Li, G. 2013; 80 (3-4): 279-280

  View details for DOI 10.1016/j.wneu.2011.09.036

  View details for PubMedID 22120249

• The incidence and significance of multiple lesions in glioblastoma JOURNAL OF NEURO-ONCOLOGY Thomas, R. P., Xu, L. W., Lober, R. M., Li, G., Nagpal, S. 2013; 112 (1): 91-97

  Abstract

  The location and distribution of glioblastoma (GBM) within the brain parenchyma plays an important role in surgical and radiation planning. Prior studies have reported incidences of multiple lesions at the time of diagnosis ranging from 0.5 to 20 %. Multiple lesions can be further categorized as multifocal (multiple areas involved, but with a clear path of spread from one lesion to another) or multicentric (multiple lesions, no clear path of spread). In this retrospective study, we reviewed our experience with GBM and found the incidence of multiple lesions at time of diagnosis was 35 %, much higher than previously suggested in the literature. Patients with single lesions had an improved overall survival when compared to patients with multiple lesions (18 vs. 10 months). Patients with multicentric lesions fared the worst, with average survival of 3 months. However, the difference between single and multiple lesions (multifocal or multicentric) was no longer significant when taking into consideration age, Karnofsky performance score (KPS) and extent of resection by multivariate analysis. Age, KPS, gross total resection, and MGMT status were independent predictors of outcome. Multiple lesions did not independently confer a worse outcome, but were associated with lower KPS scores and inability to perform gross total resection. These findings suggest that single, multiple and multicentric imaging exams represent a spectrum of presentations of a single disease. The rate of multiple lesions reported here may be the result of improved imaging technology, suggesting that incidence of multiple lesions will continue to increase as imaging technology advances.

  View details for DOI 10.1007/s11060-012-1030-1

  View details for Web of Science ID 000315487900011

  View details for PubMedID 23354652

• Neurosurgery concepts: Key perspectives on regulatory proteins, management of ossification of the posterior longitudinal ligament, and radiosurgery for intracranial lesions. Surgical neurology international Sherman, J. H., Smith, Z. A., Cho, J. M., Lim, M., Colen, C. B., Kim, C., Wang, V. Y., Zada, G., Li, G., Yang, I. 2013; 4: 35-?

  View details for DOI 10.4103/2152-7806.109525

  View details for PubMedID 23607057

• GLIOBLASTOMA CELLS EXPRESSING EGFRVIII ARE MORE SENSITIVE TO CK2 INHIBITION 17th Annual Scientific Meeting and Education Day of the Society-for-Neuro-Oncology (SNO) Nitta, R., Mitra, S., Bui, T., Li, G. OXFORD UNIV PRESS INC. 2012: 7–8

  View details for Web of Science ID 000310971300031

• The predictive value of serum myeloperoxidase for vasospasm in patients with aneurysmal subarachnoid hemorrhage NEUROSURGICAL REVIEW Lim, M., Bower, R. S., Wang, Y., Sims, L., Bower, M. R., Camara-Quintana, J., Li, G., Cheshier, S., Harsh, G. R., Steinberg, G. K., Guccione, S. 2012; 35 (3): 413-419

  Abstract

  Vasospasm is a major contributor to morbidity and mortality in aneurysmal subarachnoid hemorrhage (SAH), with inflammation playing a key role in its pathophysiology. Myeloperoxidase (MPO), an inflammatory marker, was examined as a potential marker of vasospasm in patients with SAH. Daily serum samples from patients with aneurysmal SAH were assayed for MPO, and transcranial Doppler (TCDs) and neurological exams were assessed to determine vasospasm. Suspected vasospasm was confirmed by angiography. Peak MPO levels were then compared with timing of onset of vasospasm, based on clinical exams, TCDs and cerebral angiography. Patients with vasospasm had a mean MPO level of 115.5 ng/ml, compared to 59.4 ng/ml in those without vasospasm, 42.0 ng/ml in those with unruptured aneurysms, and 4.3 ng/ml in normal controls. In patients who experienced vasospasm, MPO was elevated above the threshold on the day of, or at any point prior to, vasospasm in 10 of 15 events (66.7%), and on the day of, or within 2 days prior to, vasospasm in 8 of 15 events (53.3%). Elevated serum MPO correlates with clinically evident vasospasm following aneurysmal SAH. The potential utility of MPO as a marker of vasospasm is discussed.

  View details for DOI 10.1007/s10143-012-0375-4

  View details for Web of Science ID 000305230000023

  View details for PubMedID 22370810

• Expression of epidermal growth factor variant III (EGFRvIII) in pediatric diffuse intrinsic pontine gliomas JOURNAL OF NEURO-ONCOLOGY Li, G., Mitra, S. S., Monje, M., Henrich, K. N., Bangs, C. D., Nitta, R. T., Wong, A. J. 2012; 108 (3): 395-402

  Abstract

  Despite numerous clinical trials over the past 2 decades, the overall survival for children diagnosed with diffuse intrinsic pontine glioma (DIPG) remains 9-10 months. Radiation therapy is the only treatment with proven effect and novel therapies are needed. Epidermal growth factor receptor variant III (EGFRvIII) is the most common variant of the epidermal growth factor receptor and is expressed in many tumor types but is rarely found in normal tissue. A peptide vaccine targeting EGFRvIII is currently undergoing investigation in phase 3 clinical trials for the treatment of newly diagnosed glioblastoma (GBM), the tumor in which this variant receptor was first discovered. In this study, we evaluated EGFRvIII expression in pediatric DIPG samples using immunohistochemistry with a double affinity purified antibody raised against the EGFRvIII peptide. Staining of pediatric DIPG histological samples revealed expression in 4 of 9 cases and the pattern of staining was consistent with what has been seen in EGFRvIII transfected cells as well as GBMs from adult trials. In addition, analysis of tumor samples collected immediately post mortem and of DIPG cells in culture by RT-PCR, western blot analysis, and flow cytometry confirmed EGFRvIII expression. We were therefore able to detect EGFRvIII expression in 6 of 11 DIPG cases. These data suggest that EGFRvIII warrants investigation as a target for these deadly pediatric tumors.

  View details for DOI 10.1007/s11060-012-0842-3

  View details for Web of Science ID 000305123800007

  View details for PubMedID 22382786

• Arachnoid ossificans containing metaplastic hematopoietic marrow resulting in diffuse thoracic intrathecal cysts and severe myelopathy. European spine journal Abrams, J., Li, G., Mindea, S. A., Haynes, C. M., Cheng, I. 2012; 21: S436-40

  Abstract

  To present a rare case of multiple compressive thoracic intradural cysts with pathologic arachnoid ossification, review the literature and present the surgical options. Few reports have identified the existence of arachnoid calcifications and intrathecal cysts causing progressive myelopathy. The literature regarding each of these pathologies is limited to case reports. Their clinical significance is not well studied, although known to cause neurologic sequelae.An 81-year-old female clinically presents with rapidly progressive myelopathy. Pre-operative magnetic resonance imaging identified multiple compressive thoracic intrathecal cysts. Surgical exploration and decompression of these cysts identified calcified plaques within the arachnoid. Histopathologic examination revealed fibrocalcific tissue undergoing ossification with bone marrow elements.Due to progressive myelopathy, the thoracic cysts were decompressed and calcified plaques were excised, once identified intra-operatively.On last examination, the patient's neurologic status had not improved, but had stabilized. The rate of neurologic improvement from excision and decompression is variable, but it may still be warranted in the face of progressive neurologic deficits.

  View details for DOI 10.1007/s00586-011-2005-1

  View details for PubMedID 21892775

• The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Willingham, S. B., Volkmer, J., Gentles, A. J., Sahoo, D., Dalerba, P., Mitra, S. S., Wang, J., Contreras-Trujillo, H., Martin, R., Cohen, J. D., Lovelace, P., Scheeren, F. A., Chao, M. P., Weiskopf, K., Tang, C., Volkmer, A. K., Naik, T. J., Storm, T. A., Mosley, A. R., Edris, B., Schmid, S. M., Sun, C. K., Chua, M., Murillo, O., Rajendran, P., Cha, A. C., Chin, R. K., Kim, D., Adorno, M., Raveh, T., Tseng, D., Jaiswal, S., Enger, P. O., Steinberg, G. K., Li, G., So, S. K., Majeti, R., Harsh, G. R., van de Rijn, M., Teng, N. N., Sunwoo, J. B., Alizadeh, A. A., Clarke, M. F., Weissman, I. L. 2012; 109 (17): 6662-6667

  Abstract

  CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.

  View details for DOI 10.1073/pnas.1121623109

  View details for Web of Science ID 000303249100065

  View details for PubMedID 22451913

  View details for PubMedCentralID PMC3340046

• Pathology: Commonly Monitored Glioblastoma Markers: EFGR, EGFRvIII, PTEN, and MGMT NEUROSURGERY CLINICS OF NORTH AMERICA Camara-Quintana, J. Q., Nitta, R. T., Li, G. 2012; 23 (2): 237-?

  Abstract

  The purpose of this article is to update the neurosurgical field on current molecular markers important to glioblastoma biology, treatment, and prognosis. The highlighted biologic markers in this article include epidermal growth factor receptor (EGFR), EGFR variant III (EGFRvIII), phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and O6-methylguanine-DNA methyltransferase (MGMT).

  View details for DOI 10.1016/j.nec.2012.01.011

  View details for Web of Science ID 000303282100006

  View details for PubMedID 22440867

• Targeting EGF receptor variant III: tumor-specific peptide vaccination for malignant gliomas EXPERT REVIEW OF VACCINES Del Vecchio, C. A., Li, G., Wong, A. J. 2012; 11 (2): 133-144

  Abstract

  Glioblastoma multiforme (GBM) is the most common and deadly of the human brain cancers. The EGF receptor is often amplified in GBM and provides a potential therapeutic target. However, targeting the normal receptor is complicated by its nearly ubiquitous and high level of expression in certain tissues. A naturally occurring deletion mutant of the EGF receptor, EGFRvIII, is a constitutively active variant originally identified in a high percentage of brain cancer cases, and more importantly is rarely found in normal tissue. A peptide vaccine, rindopepimut (CDX-110, Celldex Therapeutics), is directed against the novel exon 1-8 junction produced by the EGFRvIII deletion, and it has shown high efficacy in preclinical models. Recent Phase II clinical trials in patients with newly diagnosed GBM have shown EGFRvIII-specific immune responses and significantly increased time to progression and overall survival in those receiving vaccine therapy, as compared with published results for standard of care. Rindopepimut therefore represents a very promising therapy for patients with GBM.

  View details for DOI 10.1586/ERV.11.177

  View details for Web of Science ID 000300758700009

  View details for PubMedID 22309662

• Perspectives on key articles in neurosurgery. Surgical neurology international Lim, M., Sherman, J. H., Wang, V. Y., Smith, Z. A., Cho, J. M., Colen, C. B., Kim, C. Y., Zada, G., Li, G., Yang, I. 2012; 3: 58-?

  View details for DOI 10.4103/2152-7806.96869

  View details for PubMedID 22754723

• RADIOSURGERY OF GLOMUS JUGULARE TUMORS: A META-ANALYSIS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Guss, Z. D., Batra, S., Limb, C. J., Li, G., Sughrue, M. E., Redmond, K., Rigamonti, D., Parsa, A. T., Chang, S., Kleinberg, L., Lim, M. 2011; 81 (4): E497-E502

  Abstract

  During the past two decades, radiosurgery has arisen as a promising approach to the management of glomus jugulare. In the present study, we report on a systematic review and meta-analysis of the available published data on the radiosurgical management of glomus jugulare tumors.To identify eligible studies, systematic searches of all glomus jugulare tumors treated with radiosurgery were conducted in major scientific publication databases. The data search yielded 19 studies, which were included in the meta-analysis. The data from 335 glomus jugulare patients were extracted. The fixed effects pooled proportions were calculated from the data when Cochrane's statistic was statistically insignificant and the inconsistency among studies was <25%. Bias was assessed using the Egger funnel plot test.Across all studies, 97% of patients achieved tumor control, and 95% of patients achieved clinical control. Eight studies reported a mean or median follow-up time of >36 months. In these studies, 95% of patients achieved clinical control and 96% achieved tumor control. The gamma knife, linear accelerator, and CyberKnife technologies all exhibited high rates of tumor and clinical control.The present study reports the results of a meta-analysis for the radiosurgical management of glomus jugulare. Because of its high effectiveness, we suggest considering radiosurgery for the primary management of glomus jugulare tumors.

  View details for DOI 10.1016/j.ijrobp.2011.05.006

  View details for Web of Science ID 000309412300039

  View details for PubMedID 21703782

• Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Monje, M., Mitra, S. S., Freret, M. E., Raveh, T. B., Kim, J., Masek, M., Attema, J. L., Li, G., Haddix, T., Edwards, M. S., Fisher, P. G., Weissman, I. L., Rowitch, D. H., Vogel, H., Wong, A. J., Beachy, P. A. 2011; 108 (11): 4453-4458

  Abstract

  Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive tumors of childhood that are almost universally fatal. Our understanding of this devastating cancer is limited by a dearth of available tissue for study and by the lack of a faithful animal model. Intriguingly, DIPGs are restricted to the ventral pons and occur during a narrow window of middle childhood, suggesting dysregulation of a postnatal neurodevelopmental process. Here, we report the identification of a previously undescribed population of immunophenotypic neural precursor cells in the human and murine brainstem whose temporal and spatial distributions correlate closely with the incidence of DIPG and highlight a candidate cell of origin. Using early postmortem DIPG tumor tissue, we have established in vitro and xenograft models and find that the Hedgehog (Hh) signaling pathway implicated in many developmental and oncogenic processes is active in DIPG tumor cells. Modulation of Hh pathway activity has functional consequences for DIPG self-renewal capacity in neurosphere culture. The Hh pathway also appears to be active in normal ventral pontine precursor-like cells of the mouse, and unregulated pathway activity results in hypertrophy of the ventral pons. Together, these findings provide a foundation for understanding the cellular and molecular origins of DIPG, and suggest that the Hh pathway represents a potential therapeutic target in this devastating pediatric tumor.

  View details for DOI 10.1073/pnas.1101657108

  View details for Web of Science ID 000288450900040

  View details for PubMedID 21368213

  View details for PubMedCentralID PMC3060250

• Neurosurgery concepts. Surgical neurology international Yang, I., Cho, J. M., Colen, C. B., Li, G., Lim, M., Sherman, J. H., Wang, V. Y. 2011; 2: 173-?

  View details for DOI 10.4103/2152-7806.90444

  View details for PubMedID 22259751

• Development of an EGFRvIII specific recombinant antibody BMC BIOTECHNOLOGY Gupta, P., Han, S., Holgado-Madruga, M., Mitra, S. S., Li, G., Nitta, R. T., Wong, A. J. 2010; 10

  Abstract

  EGF receptor variant III (EGFRvIII) is the most common variant of the EGF receptor observed in human tumors. It results from the in frame deletion of exons 2-7 and the generation of a novel glycine residue at the junction of exons 1 and 8. This novel juxtaposition of amino acids within the extra-cellular domain of the EGF receptor creates a tumor specific and immunogenic epitope. EGFRvIII expression has been seen in many tumor types including glioblastoma multiforme (GBM), breast adenocarcinoma, non-small cell lung carcinoma, ovarian adenocarcinoma and prostate cancer, but has been rarely observed in normal tissue. Because this variant is tumor specific and highly immunogenic, it can be used for both a diagnostic marker as well as a target for immunotherapy. Unfortunately many of the monoclonal and polyclonal antibodies directed against EGFRvIII have cross reactivity to wild type EGFR or other non-specific proteins. Furthermore, a monoclonal antibody to EGFRvIII is not readily available to the scientific community.In this study, we have developed a recombinant antibody that is specific for EGFRvIII, has little cross reactivity for the wild type receptor, and which can be easily produced. We initially designed a recombinant antibody with two anti-EGFRvIII single chain Fv's linked together and a human IgG1 Fc component. To enhance the specificity of this antibody for EGFRvIII, we mutated tyrosine H59 of the CDRH2 domain and tyrosine H105 of the CDRH3 domain to phenylalanine for both the anti-EGFRvIII sequence inserts. This mutated recombinant antibody, called RAb(DMvIII), specifically detects EGFRvIII expression in EGFRvIII expressing cell lines as well as in EGFRvIII expressing GBM primary tissue by western blot, immunohistochemistry (IHC) and immunofluorescence (IF) and FACS analysis. It does not recognize wild type EGFR in any of these assays. The affinity of this antibody for EGFRvIII peptide is 1.7 × 10⁷ M⁻¹ as determined by enzyme-linked immunosorbent assay (ELISA).This recombinant antibody thus holds great potential to be used as a research reagent and diagnostic tool in research laboratories and clinics because of its high quality, easy viability and unique versatility. This antibody is also a strong candidate to be investigated for further in vivo therapeutic studies.

  View details for DOI 10.1186/1472-6750-10-72

  View details for Web of Science ID 000283354200001

  View details for PubMedID 20925961

• Pineal Parenchymal Tumor of Intermediate Differentiation: Clinicopathological Report and Analysis of Epidermal Growth Factor Receptor Variant III Expression NEUROSURGERY Li, G., Mitra, S., Karamchandani, J., Edwards, M. S., Wong, A. J. 2010; 66 (5): 963-968

  Abstract

  Epidermal growth factor receptor (EGF) receptor gene amplification is commonly seen in cancer and is the target of many therapies. EGF receptor variant III (EGFRvIII) is the most common variant of the EGF receptor and has been detected in a large percentage of patients with glioblastoma multiforme but not in normal brain. Therapies targeting EGFRvIII are currently being investigated in clinical and preclinical trials.A 14-year-old girl who presented with headaches was found to have a pineal parenchymal tumor of intermediate differentiation. We review the histopathological properties that led to the diagnosis of this tumor. EGF receptor gene amplification and EGFRvIII expression have not been analyzed in pineal tumors. We investigated EGF receptor gene status and EGFRvIII expression in this patient's tumor.Tumor tissue was obtained and analyzed with flow cytometry, reverse-transcriptase polymerase chain reaction, and Western blot analysis. EGFRvIII was detected by all 3 methods. The tumor was further analyzed by fluorescence in situ hybridization, which did not reveal EGF receptor gene amplification.This is the first report of EGFRvIII expression in a pineal tumor. It is interesting that this variant is detected in the absence of EGF receptor gene amplification. A larger study evaluating the presence of EGFRvIII in pineal tumors is needed.

  View details for DOI 10.1227/01.NEU.0000367726.49003.F1

  View details for Web of Science ID 000276970800026

  View details for PubMedID 20404701

• Passive Antibody-Mediated Immunotherapy for the Treatment of Malignant Gliomas NEUROSURGERY CLINICS OF NORTH AMERICA Mitra, S., Li, G., Harsh, G. R. 2010; 21 (1): 67-?

  Abstract

  Despite advances in understanding the molecular mechanisms of brain cancer, the outcome of patients with malignant gliomas treated according to the current standard of care remains poor. Novel therapies are needed, and immunotherapy has emerged with great promise. The diffuse infiltration of malignant gliomas is a major challenge to effective treatment; immunotherapy has the advantage of accessing the entire brain with specificity for tumor cells. Therapeutic immune approaches include cytokine therapy, passive immunotherapy, and active immunotherapy. Cytokine therapy involves the administration of immunomodulatory cytokines to activate the immune system. Active immunotherapy is the generation or augmentation of an immune response, typically by vaccination against tumor antigens. Passive immunotherapy connotes either adoptive therapy, in which tumor-specific immune cells are expanded ex vivo and reintroduced into the patient, or passive antibody-mediated therapy. In this article, the authors discuss the preclinical and clinical studies that have used passive antibody-mediated immunotherapy, otherwise known as serotherapy, for the treatment of malignant gliomas.

  View details for DOI 10.1016/j.nec.2009.08.010

  View details for Web of Science ID 000278059500007

  View details for PubMedID 19944967

• Radiosurgery of Glomus Jugulare Tumors: A Meta-analysis 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Guss, Z. D., Batra, S., Li, G., Chang, S. D., Parsa, A. T., Rigamonti, D., Kleinberg, L., Lim, M. ELSEVIER SCIENCE INC. 2010: S288–S289

  View details for Web of Science ID 000288775700624

• The Epidermal Growth Factor Variant III Peptide Vaccine for Treatment of Malignant Gliomas NEUROSURGERY CLINICS OF NORTH AMERICA Li, G., Mitra, S., Wong, A. J. 2010; 21 (1): 87-?

  Abstract

  Epidermal growth factor variant III (EGFRvIII) is the most common alteration of the epidermal growth factor (EGF) receptor found in human tumors. It is commonly expressed in glioblastoma multiforme (GBM), where it was initially identified. This constitutively active mutant receptor leads to unregulated growth, survival, invasion, and angiogenesis in cells that express it. EGFRvIII results from an in-frame deletion of exons 2 to 7 resulting in the fusion of exon 1 to exon 8 of the EGF receptor gene creating a novel glycine at the junction in the extracellular amino terminal domain. The juxtaposition of ordinarily distant amino acids in combination with the glycine that forms at the junction leads to a novel tumor-specific epitope that would make an ideal tumor-specific target. A peptide derived from the EGFRvIII junction can be used as a vaccine to prevent or induce the regression of tumors. This peptide vaccine has now proceeded to phase 1 and 2 clinical trials where it has been highly successful and is now undergoing investigation in a larger human clinical trial for patients who have newly diagnosed GBM. In this article, the authors discuss the preclinical data that led to the human trials and the exciting preliminary data from the clinical trials.

  View details for DOI 10.1016/j.nec.2009.08.004

  View details for Web of Science ID 000278059500009

  View details for PubMedID 19944969

• Radiosurgery for glomus jugulare: history and recent progress NEUROSURGICAL FOCUS Guss, Z. D., Batra, S., Li, G., Chang, S. D., Parsa, A. T., Rigamont, D., Kleinberg, L., Lim, M. 2009; 27 (6)

  Abstract

  In this article the authors review the literature for recent studies of radiosurgical treatment for glomus jugulare. These studies demonstrate that radiosurgery results in similar glomus jugulare tumor control and a superior morbidity profile compared with surgical treatment. In addition, patients treated with radiosurgery usually remain stable clinically or improve. Given the indolent nature of these tumors, however, more follow-up is required to ensure that the immediate benefits are lasting. These preliminary reports demonstrate that the use of radiosurgery as a primary treatment for glomus jugulare should be extended to encompass more of the patients who are currently assigned to microsurgical treatment.

  View details for DOI 10.3171/2009.9.FOCUS09195

  View details for Web of Science ID 000272301500007

  View details for PubMedID 19951058

• CYBERKNIFE FOR BRAIN METASTASES OF MALIGNANT MELANOMA AND RENAL CELL CARCINOMA NEUROSURGERY Hara, W., Tran, P., Li, G., Su, Z., Puataweepong, P., Adler, J. R., Soltys, S. G., Chang, S. D., Gibbs, I. C. 2009; 64 (2): A26-A32

  Abstract

  To evaluate the efficacy of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) for patients with brain metastases of malignant melanoma and renal cell carcinoma.We conducted a retrospective review of all patients treated by image-guided radiosurgery at our institution between March 1999 and December 2005. Sixty-two patients with 145 brain metastases of renal cell carcinoma or melanoma were identified.The median follow-up period was 10.5 months. Forty-four patients had malignant melanoma, and 18 patients had renal cell carcinoma. The median age was 57 years, and patients were classified as recursive partitioning analysis Class 1 (6 patients), 2 (52 patients) or 3 (4 patients). Thirty-three patients had been treated systemically with either chemotherapy or immunotherapy, and 33 patients were taking corticosteroids at the time of treatment. The mean tumor volume was 1.47 mL (range, 0.02-35.7 mL), and the mean prescribed dose was 20 Gy (range, 14-24 Gy). The median survival after SRS was 8.3 months. Actuarial survival at 6 and 12 months was 57 and 37%, respectively. On multivariate analysis, Karnofsky Performance Scale score (P < 0.01) and previous immunotherapy/clinical trial (P = 0.01) significantly affected overall survival. One-year intracranial progression-free survival was 38%, and local control was 87%. Intracranial control was impacted by whole-brain radiotherapy (P = 0.01), previous chemotherapy (P = 0.01), and control of the primary at the time of SRS (P = 0.02). Surgical resection had no effect on intracranial or local control. Radiographic evidence of radiation necrosis developed in 4 patients (6%).CyberKnife radiosurgery provided excellent local control with acceptable toxicity in patients with melanoma or renal cell brain metastases. Initial SRS alone appeared to be a reasonable option, as survival was dictated by systemic disease.

  View details for DOI 10.1227/01.NEU.0000339118.55334.EA

  View details for Web of Science ID 000262797700009

  View details for PubMedID 19165071

• Perioperative management of ventriculoperitoneal shunts during abdominal surgery SURGICAL NEUROLOGY Li, G., Dutta, S. 2008; 70 (5): 492-497

  Abstract

  Patients with ventriculoperitoneal shunts (VPSs) inserted for a variety of disorders may subsequently undergo gastrointestinal or urologic operations, and surgeons must determine the appropriate perioperative management to minimize the risk for shunt malfunction or infection. There is currently no established set of guidelines for this scenario. The objective of this study was to determine the risks and standard of practice for patients with VPSs undergoing abdominal surgery.A retrospective review of the charts of patients with VPSs who underwent abdominal or urologic surgery at the Stanford University Medical Center between 1995 and 2003 was performed. Data regarding type of abdominal surgery, level of contamination, choice of antibiotic therapy, perioperative management of the VPS, and outcomes were obtained.Twenty-six patient charts were reviewed, for a total of 39 operations (5 urologic, 23 upper gastrointestinal, and 11 lower gastrointestinal). Of these, 3 were clean, 34 were clean-contaminated, and 2 were dirty operations. Seven cases were laparoscopic, whereas 32 were open. Thirty-four cases required opening the bowel or urologic system. No patient had preoperative shunt externalization. All except one patient received pre- and postoperative antibiotics, but the duration and type of antibiotics were widely variable. The remaining patient had an inguinal hernia repair and received only one preoperative dose of cephalexin. Purulent fluid was found in 2 cases. One VPS found lying in purulent material next to an anastomotic leak was externalized and subsequently revised. However, in another patient, a VPS found lying next to a purulent jejunal tear was not externalized. This patient returned 2 months later with a VPS malfunction. In the remaining 35 cases, no VPS infection or malfunction was noted over 2 to 10 years of follow-up.The data suggest that there is minimal risk for VPS malfunction or infection among patients undergoing routine clean and clean-contaminated abdominal and urologic surgeries. Patients with VPSs undergoing these operations do not need externalization of their shunt. None of the patients in this study had a contaminated procedure. For dirty procedures, surgeons should opt to externalize the shunt. Future studies will aim to better standardize the perioperative management of VPSs during abdominal surgery.

  View details for DOI 10.1016/j.surneu.2007.08.050

  View details for Web of Science ID 000270846100009

  View details for PubMedID 18207538

• EGF receptor variant III as a target antigen for tumor immunotherapy EXPERT REVIEW OF VACCINES Li, G., Wong, A. J. 2008; 7 (7): 977-985

  Abstract

  The EGF receptor (EGFR) is the first tyrosine kinase receptor ever cloned and remains at the forefront of targeted therapies against cancer. Currently, there are four US FDA-approved drugs and several more in Phase III studies that target the EGFR. These drugs, while resulting in some dramatic remissions, have not resulted in strong nor consistent improvements in survival. EGFR variant III (EGFRvIII) is the most common variant of the EGFR and is present in many different cancer types but not in normal tissue. It results from the fusion of exon 1 to exon 8 of the EGFR gene, which results in a novel glycine at the junction. This mutant receptor is constitutively active in these tumors and can lead directly to cancer phenotypes due to its oncogenic properties. EGFRvIII is an attractive target antigen for cancer immunotherapy because it is not expressed in normal tissue and because cells producing EGFRvIII have an enhanced capacity for dysregulated growth, survival, invasion and angiogenesis. In this review, we will discuss preclinical and clinical data from studies using EGFRvIII as the target antigen for immunotherapy, with a focus on the potential for greatly improved survival for patients diagnosed with glioblastoma multiforme.

  View details for DOI 10.1586/14760584.7.7.977

  View details for Web of Science ID 000259334600016

  View details for PubMedID 18767947

• Effects of age and Comorbidities on complication rates and adverse outcomes after lumbar laminectomy in elderly patients SPINE Li, G., Patil, C. G., Lad, S. P., Ho, C., Tian, W., Boakye, M. 2008; 33 (11): 1250-1255

  Abstract

  This is a retrospective cohort study using the National Inpatient Sample database.The objective is to report mortality and complications after lumbar laminectomy in the elderly.As the population continues to age in the United States, it is important to consider the surgical complications and outcomes in the elderly. A review of the literature reveals controversy over the safety of lumbar laminectomy in the elderly and disagreement over estimates of risks in this population.Outcome measures were abstracted from the National Inpatient Sample. Multivariate analysis was performed to analyze the effect of patient and hospital characteristics on outcome measures.A total of 471,215 patients underwent lumbar laminectomy without fusion for lumbar stenosis from 1993 to 2002. The in-hospital mortality rate was 0.17%, and the complication rate was 12.17%. Postoperative hemorrhage or hematoma (5.2%) and nonspecific renal complications (2.8%) were the most common complications. Complication and mortality rates increased with age and comorbidities with an 18.9% complication rate and 1.4% mortality rate in patients over the age of 85 with 3 or more comorbidities, 14.7% complication rate and 0.22% mortality rate in patients over 85 with no comorbidities, and only a 6% complication rate and 0.05% mortality rate in patient between 18 and 44 with no comorbidities. Multivariate analysis revealed increased odds of mortality with increasing number of comorbidities and complications in the greater than 85 year age group. Increasing age, number of comorbidities, complication rate, and female sex also increased the odds of discharge to institution other than home.Elderly patients with comorbidities are at a higher risk for complications and adverse outcome after lumbar spine surgery. The effects of age and comorbidities on patient outcomes have been quantified. This information is critical in counseling elderly patients about the risk of surgery in their age group.

  View details for Web of Science ID 000255829200014

  View details for PubMedID 18469700

• Intracranial hypotension from intrathecal baclofen pump insertion STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Lad, S. P., Li, G., Lin, S., Henderson, J. M. 2008; 86 (2): 75-79

  Abstract

  Intracranial hypotension is a syndrome of low cerebrospinal fluid pressure with a variable clinical presentation ranging from postural headaches to coma. A number of neuroradiologic techniques are now available to aid in the diagnosis of this syndrome (CT, MRI, radioisotope cisternography and CT myelography), each showing specific radiographic abnormalities. In this report, we present a case of intracranial hypotension secondary to baclofen pump placement. We review the major clinical findings, neuroimaging abnormalities, key diagnostic features as well as treatment options.

  View details for DOI 10.1159/000112427

  View details for Web of Science ID 000253247300002

  View details for PubMedID 18073519

• CyberKnife radiosurgical rhizotomy for the treatment of atypical trigeminal nerve pain. Neurosurgical focus Patil, C. G., Veeravagu, A., Bower, R. S., Li, G., Chang, S. D., Lim, M., Adler, J. R. 2007; 23 (6): E9-?

  Abstract

  Patients with atypical trigeminal neuralgia (TN) have unilateral pain in the trigeminal distribution that is dull, aching, or burning in nature and is constant or nearly constant. Studies of most radiosurgical and surgical series have shown lower response rates in patients with atypical TN. This study represents the first report of the treatment of atypical TN with frameless CyberKnife stereotactic radiosurgery (SRS).Between 2002 and 2007, 7 patients that satisfied the criteria for atypical TN and underwent SRS were included in our study. A 6-8-mm segment of the trigeminal nerve was targeted, excluding the proximal 3 mm at the brainstem. All patients were treated in a single session with a median maximum dose of 78 Gy and a median marginal dose of 64 Gy.Outcomes in 7 patients with a mean age of 61.6 years and a median follow-up of 20 months are reported. Following SRS, 4 patients had complete pain relief, 2 had minimal pain relief with some decrease in the intensity of their pain, and 1 patient experienced no pain relief. Pain relief was reported within 1 week of SRS in 4 patients and at 4 months in 2 patients. After a median follow-up of 28 months, pain did not recur in any of the 4 patients who had reported complete pain relief. Complications after SRS included bothersome numbness in 3 patients and significant dysesthesias in 1 patient.The authors have previously reported a 90% rate of excellent pain relief in patients with classic TN treated with CyberKnife SRS. Compared with patients with classic TN, patients with atypical TN have a lower rate of pain relief. Nevertheless, the nearly 60% rate of success after SRS achieved in this study is still comparable to or better than results achieved with any other treatment modality for atypical TN.

  View details for PubMedID 18081486

• Irradiation of glomus jugulare tumors: a historical perspective. Neurosurgical focus Li, G., Chang, S., Adler, J. R., Lim, M. 2007; 23 (6): E13-?

  Abstract

  Glomus jugulare tumors are rare, slow-growing vascular lesions that arise from the chief cells of the paraganglia within the jugular bulb. They can be associated with the tympanic branch of the glossopharyngeal nerve (Jacobsen nerve) or the auricular branch of the vagus nerve (Arnold nerve) and are also referred to as chemodectomas or nonchromaffin paragangliomas. Optimal treatment of these histologically benign tumors remains controversial. Surgery remains the treatment of choice, but can carry high morbidity rates. External-beam radiation was originally used for subtotal resections and in patients who were poor surgical candidates; however, radiosurgery has recently been introduced as an effective and safe treatment option for patients with these tumors. In this article the authors discuss the history of radiation therapy for glomus jugulare tumors, focusing on recent radiosurgical results.

  View details for PubMedID 18081478

• CyberKnife rhizotomy for facetogenic back pain: a pilot study. Neurosurgical focus Li, G., Patil, C., Adler, J. R., Lad, S. P., Soltys, S. G., Gibbs, I. C., Tupper, L., Boakye, M. 2007; 23 (6): E2-?

  Abstract

  By targeting the medial branches of the dorsal rami, radiofrequency ablation and facet joint injections can provide temporary amelioration of facet joint-producing (or facetogenic) back pain. The authors used CyberKnife radiosurgery to denervate affected facet joints with the goal of obtaining a less invasive yet more thorough and durable antinociceptive rhizotomy.Patients with refractory low-back pain, in whom symptoms are temporarily resolved by facet joint injections, were eligible. The patients were required to exhibit positron emission tomography-positive findings at the affected levels. Radiosurgical rhizotomy, targeting the facet joint, was performed in a single session with a marginal prescription dose of 40 Gy and a maximal dose of 60 Gy.Seven facet joints in 5 patients with presumptive facetogenic back pain underwent CyberKnife lesioning. The median follow-up was 9.8 months (range 3-16 months). The mean planning target volume was 1.7 cm(3) (range 0.9-2.7 cm(3)). A dose of 40 Gy was prescribed to a mean isodose line of 79% (range 75-80%). Within 1 month of radiosurgery, improvement in pain was observed in 3 of the 5 patients with durable responses at 16, 12, and 6 months, respectively, of follow-up. Two patients, after 12 and 3 months of follow-up, have neither improved nor worsened. No patient has experienced acute or late-onset toxicity.These preliminary results suggest that CyberKnife radiosurgery could be a safe, effective, and non-invasive alternative to radiofrequency ablation for managing facetogenic back pain. No patient suffered recurrent symptoms after radiosurgery. It is not yet known whether pain relief due to such lesions will be more durable than that produced by alternative procedures. A larger series of patients with long-term follow-up is ongoing.

  View details for PubMedID 18081475

• Robotic radiosurgery for the treatment of radioresistant brain metastases 7th Congress of the European-Association-for-Neuro-Oncology (EANO) Hara, W., Li, G., Puataweepong, P., Adler, J., Chang, S., Gibbs, I. C. OXFORD UNIV PRESS INC. 2006: 486–86

  View details for Web of Science ID 000240877301365

• Carotid and vertebral rete mirabile in man presenting with intraparenchymal hemorrhage: a case report. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Li, G., Jayaraman, M. V., Lad, S. P., Adler, J., Do, H., Steinberg, G. K. 2006; 15 (5): 228-231

  Abstract

  Carotid and vertebral rete mirabile is an unusual segmental regression of both the cavernous carotid artery and transdural vertebral arteries with a network of collateral vessels seen rarely in human beings. We present a 57-year-old woman with carotid and vertebral rete mirabile who presented with an acute intraparenchymal hemorrhage. The majority of patients present with subarachnoid hemorrhage or ischemic stroke. This is the first case of a non-Asian patient presenting with an intraparenchymal hemorrhage. In this case report, we describe the clinical and angiographic features of this unusual entity.

  View details for PubMedID 17904080

• Cerebral perfusion imaging in vasospasm. Neurosurgical focus Lad, S. P., Guzman, R., Kelly, M. E., Li, G., Lim, M., Lovbald, K., Steinberg, G. K. 2006; 21 (3): E7-?

  Abstract

  Vasospasm following cerebral aneurysm rupture is one of the most devastating sequelae and the most common cause of delayed ischemic neurological deficit (DIND). Because vasospasm also is the most common cause of morbidity and mortality in patients who survive the initial bleeding episode, it is imperative not only to diagnose the condition but also to predict which patients are likely to become symptomatic. The exact pathophysiology of vasospasm is complex and incompletely elucidated. Early recognition of vasospasm is essential because the timely use of several therapeutic interventions can counteract this disease and prevent the occurrence of DIND. However, the prompt implementation of these therapies depends on the ability to predict impending vasospasm or to diagnose it at its early stages. A number of techniques have been developed during the past several decades to evaluate cerebral perfusion, including positron emission tomography, xenon-enhanced computed tomography, single-photon emission computed tomography, perfusion- and diffusion-weighted magnetic resonance imaging, and perfusion computed tomography. In this article, the authors provide a general overview of the currently available perfusion imaging techniques and their applications in treating vasospasm after a patient has suffered a subarachnoid hemorrhage. The use of cerebral perfusion imaging techniques for the early detection of vasospasm is becoming more common and may provide opportunities for early therapeutic intervention to counteract vasospasm in its earliest stages and prevent the occurrence of DINDs.

  View details for PubMedID 17029346

• Surfactant protein-A-deficient mice display an exaggerated early inflammatory response to a beta-resistant strain of influenza A virus AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY Li, G., Siddiqui, J., Hendry, M., Akiyama, J., Edmondson, J., Brown, C., Allen, L., Levitt, S., Poulain, F., Hawgood, S. 2002; 26 (3): 277-282

  Abstract

  Surfactant protein (SP)-A is a member of the collectin family of proteins. In vitro, SP-A binds influenza A virus (IAV), neutralizes infectivity, and enhances uptake by macrophages. SP-D also binds and neutralizes certain strains of IAV. To determine if SP-A has a role in protecting the intact animal against IAV infection, we inoculated gene-targeted SP-A-deficient mice (-/-) and littermate controls (+/+) with either saline or increasing doses of an IAV strain that binds SP-A but not SP-D. IAV was more virulent in SP-A-/- compared with +/+ mice, with a significantly lower mean lethal dose (LD(50)) and significantly greater weight loss during infection. SP-A-/- mice also had increased airway epithelial injury and more alveolar cellular infiltrates than +/+ mice. On Day 2, SP-A-/- mice had more neutrophils and higher MIP-2 levels in the lung than +/+ mice. We conclude the altered host response and increased susceptibility to X-79Delta167 infection in SP-A-/- mice reflects a protective role for SP-A in regulating the host response to IAV. Because the recovery of virus from lung homogenates on Days 2 and 6 after inoculation was comparable in -/- and +/+ mice, we speculate SP-A reduces IAV virulence independently of direct viral neutralization.

  View details for Web of Science ID 000174222800006

  View details for PubMedID 11867335

• GM-CSF mediates alveolar macrophage proliferation and type II cell hypertrophy in SP-D gene-targeted mice AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY Hawgood, S., Akiyama, J., Brown, C., Allen, L., Li, G., Poulain, F. R. 2001; 280 (6): L1148-L1156

  Abstract

  Mice deficient in surfactant protein (SP) D develop increased surfactant pool sizes and dramatic changes in alveolar macrophages and type II cells. To test the hypothesis that granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates alveolar macrophage proliferation and activation and the type II cell hypertrophy seen in SP-D null mice, we bred SP-D and GM-CSF gene-targeted mice to obtain littermate double null, single null, and wild-type mice. Bronchoalveolar lavage levels of phospholipid, protein, SP-D, SP-A, and GM-CSF were measured from 1 to 4 mo. There was an approximately additive accumulation of phospholipid, total protein, and SP-A at each time point. Microscopy showed normal macrophage number and morphology in GM-CSF null mice, numerous giant foamy macrophages and hypertrophic type II cells in SP-D null mice, and large but not foamy macrophages and mostly normal type II cells in double null mice. These results suggest that the mechanisms underlying the alveolar surfactant accumulation in the SP-D-deficient and GM-CSF-deficient mice are different and that GM-CSF mediates some of the macrophage and type II cell changes seen in SP-D null mice.

  View details for Web of Science ID 000168621700009

  View details for PubMedID 11350793