Jonathon J. Parker, MD, PhD

All Publications

• Interobserver Agreement for the CT Severity Grading Scales for Acute Traumatic Brain Injury (TBI). Journal of neurotrauma Creeden, S., Ding, V., Parker, J. J., Jiang, B., Li, Y., Lanzman, B., Trinh, A., Khalaf, A., Wolman, D., Halpern, C., Boothroyd, D., Wintermark, M. 2020

  Abstract

  PURPOSE: To determine the interobserver variability among providers of different specialties and levels of experience across five established computed tomography (CT) scoring systems for acute traumatic brain injury (TBI).MATERIALS & METHODS: One hundred cases were selected at random from a retrospective population of adult patients transported to our emergency department and subjected to a non-contrast head CT due to suspicion for TBI. Eight neuroradiologists and neurosurgeons in trainee (residents and fellows) and attending roles independently scored each non-contrast head CT scan on the Marshall, Rotterdam, Helsinki, Stockholm and NeuroImaging Radiological Interpretation System (NIRIS) head CT scales. Interobserver variability of scale scores - overall and by specialty and level of training - was quantified using the intraclass correlation coefficient (ICC), and agreement with respect to National Institutes of Health Common Data Elements (NIH CDEs) was assessed using Cohen's kappa.RESULTS: All CT severity scoring systems showed high interobserver agreement as evidenced by high ICCs, ranging from 0.75 - 0.89. For all scoring systems, neuroradiologists (ICC range from 0.81 - 0.94) tended to have higher interobserver agreement than neurosurgeons (ICC range from 0.63 - 0.76). For all scoring systems, attendings (ICC range from 0.76 - 0.89) had similar interobserver agreement to trainees (ICC range from 0.73 - 0.89). Agreement with respect to NIH CDEs was high for ascertaining presence/absence of hemorrhage, skull fracture, and mass effect, with estimated kappa statistics of least 0.89.CONCLUSION: Acute TBI CT scoring systems demonstrate high interobserver agreement. These results provide scientific rigor for future use of these systems for the classification of acute TBI.

  View details for DOI 10.1089/neu.2019.6871

  View details for PubMedID 31996087

• Postoperative outcomes following pediatric intracranial electrode monitoring: A case for stereoelectroencephalography (SEEG). Epilepsy & behavior : E&B Kim, L. H., Parker, J. J., Ho, A. L., Pendharkar, A. V., Sussman, E. S., Halpern, C. H., Porter, B., Grant, G. A. 2020; 104 (Pt A): 106905

  Abstract

  For patients with medically refractory epilepsy, intracranial electrode monitoring can help identify epileptogenic foci. Despite the increasing utilization of stereoelectroencephalography (SEEG), the relative risks or benefits associated with the technique when compared with the traditional subdural electrode monitoring (SDE) remain unclear, especially in the pediatric population. Our aim was to compare the outcomes of pediatric patients who received intracranial monitoring with SEEG or SDE (grids and strips).We retrospectively studied 38 consecutive pediatric intracranial electrode monitoring cases performed at our institution from 2014 to 2017. Medical/surgical history and operative/postoperative records were reviewed. We also compared direct inpatient hospital costs associated with the two procedures.Stereoelectroencephalography and SDE cohorts both showed high likelihood of identifying epileptogenic zones (SEEG: 90.9%, SDE: 87.5%). Compared with SDE, SEEG patients had a significantly shorter operative time (118.7 versus 233.4?min, P?

  View details for DOI 10.1016/j.yebeh.2020.106905

  View details for PubMedID 32028127

• Anatomic and Thermometric Analysis of Cranial Nerve Palsy after Laser Amygdalohippocampotomy for Mesial Temporal Lobe Epilepsy. Operative neurosurgery (Hagerstown, Md.) Huang, Y., Leung, S. A., Parker, J. J., Ho, A. L., Wintermark, M., Patel, S. H., Pauly, K. B., Kakusa, B. W., Beres, S. J., Henderson, J. M., Grant, G. A., Halpern, C. H. 2019

  Abstract

  BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive therapy for treating medication-resistant mesial temporal lobe epilepsy. Cranial nerve (CN) palsy has been reported as a procedural complication, but the mechanism of this complication is not understood.OBJECTIVE: To identify the cause of postoperative CN palsy after LITT.METHODS: Four medial temporal lobe epilepsy patients with CN palsy after LITT were identified for comparison with 22 consecutive patients with no palsy. We evaluated individual variation in the distance between CN III and the uncus, and CN IV and the parahippocampal gyrus using preoperative T1- and T2-weighted magnetic resonance (MR) images. Intraoperative MR thermometry was used to estimate temperature changes.RESULTS: CN III (n=2) and CN IV palsies (n=2) were reported. On preoperative imaging, the majority of identified CN III (54%) and CN IV (43%) were located within 1 to 2 mm of the uncus and parahippocampal gyrus tissue border, respectively. Affected CN III and CN IV were more likely to be found<1 mm of the tissue border (PCNIII=.03, PCNIV<.01; chi-squared test). Retrospective assessment of thermal profile during ablation showed higher temperature rise along the mesial temporal lobe tissue border in affected CNs than unaffected CNs after controlling for distance (12.9°C vs 5.8°C; P=.03; 2-sample t-test).CONCLUSION: CN palsy after LITT likely results from direct heating of the respective CN running at extreme proximity to the mesial temporal lobe. Low-temperature thresholds set at the border of the mesial temporal lobe in patients whose CNs are at close proximity may reduce this risk.

  View details for DOI 10.1093/ons/opz279

  View details for PubMedID 31555820

• Simulating Episode-Based Bundled Payments for Cranial Neurosurgical Procedures. Neurosurgery Medress, Z., Ugiliweneza, B., Parker, J., Wang, D., Burton, E., Boakye, M., Skirboll, S. 2019

  Abstract

  BACKGROUND: Episode-based bundled payments were introduced by Medicare in 2013 as the Bundled Payments for Care Improvement (BPCI) in order to improve care coordination and cost efficiency. BPCI has not yet been applied to cranial neurosurgical procedures.OBJECTIVE: To determine projected values of episode-based bundled payments when applied to common cranial neurosurgical procedures using retrospective data from a large database.METHODS: We performed a large retrospective observational study using the MarketScan administrative database to project bundled payment payments for 4 groups of common cranial neurosurgical procedures.RESULTS: We identified 15 276 procedures that met our inclusion criteria. We observed significant variability between groups, with 90-d bundle projected payments ranging from $58,200 for craniotomy for meningioma to $102,073 for craniotomy for malignant glioma. We also found significant variability in projected bundled payments within each class of operation. On average, payment for the index hospitalization accounted for 85% of projected payments for a 30-d bundle and 70.5% of projected payments for a 90-d bundle. Multivariable analysis showed that hospital readmission, discharge to postacute care facilities, venous-thrombo-embolism, medical comorbidities, adjuvant therapies, and payer status significantly contributed to projected cranial bundle payments.CONCLUSION: For the first time, to our knowledge, we project the values of episode-based bundled payments for common vascular and tumor cranial operations. As previously identified in orthopedic procedures, there is significant variability in total bundle payments within each cranial procedure. Compared to spine and orthopedic procedures, postdischarge care significantly impacts total bundle payments in cranial neurosurgery.

  View details for DOI 10.1093/neuros/nyz353

  View details for PubMedID 31515558

• Robot-assisted versus manual navigated stereoelectroencephalography in adult medically-refractory epilepsy patients. Epilepsy research Kim, L. H., Feng, A. Y., Ho, A. L., Parker, J. J., Kumar, K. K., Chen, K. S., Grant, G. A., Henderson, J. M., Halpern, C. H. 2019; 159: 106253

  Abstract

  Stereoelectroencephalography (SEEG) has experienced a recent growth in adoption for epileptogenic zone (EZ) localization. Advances in robotics have the potential to improve the efficiency and safety of this intracranial seizure monitoring method. We present our institutional experience employing robot-assisted SEEG and compare its operative efficiency, seizure reduction outcomes, and direct hospital costs with SEEG performed without robotic assistance using navigated stereotaxy.We retrospectively identified 50 consecutive adult SEEG cases at our institution in this IRB-approved study, of which 25 were navigated with image guidance (hereafter referred to as "navigated") (02/2014-10/2016) and 25 were robot-assisted (09/2016-12/2017). A thorough review of medical/surgical history and operative records with imaging and trajectory plans was done for each patient. Direct inpatient costs related to each technique were compared.Most common seizure etiologies for patients undergoing navigated and robot-assisted SEEG included non-lesional and benign temporal lesions. Despite having a higher mean number of leads-per-patient (10.2?±?3.5 versus 7.2?±?2.6, P?=?0.002), robot-assisted cases had a significantly shorter mean operative time than navigated cases (125.5±48.5 versus 173.4±84.3?min, P?=?0.02). Comparison of robot-assisted cases over the study interval revealed no significant difference in mean operative time (136.4±51.4?min for the first ten cases versus 109.9±75.8?min for the last ten cases, P?=?0.25) and estimated operative time-per-lead (13.4±6.0?min for the first ten cases versus 12.9±7.7?min for the last ten cases, P?=?0.86). The mean depth, radial, target, and entry point errors for robot-assisted cases were 2.12±1.89, 1.66±1.58, 3.05±2.02 mm, and 1.39?±?0.75?mm, respectively. The two techniques resulted in equivalent EZ localization rate (navigated 88 %, robot-assisted 96 %, P?=?0.30). Common types of epilepsy surgery performed consisted of implantation of responsive neurostimulation (RNS) device (56 %), resection (19.1 %), and laser ablation (23.8 %) for navigated SEEG. For robot-assisted SEEG, either RNS implantation (68.2 %) or laser ablation (22.7 %) were performed or offered. A majority of navigated and robot-assisted patients who underwent epilepsy surgery achieved either Engel Class I (navigated 36.8 %, robot-assisted 31.6 %) or II (navigated 36.8 %, robot-assisted 15.8 %) outcome with no significant difference between the groups (P?=?0.14). Direct hospital cost for robot-assisted SEEG was 10 % higher than non-robotic cases.This single-institutional study suggests that robotic assistance can enhance efficiency of SEEG without compromising safety or precision when compared to image guidance only. Adoption of this technique with uniform safety and efficacy over a short period of time is feasible with favorable epilepsy outcomes.

  View details for DOI 10.1016/j.eplepsyres.2019.106253

  View details for PubMedID 31855826

• Adjunctive repetitive transcranial magnetic stimulation delivers superior quality of life for focal epilepsy compared to anti-epileptic drugs: A meta-analytic utility prediction study. Brain stimulation Mahajan, U. V., Parker, J. J., Williams, N. R., Bhati, M. T., Ku, S., Grant, G., Fisher, R. S., Stein, S. C., Halpern, C. H. 2019

  View details for DOI 10.1016/j.brs.2019.12.006

  View details for PubMedID 31874798

• Targeted genomic CRISPR-Cas9 screen identifies MAP4K4 as essential for glioblastoma invasion. Scientific reports Prolo, L. M., Li, A., Owen, S. F., Parker, J. J., Foshay, K., Nitta, R. T., Morgens, D. W., Bolin, S., Wilson, C. M., Vega L, J. C., Luo, E. J., Nwagbo, G., Waziri, A., Li, G., Reimer, R. J., Bassik, M. C., Grant, G. A. 2019; 9 (1): 14020

  Abstract

  Among high-grade brain tumors, glioblastoma is particularly difficult to treat, in part due to its highly infiltrative nature which contributes to the malignant phenotype and high mortality in patients. In order to better understand the signaling pathways underlying glioblastoma invasion, we performed the first large-scale CRISPR-Cas9 loss of function screen specifically designed to identify genes that facilitate cell invasion. We tested 4,574 genes predicted to be involved in trafficking and motility. Using a transwell invasion assay, we discovered 33 genes essential for invasion. Of the 11 genes we selected for secondary testing using a wound healing assay, 6 demonstrated a significant decrease in migration. The strongest regulator of invasion was mitogen-activated protein kinase 4 (MAP4K4). Targeting of MAP4K4 with single guide RNAs or a MAP4K4 inhibitor reduced migration and invasion in vitro. This effect was consistent across three additional patient derived glioblastoma cell lines. Analysis of epithelial-mesenchymal transition markers in U138 cells with lack or inhibition of MAP4K4 demonstrated protein expression consistent with a non-invasive state. Importantly, MAP4K4 inhibition limited migration in a subset of human glioma organotypic slice cultures. Our results identify MAP4K4 as a novel potential therapeutic target to limit glioblastoma invasion.

  View details for DOI 10.1038/s41598-019-50160-w

  View details for PubMedID 31570734

• Stereotactic laser ablation for completion corpus callosotomy. Journal of neurosurgery. Pediatrics Huang, Y., Yecies, D., Bruckert, L., Parker, J. J., Ho, A. L., Kim, L. H., Fornoff, L., Wintermark, M., Porter, B., Yeom, K. W., Halpern, C. H., Grant, G. A. 2019: 1?9

  Abstract

  Completion corpus callosotomy can offer further remission from disabling seizures when a prior partial corpus callosotomy has failed and residual callosal tissue is identified on imaging. Traditional microsurgical approaches to section residual fibers carry risks associated with multiple craniotomies and the proximity to the medially oriented motor cortices. Laser interstitial thermal therapy (LITT) represents a minimally invasive approach for the ablation of residual fibers following a prior partial corpus callosotomy. Here, the authors report clinical outcomes of 6 patients undergoing LITT for completion corpus callosotomy and characterize the radiological effects of ablation.A retrospective clinical review was performed on a series of 6 patients who underwent LITT completion corpus callosotomy for medically intractable epilepsy at Stanford University Medical Center and Lucile Packard Children's Hospital at Stanford between January 2015 and January 2018. Detailed structural and diffusion-weighted MR images were obtained prior to and at multiple time points after LITT. In 4 patients who underwent diffusion tensor imaging (DTI), streamline tractography was used to reconstruct and evaluate tract projections crossing the anterior (genu and rostrum) and posterior (splenium) parts of the corpus callosum. Multiple diffusion parameters were evaluated at baseline and at each follow-up.Three pediatric (age 8-18 years) and 3 adult patients (age 30-40 years) who underwent completion corpus callosotomy by LITT were identified. Mean length of follow-up postoperatively was 21.2 (range 12-34) months. Two patients had residual splenium, rostrum, and genu of the corpus callosum, while 4 patients had residual splenium only. Postoperative complications included asymptomatic extension of ablation into the left thalamus and transient disconnection syndrome. Ablation of the targeted area was confirmed on immediate postoperative diffusion-weighted MRI in all patients. Engel class I-II outcomes were achieved in 3 adult patients, whereas all 3 pediatric patients had Engel class III-IV outcomes. Tractography in 2 adult and 2 pediatric patients revealed time-dependent reduction of fractional anisotropy after LITT.LITT is a safe, minimally invasive approach for completion corpus callosotomy. Engel outcomes for completion corpus callosotomy by LITT were similar to reported outcomes of open completion callosotomy, with seizure reduction primarily observed in adult patients. Serial DTI can be used to assess the presence of tract projections over time but does not classify treatment responders or nonresponders.

  View details for DOI 10.3171/2019.5.PEDS19117

  View details for PubMedID 31374542

• Intratumoral heterogeneity of endogenous tumor cell invasive behavior in human glioblastoma. Scientific reports Parker, J. J., Canoll, P., Niswander, L., Kleinschmidt-DeMasters, B. K., Foshay, K., Waziri, A. 2018; 8 (1): 18002

  Abstract

  Intratumoral genetic heterogeneity is a widely accepted characteristic of human cancer, including the most common primary malignant brain tumor, glioblastoma. However, the variability in biological behaviors amongst cells within individual tumors is not well described. Invasion into unaffected brain parenchyma is one such behavior, and a leading mechanism of tumor recurrence unaddressed by the current therapeutic armamentarium. Further, providing insight into variability of tumor cell migration within individual tumors may inform discovery of novel anti-invasive therapeutics. In this study, ex vivo organotypic slice cultures from EGFR-wild type and EGFR-amplified patient tumors were treated with the EGFR inhibitor gefitinib to evaluate potential sub-population restricted intratumoral drug-specific responses. High-resolution time-lapse microscopy and quantitative path tracking demonstrated migration of individual cells are punctuated by intermittent bursts of movement. Elevation of population aggregate mean speeds were driven by subpopulations of cells exhibiting frequent high-amplitude bursts, enriched within EGFR-amplified tumors. Treatment with gefitinib specifically targeted high-burst cell subpopulations only in EGFR-amplified tumors, decreasing bursting frequency and amplitude. We provide evidence of intratumoral subpopulations of cells with enhanced migratory behavior in human glioblastoma, selectively targeted via EGFR inhibition. These data justify use of direct human tumor slice cultures to investigate patient-specific therapies designed to limit tumor invasion.

  View details for PubMedID 30573757

• A Human Glioblastoma Organotypic Slice Culture Model for Study of Tumor Cell Migration and Patient-specific Effects of Anti-Invasive Drugs JOVE-JOURNAL OF VISUALIZED EXPERIMENTS Parker, J. J., Lizarraga, M., Waziri, A., Foshay, K. M. 2017

  Abstract

  Glioblastoma (GBM) continues to carry an extremely poor clinical prognosis despite surgical, chemotherapeutic, and radiation therapy. Progressive tumor invasion into surrounding brain parenchyma represents an enduring therapeutic challenge. To develop anti-migration therapies for GBM, model systems that provide a physiologically relevant background for controlled experimentation are essential. Here, we present a protocol for generating slice cultures from human GBM tissue obtained during surgical resection. These cultures allow for ex vivo experimentation without passaging through animal xenografts or single cell cultures. Further, we describe the use of time-lapse laser scanning confocal microscopy in conjunction with cell tracking to quantitatively study the migratory behavior of tumor cells and associated response to therapeutics. Slices are reproducibly generated within 90 min of surgical tissue acquisition. Retrovirally-mediated fluorescent cell labeling, confocal imaging, and tumor cell migration analyses are subsequently completed within two weeks of culture. We have successfully used these slice cultures to uncover genetic factors associated with increased migratory behavior in human GBM. Further, we have validated the model's ability to detect patient-specific variation in response to anti-migration therapies. Moving forward, human GBM slice cultures are an attractive platform for rapid ex vivo assessment of tumor sensitivity to therapeutic agents, in order to advance personalized neuro-oncologic therapy.

  View details for PubMedID 28784966

• Cost-effectiveness of focused ultrasound, radiosurgery, and DBS for essential tremor. Movement disorders Ravikumar, V. K., Parker, J. J., Hornbeck, T. S., Santini, V. E., Pauly, K. B., Wintermark, M., Ghanouni, P., Stein, S. C., Halpern, C. H. 2017

  Abstract

  Essential tremor remains a very common yet medically refractory condition. A recent phase 3 study demonstrated that magnetic resonance-guided focused ultrasound thalamotomy significantly improved upper limb tremor. The objectives of this study were to assess this novel therapy's cost-effectiveness compared with existing procedural options.Literature searches of magnetic resonance-guided focused ultrasound thalamotomy, DBS, and stereotactic radiosurgery for essential tremor were performed. Pre- and postoperative tremor-related disability scores were collected from 32 studies involving 83 magnetic resonance-guided focused ultrasound thalamotomies, 615 DBSs, and 260 stereotactic radiosurgery cases. Utility, defined as quality of life and derived from percent change in functional disability, was calculated; Medicare reimbursement was employed as a proxy for societal cost. Medicare reimbursement rates are not established for magnetic resonance-guided focused ultrasound thalamotomy for essential tremor; therefore, reimbursements were estimated to be approximately equivalent to stereotactic radiosurgery to assess a cost threshold. A decision analysis model was constructed to examine the most cost-effective option for essential tremor, implementing meta-analytic techniques.Magnetic resonance-guided focused ultrasound thalamotomy resulted in significantly higher utility scores compared with DBS (P < 0.001) or stereotactic radiosurgery (P < 0.001). Projected costs of magnetic resonance-guided focused ultrasound thalamotomy were significantly less than DBS (P < 0.001), but not significantly different from radiosurgery.Magnetic resonance-guided focused ultrasound thalamotomy is cost-effective for tremor compared with DBS and stereotactic radiosurgery and more effective than both. Even if longer follow-up finds changes in effectiveness or costs, focused ultrasound thalamotomy will likely remain competitive with both alternatives. © 2017 International Parkinson and Movement Disorder Society.

  View details for DOI 10.1002/mds.26997

  View details for PubMedID 28370272

• Frontal and occipital horn ratio is associated with multifocal intraparenchymal hemorrhages in neonatal shunted hydrocephalus. Journal of neurosurgery. Pediatrics Oushy, S., Parker, J. J., Campbell, K., Palmer, C., Wilkinson, C., Stence, N. V., Handler, M. H., Mirsky, D. M. 2017; 20 (5): 432?38

  Abstract

  OBJECTIVE Placement of a cerebrospinal fluid diversion device (i.e., shunt) is a routine pediatric neurosurgical procedure, often performed in the first weeks of life for treatment of congenital hydrocephalus. In the postoperative period, shunt placement may be complicated by subdural, catheter tract, parenchymal, and intraventricular hemorrhages. The authors observed a subset of infants and neonates who developed multifocal intraparenchymal hemorrhages (MIPH) following shunt placement and sought to determine any predisposing perioperative variables. METHODS A retrospective review of the electronic medical record at a tertiary-care children's hospital was performed for the period 1998-2015. Inclusion criteria consisted of shunt placement, age < 30 days, and available pre- and postoperative brain imaging. The following data were collected and analyzed for each case: ventricular size ratios, laboratory values, clinical presentation, shunt and valve type, and operative timing and approach. RESULTS A total of 121 neonates met the inclusion criteria for the study, and 11 patients (9.1%) had MIPH following shunt placement. The preoperative frontal and occipital horn ratio (FOR) was significantly higher in the patients with MIPH than in those without (0.65 vs 0.57, p < 0.001). The change in FOR (?FOR) after shunt placement was significantly greater in the MIPH group (0.14 vs 0.08, p = 0.04). Among neonates who developed MIPH, aqueductal stenosis was the most common etiology (45%). The type of shunt valve was associated with incidence of MIPH (p < 0.001). Preoperative clinical parameters, including head circumference, bulging fontanelle, and coagulopathy, were not significantly associated with development of MIPH. CONCLUSIONS MIPH represents an underrecognized complication of neonatal shunted hydrocephalus. Markers of severity of ventriculomegaly (FOR) and ventricular response to CSF diversion (?FOR) were significantly associated with occurrence of MIPH. Choice of shunt and etiology of hydrocephalus were also significantly associated with MIPH. After adjusting for corrected age, etiology of hydrocephalus, and shunt setting, the authors found that ?FOR after shunting was still associated with MIPH. A prospective study of MIPH prevention strategies and assessment of possible implications for patient outcomes is needed.

  View details for PubMedID 28885094

• Vocal Tremor: Novel Therapeutic Target for Deep Brain Stimulation. Brain sciences Ravikumar, V. K., Ho, A. L., Parker, J. J., Erickson-DiRenzo, E., Halpern, C. H. 2016; 6 (4)

  Abstract

  Tremulous voice is characteristically associated with essential tremor, and is referred to as essential vocal tremor (EVT). Current estimates suggest that up to 40% of individuals diagnosed with essential tremor also present with EVT, which is associated with an impaired quality of life. Traditional EVT treatments have demonstrated limited success in long-term management of symptoms. However, voice tremor has been noted to decrease in patients receiving deep brain stimulation (DBS) with the targeting of thalamic nuclei. In this study, we describe our multidisciplinary procedure for awake, frameless DBS with optimal stimulation targets as well as acoustic analysis and laryngoscopic assessment to quantify tremor reduction. Finally, we investigate the most recent clinical evidence regarding the procedure.

  View details for PubMedID 27735866

• Gefitinib selectively inhibits tumor cell migration in EGFR-amplified human glioblastoma. Neuro-oncology Parker, J. J., Dionne, K. R., Massarwa, R., Klaassen, M., Foreman, N. K., Niswander, L., Canoll, P., Kleinschmidt-Demasters, B. K., Waziri, A. 2013; 15 (8): 1048?57

  Abstract

  Tissue invasion is a hallmark of most human cancers and remains a major source of treatment failure in patients with glioblastoma (GBM). Although EGFR amplification has been previously associated with more invasive tumor behavior, existing experimental models have not supported quantitative evaluation of interpatient differences in tumor cell migration or testing of patient-specific responses to therapies targeting invasion. To explore these questions, we optimized an ex vivo organotypic slice culture system allowing for labeling and tracking of tumor cells in human GBM slice cultures.With use of time-lapse confocal microscopy of retrovirally labeled tumor cells in slices, baseline differences in migration speed and efficiency were determined and correlated with EGFR amplification in a cohort of patients with GBM. Slices were treated with gefitinib to evaluate anti-invasive effects associated with targeting EGFR.Migration analysis identified significant patient-to-patient variation at baseline. EGFR amplification was correlated with increased migration speed and efficiency compared with nonamplified tumors. Critically, gefitinib resulted in a selective and significant reduction of tumor cell migration in EGFR-amplified tumors.These data provide the first identification of patient-to-patient variation in tumor cell migration in living human tumor tissue. We found that EGFR-amplified GBM are inherently more efficient in their migration and can be effectively targeted by gefitinib treatment. These data suggest that stratified clinical trails are needed to evaluate gefitinib as an anti-invasive adjuvant for patients with EGFR-amplified GBM. In addition, these results provide proof of principle that primary slice cultures may be useful for patient-specific screening of agents designed to inhibit tumor invasion.

  View details for DOI 10.1093/neuonc/not053

  View details for PubMedID 23749785

  View details for PubMedCentralID PMC3714155

• Preoperative evaluation of pineal tumors. Neurosurgery clinics of North America Parker, J. J., Waziri, A. 2011; 22 (3): 353?58, vii-viii

  Abstract

  The role of the neurosurgeon is critical for initiating preoperative evaluation and care for pineal region tumors. Preoperative evaluation of pineal region tumor can be simplified into a checklist: (1) evaluation for emergent surgical intervention due to symptomatic obstructive hydrocephalus or mass effect; (2) development of a focused differential after acquisition of craniospinal MRI, serum and cerebrospinal fluid oncoprotein levels, and cerebrospinal fluid cytology; and (3) decision on whether a biopsy, surgical resection, or both are necessary. Subsequent biopsy or surgical resection is the first step of tumor management and leads to coordination of consultation with medical and radiation oncology.

  View details for DOI 10.1016/j.nec.2011.04.003

  View details for PubMedID 21801983