Seunggu Jude Han, MD

All Publications

• Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma CLINICAL CANCER RESEARCH Ellingson, B. M., Sampson, J., Achrol, A., Aghi, M. K., Bankiewicz, K., Wang, C., Bexon, M., Brem, S., Brenner, A., Chowdhary, S., Floyd, J. R., Han, S., Kesari, S., Randazzo, D., Vogelbaum, M. A., Vrionis, F., Zabek, M., Butowski, N., Coello, M., Merchant, N., Merchant, F. 2021; 27 (14): 3916-3925

  Abstract

  The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM).A total of 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and centrally by an independent radiologic faculty, then standard RANO, iRANO, and mRANO criteria were applied.A total of 41 of 47 patients (mean age 56 ± 11.7) were evaluable for response. PFS was significantly shorter using standard RANO compared with iRANO (log-rank, P < 0.0001; HR = 0.3) and mRANO (P < 0.0001; HR = 0.3). In patients who died and had confirmed progression on standard RANO, no correlation was observed between PFS and OS (local, P = 0.47; central, P = 0.34). Using iRANO, a weak association was observed between confirmed PFS and OS via local site measurements (P = 0.017), but not central measurements (P = 0.18). A total of 24 of 41 patients (59%) were censored using iRANO and because they lacked confirmation of progression 3 months after initial progression. A strong correlation was observed between mRANO PFS and OS for both local (R2 = 0.66, P < 0.0001) and centrally determined reads (R2 = 0.57, P = 0.0007).No correlation between radiographic PFS and OS was observed for standard RANO or iRANO, but a correlation was observed between PFS and OS using the mRANO criteria. Also, the iRANO criteria was difficult to implement due to need to confirm progression 3 months after initial progression, censoring more than half the patients.

  View details for DOI 10.1158/1078-0432.CCR-21-0446

  View details for Web of Science ID 000674703200016

  View details for PubMedID 33863808

  View details for PubMedCentralID PMC8282697

• Novel Use of Stimulating Fence-Post Technique for Functional Mapping of Subcortical White Matter During Tumor Resection: A Technical Case Series OPERATIVE NEUROSURGERY Han, S., Teton, Z., Gupta, K., Kawamoto, A., Raslan, A. M. 2020; 19 (3): 264-270

  Abstract

  Maximal safe resection remains a key principle in infiltrating glioma management. Stimulation mapping is a key adjunct for minimizing functional morbidity while "fence-post" procedures use catheters or dye to mark the tumor border at the start of the procedure prior to brain shift.To report a novel technique using stereotactically placed electrodes to guide tumor resection near critical descending subcortical fibers.Navigated electrodes were placed prior to tumor resection along the deep margin bordering presumed eloquent tracts. Stimulation was administered through these depth electrodes for subcortical motor and language mapping.Twelve patients were included in this preliminary technical report. Seven patients (7/12, 58%) were in asleep cases, while the other 5 cases (5/12, 42%) were performed awake. Mapping of motor fibers was performed in 8 cases, and language mapping was done in 1 case. In 3 cases, both motor and language mapping were performed using the same depth electrode spanning corticospinal tract and the arcuate fasciculus.Stereotactic depth electrode placement coupled with stimulation mapping of white matter tracts can be used concomitantly to demarcate the border between deep tumor margins and eloquent brain, thus helping to maximize extent of resection while minimizing functional morbidity.

  View details for DOI 10.1093/ons/opaa027

  View details for Web of Science ID 000593127700060

  View details for PubMedID 32133508

• Association of Maximal Extent of Resection of Contrast-Enhanced and Non-Contrast-Enhanced Tumor With Survival Within Molecular Subgroups of Patients With Newly Diagnosed Glioblastoma JAMA ONCOLOGY Molinaro, A. M., Hervey-Jumper, S., Morshed, R. A., Young, J., Han, S. J., Chunduru, P., Zhang, Y., Phillips, J. J., Shai, A., Lafontaine, M., Crane, J., Chandra, A., Flanigan, P., Jahangiri, A., Cioffi, G., Ostrom, Q., Anderson, J. E., Badve, C., Barnholtz-Sloan, J., Sloan, A. E., Erickson, B. J., Decker, P. A., Kosel, M. L., LaChance, D., Eckel-Passow, J., Jenkins, R., Villanueva-Meyer, J., Rice, T., Wrensch, M., Wiencke, J. K., Bush, N., Taylor, J., Butowski, N., Prados, M., Clarke, J., Chang, S., Chang, E., Aghi, M., Theodosopoulos, P., McDermott, M., Berger, M. S. 2020; 6 (4): 495-503

  Abstract

  Per the World Health Organization 2016 integrative classification, newly diagnosed glioblastomas are separated into isocitrate dehydrogenase gene 1 or 2 (IDH)-wild-type and IDH-mutant subtypes, with median patient survival of 1.2 and 3.6 years, respectively. Although maximal resection of contrast-enhanced (CE) tumor is associated with longer survival, the prognostic importance of maximal resection within molecular subgroups and the potential importance of resection of non-contrast-enhanced (NCE) disease is poorly understood.To assess the association of resection of CE and NCE tumors in conjunction with molecular and clinical information to develop a new road map for cytoreductive surgery.This retrospective, multicenter cohort study included a development cohort from the University of California, San Francisco (761 patients diagnosed from January 1, 1997, through December 31, 2017, with 9.6 years of follow-up) and validation cohorts from the Mayo Clinic (107 patients diagnosed from January 1, 2004, through December 31, 2014, with 5.7 years of follow-up) and the Ohio Brain Tumor Study (99 patients with data collected from January 1, 2008, through December 31, 2011, with a median follow-up of 10.9 months). Image accessors were blinded to patient groupings. Eligible patients underwent surgical resection for newly diagnosed glioblastoma and had available survival, molecular, and clinical data and preoperative and postoperative magnetic resonance images. Data were analyzed from November 15, 2018, to March 15, 2019.Overall survival.Among the 761 patients included in the development cohort (468 [61.5%] men; median age, 60 [interquartile range, 51.6-67.7] years), younger patients with IDH-wild-type tumors and aggressive resection of CE and NCE tumors had survival similar to that of patients with IDH-mutant tumors (median overall survival [OS], 37.3 [95% CI, 31.6-70.7] months). Younger patients with IDH-wild-type tumors and reduction of CE tumor but residual NCE tumors fared worse (median OS, 16.5 [95% CI, 14.7-18.3] months). Older patients with IDH-wild-type tumors benefited from reduction of CE tumor (median OS, 12.4 [95% CI, 11.4-14.0] months). The results were validated in the 2 external cohorts. The association between aggressive CE and NCE in patients with IDH-wild-type tumors was not attenuated by the methylation status of the promoter region of the DNA repair enzyme O6-methylguanine-DNA methyltransferase.This study confirms an association between maximal resection of CE tumor and OS in patients with glioblastoma across all subgroups. In addition, maximal resection of NCE tumor was associated with longer OS in younger patients, regardless of IDH status, and among patients with IDH-wild-type glioblastoma regardless of the methylation status of the promoter region of the DNA repair enzyme O6-methylguanine-DNA methyltransferase. These conclusions may help reassess surgical strategies for individual patients with newly diagnosed glioblastoma.

  View details for DOI 10.1001/jamaoncol.2019.6143

  View details for Web of Science ID 000526653200009

  View details for PubMedID 32027343

  View details for PubMedCentralID PMC7042822

• Subcortical stimulation mapping of descending motor pathways for perirolandic gliomas: assessment of morbidity and functional outcome in 702 cases JOURNAL OF NEUROSURGERY Han, S. J., Morshed, R. A., Troncon, I., Jordan, K. M., Henry, R. G., Hervey-Jumper, S. L., Berger, M. S. 2019; 131 (1): 201-208

  Abstract

  OBJECTIVEHerein, the authors report their experience with intraoperative stimulation mapping to locate the descending subcortical motor pathways in patients undergoing surgery for hemispheric gliomas within or adjacent to the rolandic cortex, with particular description of the morbidity and functional outcomes associated with this technique.METHODSThis is a retrospective analysis of patients who, in the period between 1997 and 2016, had undergone resection of hemispheric perirolandic gliomas within or adjacent to descending motor pathways. Data regarding intraoperative stimulation mapping and patient postoperative neurological status were collected.RESULTSOf 702 patients, stimulation mapping identified the descending motor pathways in 300 cases (43%). A new or worsened motor deficit was seen postoperatively in 210 cases (30%). Among these 210 cases, there was improvement in motor function to baseline levels by 3 months postoperatively in 161 cases (77%), whereas the deficit remained in 49 cases (23%). The majority (65%) of long-term deficits (persisting beyond 3 months) were mild or moderate (antigravity strength or better). On multivariate analysis, patients in whom the subcortical motor pathways had been identified with stimulation mapping during surgery were more likely to develop an additional and/or worsened motor deficit postoperatively than were those in whom the subcortical pathways had not been found (45% vs 19%, respectively, p < 0.001). This difference remained when considering the likelihood of a long-term deficit (i.e., persisting > 3 months; 12% vs 3.2%, p < 0.001). A higher tumor grade and the presence of a preoperative motor deficit were also associated with higher rates of motor deficits persisting long-term. A region of restricted diffusion adjacent to the resection cavity was seen in 20 patients with long-term deficits (41%) and was more common in cases in which the motor pathways were not identified (69%). Long-term deficits that occur in settings in which the subcortical motor pathways are not identified seem in large part due to ischemic injury to descending tracts.CONCLUSIONSStimulation mapping allows surgeons to identify the descending motor pathways during resection of tumors in perirolandic regions and to attain an acceptable rate of morbidity in these high-risk cases.

  View details for DOI 10.3171/2018.3.JNS172494

  View details for Web of Science ID 000475838400026

  View details for PubMedID 30117770

• The Evolving Role of the Oncologic Neurosurgeon: Looking Beyond Extent of Resection in the Modern Era FRONTIERS IN ONCOLOGY Bowden, S. G., Han, S. 2018; 8: 406

  Abstract

  Neurosurgeons have played an essential role in glioma management and research for over a century. While the past twenty years have played witness to many exciting developments in glioma biology, diagnosis, and classification, relatively few novel, effective treatment strategies have been introduced. The role of neurosurgery in glioma management has been clarified, with a large body of evidence in support of maximal safe resection. However, neurosurgeons have also played a critical role in translational research during this period. The development of new MRI technologies has benefited greatly from validation with stereotactically-targeted human tissue. Careful banking of surgically acquired tissue was key to the development of a new classification scheme for glioma. Similarly, we have garnered a considerably deeper understanding of molecular and genetic properties of glioma through analysis of large surgical specimens. As our classification schemes become more sophisticated, incorporating targeted tissue sampling into the development of novel treatment strategies becomes essential. Such ex vivo analysis could be instrumental in determining mechanisms of treatment failure or success. Modern tumor neurosurgeons should consider themselves surgical neuro-oncologists, with engagement in translational research essential to furthering the field and improving outlooks for our patients.

  View details for DOI 10.3389/fonc.2018.00406

  View details for Web of Science ID 000445535100003

  View details for PubMedID 30319971

  View details for PubMedCentralID PMC6167541

• Resection of gliomas deemed inoperable by neurosurgeons based on preoperative imaging studies JOURNAL OF NEUROSURGERY Southwell, D. G., Birk, H. S., Han, S. J., Li, J., Sall, J. W., Berger, M. S. 2018; 129 (3): 567-575

  Abstract

  OBJECTIVE Maximal safe resection is a primary objective in the management of gliomas. Despite this objective, surgeons and referring physicians may, on the basis of radiological studies alone, assume a glioma to be unresectable. Because imaging studies, including functional MRI, may not localize brain functions (such as language) with high fidelity, this simplistic approach may exclude some patients from what could be a safe resection. Intraoperative direct electrical stimulation (DES) allows for the accurate localization of functional areas, thereby enabling maximal resection of tumors, including those that may appear inoperable based solely on radiological studies. In this paper the authors describe the extent of resection (EOR) and functional outcomes following resections of tumors deemed inoperable by referring physicians and neurosurgeons. METHODS The authors retrospectively examined the cases of 58 adult patients who underwent glioma resection within 6 months of undergoing a brain biopsy of the same lesion at an outside hospital. All patients exhibited unifocal supratentorial disease and preoperative Karnofsky Performance Scale scores ≥ 70. The EOR and 6-month functional outcomes for this population were characterized. RESULTS Intraoperative DES mapping was performed on 96.6% (56 of 58) of patients. Nearly half of the patients (46.6%, 27 of 58) underwent an awake surgical procedure with DES. Overall, the mean EOR was 87.6% ± 13.6% (range 39.0%-100%). Gross-total resection (resection of more than 99% of the preoperative tumor volume) was achieved in 29.3% (17 of 58) of patients. Subtotal resection (95%-99% resection) and partial resection (PR; < 95% resection) were achieved in 12.1% (7 of 58) and 58.6% (34 of 58) of patients, respectively. Of the cases that involved PR, the mean EOR was 79.4% ± 12.2%. Six months after surgery, no patient was found to have a new postoperative neurological deficit. The majority of patients (89.7%, 52 of 58) were free of neurological deficits both pre- and postoperatively. The remainder of patients exhibited either residual but stable deficits (5.2%, 3 of 58) or complete correction of preoperative deficits (5.2%, 3 of 58). CONCLUSIONS The use of DES enabled maximal safe resections of gliomas deemed inoperable by referring neurosurgeons. With rare exceptions, tumor resectability cannot be determined solely by radiological studies.

  View details for DOI 10.3171/2017.5.JNS17166

  View details for Web of Science ID 000443287000001

  View details for PubMedID 29125414

• Expression and prognostic impact of immune modulatory molecule PD-L1 in meningioma JOURNAL OF NEURO-ONCOLOGY Han, S. J., Reis, G., Kohanbash, G., Shrivastav, S., Magill, S. T., Molinaro, A. M., McDermott, M. W., Theodosopoulos, P. V., Aghi, M. K., Berger, M. S., Butowski, N. A., Barani, I., Phillips, J. J., Perry, A., Okada, H. 2016; 130 (3): 543-552

  Abstract

  While immunotherapy may offer promising new approaches for high grade meningiomas, little is currently known of the immune landscape in meningiomas. We sought to characterize the immune microenvironment and a potentially targetable antigen mesothelin across WHO grade I-III cases of meningiomas, and how infiltrating immune populations relate to patient outcomes. Immunohistochemistry was performed on tissue microarrays constructed from 96 meningioma cases. The cohort included 16 WHO grade I, 62 WHO grade II, and 18 WHO grade III tumors. Immunohistochemistry was performed using antibodies against CD3, CD8, CD20, CD68, PD-L1, and mesothelin. Dual staining using anti-PD-L1 and anti-CD68 antibodies was performed, and automated cell detection and positive staining detection algorithms were utilized. Greater degree of PD-L1 expression was found in higher grade tumors. More specifically, higher grade tumors contained increased numbers of intratumoral CD68-, PD-L1+ cells (p = 0.022), but did not contain higher numbers of infiltrating CD68+, PD-L1+ cells (p = 0.30). Higher PD-L1+/CD68- expression was independently predictive of worse overall survival in our cohort when accounting for grade, performance status, extent of resection, and recurrence history (p = 0.014). Higher expression of PD-L1+/CD68- was also present in tumors that had undergone prior radiotherapy (p = 0.024). Approximately quarter of meningiomas overexpressed mesothelin to levels equivalent to those found in pancreatic carcinomas and malignant mesotheliomas. The association with poor survival outcomes in our study suggests that PD-L1 may play a significant biologic role in the aggressive phenotype of higher grade meningiomas. Thus, immunotherapeutic strategies such as checkpoint inhibition may have clinical utility in PD-L1 overexpressing meningiomas.

  View details for DOI 10.1007/s11060-016-2256-0

  View details for Web of Science ID 000388950700017

  View details for PubMedID 27624915

  View details for PubMedCentralID PMC5560602

• Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma NEURO-ONCOLOGY Han, S. J., Rolston, J. D., Molinaro, A. M., Clarke, J. L., Prados, M. D., Chang, S. M., Berger, M. S., DeSilva, A., Butowski, N. A. 2014; 16 (9): 1255-1262

  Abstract

  A phase II trial was performed to evaluate the efficacy of a dose-dense, 7 days on/7 days off schedule of temozolomide for patients with recurrent high-grade gliomas (HGG).Sixty patients with recurrent HGG received temozolomide at 150 mg/m(2)/day on days 1-7 and days 15-21 during each 4-week cycle. The primary endpoint was 6-month progression-free survival (PFS-6), with a secondary endpoint of overall survival (OS). A further exploratory objective included the investigation of whether methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter within tumor tissue predicted outcomes.Among patients with glioblastoma (n = 40), PFS-6 was 10% (95% CI, 3%-24%) with median OS of 21.6 weeks (95% CI, 16.9-30.6 weeks). PFS-6 for grade III glioma patients (n = 20) was 50% (95% CI, 27%-73%), and median OS was 100.6 weeks (95% CI, 67 weeks to not reached). There were trends towards longer PFS and OS with MGMT promoter methylation (log-rank test; P = .06 for PFS; P = .07 for OS). Additionally, bevacizumab-naïve glioblastoma patients had significantly longer PFS and OS (median PFS was 8.07 weeks [95% CI, 8 weeks to not reached] vs 7.57 weeks [95% CI, 7.29-8.29 weeks], log-rank test, P < .001; median OS was 62 weeks [26.1 weeks to not reached] vs 18.2 weeks [13.9-27.3 weeks], log-rank test, P < .001).The dose-dense temozolomide regimen was well tolerated, although it has no significant activity in this population. Clinical trials.gov identified. NCT00619112 (available at http://clinicaltrials.gov/ct2/show/NCT00619112).

  View details for DOI 10.1093/neuonc/nou044

  View details for Web of Science ID 000342998100015

  View details for PubMedID 24670608

  View details for PubMedCentralID PMC4136897

• Soluble factors secreted by glioblastoma cell lines facilitate recruitment, survival, and expansion of regulatory T cells: implications for immunotherapy NEURO-ONCOLOGY Crane, C. A., Ahn, B. J., Han, S. J., Parsa, A. T. 2012; 14 (5): 584-595

  Abstract

  In patients with glioma, the tumor microenvironment can significantly impact pro-inflammatory immune cell functions. However, the mechanisms by which this occurs are poorly defined. Because immunosuppressive regulatory T cells (Treg) are over represented in the tumor microenvironment compared with peripheral blood, we hypothesized that the tumor may have an effect on Treg survival, migration, expansion, and/or induction of a regulatory phenotype from non-Treg conventional CD4+ T cells. We defined the impact of soluble factors produced by tumor cells on Treg from healthy patients in vitro to determine mechanisms by which gliomas influence T cell populations. We found that tumor-derived soluble factors allowed for preferential proliferation and increased chemotaxis of Treg, compared with conventional T cells, indicating that these mechanisms may contribute to the increased Treg in the tumor microenvironment. Conventional T cells also exhibited a significantly increased expression of pro-apoptotic transcripts in the presence of tumor-derived factors, indicating that survival of Treg in the tumor site is driven by exposure to soluble factors produced by the tumor. Together, these data suggest that tumor burden may induce increased Treg infiltration, proliferation, and survival, negating productive anti-tumor immune responses in patients treated with immunotherapies. Collectively, our data indicate that several mechanisms of Treg recruitment and retention in the tumor microenvironment exist and may need to be addressed to improve the specificity of immunotherapies seeking to eliminate Treg in patients with glioma.

  View details for DOI 10.1093/neuonc/nos014

  View details for Web of Science ID 000303334500007

  View details for PubMedID 22406925

  View details for PubMedCentralID PMC3337302

• Obesity and meningioma: a US population-based study paired with analysis of a multi-institutional cohort. Journal of neurosurgery Khazanchi, R., Nandoliya, K. R., Shahin, M. N., Rae, A. I., Chaliparambil, R. K., Bowden, S. G., Alwakeal, A., Lopez Ramos, C. G., Stedelin, B., Youngblood, M. W., Chandler, J. P., Lukas, R. V., Sanusi, O. R., Dogan, A., Wood, M. D., Han, S. J., Magill, S. T. 2024: 1-10

  Abstract

  OBJECTIVE: Whether obesity is associated with meningioma and the impact of obesity by gender has been debated. The primary objective of this study was to investigate differences in BMI between male and female patients undergoing craniotomy for meningioma and compare those with patients undergoing craniotomy for other intracranial tumors. The secondary objective was to compare meningioma location and progression-free survival (PFS) between obese and nonobese patients in a multi-institutional cohort.METHODS: National data were obtained from the National Surgical Quality Improvement Program (NSQIP) database. Male and female patients were analyzed separately. Patients undergoing craniotomies for meningioma were compared with patients of the same sex undergoing craniotomies for other intracranial tumors. Institutional data from two academic centers were collected for all male and an equivalent number of female meningioma patients undergoing meningioma resection. Multivariate regression controlling for age was used to determine differences in meningioma location. Kaplan-Meier curves and log-rank tests were computed to investigate differences in PFS.RESULTS: From NSQIP, 4163 male meningioma patients were compared with 24,266 controls, and 9372 female meningioma patients were compared with 21,538 controls. Male and female patients undergoing meningioma resection were more likely to be overweight or obese compared with patients undergoing craniotomy for other tumors, with the odds ratio increasing with increasing weight class (all p < 0.0001). In the multi-institutional cohort, meningiomas were more common along the skull base in male patients (p = 0.0123), but not in female patients (p = 0.1246). There was no difference in PFS between obese and nonobese male (p = 0.4104) or female (p = 0.5504) patients. Obesity was associated with increased risk of pulmonary embolism in both male and female patients undergoing meningioma resection (p = 0.0043).CONCLUSIONS: Male and female patients undergoing meningioma resection are more likely to be obese than patients undergoing craniotomy for other intracranial tumors. Obese males are more likely to have meningiomas in the skull base compared with other locations, but this association was not found in females. There was no significant difference in PFS among obese patients. The mechanism by which obesity increases meningioma incidence remains to be determined.

  View details for DOI 10.3171/2023.11.JNS23732

  View details for PubMedID 38241687

• Modular Phoneme Processing in Human Superior Temporal Gyrus. bioRxiv : the preprint server for biology Cleary, D. R., Tchoe, Y., Bourhis, A., Dickey, C. W., Stedelin, B., Ganji, M., Lee, S. H., Lee, J., Siler, D. A., Brown, E. C., Rosen, B. Q., Kaestner, E., Yang, J. C., Soper, D. J., Han, S. J., Paulk, A. C., Cash, S. S., Raslan, A. M., Dayeh, S. A., Halgren, E. 2024

  Abstract

  Modular organization is fundamental to cortical processing, but its presence is human association cortex is unknown. We characterized phoneme processing with 128-1024 channel micro-arrays at 50-200m pitch on superior temporal gyrus of 7 patients. High gamma responses were highly correlated within ~1.7mm diameter modules, sharply delineated from adjacent modules with distinct time-courses and phoneme-selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.

  View details for DOI 10.1101/2024.01.17.576120

  View details for PubMedID 38293030

• Multi-class glioma segmentation on real-world data with missing MRI sequences: comparison of three deep learning algorithms. Scientific reports Pemberton, H. G., Wu, J., Kommers, I., Muller, D. M., Hu, Y., Goodkin, O., Vos, S. B., Bisdas, S., Robe, P. A., Ardon, H., Bello, L., Rossi, M., Sciortino, T., Nibali, M. C., Berger, M. S., Hervey-Jumper, S. L., Bouwknegt, W., Van den Brink, W. A., Furtner, J., Han, S. J., Idema, A. J., Kiesel, B., Widhalm, G., Kloet, A., Wagemakers, M., Zwinderman, A. H., Krieg, S. M., Mandonnet, E., Prados, F., de Witt Hamer, P., Barkhof, F., Eijgelaar, R. S. 2023; 13 (1): 18911

  Abstract

  This study tests the generalisability of three Brain Tumor Segmentation (BraTS) challenge models using a multi-center dataset of varying image quality and incomplete MRI datasets. In this retrospective study, DeepMedic, no-new-Unet (nn-Unet), and NVIDIA-net (nv-Net) were trained and tested using manual segmentations from preoperative MRI of glioblastoma (GBM) and low-grade gliomas (LGG) from the BraTS 2021 dataset (1251 in total), in addition to 275 GBM and 205 LGG acquired clinically across 12 hospitals worldwide. Data was split into 80% training, 5% validation, and 15% internal test data. An additional external test-set of 158 GBM and 69 LGG was used to assess generalisability to other hospitals' data. All models' median Dice similarity coefficient (DSC) for both test sets were within, or higher than, previously reported human inter-rater agreement (range of 0.74-0.85). For both test sets, nn-Unet achieved the highest DSC (internal=0.86, external=0.93) and the lowest Hausdorff distances (10.07, 13.87mm, respectively) for all tumor classes (p<0.001). By applying Sparsified training, missing MRI sequences did not statistically affect the performance. nn-Unet achieves accurate segmentations in clinical settings even in the presence of incomplete MRI datasets. This facilitates future clinical adoption of automated glioma segmentation, which could help inform treatment planning and glioma monitoring.

  View details for DOI 10.1038/s41598-023-44794-0

  View details for PubMedID 37919354

• SURVIVAL OUTCOMES IN RECURRENT GLIOBLASTOMA (RGBM) PATIENTS TREATED WITH A SINGLE INTRA-TUMORAL ADMINISTRATION OF BIZAXOFUSP, AN IL-4R-TARGETING TOXIN, IN A PHASE IIB TRIAL Sampson, J., Achrol, A., Aghi, M., Bankiewicz, K., Bexon, M., Brem, S., Brenner, A., Chowdhary, S., Coello, M., Desjardins, A., Ellingson, B., Floyd, J., Han, S., Kesari, S., Mardor, Y., Merchant, F., Merchant, R., Randazzo, D., Vogelbaum, M. A., Vrionis, F., Wembacher-Schroeder, E., To, M. D., Zabek, M., Butowski, N. OXFORD UNIV PRESS INC. 2023

  View details for Web of Science ID 001115245400335

• On-Call Workload Differences in Neurosurgery: Resident Call "Weather" and a Departure from Colored Cloud Labels. Neurosurgery Tan, H., Bowden, S. G., Siler, D. A., O'Neill, B. E., Shahin, M. N., Fecker, A. L., Fleming-Sheffels, S., Han, S. J., Selden, N. R., Winer, J., Orina, J. N. 2023

  Abstract

  BACKGROUND AND OBJECTIVES: Labeling residents as "black" or "white" clouds based on perceived or presumed workloads is a timeworn custom across medical training and practice. Previous studies examining whether such perceptions align with objective workload patterns have offered conflicting results. We assessed whether such peer-assigned labels were associated with between-resident differences in objective, on-call workload metrics in three classes of neurosurgery junior residents. In doing so, we introduce more inclusive terminology for perceived differences in workload metrics.METHODS: Residents were instructed to complete surveys to identify "sunny", "neutral", and "stormy" residents, reflecting least to greatest perceived workloads, of their respective classes. We retrospectively reviewed department and electronic medical records to record volume of on-call work over the first 4 months of each resident's 2nd postgraduate academic year. Inter-rater agreement of survey responses was measured using Fleiss' kappa. All statistical analyses were performed with a significance threshold of P < .05.RESULTS: Across all classes, there was strong inter-rater agreement in the identification of stormy and sunny residents (Kappa = 1.000, P = .003). While differences in on-call workload measures existed within each class, "weather" designations did not consistently reflect these differences. There were significant intraclass differences in per shift consult volume in two classes (P = .035 and P = .009); however, consult volume corresponded to a resident's weather designations in only one class. Stormy residents generally saw more emergencies and, in 2 classes, performed more bedside procedures than their peers.CONCLUSION: Significant differences in objective on-call experience exist between junior neurosurgery residents. Self- and peer-assigned weather labels did not consistently align with a pattern of these differences, suggesting that other factors contribute to such labels.

  View details for DOI 10.1227/neu.0000000000002740

  View details for PubMedID 37874131

• Rapid Passive Gamma Mapping as an Adjunct to Electrical Stimulation Mapping for Functional Localization in Resection of Primary Brain Neoplasms. World neurosurgery Tan, H., Nugent, J. G., Fecker, A., Richie, E. A., Maanum, K. A., Nerison, C., Bowden, S. G., Yaylali, I., Han, S. J., Colgan, D. D., Oken, B., Raslan, A. M. 2023

  Abstract

  OBJECTIVE: We examined the utility of passive high-gamma mapping (HGM) as an adjunct to conventional awake brain mapping during glioma resection. We compared functional and survival outcomes before and after implementing intraoperative HGM.METHODS: This was a retrospective cohort study of 75 patients that underwent a first-time, awake craniotomy for glioma resection. Patients were stratified by whether their operation occurred before or after the implementation of an FDA-approved high-gamma mapping tool in July 2017.RESULTS: The pre and post-implementation cohorts included 28 and 47 patients, respectively. Median intraoperative time (261 vs. 261 minutes, p=0.250) and extent of resection (97.14% vs. 98.19%, p=0.481) were comparable between cohorts. Median Karnofsky Performance Status at initial follow-up was similar between cohorts (p=0.650). Multivariable Cox regression models demonstrated an adjusted Hazard Ratio (aHR) for overall survival of 0.10 (95% CI: 0.02-0.43, p=0.002) for the post-implementation cohort relative to the pre-implementation cohort. Progression-free survival adjusted for insular involvement showed an aHR of 1.00 (95% CI: 0.49-2.06, p=0.999) following HGM implementation. Falling short of statistical significance, prevalence of intraoperative seizures and/or afterdischarges decreased after HGM implementation as well (12.7 % vs. 25%, p = 0.150).CONCLUSION: Our results tentatively indicate that passive HGM is a safe and potentially useful adjunct to electrical stimulation mapping for awake cortical mapping, conferring at least comparable functional and survival outcomes with a non-significant lower rate of intraoperative epileptiform events. Considering the limitations of our study design and patient cohort, further investigation is needed to better identify optimal use cases for HGM.

  View details for DOI 10.1016/j.wneu.2023.10.085

  View details for PubMedID 37871691

• Intraoperative application and early experience with novel high-resolution, high-channel-count thin-film electrodes for human microelectrocorticography. Journal of neurosurgery Tan, H., Paulk, A. C., Stedelin, B., Cleary, D. R., Nerison, C., Tchoe, Y., Brown, E. C., Bourhis, A., Russman, S., Lee, J., Tonsfeldt, K. J., Yang, J. C., Oh, H., Ro, Y. G., Lee, K., Ganji, M., Galton, I., Siler, D., Han, S. J., Collins, K. L., Ben-Haim, S., Halgren, E., Cash, S. S., Dayeh, S., Raslan, A. M. 2023: 1-12

  Abstract

  The study objective was to evaluate intraoperative experience with newly developed high-spatial-resolution microelectrode grids composed of poly(3,4-ethylenedioxythiophene) with polystyrene sulfonate (PEDOT:PSS), and those composed of platinum nanorods (PtNRs).A cohort of patients who underwent craniotomy for pathological tissue resection and who had high-spatial-resolution microelectrode grids placed intraoperatively were evaluated. Patient demographic and baseline clinical variables as well as relevant microelectrode grid characteristic data were collected. The primary and secondary outcome measures of interest were successful microelectrode grid utilization with usable resting-state or task-related data, and grid-related adverse intraoperative events and/or grid dysfunction.Included in the analysis were 89 cases of patients who underwent a craniotomy for resection of neoplasms (n = 58) or epileptogenic tissue (n = 31). These cases accounted for 94 grids: 58 PEDOT:PSS and 36 PtNR grids. Of these 94 grids, 86 were functional and used successfully to obtain cortical recordings from 82 patients. The mean cortical grid recording duration was 15.3 ± 1.15 minutes. Most recordings in patients were obtained during experimental tasks (n = 52, 58.4%), involving language and sensorimotor testing paradigms, or were obtained passively during resting state (n = 32, 36.0%). There were no intraoperative adverse events related to grid placement. However, there were instances of PtNR grid dysfunction (n = 8) related to damage incurred by suboptimal preoperative sterilization (n = 7) and improper handling (n = 1); intraoperative recordings were not performed. Vaporized peroxide sterilization was the most optimal sterilization method for PtNR grids, providing a significantly greater number of usable channels poststerilization than did steam-based sterilization techniques (median 905.0 [IQR 650.8-935.5] vs 356.0 [IQR 18.0-597.8], p = 0.0031).High-spatial-resolution microelectrode grids can be readily incorporated into appropriately selected craniotomy cases for clinical and research purposes. Grids are reliable when preoperative handling and sterilization considerations are accounted for. Future investigations should compare the diagnostic utility of these high-resolution grids to commercially available counterparts and assess whether diagnostic discrepancies relate to clinical outcomes.

  View details for DOI 10.3171/2023.7.JNS23885

  View details for PubMedID 37874692

• Targeting the IL4 Receptor with MDNA55 in Patients with Recurrent Glioblastoma: Results of a Phase 2b Trial. Neuro-oncology Sampson, J. H., Singh Achrol, A., Aghi, M. K., Bankiewiecz, K., Bexon, M., Brem, S., Brenner, A., Chandhasin, C., Chowdhary, S., Coello, M., Ellingson, B. M., Floyd, J. R., Han, S., Kesari, S., Mardor, Y., Merchant, F., Merchant, N., Randazzo, D., Vogelbaum, M., Vrionis, F., Wembacher-Schroeder, E., Zabek, M., Butowski, N. 2023

  Abstract

  BACKGROUND: MDNA55 is an IL4R-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R is overexpressed in GBM as well as cells of the tumor microenvironment. High expression of IL4R is associated with poor clinical outcome.METHOD: MDNA55-05 is an open-label, single-arm Phase 2b study of MDNA55 in recurrent GBM (rGBM) patients with an aggressive form of GBM (de novo GBM, IDH wild-type, and non-resectable at recurrence) on their 1 st or 2 nd recurrence. MDNA55 was administered intratumorally as a single dose treatment (dose range of 18 to 240 ug) using convection enhanced delivery (CED) with up to 4 stereo-tactically placed catheters. It was co-infused with a contrast agent (Gd-DTPA, Magnevist) to assess distribution in and around the tumor margins. The flow rate of each catheter did not exceed 10muL/min to ensure that the infusion duration did not exceed 48 hours. Primary endpoint was mOS, with secondary endpoints determining the effects of IL4R status on mOS and PFS.RESULTS: MDNA55 showed an acceptable safety profile at doses up to 240 mug. In all evaluable patients (n=44) mOS was 11.64 months (80% one-sided CI 8.62, 15.02) and OS-12 was 46%. A sub-group (n=32) consisting of IL4R High and IL4R Low patients treated with high dose MDNA55 (>180 ug) showed best benefit with mOS of 15 months, OS-12 of 55%. Based on mRANO criteria, tumor control was observed in 81% (26/32), including those patients who exhibited pseudo-progression (15/26).CONCLUSIONS: MDNA55 demonstrated tumor control and promising survival and may benefit rGBM patients when treated at high dose irrespective of IL4R expression level.

  View details for DOI 10.1093/neuonc/noac285

  View details for PubMedID 36640127

• Response to Preoperative Dexamethasone Predicts Postoperative Neurological Improvement of Focal Neurological Deficits in Patients With Brain Metastases. Neurosurgery Bowden, S. G., Lopez Ramos, C. G., Cheaney, B. 2., Richie, E., Yaghi, N. K., Munger, D. N., Mazur-Hart, D. J., Tan, H., Wood, M. D., Cetas, J. S., Dogan, A., Raslan, A. M., Han, S. J. 2023

  Abstract

  BACKGROUND: Steroids are used ubiquitously in the preoperative management of patients with brain tumor. The rate of improvement in focal deficits with steroids and the prognostic value of such a response are not known.OBJECTIVE: To determine the rate at which focal neurological deficits respond to preoperative corticosteroids in patients with brain metastases and whether such an improvement could predict long-term recovery of neurological function after surgery.METHODS: Patients with brain metastases and related deficits in language, visual field, or motor domains who received corticosteroids before surgery were identified. Characteristics between steroid responders and nonresponders were compared.RESULTS: Ninety six patients demonstrated a visual field (13 patients), language (19), or motor (64) deficit and received dexamethasone in the week before surgery (average cumulative dose 43 mg; average duration 2.7 days). 38.5% of patients' deficits improved with steroids before surgery, while 82.3% of patients improved by follow-up. Motor deficits were more likely to improve both preoperatively (P = .014) and postoperatively (P = .010). All 37 responders remained improved at follow-up whereas 42 of 59 (71%) of nonresponders ultimately improved (P < .001). All other clinical characteristics, including dose and duration, were similar between groups.CONCLUSION: A response to steroids before surgery is highly predictive of long-term improvement postoperatively in brain metastasis patients with focal neurological deficits. Lack of a response portends a somewhat less favorable prognosis. Duration and intensity of therapy do not seem to affect the likelihood of response.

  View details for DOI 10.1227/neu.0000000000002353

  View details for PubMedID 36728251

• International Tuberculum Sellae Meningioma Study: Surgical Outcomes and Management Trends. Neurosurgery Magill, S. T., Schwartz, T. H., Couldwell, W. T., Gardner, P. A., Heilman, C. B., Sen, C., Akagami, R., Cappabianca, P., Prevedello, D. M., McDermott, M. W., International Tuberculum Sellae Meningioma Study Authors, Przybylowski, C. J., Almefty, K. K., Patel, A. J., Khan, A. B., Wu, K. C., Bi, W. L., Dunn, I. F., Mamelak, A. N., Ehsan, M. U., Bruce, J. N., Englander, Z. K., Wang, L. M., Youngerman, B., Anand, V. K., Kacker, A., Tabaee, A., Clarke, D. B., Walling, S. A., Hebb, A. L., Macki, M., Anand, S. K., Rock, J. P., Baskin, D. S., Yewah Gwei, L. K., Guthikonda, B., Kosty, J., Nanda, A., Sun, H., Culicchia, F., Morrow, K., Fannin, E., Germanwala, A. V., Prabhu, V. C., Patel, C. R., Chaichana, K., Quinones-Hinojosa, A., ReFaey, K., Chandler, J. P., Fernandez, L. G., Oyon, D. E., Youngblood, M. W., Golfinos, J. G., Placantonakis, D. G., Pacione, D., Delavari, N., Albonette-Felicio, T., Otto, B. A., Carrau, R. L., Han, S. J., Shahin, M. N., Brahimaj, B. C., Beer-Furlan, A., Byrne, R. W., Munich, S. A., Munoz, L. F., Liu, J. K., Zhao, K., Agarwalla, P. K., Hsueh, W. D., Chang, S. D., Meola, A., Teng, H., Goulart, C. R., Rai, S. S., Chin, L. S., Ahye, N., Weaver, M., Mangham, W. M., Michael, L. M., Robertson, J. H., Dowd, R. S., Amenta, P. S., Scullen, T. A., de Divitiis, O., Solari, D., Cavallo, L. M., Makarenko, S., Rizzuto, M., Prakash, S., Chen, W. C., El-Sayed, I. H., Nguyen, M. P., Morshed, R. A., Theodosopoulos, P. V., Aghi, M. K., Santarius, T., Stastna, D., Williams, B. J., Andaluz, N., Adappa, N. D., Palmer, J. N., Grady, M. S., Lee, J. Y., Buch, L., Sharma, N., Joshi, D., Champagne, P., Valappil, B., Kumar, J. I., Agarwalla, P. K., Agazzi, S., van Loveren, H., Zada, G., Strickland, B., Garrett, N. E., Plitt, A. R., Barnett, S. L., Mickey, B. E., Garzon-Muvdi, T., Nassiri, F., Gentili, F., Kalyvas, A., Zadeh, G., Karsy, M., Sayyahmelli, S., Baskaya, M. K., Morone, P. J., Cavallo, C., Sylvester, P. T., Chicoine, M. R. 2023

  Abstract

  BACKGROUND AND OBJECTIVES: Tuberculum sellae meningiomas (TSMs) can be resected through transcranial (TCA) or expanded endonasal approach (EEA). The objective of this study was to report TSM management trends and outcomes in a large multicenter cohort.METHODS: This is a 40-site retrospective study using standard statistical methods.RESULTS: In 947 cases, TCA was used 66.4% and EEA 33.6%. The median maximum diameter was 2.5 cm for TCA and 2.1 cm for EEA (P < .0001). The median follow-up was 26 months. Gross total resection (GTR) was achieved in 70.2% and did not differ between EEA and TCA (P = .5395). Vision was the same or better in 87.5%. Vision improved in 73.0% of EEA patients with preoperative visual deficits compared with 57.1% of TCA patients (P < .0001). On multivariate analysis, a TCA (odds ratio [OR] 1.78, P = .0258) was associated with vision worsening, while GTR was protective (OR 0.37, P < .0001). GTR decreased with increased diameter (OR: 0.80 per cm, P = .0036) and preoperative visual deficits (OR 0.56, P = .0075). Mortality was 0.5%. Complications occurred in 23.9%. New unilateral or bilateral blindness occurred in 3.3% and 0.4%, respectively. The cerebrospinal fluid leak rate was 17.3% for EEA and 2.2% for TCA (OR 9.1, P < .0001). The recurrence rate was 10.9% (n = 103). Longer follow-up (OR 1.01 per month, P < .0001), World Health Organization II/III (OR 2.20, P = .0262), and GTR (OR: 0.33, P < .0001) were associated with recurrence. The recurrence rate after GTR was lower after EEA compared with TCA (OR 0.33, P = .0027).CONCLUSION: EEA for appropriately selected TSM may lead to better visual outcomes and decreased recurrence rates after GTR, but cerebrospinal fluid leak rates are high, and longer follow-up is needed. Tumors were smaller in the EEA group, and follow-up was shorter, reflecting selection, and observation bias. Nevertheless, EEA may be superior to TCA for appropriately selected TSM.

  View details for DOI 10.1227/neu.0000000000002569

  View details for PubMedID 37389475

• International Tuberculum Sellae Meningioma Study: Preoperative Grading Scale to Predict Outcomes and Propensity-Matched Outcomes by Endonasal Versus Transcranial Approach. Neurosurgery Magill, S. T., Schwartz, T. H., Couldwell, W. T., Gardner, P. A., Heilman, C. B., Sen, C., Akagami, R., Cappabianca, P., Prevedello, D. M., McDermott, M. W., International Tuberculum Sellae Meningioma Study, Przybylowski, C. J., Almefty, K. K., Patel, A. J., Khan, A. B., Wu, K. C., Bi, W. L., Dunn, I. F., Mamelak, A. N., Ehsan, M. U., Bruce, J. N., Englander, Z. K., Wang, L. M., Youngerman, B., Anand, V. K., Kacker, A., Tabaee, A., Clarke, D. B., Walling, S. A., Hebb, A. L., Macki, M., Anand, S. K., Rock, J. P., Baskin, D. S., Yewah Gwei, L. K., Guthikonda, B., Kosty, J., Nanda, A., Sun, H., Culicchia, F., Morrow, K., Fannin, E., Germanwala, A. V., Prabhu, V. C., Patel, C. R., Chaichana, K., Quinones-Hinojosa, A., ReFaey, K., Chandler, J. P., Fernandez, L. G., Oyon, D. E., Youngblood, M. W., Golfinos, J. G., Placantonakis, D. G., Pacione, D., Delavari, N., Albonette-Felicio, T., Otto, B. A., Carrau, R. L., Han, S. J., Shahin, M. N., Brahimaj, B. C., Beer-Furlan, A., Byrne, R. W., Munich, S. A., Munoz, L. F., Liu, J. K., Zhao, K., Agarwalla, P. K., Hsueh, W. D., Chang, S. D., Meola, A., Teng, H., Goulart, C. R., Rai, S. S., Chin, L. S., Ahye, N., Weaver, M., Mangham, W. M., Michael, L. M., Robertson, J. H., Dowd, R. S., Amenta, P. S., Scullen, T. A., de Divitiis, O., Solari, D., Cavallo, L. M., Makarenko, S., Rizzuto, M., Prakash, S., Chen, W. C., El-Sayed, I. H., Nguyen, M. P., Morshed, R. A., Theodosopoulos, P. V., Aghi, M. K., Santarius, T., Stastna, D., Williams, B. J., Andaluz, N., Adappa, N. D., Palmer, J. N., Grady, M. S., Lee, J. Y., Buch, L., Sharma, N., Joshi, D., Champagne, P., Valappil, B., Kumar, J. I., Agarwalla, P. K., Agazzi, S., van Loveren, H., Zada, G., Strickland, B., Garrett, N. E., Plitt, A. R., Barnett, S. L., Mickey, B. E., Garzon-Muvdi, T., Nassiri, F., Gentili, F., Kalyvas, A., Zadeh, G., Karsy, M., Sayyahmelli, S., Baskaya, M. K., Morone, P. J., Cavallo, C., Sylvester, P. T., Chicoine, M. R. 2023

  Abstract

  BACKGROUND AND OBJECTIVES: Tuberculum sellae meningiomas are resected via an expanded endonasal (EEA) or transcranial approach (TCA). Which approach provides superior outcomes is debated. The Magill-McDermott (M-M) grading scale evaluating tumor size, optic canal invasion, and arterial involvement remains to be validated for outcome prediction. The objective of this study was to validate the M-M scale for predicting visual outcome, extent of resection (EOR), and recurrence, and to use propensity matching by M-M scale to determine whether visual outcome, EOR, or recurrence differ between EEA and TCA.METHODS: Forty-site retrospective study of 947 patients undergoing tuberculum sellae meningiomas resection. Standard statistical methods and propensity matching were used.RESULTS: The M-M scale predicted visual worsening (odds ratio [OR]/point: 1.22, 95% CI: 1.02-1.46, P = .0271) and gross total resection (GTR) (OR/point: 0.71, 95% CI: 0.62-0.81, P < .0001), but not recurrence (P = .4695). The scale was simplified and validated in an independent cohort for predicting visual worsening (OR/point: 2.34, 95% CI: 1.33-4.14, P = .0032) and GTR (OR/point: 0.73, 95% CI: 0.57-0.93, P = .0127), but not recurrence (P = .2572). In propensity-matched samples, there was no difference in visual worsening (P = .8757) or recurrence (P = .5678) between TCA and EEA, but GTR was more likely with TCA (OR: 1.49, 95% CI: 1.02-2.18, P = .0409). Matched patients with preoperative visual deficits who had an EEA were more likely to have visual improvement than those undergoing TCA (72.9% vs 58.4%, P = .0010) with equal rates of visual worsening (EEA 8.0% vs TCA 8.6%, P = .8018).CONCLUSION: The refined M-M scale predicts visual worsening and EOR preoperatively. Preoperative visual deficits are more likely to improve after EEA; however, individual tumor features must be considered during nuanced approach selection by experienced neurosurgeons.

  View details for DOI 10.1227/neu.0000000000002581

  View details for PubMedID 37418417

• Reply to letter to the editor: Does early adjuvant brain metastasis SRS increase mortality? Neuro-oncology practice Yaghi, N. K., Han, S. J. 2022; 9 (6): 561

  View details for DOI 10.1093/nop/npac084

  View details for PubMedID 36388413

  View details for PubMedCentralID PMC9665051

• FUNCTIONAL EX VIVO TESTING PROSPECTIVELY IDENTIFIES NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS SENSITIVE TO TEMOZOLOMIDE TREATMENT IRRESPECTIVE OF MGMT METHYLATION STATUS DesRochers, T., Lipinski, L., Abad, A., Fenstermaker, R., Fabiano, A., Edenfield, J., Kanos, C., Redjal, N., Rodriguez, A., Mansouri, A., Zacharia, B., Butowski, N., Liu, J., Han, S., Ziu, M., Cohen, A., Smith, A., Vibat, C., Ledford, A. OXFORD UNIV PRESS INC. 2022: 148-149

  View details for Web of Science ID 000888571000577

• PREOPERATIVE DEXAMETHASONE LEADS TO SIGNIFICANT REDUCTIONS IN PERITUMORAL EDEMA FOR PATIENTS WITH BRAIN METASTASES Tan, H., Bowden, S., Cheaney, B., Richie, E., de Leeuw, C., Wood, M., Raslan, A., Han, S., Barajas, R. OXFORD UNIV PRESS INC. 2022: 162

  View details for Web of Science ID 000888571000627

• Reply to letter to the editor: Does early adjuvant brain metastasis SRS increase mortality? NEURO-ONCOLOGY PRACTICE Yaghi, N. K., Han, S. 2022

  View details for DOI 10.1093/nop/npac084

  View details for Web of Science ID 000872704400001

• Effects of 24-hour versus night-float call schedules on the clinical and operative experiences of postgraduate year 2 and 3 neurosurgical residents. Neurosurgical focus Bowden, S. G., Siler, D. A., Shahin, M. N., Mazur-Hart, D. J., Munger, D. N., Ross, M. N., O'Neill, B. E., Nerison, C. S., Rothbaum, M., Han, S. J., Wright, J. M., Orina, J. N., Winer, J. L., Selden, N. R. 2022; 53 (2): E12

  Abstract

  OBJECTIVE: To comply with the removal of the 88-hour week exemption and to support additional operative experience during junior residency, Oregon Health & Science University (OHSU) switched from a night-float call schedule to a modified 24-hour call schedule on July 1, 2019. This study compared the volumes of clinical, procedural, and operative cases experienced by postgraduate year 2 (PGY-2) and PGY-3 residents under these systems.METHODS: The authors retrospectively studied billing and related clinical records, call schedules, and Accreditation Council for Graduate Medical Education case logs for PGY-2 and PGY-3 residents at OHSU, a tertiary academic health center, for the first 4 months of the academic years from 2017 to 2020. The authors analyzed the volumes of new patient consultations, bedside procedures, and operative procedures performed by each PGY-2 and PGY-3 resident during these years, comparing the volumes experienced under each call system.RESULTS: Changing from a PGY-2 resident-focused night-float call system to a 24-hour call system that was more evenly distributed between PGY-2 and PGY-3 residents resulted in decreased volume of new patient consultations, increased volume of operative procedures, and no change in volume of bedside procedures for PGY-2 residents. PGY-3 residents experienced a decrease in operative procedure volume under the 24-hour call system.CONCLUSIONS: Transition from a night-float system to a 24-hour call system altered the distribution of clinical and procedural experiences between PGY-2 and PGY-3 residents. Further research is necessary to understand the impact of these changes on educational outcomes, quality and safety of patient care, and resident satisfaction.

  View details for DOI 10.3171/2022.5.FOCUS22181

  View details for PubMedID 35916097

• Clinical application of a functional 3D ex vivo test to predict therapeutic response in patients with HGG: A progression-free survival analysis Lipinski, L. J., Abad, A., Fenstermaker, R., Fabiano, A. J., Edenfield, W., Kanos, C., Redjal, N., Rodriguez, A., Mansouri, A., Zacharia, B., Butowski, N. A., Liu, J., Han, S., Ziu, M., Cohen, A., Smith, A. M., DesRochers, T., Vibat, C. T. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680300682

• Association of Medicaid Expansion Under the Affordable Care Act with Receipt of Meningioma Treatment Ramos, C., Mazur-Hart, D., Rae, A., Bowden, S., Yaghi, N., Shahin, M., Yamamoto, E., Han, S., Raslan, A. AMER ASSOC NEUROLOGICAL SURGEONS. 2022

  View details for Web of Science ID 001132701400164

• Optimal timing of radiotherapy following brain metastases surgery. Neuro-oncology practice Yaghi, N. K., Radu, S., Nugent, J. G., Mazur-Hart, D. J., Pang, B. W., Bowden, S. G., Murphy, B., Han, S. J. 2022; 9 (2): 133-141

  Abstract

  There is growing evidence supporting the need for a short time delay before starting radiotherapy (RT) treatment postsurgery for most optimal responses. The timing of RT initiation and effects on outcomes have been evaluated in a variety of malignancies, but the relationship remains to be well established for brain metastasis.Retrospective study of 176 patients (aged 18-89 years) with brain metastases at a single institution (March 2009 to August 2018) who received RT following surgical resection. Time interval (≤22 and >22 days) from surgical resection to initiation of RT and any potential impact on patient outcomes were assessed.Patients who underwent RT >22 days after surgical resection had a decreased risk for all-cause mortality of 47.2% (95% CI: 8.60, 69.5%). Additionally, waiting >40 days for RT after surgical resection more than doubled the risk of tumor progression; adjusted hazard ratio 2.02 (95% CI: 1.12, 3.64).Findings indicate that a short interval delay (>22 days) following surgical resection is required before RT initiation for optimal treatment effects in brain metastasis. Our timing of RT postsurgical resection data adds definition to current heterogeneity in RT timing, which is especially important for standardized clinical trial design and patient outcomes.

  View details for DOI 10.1093/nop/npac007

  View details for PubMedID 35371524

  View details for PubMedCentralID PMC8965066

• Optimal timing of radiotherapy following brain metastases surgery NEURO-ONCOLOGY PRACTICE Yaghi, N. K., Radu, S., Nugent, J. G., Mazur-Hart, D. J., Pang, B. W., Bowden, S. G., Murphy, B., Han, S. J. 2022

  View details for DOI 10.1093/nop/npac007

  View details for Web of Science ID 000758321600001

• Identifying risk factors for postoperative diabetes insipidus in more than 2500 patients undergoing transsphenoidal surgery: a single-institution experience. Journal of neurosurgery Joshi, R. S., Pereira, M. P., Osorio, R. C., Oh, T., Haddad, A. F., Pereira, K. M., Donohue, K. C., Peeran, Z., Sudhir, S., Jain, S., Beniwal, A., Chandra, A., Han, S. J., Rolston, J. D., Theodosopoulos, P. V., Kunwar, S., Blevins, L. S., Aghi, M. K. 1800: 1-11

  Abstract

  OBJECTIVE: Diabetes insipidus (DI) following transsphenoidal surgery can adversely impact quality of life and be difficult to manage. This study sought to characterize pre- and perioperative risk factors that may predispose patients to DI after pituitary surgery.METHODS: A retrospective review of patients treated at a single institution from 2007 to 2019 was conducted. DI was defined as postoperative sodium > 145 mEq/L and urine output > 300 ml/hr and/or postoperative desmopressin (ddAVP) use. DI was further characterized as transient or permanent. Uni- and multivariate analyses were performed to determine variables associated with postoperative DI.RESULTS: The authors identified 2529 patients who underwent transsphenoidal surgery at their institution. Overall, DI was observed in 270 (10.7%) of the 2529 patients, with 114 (4.5%) having permanent DI and 156 (6.2%) with transient symptoms. By pathology type, DI occurred in 31 (46.3%) of 67 craniopharyngiomas, 10 (14.3%) of 70 apoplexies, 46 (14.3%) of 322 Rathke's cleft cysts, 77 (7.7%) of 1004 nonfunctioning pituitary adenomas (NFPAs), and 62 (7.6%) of 811 functioning pituitary adenomas (FPAs). Final lesion pathology significantly affected DI rates (p < 0.001). Multivariate analysis across pathologies showed that younger age (odds ratio [OR] 0.97, p < 0.001), intraoperative CSF encounter (OR 2.74, p < 0.001), craniopharyngioma diagnosis (OR 8.22, p = 0.007), and postoperative hyponatremia (OR 1.50, p = 0.049) increased the risk of DI. Because surgery for each pathology created specific risk factors for DI, the analysis was then limited to the 1815 pituitary adenomas (PAs) in the series, comprising 1004 NFPAs and 811 FPAs. For PAs, younger age (PA: OR 0.97, p < 0.001; NFPA: OR 0.97, p < 0.001; FPA: OR 0.97, p = 0.028) and intraoperative CSF encounter (PA: OR 2.99, p < 0.001; NFPA: OR 2.93, p < 0.001; FPA: OR 3.06, p < 0.001) increased DI rates in multivariate analysis. Among all PAs, patients with DI experienced peak sodium levels later than those without DI (postoperative day 11 vs 2). Increasing tumor diameter increased the risk of DI in FPAs (OR 1.52, p = 0.008), but not in NFPAs (p = 0.564).CONCLUSIONS: In more than 2500 patients treated at a single institution, intraoperative CSF encounter, craniopharyngioma diagnosis, and young age all increased the risk of postoperative DI. Patients with postoperative hyponatremia exhibited higher rates of DI, suggesting possible bi- or triphasic patterns to DI. Greater vigilance should be maintained in patients meeting these criteria following transsphenoidal surgery to ensure early recognition and treatment of DI.

  View details for DOI 10.3171/2021.11.JNS211260

  View details for PubMedID 35090129

• Regression of Multiple Meningiomas after Discontinuation of Chronic Hormone Therapy: A Case Report JOURNAL OF NEUROLOGICAL SURGERY REPORTS Shahin, M. N., Bowden, S. G., Yaghi, N. K., Bagley, J. H., Han, S. J., Varlamov, E. V., Grafe, M. R., Cetas, J. S. 2021; 82 (04): e38-e42

  Abstract

  Introduction  Meningiomas are more common in females and frequently express progesterone and estrogen receptors. Recent studies have revealed a high incidence of meningiomas in situations in which estrogen/progesterone levels are increased such as pregnancy, gender reassignment therapy, and fertility treatment. While the relationship remains unclear and controversial, these findings suggest exposure to high levels of endogenous or exogenous hormones may increase the risk of developing a meningioma. Patients and Methods  A 40-year-old female with a history of endometriosis treated with chronic progesterone therapy presented with a visual deficit and was found to have multiple meningiomas, which regressed after cessation of exogenous progesterone. Conclusion  A history of chronic hormone therapy should be included when evaluating patients diagnosed with meningiomas, particularly at a younger age and with multiple meningiomas. Cessation of exogenous progesterone resulting in regression of meningiomas suggests a direct action of progesterone on growth. Future studies are warranted to better elucidate this relationship.

  View details for DOI 10.1055/s-0041-1735553

  View details for Web of Science ID 000724481000001

  View details for PubMedID 34877245

  View details for PubMedCentralID PMC8635825

• On the cutting edge of glioblastoma surgery: where neurosurgeons agree and disagree on surgical decisions. Journal of neurosurgery Muller, D. M., Robe, P. A., Ardon, H., Barkhof, F., Bello, L., Berger, M. S., Bouwknegt, W., Van den Brink, W. A., Conti Nibali, M., Eijgelaar, R. S., Furtner, J., Han, S. J., Hervey-Jumper, S. L., Idema, A. J., Kiesel, B., Kloet, A., Mandonnet, E., De Munck, J. C., Rossi, M., Sciortino, T., Vandertop, W. P., Visser, M., Wagemakers, M., Widhalm, G., Witte, M. G., Zwinderman, A. H., De Witt Hamer, P. C. 2021: 1-11

  Abstract

  OBJECTIVE: The aim of glioblastoma surgery is to maximize the extent of resection while preserving functional integrity. Standards are lacking for surgical decision-making, and previous studies indicate treatment variations. These shortcomings reflect the need to evaluate larger populations from different care teams. In this study, the authors used probability maps to quantify and compare surgical decision-making throughout the brain by 12 neurosurgical teams for patients with glioblastoma.METHODS: The study included all adult patients who underwent first-time glioblastoma surgery in 2012-2013 and were treated by 1 of the 12 participating neurosurgical teams. Voxel-wise probability maps of tumor location, biopsy, and resection were constructed for each team to identify and compare patient treatment variations. Brain regions with different biopsy and resection results between teams were identified and analyzed for patient functional outcome and survival.RESULTS: The study cohort consisted of 1087 patients, of whom 363 underwent a biopsy and 724 a resection. Biopsy and resection decisions were generally comparable between teams, providing benchmarks for probability maps of resections and biopsies for glioblastoma. Differences in biopsy rates were identified for the right superior frontal gyrus and indicated variation in biopsy decisions. Differences in resection rates were identified for the left superior parietal lobule, indicating variations in resection decisions.CONCLUSIONS: Probability maps of glioblastoma surgery enabled capture of clinical practice decisions and indicated that teams generally agreed on which region to biopsy or to resect. However, treatment variations reflecting clinical dilemmas were observed and pinpointed by using the probability maps, which could therefore be useful for quality-of-care discussions between surgical teams for patients with glioblastoma.

  View details for DOI 10.3171/2020.11.JNS202897

  View details for PubMedID 34243150

• Safety assessment of intraparenchymal central nervous system biopsies: Single institution healthcare value review JOURNAL OF CLINICAL NEUROSCIENCE Mazur-Hart, D. J., Yaghi, N. K., Goh, J., Lin, Y., Han, S. 2021; 87: 112-115

  Abstract

  The study objective was to evaluate a single institution experience with adult stereotactic intracranial biopsies and review any projected cost savings as a result of bypassing intensive care unit (ICU) admission and limited routine head computed tomography (CT). The authors retrospectively reviewed all stereotactic intracranial biopsies performed at a single institution between February 2012 and March 2019. Primary data collection included ICU length of stay (LOS), hospital LOS, ICU interventions, need for reoperation, and CT use. Secondarily, location of lesion, postoperative hematoma, neurological deficit, pathology, and preoperative coagulopathy data were collected. There were 97 biopsy cases (63% male). Average age, ICU LOS, and total hospital stay were 58.9 years (range; 21-92 years), 2.3 days (range; 0-40 days), and 8.8 days (range 1-115 days), respectively. Seventy-five (75 of 97) patients received a postoperative head CT. No patients required medical or surgical intervention for complications related to biopsy. Eight patients required transfer from the ward to the ICU (none directly related to biopsy). Nine patients transferred directly to the ward postoperatively (none required transfer to ICU). Of the patients who did not receive CT or went directly to the ward, none had extended LOS or required transfer to ICU for neurosurgical concerns. Eliminating routine head CT and ICU admission translates to approximately $584,971 in direct cost savings in 89 cases without a postoperative ICU requirement. These practice changes would save patients' significant hospitalization costs, decrease healthcare expenditures, and allow for more appropriate hospital resource use.

  View details for DOI 10.1016/j.jocn.2021.02.008

  View details for Web of Science ID 000640577800022

  View details for PubMedID 33863517

• Quantifying eloquent locations for glioblastoma surgery using resection probability maps JOURNAL OF NEUROSURGERY Muller, D. J., Robe, P. A., Ardon, H., Barkhof, F., Bello, L., Berger, M. S., Bouwknegt, W., Van den Brink, W. A., Nibali, M., Eijgelaar, R. S., Furtner, J., Han, S. J., Hervey-Jumper, S. L., Idema, A. S., Kiesel, B., Kloet, A., De Munck, J. C., Rossi, M., Sciortino, T., Vandertop, W., Visser, M., Wagemakers, M., Widhalm, G., Witte, M. G., Zwinderman, A. H., Hamer, P. 2021; 134 (4): 1091-1101

  Abstract

  Decisions in glioblastoma surgery are often guided by presumed eloquence of the tumor location. The authors introduce the "expected residual tumor volume" (eRV) and the "expected resectability index" (eRI) based on previous decisions aggregated in resection probability maps. The diagnostic accuracy of eRV and eRI to predict biopsy decisions, resectability, functional outcome, and survival was determined.Consecutive patients with first-time glioblastoma surgery in 2012-2013 were included from 12 hospitals. The eRV was calculated from the preoperative MR images of each patient using a resection probability map, and the eRI was derived from the tumor volume. As reference, Sawaya's tumor location eloquence grades (EGs) were classified. Resectability was measured as observed extent of resection (EOR) and residual volume, and functional outcome as change in Karnofsky Performance Scale score. Receiver operating characteristic curves and multivariable logistic regression were applied.Of 915 patients, 674 (74%) underwent a resection with a median EOR of 97%, functional improvement in 71 (8%), functional decline in 78 (9%), and median survival of 12.8 months. The eRI and eRV identified biopsies and EORs of at least 80%, 90%, or 98% better than EG. The eRV and eRI predicted observed residual volumes under 10, 5, and 1 ml better than EG. The eRV, eRI, and EG had low diagnostic accuracy for functional outcome changes. Higher eRV and lower eRI were strongly associated with shorter survival, independent of known prognostic factors.The eRV and eRI predict biopsy decisions, resectability, and survival better than eloquence grading and may be useful preoperative indices to support surgical decisions.

  View details for DOI 10.3171/2020.1.JNS193049

  View details for Web of Science ID 000646501900001

  View details for PubMedID 32244208

• Prospective prediction of clinical drug response in high-grade gliomas using an ex vivo 3D cell culture assay. Neuro-oncology advances Shuford, S., Lipinski, L., Abad, A., Smith, A. M., Rayner, M., O'Donnell, L., Stuart, J., Mechtler, L. L., Fabiano, A. J., Edenfield, J., Kanos, C., Gardner, S., Hodge, P., Lynn, M., Butowski, N. A., Han, S. J., Redjal, N., Crosswell, H. E., Vibat, C. R., Holmes, L., Gevaert, M., Fenstermaker, R. A., DesRochers, T. M. 2021; 3 (1): vdab065

  Abstract

  Background: Clinical outcomes in high-grade glioma (HGG) have remained relatively unchanged over the last 3 decades with only modest increases in overall survival. Despite the validation of biomarkers to classify treatment response, most newly diagnosed (ND) patients receive the same treatment regimen. This study aimed to determine whether a prospective functional assay that provides a direct, live tumor cell-based drug response prediction specific for each patient could accurately predict clinical drug response prior to treatment.Methods: A modified 3D cell culture assay was validated to establish baseline parameters including drug concentrations, timing, and reproducibility. Live tumor tissue from HGG patients were tested in the assay to establish response parameters. Clinical correlation was determined between prospective ex vivo response and clinical response in ND HGG patients enrolled in 3D-PREDICT (ClinicalTrials.gov Identifier: NCT03561207). Clinical case studies were examined for relapsed HGG patients enrolled on 3D-PREDICT, prospectively assayed for ex vivo drug response, and monitored for follow-up.Results: Absent biomarker stratification, the test accurately predicted clinical response/nonresponse to temozolomide in 17/20 (85%, P = .007) ND patients within 7 days of their surgery, prior to treatment initiation. Test-predicted responders had a median overall survival post-surgery of 11.6 months compared to 5.9 months for test-predicted nonresponders (P = .0376). Case studies provided examples of the clinical utility of the assay predictions and their impact upon treatment decisions resulting in positive clinical outcomes.Conclusion: This study both validates the developed assay analytically and clinically and provides case studies of its implementation in clinical practice.

  View details for DOI 10.1093/noajnl/vdab065

  View details for PubMedID 34142085

• Compassion, communication, and the perception of control: a mixed methods study to investigate patients' perspectives on clinical practices for alleviating distress and promoting empowerment during awake craniotomies. British journal of neurosurgery Colgan, D. D., Eddy, A., Aulet-Leon, M., Green, K., Peters, B., Shangraw, R., Han, S. J., Raslan, A., Oken, B. 2021: 1-12

  Abstract

  To inquire into clinical practices perceived to mitigate patients' intraoperative distress during awake craniotomies.This mixed-methods study involved administration of Amsterdam Preoperative Anxiety and Information Scale and PTSD Checklist prior to the awake craniotomy to evaluate anxiety and information-seeking related to the procedure and symptoms of PTSD. Generalized Anxiety Disorder Scale and Depression Module of the Patient Health Questionnaire were administered before and after the procedure to evaluate generalized anxiety and depression. Patient interviews were conducted 2-weeks postprocedure and included a novel set of patient experience scales to assess patients' recollection of intraoperative pain, overall distress, anxiety, distress due to noise, perception of empowerment, perception of being well-prepared, overall satisfaction with anaesthesia management, and overall satisfaction with the procedure. Qualitative data were analysed using conventional content analysis.Participants (n = 14) had undergone an awake craniotomy for tissue resection due to primary brain tumours or medically-refractory focal epilepsy. Validated self-report questionnaires demonstrated reduced levels of generalized anxiety (pre mean = 8.66; SD = 6.41; post mean= 4.36; SD = 4.24) following the awake craniotomy. Postprocedure interviews revealed very high satisfaction with the awake craniotomy and anaesthesia management and minimal levels of intraoperative pain, anxiety, and distress. The most stressful aspects of the procedure included global recognition of medical diagnosis, anxiety provoked by unfamiliar sights, sounds, and sensations, a perception of a lack of information or misinformation, and long periods of immobility. Important factors in alleviating intraoperative distress included the medical team's ability to promote patient perceptions of control, establish compassionate relationships, address unfamiliar intraoperative sensations, and deliver effective anaesthesia management.Compassion, communication, and patient perception of control were critical in mitigating intraoperative distress. Clinical practice recommendations with implications for all clinicians involved in patient care during awake craniotomies are provided. Use of these interventions and strategies to reduce distress are important to holistic patient care and patient experiences of care and may improve the likelihood of optimal brain mapping procedures to improve clinical outcomes during awake craniotomies.

  View details for DOI 10.1080/02688697.2021.2005773

  View details for PubMedID 34850642

• Changing Hands: A Rising Role of the Tumor Surgeon in Teaching Sylvian Fissure Dissection. World neurosurgery Bowden, S. G., Siler, D. A., Radu, S., Woll, S. C., Rae, A. I., Cheaney, B., Nugent, J. G., Stedelin, B., Cetas, J. S., Dogan, A., Han, S. J. 2021; 146: e86-e90

  Abstract

  The landscape of microneurosurgery has changed considerably over the past 2 decades, with a decline in indications for open surgery on cerebrovascular pathology and ever-increasing indications for open resection of brain tumors. This study investigated how these trends in case volume affected residents' training experiences in microsurgery and, specifically, Sylvian fissure dissection.Resident case logs were reviewed, identifying open cerebrovascular operations and craniotomies for tumor. Operations involving Sylvian fissure dissection were identified through operative reports. Changes in case number by resident were plotted over time, and linear regression was applied.Among 23 chief residents, 3045 operations were identified, 1071 of which were for cerebrovascular pathology and 1974 for tumor. Open cerebrovascular experience decreased (P < 0.0001) while tumor volume remained unchanged (P = 0.221). The number of Sylvian fissure dissections per resident did not change over time overall (P = 0.583) or within cerebrovascular operations (P = 0.071). The number of Sylvian fissure dissections in tumor operations increased (P = 0.004). This effect was predominated by an increase in intraaxial tumors approached via Sylvian fissure dissection (P = 0.003). The proportion of Sylvian fissure dissections in tumor surgery increased from 15% in 2009 to 34% by 2019 (P = 0.003).Residents are seeing an increasing proportion of their Sylvian fissure dissection experience during tumor operations. The distribution of this experience will continue to evolve as surgical indications change but suggests a growing role for tumor surgeons in resident training in microsurgery.

  View details for DOI 10.1016/j.wneu.2020.10.026

  View details for PubMedID 33059079

• The clinical heterogeneity of entirely nonenhancing CNS lymphoma: acase series. CNS oncology Bowden, S. G., Munger, D. N., Thiessen, J., Woll, S. C., Han, S. J., Neuwelt, E. A., Barajas, R. F., Ambady, P. 2021; 10 (1): CNS67

  Abstract

  CNS lymphoma often presents with atypical imaging characteristics leading to delay in diagnosis and initiation of treatment. Among the most rarely reported of these is entirely nonenhancing CNS lymphoma, which is estimated at an incidence of about 1%. Here, we present three cases of nonenhancing CNS lymphoma in immune competent patients at both initial presentation and recurrence and in primary as well as secondary CNS lymphoma. Diffusion- and perfusion-weighted imaging was found helpful in diagnosis in some cases.

  View details for DOI 10.2217/cns-2020-0020

  View details for PubMedID 33322942

• Timing of glioblastoma surgery and patient outcomes: a multicenter cohort study. Neuro-oncology advances Muller, D. M., De Swart, M. E., Ardon, H., Barkhof, F., Bello, L., Berger, M. S., Bouwknegt, W., Van den Brink, W. A., Conti Nibali, M., Eijgelaar, R. S., Furtner, J., Han, S. J., Hervey-Jumper, S., Idema, A. J., Kiesel, B., Kloet, A., Mandonnet, E., Robe, P. A., Rossi, M., Sciortino, T., Vandertop, W. P., Visser, M., Wagemakers, M., Widhalm, G., Witte, M. G., De Witt Hamer, P. C. 2021; 3 (1): vdab053

  Abstract

  Background: The impact of time-to-surgery on clinical outcome for patients with glioblastoma has not been determined. Any delay in treatment is perceived as detrimental, but guidelines do not specify acceptable timings. In this study, we relate the time to glioblastoma surgery with the extent of resection and residual tumor volume, performance change, and survival, and we explore the identification of patients for urgent surgery.Methods: Adults with first-time surgery in 2012-2013 treated by 12 neuro-oncological teams were included in this study. We defined time-to-surgery as the number of days between the diagnostic MR scan and surgery. The relation between time-to-surgery and patient and tumor characteristics was explored in time-to-event analysis and proportional hazard models. Outcome according to time-to-surgery was analyzed by volumetric measurements, changes in performance status, and survival analysis with patient and tumor characteristics as modifiers.Results: Included were 1033 patients of whom 729 had a resection and 304 a biopsy. The overall median time-to-surgery was 13 days. Surgery was within 3 days for 235 (23%) patients, and within a month for 889 (86%). The median volumetric doubling time was 22 days. Lower performance status (hazard ratio [HR] 0.942, 95% confidence interval [CI] 0.893-0.994) and larger tumor volume (HR 1.012, 95% CI 1.010-1.014) were independently associated with a shorter time-to-surgery. Extent of resection, residual tumor volume, postoperative performance change, and overall survival were not associated with time-to-surgery.Conclusions: With current decision-making for urgent surgery in selected patients with glioblastoma and surgery typically within 1 month, we found equal extent of resection, residual tumor volume, performance status, and survival after longer times-to-surgery.

  View details for DOI 10.1093/noajnl/vdab053

  View details for PubMedID 34056605

• The value of visible 5-ALA fluorescence and quantitative protoporphyrin IX analysis for improved surgery of suspected low-grade gliomas JOURNAL OF NEUROSURGERY Widhalm, G., Olson, J., Weller, J., Bravo, J., Han, S. J., Phillips, J., Hervey-Jumper, S. L., Chang, S. M., Roberts, D. W., Berger, M. S. 2020; 133 (1): 79-88

  Abstract

  OBJECTIVEIn patients with suspected diffusely infiltrating low-grade gliomas (LGG), the prognosis is dependent especially on extent of resection and precision of tissue sampling. Unfortunately, visible 5-aminolevulinic acid (5-ALA) fluorescence is usually only present in high-grade gliomas (HGGs), and most LGGs cannot be visualized. Recently, spectroscopic probes were introduced allowing in vivo quantitative analysis of intratumoral 5-ALA-induced protoporphyrin IX (PpIX) accumulation. The aim of this study was to intraoperatively investigate the value of visible 5-ALA fluorescence and quantitative PpIX analysis in suspected diffusely infiltrating LGG.METHODSPatients with radiologically suspected diffusely infiltrating LGG were prospectively recruited, and 5-ALA was preoperatively administered. During resection, visual fluorescence and absolute tissue PpIX concentration (CPpIX) measured by a spectroscopic handheld probe were determined in different intratumoral areas. Subsequently, corresponding tissue samples were safely collected for histopathological analysis. Tumor diagnosis was established according to the World Health Organization 2016 criteria. Additionally, the tumor grade and percentage of tumor cells were investigated in each sample.RESULTSAll together, 69 samples were collected from 22 patients with histopathologically confirmed diffusely infiltrating glioma. Visible fluorescence was detected in focal areas in most HGGs (79%), but in none of the 8 LGGs. The mean CPpIX was significantly higher in fluorescing samples than in nonfluorescing samples (0.693 μg/ml and 0.008 μg/ml, respectively; p < 0.001). A significantly higher mean percentage of tumor cells was found in samples with visible fluorescence compared to samples with no fluorescence (62% and 34%, respectively; p = 0.005), and significant correlation of CPpIX and percentage of tumor cells was found (r = 0.362, p = 0.002). Moreover, high-grade histology was significantly more common in fluorescing samples than in nonfluorescing samples (p = 0.001), whereas no statistically significant difference in mean CPpIX was noted between HGG and LGG samples. Correlation between maximum CPpIX and overall tumor grade was highly significant (p = 0.005). Finally, 14 (40%) of 35 tumor samples with no visible fluorescence and 16 (50%) of 32 LGG samples showed significantly increased CPpIX (cutoff value: 0.005 μg/ml).CONCLUSIONSVisible 5-ALA fluorescence is able to detect focal intratumoral areas of malignant transformation, and additional quantitative PpIX analysis is especially useful to visualize mainly LGG tissue that usually remains undetected by conventional fluorescence. Thus, both techniques will support the neurosurgeon in achieving maximal safe resection and increased precision of tissue sampling during surgery for suspected LGG.Clinical trial registration no.: NCT01116661 (clinicaltrials.gov).

  View details for DOI 10.3171/2019.1.JNS182614

  View details for Web of Science ID 000584371500022

  View details for PubMedID 31075771

• Distinguishing Extravascular from Intravascular Ferumoxytol Pools within the Brain: Proof of Concept in Patients with Treated Glioblastoma. AJNR. American journal of neuroradiology Barajas, R. F., Schwartz, D., McConnell, H. L., Kersch, C. N., Li, X., Hamilton, B. E., Starkey, J., Pettersson, D. R., Nickerson, J. P., Pollock, J. M., Fu, R. F., Horvath, A., Szidonya, L., Varallyay, C. G., Jaboin, J. J., Raslan, A. M., Dogan, A., Cetas, J. S., Ciporen, J., Han, S. J., Ambady, P., Muldoon, L. L., Woltjer, R., Rooney, W. D., Neuwelt, E. A. 2020; 41 (7): 1193-1200

  Abstract

  Glioblastoma-associated macrophages are a major constituent of the immune response to therapy and are known to engulf the iron-based MR imaging contrast agent, ferumoxytol. Current ferumoxytol MR imaging techniques for localizing macrophages are confounded by contaminating intravascular signal. The aim of this study was to assess the utility of a newly developed MR imaging technique, segregation and extravascular localization of ferumoxytol imaging, for differentiating extravascular-from-intravascular ferumoxytol contrast signal at a delayed 24-hour imaging time point.Twenty-three patients with suspected post-chemoradiotherapy glioblastoma progression underwent ferumoxytol-enhanced SWI. Segregation and extravascular localization of ferumoxytol imaging maps were generated as the voxelwise difference of the delayed (24 hours) from the early (immediately after administration) time point SWI maps. Continuous segregation and extravascular localization of ferumoxytol imaging map values were separated into positive and negative components. Image-guided biologic correlation was performed.Negative segregation and extravascular localization of ferumoxytol imaging values correlated with early and delayed time point SWI values, demonstrating that intravascular signal detected in the early time point persists into the delayed time point. Positive segregation and extravascular localization of ferumoxytol imaging values correlated only with delayed time point SWI values, suggesting successful detection of the newly developed extravascular signal.Segregation and extravascular localization of ferumoxytol MR imaging improves on current techniques by eliminating intrinsic tissue and intravascular ferumoxytol signal and may inform glioblastoma outcomes by serving as a more specific metric of macrophage content compared with uncorrected T1 and SWI techniques.

  View details for DOI 10.3174/ajnr.A6600

  View details for PubMedID 32527840

  View details for PubMedCentralID PMC7357650

• Measure Twice: Promise of Liquid Biopsy in Pediatric High-Grade Gliomas ADVANCES IN RADIATION ONCOLOGY Dietz, M. S., Beach, C. Z., Barajas, R., Parappilly, M. S., Sengupta, S. K., Baird, L. C., Ciporen, J. N., Han, S. J., de Mola, R., Cho, Y., Nazemi, K. J., McClelland, S., Wong, M. H., Jaboin, J. J. 2020; 5 (2): 152-162

  Abstract

  To review and critique the current state of liquid biopsy in pHGG.Published literature was reviewed for articles related to liquid biopsy in pediatric glioma and adult glioma with a focus on high-grade gliomas.This review discusses the current state of liquid biomarkers of pHGG and their potential applications for liquid biopsy development.While nascent, the progress toward identifying circulating analytes of pHGG primes the field of neuro-oncoogy for liquid biopsy development.

  View details for DOI 10.1016/j.adro.2019.12.008

  View details for Web of Science ID 000523694100003

  View details for PubMedID 32280814

  View details for PubMedCentralID PMC7136635

• Perioperative outcomes following reoperation for recurrent insular gliomas JOURNAL OF NEUROSURGERY Morshed, R. A., Young, J. S., Han, S. J., Hervey-Jumper, S. L., Berger, M. S. 2019; 131 (2): 467-473

  Abstract

  OBJECTIVEGreater extent of resection (EOR) improves overall survival and progression-free survival for patients with low- and high-grade glioma. While resection for newly diagnosed insular gliomas can be performed with minimal morbidity, perioperative morbidity is not clearly defined for patients undergoing a repeat resection for recurrent insular gliomas. In this study the authors report on tumor characteristics, tumor EOR, and functional outcomes in patients undergoing reoperation for recurrent insular glioma.METHODSAdult patients with insular gliomas (WHO grades II-IV) who underwent index resection followed by reoperation were identified through the University of California San Francisco Brain Tumor Center. Treatment history and functional outcomes were collected retrospectively from the electronic medical record. Pre- and postoperative tumor volumes were quantified using software with region-of-interest analysis based on FLAIR and T1-weighted postgadolinium sequences from pre- and postoperative MRI.RESULTSForty-four patients (63.6% male, 36.4% female) undergoing 49 reoperations for recurrent insular tumors were identified with a median follow-up of 741 days. Left- and right-sided tumors comprised 52.3% and 47.7% of the cohort, respectively. WHO grade II, III, and IV gliomas comprised 46.9%, 28.6%, and 24.5% of the cohort, respectively. Ninety-five percent (95.9%) of cases involved language and/or motor mapping. Median EOR of the insular component of grade II, III, and IV tumors were 82.1%, 75.0%, and 94.6%, respectively. EOR during reoperation was not impacted by Berger-Sanai insular zone or tumor side. At the time of reoperation, 44.9% of tumors demonstrated malignant transformation to a higher WHO grade. Ninety-day postoperative assessment confirmed that 91.5% of patients had no new postoperative deficit attributable to surgery. Of those with new deficits, 3 (6.4%) had a visual field cut and 1 (2.1%) had hemiparesis (strength grade 1-2/5). The presence of a new postoperative deficit did not vary with EOR.CONCLUSIONSRecurrent insular gliomas, regardless of insular zone and pathology, may be reoperated on with an overall acceptable degree of resection and safety despite their anatomical and functional complexities. The use of intraoperative mapping utilizing asleep or awake methods may reduce morbidity to acceptable rates despite prior surgery.

  View details for DOI 10.3171/2018.4.JNS18375

  View details for Web of Science ID 000478642100018

  View details for PubMedID 30239317

• An unusual recurrent high-grade glioneuronal tumor with MAP2K1 mutation and CDKN2A/B homozygous deletion ACTA NEUROPATHOLOGICA COMMUNICATIONS Cheaney, B., Bowden, S., Krause, K., Sloan, E. A., Perry, A., Solomon, D. A., Han, S., Wood, M. D. 2019; 7: 110

  View details for DOI 10.1186/s40478-019-0763-x

  View details for Web of Science ID 000475520800001

  View details for PubMedID 31288852

  View details for PubMedCentralID PMC6617605

• The transcortical equatorial approach for gliomas of the mesial temporal lobe: techniques and functional outcomes JOURNAL OF NEUROSURGERY Morshed, R. A., Young, J. S., Han, S. J., Hervey-Jumper, S. L., Berger, M. S. 2019; 130 (3): 822-830

  Abstract

  OBJECTIVEMany surgical approaches have been described for lesions within the mesial temporal lobe (MTL), but there are limited reports on the transcortical approach for the resection of tumors within this region. Here, the authors describe the technical considerations and functional outcomes in patients undergoing transcortical resection of gliomas of the MTL.METHODSPatients with a glioma (WHO grades I-IV) located within the MTL who had undergone the transcortical approach in the period between 1998 and 2016 were identified through the University of California, San Francisco (UCSF) tumor registry and were classified according to tumor location: preuncus, uncus, hippocampus/parahippocampus, and various combinations of the former groups. Patient and tumor characteristics and outcomes were determined from operative, radiology, pathology, and other clinical reports that were available through the UCSF electronic medical record.RESULTSFifty patients with low- or high-grade glioma were identified. The mean patient age was 46.8 years, and the mean follow-up was 3 years. Seizures were the presenting symptom in 82% of cases. Schramm types A, C, and D represented 34%, 28%, and 38% of the tumors, and the majority of lesions were located at least in part within the hippocampus/parahippocampus. For preuncus and preuncus/uncus tumors, a transcortical approach through the temporal pole allowed for resection. For most tumors of the uncus and those extending into the hippocampus/parahippocampus, a corticectomy was performed within the middle and/or inferior temporal gyri to approach the lesion. To locate the safest corridor for the corticectomy, language mapping was performed in 96.9% of the left-sided tumor cases, and subcortical motor mapping was performed in 52% of all cases. The mean volumetric extent of resection of low- and high-grade tumors was 89.5% and 96.0%, respectively, and did not differ by tumor location or Schramm type. By 3 months' follow-up, 12 patients (24%) had residual deficits, most of which were visual field deficits. Three patients with left-sided tumors (9.4% of dominant-cortex lesions) experienced word-finding difficulty at 3 months after resection, but 2 of these patients demonstrated complete resolution of symptoms by 1 year.CONCLUSIONSMesial temporal lobe gliomas, including larger Schramm type C and D tumors, can be safely and aggressively resected via a transcortical equatorial approach when used in conjunction with cortical and subcortical mapping.

  View details for DOI 10.3171/2017.10.JNS172055

  View details for Web of Science ID 000461011900016

  View details for PubMedID 29676697

• Molecular features and clinical outcomes in surgically treated low-grade diffuse gliomas in patients over the age of 60 JOURNAL OF NEURO-ONCOLOGY Morshed, R. A., Han, S. J., Hervey-Jumper, S. L., Pekmezci, M., Troncon, I., Chang, S. M., Butowski, N. A., Berger, M. S. 2019; 141 (2): 383-391

  Abstract

  WHO grade II gliomas are uncommon in patients over the age of 60, and there is a lack in consensus regarding their management. We present molecular tumor characteristics as well as clinical outcomes in patients over the age of 60 undergoing surgical resection of a WHO grade II glioma.After receiving IRB approval, patients were identified through the UCSF Brain Tumor Center. Pathologic diagnosis was completed using WHO 2016 grading criteria.Twenty-six patients with a mean age of 66 years met inclusion criteria with a median follow-up of 5.2 years. Diagnoses included diffuse astrocytoma IDH-mutant (19.2%), diffuse astrocytoma IDH-wildtype (26.9%), Oligodendroglioma IDH-mutant and 1p/19q-codeleted (50%), and a rare case of mixed oligoastrocytoma (3.9%). 66% of astrocytoma IDH-wildtype tumors possessed TERT mutation. Median extent of resection was 75.4%. Progression-free (PFS) and overall survival (OS) were 23.5 and 62.6 months, respectively. Shorter PFS was associated with the astrocytoma IDH-wildtype subtype despite similar extent of resection and adjuvant treatment rates compared to the other subtypes. OS did not differ between subtypes. Malignant transformation and death were associated with larger preoperative and residual tumor volume.Older patients with diffuse gliomas may safely undergo aggressive treatment with surgical resection and adjuvant therapy. Elderly patients with low grade gliomas have worse clinical outcomes compared to their younger counterparts. This may be due to an increased frequency of diffuse astrocytoma IDH-wildtype tumors in this age group.

  View details for DOI 10.1007/s11060-018-03044-4

  View details for Web of Science ID 000456445800014

  View details for PubMedID 30498891

• Combined iron oxide nanoparticle ferumoxytol and gadolinium contrast enhanced MRI define glioblastoma pseudoprogression. Neuro-oncology Barajas, R. F., Hamilton, B. E., Schwartz, D., McConnell, H. L., Pettersson, D. R., Horvath, A., Szidonya, L., Varallyay, C. G., Firkins, J., Jaboin, J. J., Kubicky, C. D., Raslan, A. M., Dogan, A., Cetas, J. S., Ciporen, J., Han, S. J., Ambady, P., Muldoon, L. L., Woltjer, R., Rooney, W. D., Neuwelt, E. A. 2019; 21 (4): 517-526

  Abstract

  Noninvasively differentiating therapy-induced pseudoprogression from recurrent disease in patients with glioblastoma is prospectively difficult due to the current lack of a biologically specific imaging metric. Ferumoxytol iron oxide nanoparticle MRI contrast characterizes innate immunity mediated neuroinflammation; therefore, we hypothesized that combined ferumoxytol and gadolinium enhanced MRI could serve as a biomarker of glioblastoma pseudoprogression.In this institutional review board-approved, retrospective study, we analyzed ferumoxytol and gadolinium contrast enhanced T1-weighted 3T MRI in 45 patients with glioblastoma over multiple clinical timepoints. Isocitrate dehydrogenase 1 (IDH-1) mutational status was characterized by exome sequencing. Sum of products diameter measurements were calculated according to Response Assessment in Neuro-Oncology criteria from both gadolinium and ferumoxytol enhanced sequences. Enhancement mismatch was calculated as the natural log of the ferumoxytol to gadolinium sum of products diameter ratio. Analysis of variance and Student's t-test assessed differences in mismatch ratios. P-value <0.05 indicated statistical significance.With the development of pseudoprogression we observed a significantly elevated mismatch ratio compared with disease recurrence (P < 0.01) within IDH-1 wild type patients. Patients with IDH-1 mutation demonstrated significantly reduced mismatch ratio with the development of pseudoprogression compared with disease recurrence (P < 0.01). Receiver operator curve analysis demonstrated 100% sensitivity and specificity for the use of mismatch ratios as a diagnostic biomarker of pseudoprogression.Our study suggests that ferumoxytol to gadolinium contrast mismatch ratios are an MRI biomarker for the diagnosis of pseudoprogression in patients with glioblastoma. This may be due to the unique characterization of therapy-induced neuroinflammation.

  View details for DOI 10.1093/neuonc/noy160

  View details for PubMedID 30277536

  View details for PubMedCentralID PMC6422439

• A single case design to examine short-term intracranial EEG patterns during focused meditation. Neuroscience letters Colgan, D. D., Memmott, T., Klee, D., Ernst, L., Han, S. J., Oken, B. 2019; 711: 134441

  Abstract

  This study used a multiple crossover ABAB single case design to examine intracranial EEG data during a breath awareness meditation and an active control task.Visual analyses suggest that a brief breath awareness mediation was consistently associated with increased alpha power when compared to the active control. Less consistent effects were found with theta, beta, and high gamma activity. Nonparametric tests provided additional support for this finding.Acquiring intracranial EEG patterns during a meditative state may provide more insight into the physiology of meditation with less contamination of high-frequency muscle activity. While access to intracranial EEG during meditation is rarely available, single case design studies are considered adaptations of interrupted time-series designs and can provide an experimental evaluation of intervention effects.

  View details for DOI 10.1016/j.neulet.2019.134441

  View details for PubMedID 31430545

  View details for PubMedCentralID PMC6779128

• Resection of primary motor cortex tumors: feasibility and surgical outcomes. Journal of neurosurgery Magill, S. T., Han, S. J., Li, J., Berger, M. S. 2018; 129 (4): 961-972

  Abstract

  Brain tumors involving the primary motor cortex are often deemed unresectable due to the potential neurological consequences that result from injury to this region. Nevertheless, we have challenged this dogma for many years and used asleep, as well as awake, intraoperative stimulation mapping to maximize extent of resection. It remains unclear whether these tumors can be resected with acceptable morbidity, whether performing the surgery with the patient awake or asleep impacts extent of resection, and how stimulation mapping influences outcomes.A retrospective chart review was performed on the senior author's cohort to identify patients treated between 1998 and 2016 who underwent resection of tumors that were located within the primary motor cortex. Clinical notes, operative reports, and radiographic images were reviewed to identify intraoperative stimulation mapping findings and functional outcomes following tumor resection. Extent of resection was quantified volumetrically. Characteristics of patients were analyzed to identify factors associated with postoperative motor deficits.Forty-nine patients underwent 53 resections of tumors located primarily within the motor cortex. Stimulation mapping was performed in all cases. Positive cortical sites for motor response were identified in 91% of cases, and subcortical sites in 74%. Awake craniotomy was performed in 65% of cases, while 35% were done under general anesthesia. The mean extent of resection was 91%. There was no statistically significant difference in extent of resection in cases done awake compared with those done under general anesthesia. New or worsened postoperative motor deficits occurred in 32 patients (60%), and 20 patients (38%) had a permanent deficit. Of the permanent deficits, 14 were mild, 4 were moderate, and 2 were severe (3.8% of cases). Decreased intraoperative motor response and diffusion restriction on postoperative MRI were associated with permanent deficit. Awake motor mapping surgery was associated with increased diffusion signal on postoperative MRI.Resection of tumors from the primary motor cortex is associated with an increased risk of motor deficit, but most of these deficits are transient or mild and have little functional impact. Excellent extent of resection can be achieved with intraoperative stimulation mapping, suggesting that these tumors are indeed amenable to resection and should not be labeled unresectable. Injury to small perforating or en passage blood vessels was the most common cause of infarction that led to moderate or severe deficits. Awake motor mapping was not superior to mapping done under general anesthesia with regard to long-term functional outcome.

  View details for DOI 10.3171/2017.5.JNS163045

  View details for PubMedID 29219753

• Intraoperative perception and estimates on extent of resection during awake glioma surgery: overcoming the learning curve JOURNAL OF NEUROSURGERY Lau, D., Hervey-Jumper, S. L., Han, S. J., Berger, M. S. 2018; 128 (5): 1410-1418

  Abstract

  OBJECTIVE There is ample evidence that extent of resection (EOR) is associated with improved outcomes for glioma surgery. However, it is often difficult to accurately estimate EOR intraoperatively, and surgeon accuracy has yet to be reviewed. In this study, the authors quantitatively assessed the accuracy of intraoperative perception of EOR during awake craniotomy for tumor resection. METHODS A single-surgeon experience of performing awake craniotomies for tumor resection over a 17-year period was examined. Retrospective review of operative reports for quantitative estimation of EOR was recorded. Definitive EOR was based on postoperative MRI. Analysis of accuracy of EOR estimation was examined both as a general outcome (gross-total resection [GTR] or subtotal resection [STR]), and quantitatively (5% within EOR on postoperative MRI). Patient demographics, tumor characteristics, and surgeon experience were examined. The effects of accuracy on motor and language outcomes were assessed. RESULTS A total of 451 patients were included in the study. Overall accuracy of intraoperative perception of whether GTR or STR was achieved was 79.6%, and overall accuracy of quantitative perception of resection (within 5% of postoperative MRI) was 81.4%. There was a significant difference (p = 0.049) in accuracy for gross perception over the 17-year period, with improvement over the later years: 1997-2000 (72.6%), 2001-2004 (78.5%), 2005-2008 (80.7%), and 2009-2013 (84.4%). Similarly, there was a significant improvement (p = 0.015) in accuracy of quantitative perception of EOR over the 17-year period: 1997-2000 (72.2%), 2001-2004 (69.8%), 2005-2008 (84.8%), and 2009-2013 (93.4%). This improvement in accuracy is demonstrated by the significantly higher odds of correctly estimating quantitative EOR in the later years of the series on multivariate logistic regression. Insular tumors were associated with the highest accuracy of gross perception (89.3%; p = 0.034), but lowest accuracy of quantitative perception (61.1% correct; p < 0.001) compared with tumors in other locations. Even after adjusting for surgeon experience, this particular trend for insular tumors remained true. The absence of 1p19q co-deletion was associated with higher quantitative perception accuracy (96.9% vs 81.5%; p = 0.051). Tumor grade, recurrence, diagnosis, and isocitrate dehydrogenase-1 (IDH-1) status were not associated with accurate perception of EOR. Overall, new neurological deficits occurred in 8.4% of cases, and 42.1% of those new neurological deficits persisted after the 3-month follow-up. Correct quantitative perception was associated with lower postoperative motor deficits (2.4%) compared with incorrect perceptions (8.0%; p = 0.029). There were no detectable differences in language outcomes based on perception of EOR. CONCLUSIONS The findings from this study suggest that there is a learning curve associated with the ability to accurately assess intraoperative EOR during glioma surgery, and it may take more than a decade to be truly proficient. Understanding the factors associated with this ability to accurately assess EOR will provide safer surgeries while maximizing tumor resection.

  View details for DOI 10.3171/2017.1.JNS161811

  View details for Web of Science ID 000440650000018

  View details for PubMedID 28731401

• Wavelength-specific lighted suction instrument for 5-aminolevulinic acid fluorescence-guided resection of deep-seated malignant glioma: technical note. Journal of neurosurgery Morshed, R. A., Han, S. J., Lau, D., Berger, M. S. 2018; 128 (5): 1448-1453

  Abstract

  Surgery guided by 5-aminolevulinic acid (ALA) fluorescence has become a valuable adjunct in the resection of malignant intracranial gliomas. Furthermore, the fluorescence intensity of biopsied areas of a resection cavity correlates with histological identification of tumor cells. However, in the case of lesions deep within a resection cavity, light penetration may be suboptimal, resulting in less excitation of 5-ALA metabolites, leading to decreased fluorescence emission. To address this obstacle, the authors report on the use of a 400-nm wavelength fiber-optic lighted suction instrument that can be used both during resection of a tumor and to provide direct light to deeper areas of a resection cavity. In the presented case, this wavelength-specific lighted suction instrument improved the fluorescence intensity of patches of malignant tissue within the resection cavity. This technique may further improve the utility of 5-ALA in identifying tumor-infiltrated tissue for deep-seated lesions. Additionally, this tool may have implications for scoring systems that correlate 5-ALA fluorescence intensity with histological identification of malignant cells.

  View details for DOI 10.3171/2017.1.JNS161949

  View details for PubMedID 28665248

• Familial melanoma-astrocytoma syndrome: synchronous diffuse astrocytoma and pleomorphic xanthoastrocytoma in a patient with germline CDKN2A/B deletion and a significant family history. Clinical neuropathology Chan, A. K., Han, S. J., Choy, W., Beleford, D., Aghi, M. K., Berger, M. S., Shieh, J. T., Bollen, A. W., Perry, A., Phillips, J. J., Butowski, N., Solomon, D. A. 2017; 36 (5): 213-221

  Abstract

  Familial melanoma-astrocytoma syndrome is a tumor predisposition syndrome caused by inactivating germline alteration of the CDKN2A tumor suppressor gene on chromosome 9p21. While some families with germline CDKN2A mutations are prone to development of just melanomas, other families develop both melanomas, astrocytomas, and occasionally other nervous-system neoplasms including peripheral nerve sheath tumors and meningiomas. The histologic spectrum of the astrocytomas that arise as part of this syndrome is not well described, nor are the additional genetic alterations that drive these astrocytomas apart from the germline CDKN2A inactivation. Herein, we report the case of a young man with synchronous development of a pleomorphic xanthoastrocytoma, diffuse astrocytoma, and paraspinal mass radiographically consistent with a peripheral nerve sheath tumor. His paternal family history is significant for melanoma, glioblastoma, and oral squamous cell carcinoma. Genomic profiling revealed that he harbors a heterozygous deletion in the germline of chromosome 9p21.3 encompassing the CDKN2A and CDKN2B tumor suppressor genes. Both the pleomorphic xanthoastrocytoma and diffuse astrocytoma were found to have homozygous deletion of CDKN2A/B due to somatic loss of the other copy of chromosome 9p containing the remaining intact alleles. Additional somatic alterations included BRAF p.V600E mutation in the pleomorphic xanthoastrocytoma and PTPN11, ATRX, and NF1 mutations in the diffuse astrocytoma. The presence of germline CDKN2A/B inactivation together with the presence of multiple anatomically, histologically, and genetically distinct astrocytic neoplasms, both with accompanying somatic loss of heterozygosity for the CDKN2A/B deletion, led to a diagnosis of familial melanoma-astrocytoma syndrome. This remarkable case illustrates the histologic and genetic diversity that astrocytomas arising as part of this rare glioma predisposition syndrome can demonstrate..

  View details for DOI 10.5414/NP301022

  View details for PubMedID 28699883

  View details for PubMedCentralID PMC5628627

• Early tumor growth between initial resection and radiotherapy of glioblastoma: incidence and impact on clinical outcomes. Journal of neuro-oncology Villanueva-Meyer, J. E., Han, S. J., Cha, S., Butowski, N. A. 2017; 134 (1): 213-219

  Abstract

  Early tumor growth, or increased contrast-enhancing tumor not related to evolving post-surgical injury, in the interval between surgical resection and initiation of radiotherapy has implications for treatment planning and clinical outcomes. In this study we evaluated the incidence of early tumor growth, correlated tumor growth with survival outcome measures, and assessed predictors of early tumor growth in glioblastoma. We reviewed the records of patients with newly-diagnosed glioblastoma who underwent surgical resection and chemoradiotherapy at our institution. Patients with preoperative, immediate postoperative, and preradiotherapy MRI were included. Conventional MRI and DWI features were assessed. The correlation between early tumor growth and extent of resection with survival was assessed with Kaplan-Meier analysis. Logistic regression was carried out to evaluate predictors of early tumor growth. Of 140 included patients, sixty-seven cases (48%) had new or increased contrast enhancement attributed to early tumor growth. Median progression free survival (PFS) and overall survival (OS) were shorter in patients with early tumor growth compared to those without early tumor growth (p < 0.001 for both). Additionally, PFS and OS were longer in patients who underwent gross total resection of enhancing tumor (p = 0.016 and <0.001, respectively). Of the evaluated predictors of early growth, subtotal resection was most likely to result in early growth (p < 0.001). Imaging evidence of early tumor growth is often observed at preradiotherapy MRI and is associated with shorter survival. Gross total resection of contrast enhancing tumor decreases likelihood of early tumor growth.

  View details for DOI 10.1007/s11060-017-2511-z

  View details for PubMedID 28567589

  View details for PubMedCentralID PMC5563441

• RESECTION OF PRIMARY MOTOR CORTEX TUMORS: FEASIBILITY AND SURGICAL OUTCOMES Magill, S. T., Han, S. J., Li, J., Berger, M. S. OXFORD UNIV PRESS INC. 2017: 111

  View details for Web of Science ID 000402732900426

• Cost-Effectiveness Analysis of Surgical versus Medical Treatment of Prolactinomas. Journal of neurological surgery. Part B, Skull base Zygourakis, C. C., Imber, B. S., Chen, R., Han, S. J., Blevins, L., Molinaro, A., Kahn, J. G., Aghi, M. K. 2017; 78 (2): 125-131

  Abstract

  Background Few studies address the cost of treating prolactinomas. We performed a cost-utility analysis of surgical versus medical treatment for prolactinomas. Materials and Methods We determined total hospital costs for surgically and medically treated prolactinoma patients. Decision-tree analysis was performed to determine which treatment produced the highest quality-adjusted life years (QALYs). Outcome data were derived from published studies. Results Average total costs for surgical patients were $19,224 ( ± 18,920). Average cost for the first year of bromocriptine or cabergoline treatment was $3,935 and $6,042, with $2,622 and $4,729 for each additional treatment year. For a patient diagnosed with prolactinoma at 40 years of age, surgery has the lowest lifetime cost ($40,473), followed by bromocriptine ($41,601) and cabergoline ($70,696). Surgery also appears to generate high health state utility and thus more QALYs. In sensitivity analyses, surgery appears to be a cost-effective treatment option for prolactinomas across a range of ages, medical/surgical costs, and medical/surgical response rates, except when surgical cure rates are ≤ 30%. Conclusion Our single institution analysis suggests that surgery may be a more cost-effective treatment for prolactinomas than medical management for a range of patient ages, costs, and response rates. Direct empirical comparison of QALYs for different treatment strategies is needed to confirm these findings.

  View details for DOI 10.1055/s-0036-1592193

  View details for PubMedID 28321375

  View details for PubMedCentralID PMC5357228

• Systemic inaccuracies in the National Surgical Quality Improvement Program database: Implications for accuracy and validity for neurosurgery outcomes research JOURNAL OF CLINICAL NEUROSCIENCE Rolston, J. D., Han, S. J., Chang, E. F. 2017; 37: 44-47

  Abstract

  The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) provides a rich database of North American surgical procedures and their complications. Yet no external source has validated the accuracy of the information within this database. Using records from the 2006 to 2013 NSQIP database, we used two methods to identify errors: (1) mismatches between the Current Procedural Terminology (CPT) code that was used to identify the surgical procedure, and the International Classification of Diseases (ICD-9) post-operative diagnosis: i.e., a diagnosis that is incompatible with a certain procedure. (2) Primary anesthetic and CPT code mismatching: i.e., anesthesia not indicated for a particular procedure. Analyzing data for movement disorders, epilepsy, and tumor resection, we found evidence of CPT code and postoperative diagnosis mismatches in 0.4-100% of cases, depending on the CPT code examined. When analyzing anesthetic data from brain tumor, epilepsy, trauma, and spine surgery, we found evidence of miscoded anesthesia in 0.1-0.8% of cases. National databases like NSQIP are an important tool for quality improvement. Yet all databases are subject to errors, and measures of internal consistency show that errors affect up to 100% of case records for certain procedures in NSQIP. Steps should be taken to improve data collection on the frontend of NSQIP, and also to ensure that future studies with NSQIP take steps to exclude erroneous cases from analysis.

  View details for DOI 10.1016/j.jocn.2016.10.045

  View details for Web of Science ID 000394396400011

  View details for PubMedID 27863971

• Treatment options for recurrent high-grade gliomas. CNS oncology Birk, H. S., Han, S. J., Butowski, N. A. 2017; 6 (1): 61-70

  Abstract

  High-grade gliomas are aggressive brain tumors encompassing Grade III and IV classifications. Of these, glioblastoma (GB) is the most malignant with a high rate of recurrence after initial resection. Although standard treatment does exist for newly diagnosed GBs, therapeutic strategies for recurrent GB are less solidified. However, mounting evidence describes the role of re-resection, bevacizumab, chemotherapy, targeted molecular therapies, immunotherapeutic approaches and radiotherapy in recurrent GB management. This review article provides analysis of the aforementioned therapies, through assessing their effect on overall survival. Because GB tumor heterogeneity is prevalent there is a constant need to investigate therapies targeting recurrence. Studies evaluating both therapeutic targets and strategies for high-grade gliomas are and will remain invaluable.

  View details for DOI 10.2217/cns-2016-0013

  View details for PubMedID 28001091

• The transsylvian approach for resection of insular gliomas: technical nuances of splitting the Sylvian fissure JOURNAL OF NEURO-ONCOLOGY Safaee, M. M., Englot, D. J., Han, S. J., Lawton, M. T., Berger, M. S. 2016; 130 (2): 283-287

  Abstract

  Insular gliomas represent a unique surgical challenge due to the complex anatomy and nearby vascular elements associated within the Sylvian fissure. For certain tumors, the transsylvian approach provides an effective technique for achieving maximal safe resection. The goal of this manuscript and video are to present and discuss the surgical nuances and appropriate application of splitting the Sylvian fissure. Our hope is that this video highlights the safety and efficacy of the transsylvian approach for appropriately selected insular gliomas.

  View details for DOI 10.1007/s11060-016-2154-5

  View details for Web of Science ID 000386566100006

  View details for PubMedID 27294356

• Direct visualization of improved optic nerve pial vascular supply following tuberculum meningioma resection: case report JOURNAL OF NEUROSURGERY Han, S. J., Magill, S. T., Tarapore, P. E., Horton, J. C., McDermott, M. W. 2016; 125 (3): 565-569

  Abstract

  Tuberculum sellae meningiomas frequently produce visual loss by direct compression from tumor, constriction of the optic nerve (ON) under the falciform ligament, and/or ON ischemia. The authors hypothesized that changes in visual function after tumor removal may be related to changes in blood supply to the ON that might be seen in the pial circulation at surgery. Indocyanine green (ICG) angiography was used to attempt to document these changes at surgery. The first patient in whom the technique was used had a left-sided, 1.4-cm, tuberculum meningioma. Time-lapse comparison of images was done postsurgery, and the comparison of video images revealed both faster initial filling and earlier complete filling of the ON pial circulation, suggesting improved pial blood flow after surgical decompression. In follow-up the patient had significant improvements in both visual acuity and visual fields function. Intraoperative ICG angiography of the ON can demonstrate measurable changes in pial vascular flow that may be predictive of postoperative visual outcome. The predictive value of this technique during neurosurgical procedures around the optic apparatus warrants further investigation in a larger cohort.

  View details for DOI 10.3171/2015.6.JNS15765

  View details for Web of Science ID 000381782300006

  View details for PubMedID 26684783

  View details for PubMedCentralID PMC5125447

• Seizures in supratentorial meningioma: a systematic review and meta-analysis JOURNAL OF NEUROSURGERY Englot, D. J., Magill, S. T., Han, S. J., Chang, E. F., Berger, M. S., McDermott, M. W. 2016; 124 (6): 1552-1561

  Abstract

  OBJECT Meningioma is the most common benign intracranial tumor, and patients with supratentorial meningioma frequently suffer from seizures. The rates and predictors of seizures in patients with meningioma have been significantly under-studied, even in comparison with other brain tumor types. Improved strategies for the prediction, treatment, and prevention of seizures in patients with meningioma is an important goal, because tumor-related epilepsy significantly impacts patient quality of life. METHODS The authors performed a systematic review of PubMed for manuscripts published between January 1980 and September 2014, examining rates of pre- and postoperative seizures in supratentorial meningioma, and evaluating potential predictors of seizures with separate meta-analyses. RESULTS The authors identified 39 observational case series for inclusion in the study, but no controlled trials. Preoperative seizures were observed in 29.2% of 4709 patients with supratentorial meningioma, and were significantly predicted by male sex (OR 1.74, 95% CI 1.30-2.34); an absence of headache (OR 1.77, 95% CI 1.04-3.25); peritumoral edema (OR 7.48, 95% CI 6.13-9.47); and non-skull base location (OR 1.77, 95% CI 1.04-3.25). After surgery, seizure freedom was achieved in 69.3% of 703 patients with preoperative epilepsy, and was more than twice as likely in those without peritumoral edema, although an insufficient number of studies were available for formal meta-analysis of this association. Of 1085 individuals without preoperative epilepsy who underwent resection, new postoperative seizures were seen in 12.3% of patients. No difference in the rate of new postoperative seizures was observed with or without perioperative prophylactic anticonvulsants. CONCLUSIONS Seizures are common in supratentorial meningioma, particularly in tumors associated with brain edema, and seizure freedom is a critical treatment goal. Favorable seizure control can be achieved with resection, but evidence does not support routine use of prophylactic anticonvulsants in patients without seizures. Limitations associated with systematic review and meta-analysis should be considered when interpreting these results.

  View details for DOI 10.3171/2015.4.JNS142742

  View details for Web of Science ID 000376476200003

  View details for PubMedID 26636386

  View details for PubMedCentralID PMC4889504

• Nationwide shift from microscopic to endoscopic transsphenoidal pituitary surgery. Pituitary Rolston, J. D., Han, S. J., Aghi, M. K. 2016; 19 (3): 248-50

  Abstract

  Transsphenoidal pituitary surgery can be carried out with either an operating microscope or with an endoscope, but the relative frequency of both techniques is unknown.All microscopic and endoscopic transsphenoidal pituitary surgeries were extracted from the Centers for Medicare and Medicaid Services Part B data files between the years 2003 and 2013. National and state-level trends were compared over time.Endoscopic surgery significantly increased and microscopic surgery significantly decreased over the years 2003-2013. Thirty-eight of 48 states increased their use of endoscopic surgery, while 38 of 48 states decreased their use of microscopic surgery.Nationwide data show a clear trend for an increasing use of endoscopic transsphenoidal surgery at the expense of microscopic surgery. The underlying causes of these trends are unknown, but clearly deserve further investigation.

  View details for DOI 10.1007/s11102-015-0685-y

  View details for PubMedID 26441387

  View details for PubMedCentralID PMC4823179

• In Reply: Survival With Glioblastoma Multiforme and the Timing of Chemoradiation NEUROSURGERY Han, S. J., Butowski, N. A. 2016; 78 (2): E315

  View details for DOI 10.1227/NEU.0000000000001078

  View details for Web of Science ID 000368598400007

  View details for PubMedID 26492432

• Awake brain tumor resection during pregnancy: Decision making and technical nuances JOURNAL OF CLINICAL NEUROSCIENCE Meng, L., Han, S. J., Rollins, M. D., Gelb, A. W., Chang, E. F. 2016; 24: 160-162

  Abstract

  The co-occurrence of primary brain tumor and pregnancy poses unique challenges to the treating physician. If a rapidly growing lesion causes life-threatening mass effect, craniotomy for tumor debulking becomes urgent. The choice between awake craniotomy versus general anesthesia becomes complicated if the tumor is encroaching on eloquent brain because considerations pertinent to both patient safety and oncological outcome, in addition to fetal wellbeing, are involved. A 31-year-old female at 30 weeks gestation with twins presented to our hospital seeking awake craniotomy to resect a 7 × 6 × 5 cm left frontoparietal brain tumor with 7 mm left-to-right subfalcine herniation on imaging that led to word finding difficulty, dysfluency, right upper extremity paralysis, and right lower extremity weakness. She had twice undergone tumor debulking under general anesthesia during the same pregnancy at an outside hospital at 16 weeks and 28 weeks gestation. There were considerations both for and against awake brain tumor resection over surgery under general anesthesia. The decision-making process and the technical nuances related to awake brain tumor resection in this neurologically impaired patient are discussed. Awake craniotomy benefits the patient who harbors a tumor that encroaches on the eloquent brain by allowing a greater extent of resection while preserving the language and sensorimotor function. It can be successfully done in pregnant patients who are neurologically impaired. The patient should be motivated and well informed of the details of the process. A multidisciplinary and collaborative effort is also crucial.

  View details for DOI 10.1016/j.jocn.2015.08.021

  View details for Web of Science ID 000369558600038

  View details for PubMedID 26498092

• Preventing Delays in First-Case Starts on the Neurosurgery Service: A Resident-Led Initiative at an Academic Institution. Journal of surgical education Han, S. J., Rolston, J. D., Zygourakis, C. C., Sun, M. Z., McDermott, M. W., Lau, C. Y., Aghi, M. K. 2016; 73 (2): 291–95

  Abstract

  On-time starts for the first case of the day are critical to maintaining efficiency in operating rooms (ORs). We studied whether a resident-led initiative to ensure on-time site marking and documentation of surgical consent could lead to improved first-case start time.In a resident-led initiative at a large 600-bed academic hospital with 25 ORs, we aimed to complete site marking and surgical consents half an hour before the scheduled start time for all first-case neurosurgical patients. We monitored the occurrence of delayed first starts and the length of delay during our initiative, and compared these cases to neurosurgical cases 3 months before the implementation of the initiative and to first-start nonneurosurgical cases.In the year of the initiative, both site marking and surgical consents were completed 30 minutes before the case start in 97% of neurosurgical cases. The average delay across all first-case starts was reduced to 7.17 minutes (N = 1271), compared with 9.67 minutes before the intervention (N = 345). During the study period, non-neurosurgical cases were delayed on average 10.3 minutes (N = 3592). There was a significant difference in latencies between the study period and the period before the initiative (p < 0.001), and also between neurosurgical cases and nonneurosurgical cases (p < 0.001). There was no reduction in delay times seen on the non-neurosurgical services in the study period when compared to the case 3 months before. Considering its effect across 1271 cases, this initiative over 1 year resulted in a total reduction of 52 hours and 57 minutes in delays.Through a resident-led quality improvement program, neurosurgical trainees successfully reduced delays in first-case starts on a surgical service. Engaging physician trainees in quality improvement and enhancing OR efficiency can be successfully achieved and can have a significant clinical and financial effect.

  View details for PubMedID 26774935

• Resident-led Implementation of a Standardized Handoff System to Facilitate Transfer of Postoperative Neurosurgical Patients to the ICU CUREUS Birk, H. S., Han, S. J., Rolston, J. D., Rowland, N. C., Lau, C., Theodosopoulos, P. V., McDermott, M. 2016; 8 (1): e461

  Abstract

  Transitions in care are pivotal moments for patient safety. Although many strategies have been suggested for handoff improvement in the healthcare realm, little focus has been placed on patient safety during the transition from the operative to the postoperative setting. Many surgical trainees have received limited instruction, if any, on how to conduct comprehensive handoffs that ensure the safe transition of care and optimize continuity of care. Therefore, structured transfers of patient care can be invaluable. Here, we describe the implementation of a standardized handoff system developed by residents in an academic neurosurgery department to communicate key perioperative data via both electronic documentation and in-person discussion as a means of reinforcement. Our results are part of a comprehensive effort to strengthen the culture of safety surrounding the care and treatment of neurosurgical patients at our institution.

  View details for DOI 10.7759/cureus.461

  View details for Web of Science ID 000453609800018

  View details for PubMedID 26929888

  View details for PubMedCentralID PMC4762767

• Interventional MRI-guided catheter placement and real time drug delivery to the central nervous system EXPERT REVIEW OF NEUROTHERAPEUTICS Han, S. J., Bankiewicz, K., Butowski, N. A., Larson, P. S., Aghi, M. K. 2016; 16 (6): 635-639

  Abstract

  Local delivery of therapeutic agents into the brain has many advantages; however, the inability to predict, visualize and confirm the infusion into the intended target has been a major hurdle in its clinical development. Here, we describe the current workflow and application of the interventional MRI (iMRI) system for catheter placement and real time visualization of infusion. We have applied real time convection-enhanced delivery (CED) of therapeutic agents with iMRI across a number of different clinical trials settings in neuro-oncology and movement disorders. Ongoing developments and accumulating experience with the technique and technology of drug formulations, CED platforms, and iMRI systems will continue to make local therapeutic delivery into the brain more accurate, efficient, effective and safer.

  View details for DOI 10.1080/14737175.2016.1175939

  View details for Web of Science ID 000377252700007

  View details for PubMedID 27054877

  View details for PubMedCentralID PMC5553275

• Laser Ablation vs Open Resection for Deep-Seated Tumors: The Case for Open Resection. Neurosurgery Han, S. J., Chang, S. M., Berger, M. S. 2016; 63 Suppl 1: 10-14

  View details for DOI 10.1227/NEU.0000000000001288

  View details for PubMedID 27399358

• The Presto 1000: A novel automated transcranial Doppler ultrasound system JOURNAL OF CLINICAL NEUROSCIENCE Han, S. J., Rutledge, W., Englot, D. J., Winkler, E. A., Browne, J. L., Pflugrath, L., Cronsier, D., Abla, A. A., Kliot, M., Lawton, M. T. 2015; 22 (11): 1771-1775

  Abstract

  We examined the reliability and ease of use of a novel automated transcranial Doppler (TCD) system in comparison to a conventional TCD system. TCD ultrasound allows non-invasive monitoring of cerebral blood flow, and can predict arterial vasospasm after a subarachnoid hemorrhage (SAH). The Presto 1000 TCD system (PhysioSonics, Bellevue, WA, USA) is designed for monitoring flow through the M1 segment of the middle cerebral artery (MCA) via temporal windows. The Presto 1000 system was tested across multiple preclinical and clinical settings in parallel with a control predicate TCD system. In a phantom flow generating device, both the Presto 1000 and Spencer system (Spencer Technologies, Redmond, WA, USA) were able to detect velocities with high accuracy. In nine volunteer patients, the Presto system was able to locate the MCA in 14 out of 18 temporal windows, in an average of 12.5s. In the SAH cohort of five patients with a total of 25 paired measurements, the mean absolute difference in flow velocities of the M1 segment, as measured by the two systems, was 17.5 cm/s. These data suggest that the Presto system offers an automated TCD that can reliably localize and detect flow of the MCA, with relative ease of use. The system carries the additional benefit of requiring minimal training for the operator, and can be used by many providers across multiple bedside settings. The mean velocities that were generated warrant further validation across an extended group of patients, and the predictive value for vasospasm should be checked against the current standard of angiography.

  View details for DOI 10.1016/j.jocn.2015.05.026

  View details for Web of Science ID 000363351100012

  View details for PubMedID 26238693

  View details for PubMedCentralID PMC5240787

• Impact of Timing of Concurrent Chemoradiation for Newly Diagnosed Glioblastoma: A Critical Review of Current Evidence. Neurosurgery Han, S. J., Englot, D. J., Birk, H., Molinaro, A. M., Chang, S. M., Clarke, J. L., Prados, M. D., Taylor, J. W., Berger, M. S., Butowski, N. A. 2015; 62 Suppl 1: 160-5

  Abstract

  ABBREVIATIONS: EORTC/NCIC, European Organisation for Research and Treatment of Cancer/National Cancer Institute of CanadaGBM, glioblastomaOS, overall survivalPFS, progression-free survivalSEER, Surveillance, Epidemiology, and End ResultsTMZ, temozolomide.

  View details for DOI 10.1227/NEU.0000000000000801

  View details for PubMedID 26181937

• The Effect of Timing of Concurrent Chemoradiation in Patients With Newly Diagnosed Glioblastoma. Neurosurgery Han, S. J., Rutledge, W. C., Molinaro, A. M., Chang, S. M., Clarke, J. L., Prados, M. D., Taylor, J. W., Berger, M. S., Butowski, N. A. 2015; 77 (2): 248-53; discussion 253

  Abstract

  The effect of timing of initiation of concurrent radiation and chemotherapy after surgery on outcome of patients with glioblastoma (GBM) remains unclear.To further explore this issue, we analyzed 4 clinical trials for patients newly diagnosed with GBM receiving concurrent and adjuvant temozolomide.The cohort study included 198 adult patients with newly diagnosed supratentorial GBM who were enrolled from 2004 to 2010 in 4 clinical trials consisting of radiation plus temozolomide and an experimental agent. The interval to initiation of therapy was determined from the time of surgical resection. The partitioning deletion/substitution/addition algorithm was used to determine the cutoff points for timing of chemoradiation at which there was a significant difference in overall survival (OS) and progression-free survival (PFS).The median wait time between surgery and initiation of concurrent chemoradiation was 29.5 days (range, 7-56 days). A short delay in chemoradiation administration (at 30-34 days) was predictive of prolonged OS (hazard ratio [HR]: 0.63, P = .03) and prolonged PFS (HR: 0.68, P = .06) compared with early initiation of concurrent chemoradiation (<30 days), after adjusting for protocol and baseline prognostic variables including extent of resection by multivariate analysis. A longer delay to chemoradiation beyond 34 days was not associated with improved OS or PFS compared with early initiation (HR: 0.94, P = .77 and HR: 0.91, P = .63, respectively).A short delay in the start of concurrent chemoradiation is beyond the classic paradigm of 4 weeks post-resection and may be associated with prolonged OS and PFS.

  View details for DOI 10.1227/NEU.0000000000000766

  View details for PubMedID 25856113

  View details for PubMedCentralID PMC4506198

• Improving Patient Safety in Neurologic Surgery NEUROSURGERY CLINICS OF NORTH AMERICA Han, S. J., Rolston, J. D., Lau, C. Y., Berger, M. S. 2015; 26 (2): 143-+

  Abstract

  The delivery of safe healthcare is one of the fundamental tenets of medicine, but the study of patient safety has lagged in neurosurgery. Patients are at high risk for medical errors, adverse events, and complications. To prevent and mitigate these risks, it is not enough to shame and blame individual practitioners for mistakes or errors. Complete health care delivery systems should be evaluated for ways to reduce adverse events and errors, and restrict the harm they cause. This article reviews the context of patient safety in history, and outlines the ways in which patient safety is being improved.

  View details for DOI 10.1016/j.nec.2014.11.007

  View details for Web of Science ID 000352518800002

  View details for PubMedID 25771269

• Quality Improvement in Neurosurgery Preface NEUROSURGERY CLINICS OF NORTH AMERICA Rolston, J. D., Han, S. J., Parsa, A. T. 2015; 26 (2): XIII-XIV

  View details for DOI 10.1016/j.nec.2015.01.001

  View details for Web of Science ID 000352518800001

  View details for PubMedID 25771287

• Surgery of basal ganglia, thalamic and brainstem arteriovenous malformations Comprehensive management of of AVMS of the Brain and Spine Potts, M. B., Han, S. J., Lawton, M. T. Cambridge University Press. 2015
• Brainstem arteriovenous malformations: anatomical subtypes, assessment of "occlusion in situ" technique, and microsurgical results. Journal of neurosurgery Han, S. J., Englot, D. J., Kim, H., Lawton, M. T. 2015; 122 (1): 107-17

  Abstract

  The surgical management of brainstem arteriovenous malformations (AVMs) might benefit from the definition of anatomical subtypes and refinements of resection techniques. Many brainstem AVMs sit extrinsically on pia mater rather than intrinsically in the parenchyma, allowing treatment by occluding feeding arteries circumferentially, interrupting draining veins after arteriovenous shunting is eliminated, and leaving the obliterated nidus behind. The authors report here the largest series of brainstem AVMs to define 6 subtypes, assess this "occlusion in situ" technique, and analyze the microsurgical results.Brainstem AVMs were categorized as 1 of 6 types: anterior midbrain, posterior midbrain, anterior pontine, lateral pontine, anterior medullary, and lateral medullary AVMs. Data from a prospectively maintained AVM registry were reviewed to evaluate multidisciplinary treatment results.During a 15-year period, the authors treated 29 patients with brainstem AVMs located in the midbrain (1 anterior and 6 posterior), pons (6 anterior and 7 lateral), and medulla (1 anterior and 8 lateral). The nidus was pial in 26 cases and parenchymal in 3 cases. Twenty-three patients (79%) presented with hemorrhage. Brainstem AVMs were either resected (18 patients, 62%) or occluded in situ (11 patients, 38%). All lateral pontine AVMs were resected, and the occlusion in situ rate was highest with anterior pontine AVMs (83%). Angiography confirmed complete obliteration in 26 patients (89.6%). The surgical mortality rate was 6.9%, and the rate of permanent neurological deterioration was 13.8%. At follow-up (mean 1.3 years), good outcomes (modified Rankin Scale [mRS] score ≤ 2) were observed in 18 patients (66.7%) and poor outcomes (mRS score of 3-5) were observed in 9 patients (33.3%). The mRS scores in 21 patients (77.8%) were unchanged or improved. The best outcomes were observed with lateral pontine (100%) and lateral medullary (75%) AVMs, and the rate of worsening/death was greatest with posterior midbrain and anterior pontine AVMs (50% each).Brainstem AVMs can be differentiated by their location in the brainstem (midbrain, pons, or medulla) and the surface on which they are based (anterior, posterior, or lateral). Anatomical subtypes can help the neurosurgeon determine how to advise patients, with lateral subtypes being a favorable surgical indication along with extrinsic pial location and hemorrhagic presentation. Most AVMs are dissected with the intention to resect them, and occlusion in situ is reserved for those AVMs that do not separate cleanly from the brainstem, that penetrate into the parenchyma, or are more anterior in location, where it is difficult to visualize and preserve perforating arteries (anterior pontine and lateral medullary AVMs). Although surgical morbidity is considerable, surgery results in a better obliteration rate than nonoperative management and is indicated in highly selected patients with high rerupture risks.

  View details for DOI 10.3171/2014.8.JNS1483

  View details for PubMedID 25343188

  View details for PubMedCentralID PMC5261863

• Gangliogliomas of the optic pathway JOURNAL OF CLINICAL NEUROSCIENCE Rolston, J. D., Han, S. J., Cotter, J. A., El-Sayed, I. H., Aghi, M. K. 2014; 21 (12): 2244-2249

  Abstract

  Gangliogliomas involving the optic apparatus are rare, with only 23 cases described in the literature to our knowledge. Because of their location, they are resistant to gross total resection and command careful consideration of adjuvant treatment. Here, we review the existing literature describing these cases, along with our own additional patient. Most patients (91.3%) with optic gangliogliomas presented with progressive visual disturbances, and the majority were male (69.6%), as with gangliogliomas in general. Ophthalmological evaluation is warranted in these patients, followed by neurological imaging (preferably MRI). Screening for neurofibromatosis type 1 (NF1) is essential, as NF1 patients represent a disproportionate number of optic ganglioglioma cases (13.0%). Gross total resection should be attempted only if vision is beyond salvage, as this can be curative. Otherwise, when serviceable vision remains, subtotal resection with adjuvant radiation should be carried out when feasible. Despite treatment, the prognosis remains mixed, with roughly one-third of patients progressing.

  View details for DOI 10.1016/j.jocn.2014.05.018

  View details for Web of Science ID 000346622900038

  View details for PubMedID 25043166

• Medical errors in neurosurgery. Surgical neurology international Rolston, J. D., Zygourakis, C. C., Han, S. J., Lau, C. Y., Berger, M. S., Parsa, A. T. 2014; 5 (Suppl 10): S435-40

  Abstract

  Medical errors cause nearly 100,000 deaths per year and cost billions of dollars annually. In order to rationally develop and institute programs to mitigate errors, the relative frequency and costs of different errors must be documented. This analysis will permit the judicious allocation of scarce healthcare resources to address the most costly errors as they are identified.Here, we provide a systematic review of the neurosurgical literature describing medical errors at the departmental level. Eligible articles were identified from the PubMed database, and restricted to reports of recognizable errors across neurosurgical practices. We limited this analysis to cross-sectional studies of errors in order to better match systems-level concerns, rather than reviewing the literature for individually selected errors like wrong-sided or wrong-level surgery.Only a small number of articles met these criteria, highlighting the paucity of data on this topic. From these studies, errors were documented in anywhere from 12% to 88.7% of cases. These errors had many sources, of which only 23.7-27.8% were technical, related to the execution of the surgery itself, highlighting the importance of systems-level approaches to protecting patients and reducing errors.Overall, the magnitude of medical errors in neurosurgery and the lack of focused research emphasize the need for prospective categorization of morbidity with judicious attribution. Ultimately, we must raise awareness of the impact of medical errors in neurosurgery, reduce the occurrence of medical errors, and mitigate their detrimental effects.

  View details for DOI 10.4103/2152-7806.142777

  View details for PubMedID 25371849

  View details for PubMedCentralID PMC4209704

• What clinical factors predict the incidence of deep venous thrombosis and pulmonary embolism in neurosurgical patients? JOURNAL OF NEUROSURGERY Rolston, J. D., Han, S. J., Bloch, O., Parsa, A. T. 2014; 121 (4): 908-918

  Abstract

  Venous thromboembolisms (VTEs) occur frequently in surgical patients and can manifest as pulmonary emboli (PEs) or deep venous thromboses (DVTs). While many medical therapies have been shown to prevent VTEs, neurosurgeons are concerned about the use of anticoagulants in the postoperative setting. To better understand the prevalence of and the patient-level risk factors for VTE, the authors analyzed data from the National Surgical Quality Improvement Program (NSQIP).Retrospective data on 1,777,035 patients for the years from 2006 to 2011 were acquired from the American College of Surgeons NSQIP database. Neurosurgical cases were extracted by querying the data for which the surgical specialty was listed as "neurological surgery." Univariate statistics were calculated using the chi-square test, with 95% confidence intervals used for the resultant risk ratios. Multivariate models were constructed using binary logistic regression with a maximum number of 20 iterations.Venous thromboembolisms were found in 1.7% of neurosurgical patients, with DVTs roughly twice as common as PEs (1.3% vs 0.6%, respectively). Significant independent predictors included ventilator dependence, immobility (that is, quadriparesis, hemiparesis, or paraparesis), chronic steroid use, and sepsis. The risk of VTE was significantly higher in patients who had undergone cranial procedures (3.4%) than in those who had undergone spinal procedures (1.1%).Venous thromboembolism is a common complication in neurosurgical patients, and the frequency has not changed appreciably over the past several years. Many factors were identified as independently predictive of VTEs in this population: ventilator dependence, immobility, and malignancy. Less anticipated predictors included chronic steroid use and sepsis. Venous thromboembolisms appear significantly more likely to occur in patients undergoing cranial procedures than in those undergoing spinal procedures. A better appreciation of the prevalence of and the risk factors for VTEs in neurosurgical patients will allow targeting of interventions and a better understanding of which patients are most at risk.

  View details for DOI 10.3171/2014.6.JNS131419

  View details for Web of Science ID 000342973300022

  View details for PubMedID 25084467

• Epilepsy surgery failure in children: a quantitative and qualitative analysis. Journal of neurosurgery. Pediatrics Englot, D. J., Han, S. J., Rolston, J. D., Ivan, M. E., Kuperman, R. A., Chang, E. F., Gupta, N., Sullivan, J. E., Auguste, K. I. 2014; 14 (4): 386-95

  Abstract

  Resection is a safe and effective treatment option for children with pharmacoresistant focal epilepsy, but some patients continue experience seizures after surgery. While most studies of pediatric epilepsy surgery focus on predictors of postoperative seizure outcome, these factors are often not modifiable, and the reasons for surgical failure may remain unclear.The authors performed a retrospective cohort study of children and adolescents who received focal resective surgery for pharmacoresistant epilepsy. Both quantitative and qualitative analyses of factors associated with persistent postoperative seizures were conducted.Records were reviewed from 110 patients, ranging in age from 6 months to 19 years at the time of surgery, who underwent a total of 115 resections. At a mean 3.1-year follow-up, 76% of patients were free of disabling seizures (Engel Class I outcome). Seizure freedom was predicted by temporal lobe surgery compared with extratemporal resection, tumor or mesial temporal sclerosis compared with cortical dysplasia or other pathologies, and by a lower preoperative seizure frequency. Factors associated with persistent seizures (Engel Class II-IV outcome) included residual epileptogenic tissue adjacent to the resection cavity (40%), an additional epileptogenic zone distant from the resection cavity (32%), and the presence of a hemispheric epilepsy syndrome (28%).While seizure outcomes in pediatric epilepsy surgery may be improved by the use of high-resolution neuroimaging and invasive electrographic studies, a more aggressive resection should be considered in certain patients, including hemispherectomy if a hemispheric epilepsy syndrome is suspected. Family counseling regarding treatment expectations is critical, and reoperation may be warranted in select cases.

  View details for DOI 10.3171/2014.7.PEDS13658

  View details for PubMedID 25127098

  View details for PubMedCentralID PMC4393949

• Tumors of the anterior skull base EXPERT REVIEW OF NEUROTHERAPEUTICS Ivan, M. E., Han, S. J., Aghi, M. K. 2014; 14 (4): 425-438

  Abstract

  A variety of histologic tumor types are present in the anterior skull base. Primary tumors of this area may be derived from the bone, paranasal sinuses, nasopharynx, dura, cranial nerves, pituitary gland and brain. Symptoms are caused mostly through mass effect but, if the tumor becomes aggressive, also through invasion. Selection of surgical approaches to the anterior skull base is based upon balancing risk reduction with maximizing extent of resection. Here we review a spectrum of neoplastic entities found in the anterior skull base in adults and discuss clinical and radiographic presentation, treatment options, and outcomes. Surgical resection remains the mainstay in treatment of these tumors, particularly in the hands of experienced surgeons exercising proper patient and case selection.

  View details for DOI 10.1586/14737175.2014.892830

  View details for Web of Science ID 000335329800009

  View details for PubMedID 24564556

• Rathke's cleft cysts: review of natural history and surgical outcomes. Journal of neuro-oncology Han, S. J., Rolston, J. D., Jahangiri, A., Aghi, M. K. 2014; 117 (2): 197-203

  Abstract

  Rathke's cleft cysts (RCCs), also known as pars intermedia cysts, represent benign lesions formed from remnants of the embryologic Rathke's pouch. Commonly asymptomatic, they are identified in nearly 1 in 6 healthy volunteers undergoing brain imaging. When symptomatic, they can cause headaches, endocrine dysfunction, and, rarely, visual disturbances. A systematic review of the published English literature was performed focusing on large modern case series of RCCs to describe their natural history, clinicopathologic features, radiographic features, and surgical outcomes, including rates of recurrence. The natural history of asymptomatic RCCs is one of slow growth, suggesting that observation through serial magnetic resonance imaging is appropriate for smaller asymptomatic RCCs. Symptomatic RCCs can be treated by surgical resection with low morbidity, usually through an endonasal transsphenoidal corridor using either a microscope or an endoscope. Surgical treatment frequently provides symptomatic relief of headaches and visual disturbances, and sometimes even improves endocrine dysfunction. Rates of recurrence after surgical treatment range from 16 to 18 % in large series, and higher rates of recurrence are associated with suprasellar location, inflammation and reactive squamous metaplasia in the cyst wall, superinfection of the cyst, and use of a fat graft into the cyst cavity.

  View details for DOI 10.1007/s11060-013-1272-6

  View details for PubMedID 24146189

• Frequency and predictors of complications in neurological surgery: national trends from 2006 to 2011 JOURNAL OF NEUROSURGERY Rolston, J. D., Han, S. J., Lau, C. Y., Berger, M. S., Parsa, A. T. 2014; 120 (3): 736-745

  Abstract

  Surgical complications increase the cost of health care worldwide and directly contribute to patient morbidity and mortality. In an effort to mitigate morbidity and incentivize best practices, stakeholders such as health insurers and the US government are linking reimbursement to patient outcomes. In this study the authors analyzed a national database to determine basic metrics of how comorbidities specifically affect the subspecialty of neurosurgery.Data on 1,777,035 patients for the years 2006-2011 were acquired from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Neurosurgical cases were extracted by querying the data for which the surgical specialty was listed as "neurological surgery." Univariate statistics were calculated using the chi-square test, and 95% confidence intervals were determined for the resultant risk ratios. A multivariate model was constructed using significant variables from the univariate analysis (p < 0.05) with binary logistic regression.Over 38,000 neurosurgical cases were analyzed, with complications occurring in 14.3%. Cranial cases were 2.6 times more likely to have complications than spine cases, and African Americans and Asians/Pacific Islanders were also at higher risk. The most frequent complications were bleeding requiring transfusion (4.5% of patients) and reoperation within 30 days of the initial operation (4.3% of patients), followed by failure to wean from mechanical ventilation postoperatively (2.5%). Significant predictors of complications included preoperative stroke, sepsis, blood transfusion, and chronic steroid use.Understanding the landscape of neurosurgical complications will allow better targeting of the most costly and harmful complications of preventive measures. Data from the ACS NSQIP database provide a starting point for developing paradigms of improved care of neurosurgical patients.

  View details for DOI 10.3171/2013.10.JNS122419

  View details for Web of Science ID 000332048800024

  View details for PubMedID 24266542

• Two-part parasagittal craniotomy: technical note Cureus Burke, J. F., Han, S. J., Han, J. H., et al 2014
• Targeted reduction in neurosurgical laboratory utilization: resident-led effort at a single academic institution. Journal of neurosurgery Han, S. J., Saigal, R., Rolston, J. D., Cheng, J. S., Lau, C. Y., Mistry, R. I., McDermott, M. W., Berger, M. S. 2014; 120 (1): 173-7

  Abstract

  Given economic limitations and burgeoning health care costs, there is a need to minimize unnecessary diagnostic laboratory tests.The authors studied whether a financial incentive program for trainees could lead to fewer unnecessary laboratory tests in neurosurgical patients in a large, 600-bed academic hospital setting. The authors identified 5 laboratory tests that ranked in the top 13 of the most frequently ordered during the 2010-2011 fiscal year, yet were least likely to be abnormal or influence patient management.In a single year of study, there was a 47% reduction in testing of serum total calcium, ionized calcium, chloride, magnesium, and phosphorus. This reduction led to a savings of $1.7 million in billable charges to health care payers and $75,000 of direct costs to the medical center. In addition, there were no significant negative changes in the quality of care delivered, as recorded in a number of metrics, showing that this cost savings did not negatively impact patient care.Engaging physician trainees in quality improvement can be successfully achieved by financial incentives. Through the resident-led quality improvement incentive program, neurosurgical trainees successfully reduced unnecessary laboratory tests, resulting in significant cost savings to both the medical center and the health care system. Similar programs that engage trainees could improve the value of care being provided at other academic medical centers.

  View details for DOI 10.3171/2013.8.JNS13512

  View details for PubMedID 24125592

• Morbidity of repeat transsphenoidal surgery assessed in more than 1000 operations. Journal of neurosurgery Jahangiri, A. n., Wagner, J. n., Han, S. W., Zygourakis, C. C., Han, S. J., Tran, M. T., Miller, L. M., Tom, M. W., Kunwar, S. n., Blevins, L. S., Aghi, M. K. 2014; 121 (1): 67–74

  Abstract

  OBJECT.: While transsphenoidal surgery is associated with low morbidity, the degree to which morbidity increases after reoperation remains unclear. The authors determined the morbidity associated with repeat versus initial transsphenoidal surgery after 1015 consecutive operations.The authors conducted a 5-year retrospective review of the first 916 patients undergoing transsphenoidal surgery at their institution after a pituitary center of expertise was established, and they analyzed morbidities.The authors analyzed 907 initial and 108 repeat transsphenoidal surgeries performed in 916 patients (9 initial surgeries performed outside the authors' center were excluded). The most common diagnoses were endocrine inactive (30%) or active (36%) adenomas, Rathke's cleft cysts (10%), and craniopharyngioma (3%). Morbidity of initial surgery versus reoperation included diabetes insipidus ([DI] 16% vs 26%; p = 0.03), postoperative hyponatremia (20% vs 16%; p = 0.3), new postoperative hypopituitarism (5% vs 8%; p = 0.3), CSF leak requiring repair (1% vs 4%; p = 0.04), meningitis (0.4% vs 3%; p = 0.02), and length of stay ([LOS] 2.8 vs 4.5 days; p = 0.006). Of intraoperative parameters and postoperative morbidities, 1) some (use of lumbar drain and new postoperative hypopituitarism) did not increase with second or subsequent reoperations (p = 0.3-0.9); 2) some (DI and meningitis) increased upon second surgery (p = 0.02-0.04) but did not continue to increase for subsequent reoperations (p = 0.3-0.9); 3) some (LOS) increased upon second surgery and increased again for subsequent reoperations (p < 0.001); and 4) some (postoperative hyponatremia and CSF leak requiring repair) did not increase upon second surgery (p = 0.3) but went on to increase upon subsequent reoperations (p = 0.001-0.02). Multivariate analysis revealed that operation number, but not sex, age, pathology, radiation therapy, or lesion size, increased the risk of CSF leak, meningitis, and increased LOS. Separate analysis of initial versus repeat transsphenoidal surgery on the 2 most common benign pituitary lesions, pituitary adenomas and Rathke's cleft cysts, revealed that the increased incidence of DI and CSF leak requiring repair seen when all pathologies were combined remained significant when analyzing only pituitary adenomas and Rathke's cleft cysts (DI, 13% vs 35% [p = 0.001]; and CSF leak, 0.3% vs 9% [p = 0.0009]).Repeat transsphenoidal surgery was associated with somewhat more frequent postoperative DI, meningitis, CSF leak requiring repair, and greater LOS than the low morbidity characterizing initial transsphenoidal surgery. These results provide a framework for neurosurgeons in discussing reoperation for pituitary disease with their patients.

  View details for DOI 10.3171/2014.3.JNS131532

  View details for PubMedID 24834943

• Socioeconomic factors associated with pituitary apoplexy JOURNAL OF NEUROSURGERY Jahangiri, A., Clark, A. J., Han, S. J., Kunwar, S., Blevins, L. S., Aghi, M. K. 2013; 119 (6): 1432-1436

  Abstract

  Pituitary apoplexy is associated with worse outcomes than are pituitary adenomas detected without acute clinical deterioration. The association between pituitary apoplexy and socioeconomic factors that may limit access to health care has not been examined in prior studies.This study involved retrospectively evaluating data obtained in all patients who underwent surgery for nonfunctioning pituitary adenoma causing visual symptoms between January 2003 and July 2012 at the University of California, San Francisco. Patients were grouped into those who presented with apoplexy and those who did not ("no apoplexy"). The 2 groups were compared with respect to annual household income, employment status, health insurance status, and whether or not the patient had a primary health care provider. Associations between categorical variables were analyzed by chi-square test and continuous variables by Student t-test. Multivariate logistic regression was also performed.One hundred thirty-five patients were identified, 18 of whom presented with apoplexy. There were significantly more unmarried patients and emergency room presentations in the apoplexy group than in the "no apoplexy" group. There was a nonsignificant trend toward lower mean household income in the apoplexy group. Lack of health insurance and lack of a primary health care provider were both highly significantly associated with apoplexy. In a multivariate analysis including marital status, emergency room presentation, income, insurance status, and primary health care provider status as variables, lack of insurance remained associated with apoplexy (OR 11.6; 95% CI 1.9-70.3; p = 0.008).The data suggest that patients with limited access to health care may be more likely to present with pituitary apoplexy than those with adequate access.

  View details for DOI 10.3171/2013.6.JNS122323

  View details for Web of Science ID 000327367200011

  View details for PubMedID 23889139

• Multidisciplinary Care of Patients with Brain Tumors SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA Huang, T., Mueller, S., Rutkowski, M. J., Han, S. J., Bloch, O., Barani, I. J., Parsa, A. T., Chang, S. M. 2013; 22 (2): 161-?

  Abstract

  Patients with brain tumors are some of the most complex patients in the medical system, necessitating treatment teams of multiple subspecialists for optimal care. This article examines the roles of these subspecialists, with the goal of summarizing standard-of-care practices, recent therapeutic advances, and ongoing clinical investigations within each subspecialty.

  View details for DOI 10.1016/j.soc.2012.12.011

  View details for Web of Science ID 000316973500003

  View details for PubMedID 23453330

• Keyhole revision after failed subdural craniostomy for chronic subdural hematoma: technical note Cureus Rolston, J. D., Han, S. J., McDermott, M. W. 2013
• Individual Patient-Specific Immunity against High-Grade Glioma after Vaccination with Autologous Tumor Derived Peptides Bound to the 96 KD Chaperone Protein CLINICAL CANCER RESEARCH Crane, C. A., Han, S. J., Ahn, B., Oehlke, J., Kivett, V., Fedoroff, A., Butowski, N., Chang, S. M., Clarke, J., Berger, M. S., McDermott, M. W., Prados, M. D., Parsa, A. T. 2013; 19 (1): 205-214

  Abstract

  Cancer immunotherapy offers hope of a highly specific nontoxic adjuvant treatment. Heat shock protein peptide complexes (HSPPCs) found in cancer cells carry tumor-specific antigenic proteins and can facilitate adaptive and innate immune responses. Here we show that peptides bound to a 96 kD chaperone protein (HSP-96) from brain tissue containing glioblastoma multiforme (GBM) can be used to safely immunize patients with recurrent GBM.Multimodality immunomonitoring was completed on 12 patients with recurrent GBM before and after immunization with an autologous HSPPC vaccine derived from surgically resected tumor. Clinical endpoints included safety assessments and overall survival.No adverse events attributable to the vaccine were found. Testing of peripheral blood leukocytes before and after vaccination revealed a significant peripheral immune response specific for the peptides bound to HSP-96, in 11 of the 12 patients treated. Brain biopsies of immune responders after vaccination revealed focal CD4, CD8, and CD56 IFNγ positive cell infiltrates, consistent with tumor site specific immune responses. Immune responders had a median survival of 47 weeks after surgery and vaccination, compared with 16 weeks for the single nonresponder.These data provide the first evidence in humans of individual patient-specific immune responses against autologous tumor derived peptides bound to HSP-96.

  View details for DOI 10.1158/1078-0432.CCR-11-3358

  View details for Web of Science ID 000313051100022

  View details for PubMedID 22872572

• Rathke’s cleft cysts Pituitary Disorders: Diagnosis and Management Han, S. J., Jahangiri, A., Aghi, M. K. Wiley-Blackwell Publishers. 2013; 1
• Impact of extent of resection for recurrent glioblastoma on overall survival Clinical article JOURNAL OF NEUROSURGERY Bloch, O., Han, S. J., Cha, S., Sun, M. Z., Aghi, M. K., McDermott, M. W., Berger, M. S., Parsa, A. T. 2012; 117 (6): 1032-1038

  Abstract

  Extent of resection (EOR) has been shown to be an important prognostic factor for survival in patients undergoing initial resection of glioblastoma (GBM), but the significance of EOR at repeat craniotomy for recurrence remains unclear. In this study the authors investigate the impact of EOR at initial and repeat resection of GBM on overall survival.Medical records were reviewed for all patients undergoing craniotomy for GBM at the University of California San Francisco Medical Center from January 1, 2005, through August 15, 2009. Patients who had a second craniotomy for pathologically confirmed recurrence following radiation and chemotherapy were evaluated. Volumetric EOR was measured and classified as gross-total resection (GTR, > 95% by volume) or subtotal resection (STR, ≤ 95% by volume) after independent radiological review. Overall survival was compared between groups using univariate and multivariate analysis accounting for known prognostic factors, including age, eloquent location, Karnofsky Performance Status (KPS), and adjuvant therapies.Multiple resections were performed in 107 patients. Fifty-two patients had initial GTR, of whom 31 (60%) had GTR at recurrence, with a median survival of 20.4 months (standard error [SE] 1.0 months), and 21 (40%) had STR at recurrence, with a median survival of 18.4 months (SE 0.5 months) (difference not statistically significant). Initial STR was performed in 55 patients, of whom 26 (47%) had GTR at recurrence, with a median survival of 19.0 months (SE 1.2 months), and 29 (53%) had STR, with a median survival of 15.9 months (SE 1.2 months) (p = 0.004). A Cox proportional hazards model was constructed demonstrating that age (HR 1.03, p = 0.004), KPS score at recurrence (HR 2.4, p = 0.02), and EOR at repeat resection (HR 0.62, p = 0.02) were independent predictors of survival. Extent of initial resection was not a statistically significant factor (p = 0.13) when repeat EOR was included in the model, suggesting that GTR at second craniotomy could overcome the effect of an initial STR.Extent of resection at recurrence is an important predictor of overall survival. If GTR is achieved at recurrence, overall survival is maximized regardless of initial EOR, suggesting that patients with initial STR may benefit from surgery with a GTR at recurrence.

  View details for DOI 10.3171/2012.9.JNS12504

  View details for Web of Science ID 000311463900008

  View details for PubMedID 23039151

• Creating a culture of safety within operative neurosurgery: the design and implementation of a perioperative safety video NEUROSURGICAL FOCUS Lau, C. Y., Greys, S., Mistry, R. I., Han, S. J., Mummaneni, P. V., Berger, M. S. 2012; 33 (5): E3

  Abstract

  Surgical and medical errors result from failures in communication and handoffs as well as lack of standardization in clinical protocols and safety practices. Checklists, simulation training, and teamwork training have been shown to decrease adverse patient events and increase the safety culture of surgical teams. The goal of this project was to simplify and standardize perioperative patient safety practices and team communication processes within operative neurosurgery through the creation of an educational safety video targeted at a neurosurgical provider audience.A multidisciplinary group consisting of neurosurgeons, anesthesiologists, nurses, neuromonitoring specialists, quality champions, and a professional video production company met over several months in an iterative process to 1) determine the overall objectives of the video, 2) decide on the content and format of the video, 3) modify the proposed content and format based on stakeholder feedback, and 4) record the video and complete final revisions during postproduction.The video was launched within the authors' institution in July 2012 in conjunction with ongoing research projects to study the effects of the video on 1) multidisciplinary providers' knowledge of perioperative safety practices, 2) provider safety attitudes and safety culture in the operating room, and 3) provider behavior in performing predetermined elements of the preoperative timeout and postoperative debrief.The neurosurgical perioperative safety video can serve as a national model for how quality champions can drive changes in safety culture and provider behavior among multidisciplinary perioperative patient care teams. Ongoing research is being performed to assess the impact of the video on provider knowledge, behavior, and safety attitudes and culture.

  View details for DOI 10.3171/2012.9.FOCUS12244

  View details for Web of Science ID 000310628100004

  View details for PubMedID 23116098

• Seizure Predictors and Control After Microsurgical Resection of Supratentorial Arteriovenous Malformations in 440 Patients NEUROSURGERY Englot, D. J., Young, W. L., Han, S. J., McCulloch, C. E., Chang, E. F., Lawton, M. T. 2012; 71 (3): 572-579

  Abstract

  Seizures are a common symptom of supratentorial arteriovenous malformations (AVMs), and uncontrolled epilepsy can considerably reduce patient quality of life. Potential risk factors for epilepsy in patients with AVMs are poorly understood, and the importance of achieving freedom from seizures in their surgical treatment remains underappreciated.To characterize risks factors for preoperative seizures and factors associated with postoperative freedom from seizures in patients with surgically resected supratentorial AVMs.We analyzed prospectively collected patient data for 440 patients who underwent microsurgical resection of supratentorial AVMs at our institution.Among 440 patients with supratentorial AVMs, 130 (30%) experienced preoperative seizures, and 23 (18%) with seizures progressed to medically refractory epilepsy. Seizures were associated with a history of AVM hemorrhage (relative risk, 6.65; 95% confidence interval [CI], 3.81-11.6), male sex (relative risk, 2.07; 95% CI, 1.26-3.39), and frontotemporal lesion location (relative risk, 1.75; 95% CI, 1.05-2.93). After resection, 96% of patients had a modified Engel class I outcome, characterized by freedom from seizures (80%) or only 1 postoperative seizure (16%; mean follow-up, 20.7 ± 2.3 months). Comparable rates of postoperative seizures were seen in patients with (7%) or without (3%) preoperative seizures. AVMs with deep artery perforators were significantly associated with postoperative seizures (hazard ratio, 4.35; 95% CI, 1.61-11.7).In the microsurgical treatment of supratentorial AVMs, hemorrhage, male sex, and frontotemporal location are associated with higher rates of preoperative seizures, whereas deep artery perforators are associated with postoperative seizures. Achieving freedom from seizure is an important goal that can be achieved in the surgical treatment of AVMs because epilepsy can significantly diminish patient quality of life.

  View details for DOI 10.1227/NEU.0b013e31825ea3ba

  View details for Web of Science ID 000308074400012

  View details for PubMedID 22592327

  View details for PubMedCentralID PMC5815296

• The effect of the 2003 Consensus Reporting Standards on publications describing patients with vestibular schwannoma treated with stereotactic radiosurgery. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Han, S. J., Oh, M. C., Sughrue, M. E., Rutkowski, M. J., Aranda, D., Barani, I. J., Parsa, A. T. 2012; 19 (8): 1144-7

  Abstract

  In an effort to promote a uniform standard for reporting clinical results, the Consensus Meeting on Systems for Reporting Results in Acoustic Neuroma was convened in 2001, and the results of this meeting have been summarized by Kanzaki et al. in 2003. We describe publication compliance to these reporting parameters in a systematic analysis of publications obtained through a comprehensive literature search on patients with vestibular schwannoma (VS) treated with stereotactic radiosurgery (SRS). Each publication was scored based on whether it had properly reported each of eight elements described in the Consensus Meeting Reporting Guidelines (Guidelines). We compared the proportions of studies and cases that included each of the eight items prior to, and after, publication of the Guidelines. A significantly greater proportion of studies appropriately reported the size of the tumor after the release of the Guidelines (98% compared to 85%, p=0.04). A significantly greater number of cases were reported properly adhering to the Guidelines in seven of the eight elements, with the exception of the cystic nature of the tumor. Report of post-treatment neurologic symptoms and complications saw the greatest degree of increase from before to after the publication of the Guidelines (47% to 68% of cases published, p<0.001). Our findings suggest a potentially significant impact of the Guidelines on the quality of the information included in studies.

  View details for DOI 10.1016/j.jocn.2012.01.019

  View details for PubMedID 22682649

• Modern management of high grade glioma, part II. Neurosurgery clinics of North America Yang, I., Han, S. J. 2012; 23 (3): xiii-xiv

  View details for DOI 10.1016/j.nec.2012.05.004

  View details for PubMedID 22748664

• Reporting standard compliance in publications of vestibular schwannoma patients treated with microsurgery. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Han, S. J., Oh, M. C., Sughrue, M. E., Aranda, D., Rutkowski, M. J., Parsa, A. T. 2012; 33 (4): 648-50

  Abstract

  In 2003, Kanzaki and colleagues published a set of reporting standards for vestibular schwannoma (VS) to serve as a guide for future publication, with the specific purpose of promoting standardization of reporting results in VS.Here, the current published body of literature on VS cases treated with microsurgery was reviewed to determine its degree of adherence to consensus guidelines.A comprehensive search of the English language literature was performed to identify studies reporting outcome data in patients treated with microsurgery for VSs. Each publication was reviewed to determine whether it had properly reported each of the 7 items relevant to surgical management described in the Consensus Meeting reporting guidelines. The number of studies that had included each of the key items before and after the publication of the reporting guidelines was compared.After the publication of the standards, there were a significantly greater proportion of studies that properly reported the nature of the tumor and facial nerve function. Since the publication of the Consensus Meeting Guidelines, there also were trends toward greater proportions of articles that properly reported the size, hearing function, preoperative symptoms, and postoperative complications of the patients treated.Since the release of the reporting system guidelines for VS, the focus of the publications seems to have shifted away from basic clinical characteristics and toward posttreatment neurologic function. Future studies reporting the clinical characteristics and surgical outcomes for patients with VS cases should strive to include all the elements described in the Consensus Meeting guidelines.

  View details for DOI 10.1097/MAO.0b013e31824f998b

  View details for PubMedID 22525214

• The Rise and Fall of "Biopsy and Radiate": A History of Surgical Nihilism in Glioma Treatment NEUROSURGERY CLINICS OF NORTH AMERICA Han, S. J., Sughrue, M. F. 2012; 23 (2): 207-+

  Abstract

  Many neurosurgeons take a nihilistic approach to surgical treatment of gliomas, stating the inability to achieve a cure. Where this idea comes from is somewhat nebulous to most neurosurgeons. A review of the scientific studies supporting the commonly held beliefs about gliomas shows that these ideas regarding the surgical treatment of gliomas are based on overgeneralizations of data from older studies. One should avoid the temptation to apply them to the greater concept of what gliomas are, how they behave, and what should be done, but rather we should continue to scientifically evaluate the role of surgical resection in glioma treatment.

  View details for DOI 10.1016/j.nec.2012.02.002

  View details for Web of Science ID 000303282100003

  View details for PubMedID 22440864

• Extent of Surgical Resection Predicts Seizure Freedom in Low-Grade Temporal Lobe Brain Tumors NEUROSURGERY Englot, D. J., Han, S. J., Berger, M. S., Barbaro, N. M., Chang, E. F. 2012; 70 (4): 921-928

  Abstract

  Achieving seizure control in patients with low-grade temporal lobe gliomas or glioneuronal tumors remains highly underappreciated, because seizures are the most frequent presenting symptom and significantly impact patient quality-of-life.To assess how the extent of temporal lobe resection influences seizure outcome.We performed a quantitative, comprehensive systematic literature review of seizure control outcomes in 1181 patients with epilepsy across 41 studies after surgical resection of low-grade temporal lobe gliomas and glioneuronal tumors. We measured seizure-freedom rates after subtotal resection vs gross-total lesionectomy alone vs tailored resection, including gross-total lesionectomy with hippocampectomy and/or anterior temporal lobe corticectomy.Included studies were observational case series, and no randomized, controlled trials were identified. Although only 43% of patients were seizure-free after subtotal tumor resection, 79% of individuals were seizure-free after gross-total lesionectomy (OR = 5.00, 95% confidence interval [CI]: 3.33-7.14). Furthermore, tailored resection with hippocampectomy plus corticectomy conferred additional benefit over gross-total lesionectomy alone, with 87% of patients achieving seizure freedom (OR = 1.82, 95% CI: 1.23-2.70). Overall, extended resection with hippocampectomy and/or corticectomy over gross-total lesionectomy alone significantly predicted seizure freedom (OR = 1.18, 95% CI: 1.11-1.26). Age <18 years and mesial temporal location also prognosticated favorable seizure outcome.Gross-total lesionectomy of low-grade temporal lobe tumors results in significantly improved seizure control over subtotal resection. Additional tailored resection including the hippocampus and/or adjacent cortex may further improve seizure control, suggesting dual pathology may sometimes allow continued seizures after lesional excision.

  View details for DOI 10.1227/NEU.0b013e31823c3a30

  View details for Web of Science ID 000301934000052

  View details for PubMedID 21997540

• Immunotherapy for glioma: promises and challenges. Neurosurgery clinics of North America Han, S. J., Zygourakis, C. n., Lim, M. n., Parsa, A. T. 2012; 23 (3): 357–70

  Abstract

  Novel immunotherapeutic modalities are being pursed in the treatment of high-grade gliomas. This article explains how tumors suppress immune function in the brain. It specifically describes the ways in which tumors limit effective communication with immune cells, secrete immune-inhibitory cytokines and molecules, and express molecules that induce apoptosis of immune cells. It also defines 3 different immunotherapeutic approaches to counteract this tumor-associated immunosuppression: cytokine therapy, passive immunotherapy (either serotherapy or adoptive immunotherapy), and active immunotherapy. Although immunotherapeutic approaches have met with mixed success so far, immunotherapy continues to be actively pursued because of its potential to attack infiltrating high-grade gliomas.

  View details for DOI 10.1016/j.nec.2012.05.001

  View details for PubMedID 22748649

• Predictors of seizure freedom in the surgical treatment of supratentorial cavernous malformations Clinical article JOURNAL OF NEUROSURGERY Englot, D. J., Han, S. J., Lawton, M. T., Chang, E. F. 2011; 115 (6): 1169-1174

  Abstract

  Seizures are the most common presenting symptom of supratentorial cerebral cavernous malformations (CCMs) and progress to medically refractory epilepsy in 40% of patients. Predictors of seizure freedom in the resection of CCMs are incompletely understood.The authors systematically reviewed the published literature on seizure freedom following the resection of supratentorial CCMs in patients presenting with seizures. Seizure outcomes were stratified across 12 potential prognostic variables. A total of 1226 patients with supratentorial CCMs causing seizures were identified across 31 predominantly retrospective studies; 361 patients had medically refractory epilepsy.Seventy-five percent of the patients were seizure free after microsurgical lesion removal, whereas 25% continued to have seizures. All patients had had preoperative seizures and > 6 months of postoperative follow-up. Modifiable predictors of postoperative seizure freedom included gross-total resection (OR 36.6, 95% CI 8.5-157.5) and surgery within 1 year of symptom onset (OR 1.83, 95% CI 1.30-2.58). Additional prognostic indicators of a favorable outcome were a CCM size < 1.5 cm (OR 15.4, 95% CI 5.2-45.4), the absence of multiple CCMs (OR 2.02, 95% CI 1.13-3.60), medically controlled seizures (OR 2.38, 95% CI 1.29-4.39), and the lack of secondarily generalized seizures (OR 3.33, 95% CI 2.09-5.30). Other factors, including extended resection of the hemosiderin ring, were not significantly predictive.In the surgical treatment of supratentorial CCMs, gross-total resection and early operative intervention may improve seizure outcome. While surgery should not be considered the first-line treatment for CCM-related epilepsy, it is important to understand the variables associated with seizure freedom in CCM resection given the considerable morbidity and diminished quality of life associated with epilepsy.

  View details for DOI 10.3171/2011.7.JNS11536

  View details for Web of Science ID 000297450700016

  View details for PubMedID 21819194

• Awake far lateral craniotomy for resection of foramen magnum meningioma in a patient with tenuous motor and somatosensory evoked potentials. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia deipolyi, A. R., Han, S. J., Sughrue, M. E., Litt, L., Parsa, A. T. 2011; 18 (9): 1254-6

  Abstract

  We report a patient with an infratentorial lesion resected under a far-lateral approach during awake craniotomy to optimize intraoperative monitoring. A 72-year-old man presented with falls, difficulty walking, and lower extremity weakness. MRI revealed a 2.2 by 2.3 by 2.8 cm mass at the right cervicomedullary junction, with mass effect on the adjacent spinal cord. During two attempts during surgical positioning under general anesthesia, motor evoked potentials were lost. Each time the operation was aborted. During the third operation, the patient underwent monitored, light anaesthesia and was awakened periodically to confirm conscious motor function. The operation proceeded without complication, and postoperatively there was no further decrease in motor function. This is, to our knowledge, the first use of an awake operation for an infratentorial meningioma via the far-lateral approach, demonstrating the technique may be used safely and can be useful in optimizing motor function monitoring.

  View details for DOI 10.1016/j.jocn.2010.12.046

  View details for PubMedID 21741245

• Immune cell infiltrate differences in pilocytic astrocytoma and glioblastoma: evidence of distinct immunological microenvironments that reflect tumor biology. Journal of neurosurgery Yang, I., Han, S. J., Sughrue, M. E., Tihan, T., Parsa, A. T. 2011; 115 (3): 505-11

  Abstract

  The tumor microenvironment in astrocytomas is composed of a variety of cell types, including infiltrative inflammatory cells that are dynamic in nature, potentially reflecting tumor biology. In this paper the authors demonstrate that characterization of the intratumoral inflammatory infiltrate can distinguish high-grade glioblastoma from low-grade pilocytic astrocytoma.Tumor specimens from ninety-one patients with either glioblastoma or pilocytic astrocytoma were analyzed at the University of California, San Francisco. A systematic neuropathology analysis was performed. All tissue was collected at the time of the initial surgery prior to adjuvant treatment. Immune cell infiltrate not associated with necrosis or hemorrhage was analyzed on serial 4-μm sections. Analysis was performed for 10 consecutive hpfs and in 3 separate regions (total 30 × 0.237 mm(2)). Using immunohistochemistry for markers of infiltrating cytotoxic T cells (CD8), natural killer cells (CD56), and macrophages (CD68), the inflammatory infiltrates in these tumors were graded quantitatively and classified based on microanatomical location (perivascular vs intratumoral). Control markers included CD3, CD20, and human leukocyte antigen.Glioblastomas exhibited significantly higher perivascular (CD8) T-cell infiltration than pilocytic astrocytomas (62% vs 29%, p = 0.0005). Perivascular (49%) and intratumoral (89%; p = 0.004) CD56-positive cells were more commonly associated with glioblastoma. The CD68-positive cells also were more prevalent in the perivascular and intratumoral space in glioblastoma. In the intratumoral space, all glioblastomas exhibited CD68-positive cells compared with 86% of pilocytic astrocytomas (p = 0.0014). Perivascularly, CD68-positive infiltrate was also more prevalent in glioblastoma when compared with pilocytic astrocytoma (97% vs 86%, respectively; p = 0.0003). The CD3-positive, CD20-positive, and human leukocyte antigen-positive infiltrates did not differ between glioblastoma and pilocytic astrocytoma.This analysis suggests a significantly distinct immune profile in the microenvironment of high-grade glioblastoma versus low-grade pilocytic astrocytoma. This difference in tumor microenvironment may reflect an important difference in the tumor biology of glioblastoma.

  View details for DOI 10.3171/2011.4.JNS101172

  View details for PubMedID 21663411

• A comprehensive analysis of intracranial chordoma and survival: a systematic review. British journal of neurosurgery Jian, B. J., Bloch, O. G., Yang, I., Han, S. J., Aranda, D., Parsa, A. T. 2011; 25 (4): 446-53

  Abstract

  Despite the published information on cranial chordoma, most of the data regarding survival in these patients has come from a single institution. Here, we perform a systematic review of the literature to evaluate across multiple institutions the overall survival after treatment for intracranial chordoma.We systematically analysed every study published in English and found a total of over 2000 patients being treated for intracranial chordoma. The overall 5-year and 10-year survivals in these patients were stratified according to the age (<5 years vs. >5 years and  <40 years vs. >40 years), treatment (surgery and radiation vs. surgery alone) and histological findings (chondroid vs. typical). Data were analysed via Pearson chi-square test and student t-test when appropriate.A total of 560 non-duplicated patients treated for cranial chordoma met inclusion criteria for this systematic analysis. The survival rate among these patients was 63% (299 patients) and 16% (176 patients) for 5-year and 10-year survivals, respectively. There was no difference in overall survival between the two groups when a cut-off age of 40 years was used (<40 years = 50% vs.  >40 years = 51% at 5-year survival; p = 0.1), but when 5 years was used as the cut-off age, then survival was better for patients in the group older than 5 years of age (<5 years = 14% vs.  >5 years = 66%; p = 0.001). There was no difference between 5-year survival in patients with chordoma with histological chondroid features and those with chordoma possessing typical histology (45% vs. 67%; p = 0.06). When patients who only received surgery were compared to those patients who were treated with surgical intervention in combination with adjuvant radiation treatment, no difference in survival rate was found (54% vs. 56% at 5 years; p = 0.8).The results of our systematic study provide data to predict the survival of intracranial chordoma patients across multiple institutions. Our data suggest that patients younger than 5 years of age may be associated with a worse prognosis, and adjuvant radiation therapy and histological type were not associated with the improvement of survival rates.

  View details for DOI 10.3109/02688697.2010.546896

  View details for PubMedID 21749184

• Pathology of Pineal Parenchymal Tumors NEUROSURGERY CLINICS OF NORTH AMERICA Han, S. J., Clark, A. J., Ivan, M. E., Parsa, A. T., Perry, A. 2011; 22 (3): 335-+

  Abstract

  Tumors of the pineal region can arise from multiple cellular origins and thus represent a very heterogeneous group of pathologies. Such tumors include pineal parenchymal tumors, germ cell tumors, astrocytomas, ependymomas, and papillary pineal tumors. Within the subgroup of pineal parenchymal tumors, there is a histopathologic spectrum ranging from pineocytoma to pineal parenchymal tumors of intermediate differentiation to pineoblastoma. The current World Health Organization classification and the pathologic features of each of the pineal parenchymal tumor subtypes are reviewed in this article.

  View details for DOI 10.1016/j.nec.2011.05.006

  View details for Web of Science ID 000294372100003

  View details for PubMedID 21801981

• Heat shock protein-peptide complex in the treatment of glioblastoma EXPERT REVIEW OF VACCINES See, A. P., Pradilla, G., Yang, I., Han, S., Parsa, A. T., Lim, M. 2011; 10 (6): 721–31

  Abstract

  Vaccination immunotherapies offer the promise of long-term tumor control, and preclinical trials have found promising results. Active immunotherapy uses the adaptive immune response to specifically kill tumor cells. Tumor-specific antigens are processed by antigen-presenting cells and recognized by specific effector lymphocytes. However, basic vaccination strategies with tumor lysates have been unsuccessful in inducing antiglioma immunity in clinical trials. Gliomas are known to modulate the activity of antigen-presenting cells to reduce antitumor immune activity. Recently, tumor-derived heat shock proteins have been found to more effectively activate the immune response. Widely expressed, heat shock proteins are thought to present protein peptide fragments in a format conducive to processing by antigen-presenting cells. As a part of the protein synthesis machinery, peptides complexed with heat shock proteins are effectively representative of antigens expressed by the cell; these peptides convey the specificity of this vaccination strategy. The heat shock protein-peptide vaccine is one of many promising immunotherapeutic strategies being evaluated in clinical trials. These can be broadly classified as active, passive and adoptive, each with advantages and disadvantages. Here, we compare and contrast heat shock protein-peptide vaccines with other immunotherapies and describe the outcomes of clinical trials to date.

  View details for DOI 10.1586/ERV.11.49

  View details for Web of Science ID 000293115800010

  View details for PubMedID 21692695

• Complications and perioperative factors associated with learning the technique of minimally invasive transforaminal lumbar interbody fusion (TLIF) JOURNAL OF CLINICAL NEUROSCIENCE Lau, D., Lee, J. G., Han, S. J., Lu, D. C., Chou, D. 2011; 18 (5): 624-627

  Abstract

  Before the advent of minimally invasive spine surgery (MIS), open transforaminal lumbar interbody fusion (TLIF) was performed to treat spondylosis, spondylolisthesis, and spondylolysis. Minimally invasive TLIF has recently become more popular based upon the premise that a smaller, less traumatic incision should afford better recovery and outcomes. However, the learning curve associated with this technique must be considered. To analyze the perioperative factors associated with the learning curve in patients who underwent MIS TLIF versus open TLIF, we identified 22 patients who underwent TLIF from 2005 to 2008 within levels L4-S1 by the senior author (D.C.). Patients were subdivided into two groups according to whether they underwent: (i) MIS TLIF (10 patients, the first MIS TLIF procedures performed by D.C.); or (ii) open TLIF (12 patients). Preoperative, perioperative and postoperative factors were evaluated. Patients who underwent MIS TLIF had a statistically significant lower intraoperative transfusion rate, and rate of required postoperative surgical drains; and shorter periods of required drainage, and time to ambulation. However, the MIS TLIF group tended to have a higher rate of complications, which might have been associated with the learning curve. Both groups had a minimum of 1-year follow-up.

  View details for DOI 10.1016/j.jocn.2010.09.004

  View details for Web of Science ID 000289813900006

  View details for PubMedID 21349719

• Anterior Thoracolumbar Corpectomies: Approach Morbidity With and Without an Access Surgeon NEUROSURGERY Han, S. J., Lau, D., Lu, D. C., Theodore, P., Chou, D. 2011; 68 (5): 1220-1225

  Abstract

  Anterior approaches for thoracolumbar corpectomies can have significant morbidity. Spine surgeons have historically performed their own anterior approaches, but recently access surgeons are being used more frequently.To evaluate the morbidity rates of approaches performed by an access surgeon and by an approach-trained spinal neurosurgeon.From 2004 to 2008, 46 patients undergoing anterior thoracolumbar corpectomies (levels T2-L5) by the senior author (D.C.) were identified and subdivided into 2 groups based on whether an access surgeon was involved. Nine patients were excluded, leaving 37 patients in the final analysis. Blood loss, operative times, length of hospital stay, complications, and neurological outcomes were evaluated.Eighteen patients had anterior spinal access by an approach-trained spinal neurosurgeon, and 19 patients underwent the approach by an access surgeon. Surgeries performed by the spinal neurosurgeon alone were comparable to those performed by an access surgeon with respect to operative time, days spent in the hospital, blood loss, complication rates, and improvement in neurological function.There appears to be no increased morbidity of anterior approaches performed by an approach-trained spinal neurosurgeon compared with approaches performed by an access surgeon in terms of operative time, complication rate, and improvement in neurological function.

  View details for DOI 10.1227/NEU.0b013e31820eb287

  View details for Web of Science ID 000289230300037

  View details for PubMedID 21307792

• Early surgical intervention in adult patients with ganglioglioma is associated with improved clinical seizure outcomes. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Yang, I., Chang, E. F., Han, S. J., Barry, J. J., Fang, S., Tihan, T., Barbaro, N. M., Parsa, A. T. 2011; 18 (1): 29-33

  Abstract

  Gangliogliomas are rare central nervous system tumors, most commonly affecting children and young adults. Chronic seizure and epilepsy are the most frequent presentation of patients with gangliogliomas. In this report, we review the modern literature regarding the effects of early surgical intervention on the clinical outcome of patients with ganglioglioma. A boolean search of PubMed using key words "ganglioglioma", "adult", "seizure control", "treatment", "surgical intervention", and "observation", alone and in combination was performed. The inclusion criteria for articles were that: (i) clinical outcomes were reported specifically for gangliogliomas; (ii) data were reported for adult patients older than the age of 18 years; (iii) treatment data were included for the treatment of gangliogliomas; and (iv) ganglioglioma was the only pathological diagnosis for the evaluation of the tumor. Data were analyzed as a whole then stratified into two groups: early and late treatment intervention. The query identified a total of 99 articles including 1,089 cases of ganglioglioma meeting our inclusion and exclusion criteria. There was a 55% prevalence of males, representing a statistically significant predilection (51-59%, 95% confidence interval). Seizure control was significantly improved when surgical intervention occurred less than 3 years after symptom onset (78% versus 48%; p = 0.0001). Ganglioglioma in adults represents a rare group of tumors, and our systematic analysis suggests a higher prevalence in males. Our findings also support that an early surgical intervention is significantly associated with improved clinical seizure control.

  View details for DOI 10.1016/j.jocn.2010.05.002

  View details for PubMedID 20961765

• Minimally invasive compared to open microdiscectomy for lumbar disc herniation. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Lau, D., Han, S. J., Lee, J. G., Lu, D. C., Chou, D. 2011; 18 (1): 81-4

  Abstract

  Before the advent of minimally invasive surgery for microdiscectomy, an open microdiscectomy had been the standard surgical intervention. Minimally invasive techniques have recently become more popular based upon the premise that smaller, less traumatic incisions should afford better recovery times and outcomes. From 2005 to 2008 we analyzed the outcomes of 25 patients who received an open microdiscectomy compared to 20 patients who received a minimally invasive microdiscectomy by the senior author (DC) in the lumbar region for disc herniation. A retrospective analysis was performed by carefully reviewing medical records for perioperative and immediate postoperative outcomes, and clinical follow-up was obtained either in the clinic or by telephone. There were no statistically significant differences between the minimally invasive and open groups in terms of operative time, length of stay, neurological outcome, complication rate, or change in pain score (pain improvement).

  View details for DOI 10.1016/j.jocn.2010.04.040

  View details for PubMedID 20851604

• Implications for immunotherapy of tumor-mediated T-cell apoptosis associated with loss of the tumor suppressor PTEN in glioblastoma. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Waldron, J. S., Yang, I., Han, S., Tihan, T., Sughrue, M. E., Mills, S. A., Pieper, R. O., Parsa, A. T. 2010; 17 (12): 1543-7

  Abstract

  The ability of glioma cells to escape the immune system remains a significant barrier to successful immunotherapy. Here we demonstrate that loss of the PTEN tumor suppressor gene, with associated activation of the PI3K/Akt/mTOR pathway, leads to a human glioma phenotype that induces autologous T-cell apoptosis upon contact. The PTEN status of pathologically confirmed glioblastoma specimens was defined, and primary cultures established after surgical resection of tumor from 26 patients. Autologous T-cells were isolated from these patients, and after T-cell activation was induced, these cells were co-cultured with matched autologous glioma cells, either alone, or after treatment with one of three inhibitors of the PI3K/Akt/mTOR pathway. When co-cultured with autologous T-cells, PTEN wild-type tumor cells induced apoptosis in a minimal number of activated T-cells (6-12% of T-cells), whereas tumors with PTEN loss induced much more profound levels of T-cell apoptosis (42-56% of T-cells). Prior treatment of PTEN-deficient tumor cells with specific inhibitors of the PI3K/Akt/mTOR pathway diminished T-cell apoptosis to levels seen after co-culture with wild-type PTEN tumor cells, suggesting that PTEN loss confers this immunoresistant phenotype through the PI3K/Akt/mTOR pathway. These results suggest that PTEN-deficient glioblastoma patients are suboptimal candidates for immunotherapy. In addition, our results raise the possibility of combining T-cell based immunotherapy protocols with clinical inhibitors of the PI3K/Akt/mTOR pathway.

  View details for DOI 10.1016/j.jocn.2010.04.021

  View details for PubMedID 20822910

  View details for PubMedCentralID PMC3795509

• CD8+ T-cell infiltrate in newly diagnosed glioblastoma is associated with long-term survival. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Yang, I., Tihan, T., Han, S. J., Wrensch, M. R., Wiencke, J., Sughrue, M. E., Parsa, A. T. 2010; 17 (11): 1381-5

  Abstract

  A growing body of evidence supports the significant interplay between the immune system and glioma pathogenesis. Here we investigate whether the extent of local glioma-associated CD8+ T-cell infiltrate at initial presentation correlates with long-term survival in patients with glioblastoma multiforme (GBM). The study was conducted by the University of California San Francisco Brain Tumor Research Center as part of the San Francisco Bay Area Adult Glioma Study, which included over 519 patients with GBM. A central neuropathology review was performed and populations of infiltrating CD8+ T-cells were quantified histologically. Of 108 patients studied, 43 patients had poor survival (<95days) and 65 patients had extended long-term survival of >403days. Tumors from long-term survivors were more likely than short-term survivors to have intermediate or extensive T-cell infiltrates compared to focal or rare infiltrates, and this association appears to be most significant in Caucasian women (p < 0.006). Thus, CD8+ T-cell infiltrate is associated with prolonged survival. Our data provide the impetus for more sophisticated studies to further elucidate prospectively the specific T-cell subtypes associated with long-term survival.

  View details for DOI 10.1016/j.jocn.2010.03.031

  View details for PubMedID 20727764

  View details for PubMedCentralID PMC3064460

• Development of a symptomatic intracranial meningioma in a male-to-female transsexual after initiation of hormone therapy. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Deipolyi, A. R., Han, S. J., Parsa, A. T. 2010; 17 (10): 1324-6

  Abstract

  Transsexual patients are routinely treated with sex hormone therapy, which may be a risk factor for meningiomas, although the data are largely inconclusive. Here we describe a male-to-female transsexual patient treated with estradiol patches, who developed an occipital meningioma causing generalized seizures. This is the second report of a male-to-female transsexual patient who developed a symptomatic meningioma after sex hormone treatment, adding to the growing evidence that sex hormones contribute to the pathogenesis of meningiomas. Meningiomas may therefore complicate hormone therapy and sex hormones may be contraindicated in transsexual candidates with meningiomas identified upon screening.

  View details for DOI 10.1016/j.jocn.2010.01.036

  View details for PubMedID 20594855

• Surgical resection and adjuvant radiotherapy for a large pineal hemangiopericytoma. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Jian, B. J., Han, S. J., Yang, I., Waldron, J. S., Tihan, T., Parsa, A. T. 2010; 17 (9): 1209-11

  Abstract

  Hemangiopericytoma of the pineal region is exceedingly rare. We describe a patient with a large pineal region hemangiopericytoma who underwent a third ventriculostomy followed by a gross total resection by a unilateral interhemispheric approach with adjuvant radiotherapy. The patient remains recurrence free 4 years after treatment.

  View details for DOI 10.1016/j.jocn.2010.01.022

  View details for PubMedID 20598546

• Tumor control after surgery and radiotherapy for pineocytoma Clinical article JOURNAL OF NEUROSURGERY Clark, A. J., Ivan, M. E., Sughrue, M. E., Yang, I., Aranda, D., Han, S. J., Kane, A. J., Parsa, A. T. 2010; 113 (2): 319-324

  Abstract

  Pineocytoma is a rare tumor, and the current literature on these tumors is primarily composed of case reports and small case series. Thus, recommendations on appropriate treatment of these tumors are highly varied. Therefore, the authors performed a systematic review of the literature on tumor control after surgery for pineocytoma to determine the relative benefits of aggressive resection and postoperative adjuvant radiotherapy.A comprehensive search of the published English-language literature was performed to identify studies citing outcome data of patients undergoing surgery for pineocytoma. Determination of rates of progression-free survival (PFS) was performed using Kaplan-Meier analysis.Sixty-four articles met the criteria of the established search protocol, which combined for a total of 166 patients. Twenty-one percent of these patients had undergone a biopsy procedure, 38% had undergone subtotal resection (STR), 42% had undergone gross-total resection, and 28% were treated with radiation therapy. The 1- and 5-year PFS rates for the resection group versus the biopsy group were 97 and 90% (1 year), and 89 and 75% (5 years), respectively (p < 0.05, log-rank test). The 1- and 5-year PFS rates for the GTR group versus the group undergoing STR combined with radiation therapy were 100 and 94% (1 year), and 100 and 84% (5 years), respectively (p < 0.05, log-rank test). There was no significant difference in PFS for STR only compared with STR in addition to radiation therapy.Gross-total resection is the ideal treatment for pineocytoma and might represent a cure for these lesions. When gross-total resection is not possible, adjuvant radiation therapy after STR is of questionable benefit for these patients.

  View details for DOI 10.3171/2009.12.JNS091683

  View details for Web of Science ID 000280405900029

  View details for PubMedID 20136388

• Secondary gliosarcoma after diagnosis of glioblastoma: clinical experience with 30 consecutive patients Clinical article JOURNAL OF NEUROSURGERY Han, S. J., Yang, I., Otero, J. J., Ahn, B. J., Tihan, T., McDermott, M. W., Berger, M. S., Chang, S. M., Parsa, A. T. 2010; 112 (5): 990-996

  Abstract

  Gliosarcoma can arise secondarily, after conventional adjuvant treatment of high-grade glioma. The current literature on the occurrence of secondary gliosarcoma (SGS) after glioblastoma multiforme (GBM) is limited, with only 12 reported cases. The authors present a large series of histologically confirmed SGSs, with follow-up to describe the clinical and radiological presentation, pathological diagnosis, and treatment outcomes.Gliosarcoma cases were identified using the University of California, San Francisco's Departments of Neurological Surgery and Neuropathology databases. Through a retrospective chart review, cases of gliosarcoma were considered SGS if the following inclusion criteria were met: 1) the patient had a previously diagnosed intracranial malignant glioma that did not have gliosarcoma components; and 2) the histopathological tissue diagnosis of the recurrence confirmed gliosarcoma according to the most current WHO criteria. Extensive review of clinical, surgical, and pathology notes was performed to gather clinical and pathological data on these cases.Thirty consecutive patients in whom SGS had been diagnosed between 1996 and 2008 were included in the analysis. All patients had previously received a diagnosis of malignant glioma. For the initial malignant glioma, all patients underwent resection, and 25 patients received both external-beam radiation and chemotherapy. Three patients received radiotherapy alone, 1 patient was treated with chemotherapy alone, and 1 patient's tumor rapidly recurred as gliosarcoma, requiring surgical intervention prior to initiation of adjuvant therapy. The median time from diagnosis of the initial tumor to diagnosis of gliosarcoma was 8.5 months (range 0.5-25 months). All but 1 patient (who only had a biopsy) underwent a second operation for gliosarcoma; 8 patients went on to receive radiotherapy (4 had brachytherapy, 3 had external-beam radiation, and 1 had Gamma Knife surgery); and 14 patients received additional chemotherapy. The median length of survival from the time of gliosarcoma diagnosis was 4.4 months (range 0.7-46 months). The median survival from the time of the original GBM diagnosis was 12.6 months (range 5.7-47.4 months). Patients who had received concurrent and adjuvant temozolomide for GBM had worse outcomes than those who had not (4.3 and 10.5 months, respectively; p = 0.045). There was no difference in time to diagnosis of gliosarcoma in these 2 groups (8 and 8.5 months; p = 0.387). Two patients who had not received radiation therapy for GBM had an anecdotally very prolonged survival (20.9 and 46.4 months).The data underscore the difficulty associated with management of this disease. The strikingly poor survival of patients with SGS who had previously received combined radiation and temozolomide chemotherapy for GBM may reflect a unique molecular profile of GBM that eventually recurs as SGS. Further work will be required, controlling for multiple prognostic factors with larger numbers of patients.

  View details for DOI 10.3171/2009.9.JNS09931

  View details for Web of Science ID 000277273600014

  View details for PubMedID 19817543

• Adjuvant radiation therapy and chondroid chordoma subtype are associated with a lower tumor recurrence rate of cranial chordoma. Journal of neuro-oncology Jian, B. J., Bloch, O. G., Yang, I., Han, S. J., Aranda, D., Tihan, T., Parsa, A. T. 2010; 98 (1): 101-8

  Abstract

  Cranial chordomas are rare tumors that have been difficult to study given their low prevalence. Individual case series with decades of data collection provide some insight into the pathobiology of this tumor and its responses to treatment. This meta-analysis is an attempt to aggregate the sum experiences and present a comprehensive review of their findings. We performed a comprehensive review of studies published in English language literature and found a total of over 2,000 patients treated for cranial chordoma. Patient information was then extracted from each paper and aggregated into a comprehensive database. The tumor recurrences in these patients were then stratified according to age (<21 vs. >21 years), histological findings (chondroid vs. typical) and treatment (surgery and radiation vs. surgery only). Data was analyzed via Pearson chi-square and t-test. A total of 464 non-duplicated patients from 121 articles treated for cranial chordoma met the inclusion criteria. The recurrence rate among all patients was 68% (314 patients) with an average disease-free interval of 45 months (median, 23 months). The mean follow-up time was 39 months (median, 27 months). The patients in younger group, patients with chordoma with chondroid histologic type, and patients who received surgery and adjuvant radiotherapy had significantly lower recurrence rate than their respective counterparts. The results of our systematic analysis provide useful data for practitioners in objectively summarizing the tumor recurrence in patients with cranial chordomas. Our data suggests that younger patients with chondroid type cranial chordoma treated with both surgery and radiation may have improved rates of tumor recurrence in the treatment of these tumors.

  View details for DOI 10.1007/s11060-009-0068-1

  View details for PubMedID 19953297

• Cranial chondrosarcoma and recurrence. Skull base : official journal of North American Skull Base Society ... [et al.] Bloch, O. G., Jian, B. J., Yang, I., Han, S. J., Aranda, D., Ahn, B. J., Parsa, A. T. 2010; 20 (3): 149-56

  Abstract

  The literature regarding recurrences in patients with cranial chondrosarcoma is limited to small series performed at single institutions, raising the question if these data precisely reflect the true recurrence of this tumor for guiding the clinician in the management of these patients. An extensive systematic review of the English literature was performed. The patients were stratified according to treatment modality, treatment history, histological subtype, and histological grade, and the recurrence rates were analyzed. A total of 560 patients treated for cranial chondrosarcoma were included. Five-year recurrence rate among all patients was 22% with median follow-up of 60 months and median disease-free interval of 16 months. Tumor recurrence was more common in patients who only received surgery or had mesenchymal subtype tumors. Our systematic review closely reflects the actuarial recurrence rate and provides predictive factors in the recurrence of cranial chondrosarcoma.

  View details for DOI 10.1055/s-0029-1246218

  View details for PubMedID 21318031

  View details for PubMedCentralID PMC3037109

• Clinical Characteristics and Outcomes for a Modern Series of Primary Gliosarcoma Patients CANCER Han, S. J., Yang, I., Ahn, B. J., Otero, J. J., Tihan, T., McDermott, M. W., Berger, M. S., Prados, M. D., Parsa, A. T. 2010; 116 (5): 1358-1366

  Abstract

  Primary gliosarcoma (PGS) is a rare central nervous system tumor with limited experience reported in the literature. In the current study, the authors present a modern series of confirmed PGS cases treated in the era of magnetic resonance imaging (MRI), after the accepted glioblastoma management of resection, radiation, and temozolomide.Using a retrospective review, patients with confirmed PGS were identified (1996-2008). Cases were determined to be PGS by central pathology review using the 2007 World Health Organization criteria. Extensive chart review was performed to gather clinical and pathologic data on these cases.All but 1 patient had undergone a preoperative MRI, with 1 patient receiving a computed tomography scan due to a cardiac pacemaker. A total of 10 patients received radiotherapy with concurrent and adjuvant temozolomide chemotherapy, and 8 patients received radiotherapy alone or in combination with other chemotherapeutic agents. In 2 patients, the history of adjuvant treatment could not be confirmed. The overall median survival was 13.9 months (range, 2.2-22.9 months). Patients with gliosarcomas resembling meningioma were found to have a significantly prolonged median survival compared with patients harboring gliosarcoma resembling glioblastoma multiforme (16 months vs 9.6 months; P = .011). However, no difference in survival was noted between patients who received concurrent radiotherapy and temozolomide compared with those who did not (10.4 months vs 13.9 months; P = .946).The results of the current study support previous hypotheses that there are 2 distinct types of PGS. The type mimicking the appearance of a meningioma appears to carry a significantly more favorable prognosis, most likely due to an increased chance at achieving macroscopic total resection.

  View details for DOI 10.1002/cncr.24857

  View details for Web of Science ID 000274772300027

  View details for PubMedID 20052717

• Primary gliosarcoma: key clinical and pathologic distinctions from glioblastoma with implications as a unique oncologic entity. Journal of neuro-oncology Han, S. J., Yang, I., Tihan, T., Prados, M. D., Parsa, A. T. 2010; 96 (3): 313-20

  Abstract

  This report presents the historical experience, clinical presentation, treatment, prognosis, and pathogenesis of gliosarcoma described to date in the English literature. PubMed query of term "gliosarcoma" was performed, followed by a rigorous review of cited literature. Articles selected for analysis included: (1) case reports of gliosarcoma, (2) review articles of gliosarcoma, and (3) studies of the pathogenesis or genetics of gliosarcoma in humans. Our review identified 219 cases of gliosarcoma in 34 reports and eight articles addressing the pathogenesis. Survival in larger series ranged 4-11.5 months. Features unique to gliosarcoma compared to glioblastoma (GBM) include their temporal lobe predilection, potential to appear similar to a meningioma at surgery, repeated reports of extracranial metastases, and infrequency of EGFR mutations. Published experience is limited to small case series, and the pathogenesis remains unclear. Clinical and pathologic characteristics distinct from GBM suggest that they may warrant specific treatment, separate from conventional GBM therapy.

  View details for DOI 10.1007/s11060-009-9973-6

  View details for PubMedID 19618114

  View details for PubMedCentralID PMC2808523

• Secondary gliosarcoma: a review of clinical features and pathological diagnosis Clinical article JOURNAL OF NEUROSURGERY Han, S. J., Yang, I., Tihan, T., Chang, S. M., Parsa, A. T. 2010; 112 (1): 26-32

  Abstract

  Although secondary gliosarcoma after treatment of primary glioblastoma multiforme has been described, little is known of these rare tumors. In this article the authors review the literature on secondary gliosarcoma, with attention to clinical course and pathological features.A PubMed search of the key word intracranial "gliosarcoma" with and without "radiation" or "radiotherapy" in humans was performed. The 204 citations yielded were screened for relevancy to gliosarcomas that occur after treatment of previous intracranial neoplasms.A search of the literature yielded 24 relevant articles, combined for a total of only 12 cases of secondary gliosarcoma and 12 cases of radiation-induced gliosarcoma. Of the 12 cases of secondary gliosarcoma, all were previously treated with surgery and radiotherapy (mean dose 50.7 Gy), with a mean survival of 13 months since time of gliosarcoma diagnosis (range 6.9-19.4 months). In the cases of radiation-induced gliosarcoma, the mean dose of previous radiotherapy was 51.3 Gy (median 54 Gy, range 24-60 Gy), and the mean survival since gliosarcoma diagnosis was 6.7 months (median 6 months, range 2-10 months).Secondary gliosarcoma and radiation-induced gliosarcoma are exceedingly rare. The literature on secondary gliosarcoma illustrates a more favorable survival than for primary gliosarcoma but remains limited regarding clinical and radiographic presentation, response to treatment, and pathogenesis. The results of the present review also support the notion that secondary gliosarcomas and radiation-induced gliosarcomas are distinct entities, with longer survival and shorter latency of gliosarcoma induction seen in the former. Efforts to elucidate the role of radiotherapy in the induction of gliosarcomas may yield new insights into therapeutic risks of cranial radiation and CNS tumor pathogenesis.

  View details for DOI 10.3171/2009.3.JNS081081

  View details for Web of Science ID 000273153400004

  View details for PubMedID 19408981

• The role of microglia in central nervous system immunity and glioma immunology. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Yang, I., Han, S. J., Kaur, G., Crane, C., Parsa, A. T. 2010; 17 (1): 6-10

  Abstract

  The central nervous system (CNS) historically has been considered an immune-privileged organ, lacking a lymphatic system and shielded from the circulatory system by the blood-brain barrier. Microglia are an abundant portion of the CNS cell population, comprising 5% to 20% of the total glial cell population, and are as numerous as neurons. A crucial function of microglia is the ability to generate significant innate and adaptive immune responses. Microglia are involved in first line innate immunity of the CNS. Proper antigen presentation is critical in the generation of specific, durable responses by the adaptive immune system, and requires interaction between the T cell receptor and processed antigen peptide presented on major histocompatibility complex (MHC) molecules by the antigen presenting cells (APC). Microglia also have a large regulatory role in CNS immunity. Histopathologic studies of glioma tissue have consistently shown high levels of infiltrating microglia. Microglia are also localized diffusely throughout the tumor, rather than to the areas of necrosis, and phagocytosis of glioma cells or debris by microglia is not observed. Recent evidence indicates that glioma-infiltrating microglia/macrophages might be promoting tumor growth by facilitating immunosuppression of the tumor microenvironment. When activated, microglia can be potent immune effector cells, able to perform a broad range of functions, and they mediate both innate and adaptive responses during CNS injury and disease while remaining quiescent in the steady state. Their versatility in bridging the gap between the immune-privileged CNS and the peripheral immune system, in addition to their significant numbers in gliomas, makes them an attractive candidate in immunotherapy for gliomas. An enhanced understanding of microglia-glioma interaction may provide better methods to manipulate the glioma microenvironment to allow the generation of a specific and durable anti-glioma immunity. The role of microglia in CNS immunity is reviewed, with a focus on key advances made in glioma immunology.

  View details for DOI 10.1016/j.jocn.2009.05.006

  View details for PubMedID 19926287

  View details for PubMedCentralID PMC3786731

• Distinguishing glioma recurrence from treatment effect after radiochemotherapy and immunotherapy. Neurosurgery clinics of North America Yang, I., Huh, N. G., Smith, Z. A., Han, S. J., Parsa, A. T. 2010; 21 (1): 181-6

  Abstract

  Recent advancements have made radiation and chemotherapy the standard of care for newly diagnosed glioblastomas. The use of these therapies has resulted in an increased diagnosis of pseudoprogression and radiation-induced necrosis. Standard MRI techniques are inadequate in differentiating tumor recurrence from posttreatment effects. Diagnosis of a posttreatment lesion as glioma recurrence rather than radiochemotherapy or immunotherapy treatment effect is critical. This increase in accuracy plays a role as newer immunotherapies incurring posttreatment effects on MRI emerge. Advancements with magnetic resonance spectroscopy, diffusion-weighted imaging, and functional positron emission tomography scans have shown promising capabilities. Further investigations are necessary to assess the imaging algorithms and accuracy of these modalities to differentiate true glioma recurrence from radiotherapy or immunotherapy treatment effect.

  View details for DOI 10.1016/j.nec.2009.08.003

  View details for PubMedID 19944976

• Biologic Principles of Immunotherapy for Malignant Gliomas NEUROSURGERY CLINICS OF NORTH AMERICA Han, S. J., Kaur, G., Yang, I., Lim, M. 2010; 21 (1): 1-+

  Abstract

  The most common primary brain neoplasm is glioblastoma multiforme, which is associated with a dismal prognosis. Despite the recommended treatment regimen of aggressive surgical resection, radiation, and chemotherapy, the median survival remains approximately only 14 months. Due to these minimal improvements in survival of patients despite recent advances in conventional treatments, new modalities such as immunotherapy are being investigated and studied. A hurdle to developing effective immunotherapy is the immunosuppressive characteristics that are the hallmark of malignant gliomas. Effective therapeutic strategies will require overcoming these mechanisms, by augmenting tumor antigen presentation, perhaps in a setting isolated from the tumor microenvironment. The heterogeneity of potential glioma antigens warrants potential targeting of multiple tumor-specific antigens, and discovery and investigation of additional antigens. This article describes the current strategies and principles of immunotherapy for malignant gliomas.

  View details for DOI 10.1016/j.nec.2009.08.001

  View details for Web of Science ID 000278059500002

  View details for PubMedID 19944962

• Microglia and central nervous system immunity. Neurosurgery clinics of North America Kaur, G., Han, S. J., Yang, I., Crane, C. 2010; 21 (1): 43-51

  Abstract

  The central nervous system (CNS) has evolved as an immune-privileged site to protect its vital functions from damaging immune-mediated inflammation. There must be a CNS-adapted system of surveillance that continuously evaluates local changes in the nervous system and communicates to the peripheral immune system during an injury or a disease. Recent advances leading to a better understanding of the CNS disease processes has placed microglia, the CNS-based resident macrophages, at center stage in this system of active surveillance. Evidence points to microglia cells contributing to the immunosuppressive environment of gliomas and actually promoting tumor growth. Microglia accumulation exists in almost every CNS disease process, including CNS tumors. This article discusses the role of microglia in CNS immunity and highlights key advances made in glioma immunology.

  View details for DOI 10.1016/j.nec.2009.08.009

  View details for PubMedID 19944965

• TGF-beta downregulates the activating receptor NKG2D on NK cells and CD8(+) T cells glioma patients NEURO-ONCOLOGY Crane, C. A., Han, S. J., Barry, J. J., Ahn, B. J., Lanier, L. L., Parsa, A. T. 2010; 12 (1): 7-13

  Abstract

  The activating receptor NKG2D, expressed by natural killer (NK) cells and CD8(+) T cells, has a role in the specific killing of transformed cells. We examined NKG2D expression in patients with glioblastoma multiforme and found that NKG2D was downregulated on NK cells and CD8(+) T cells. Expression of NKG2D on lymphocytes significantly increased following tumor resection and correlated with an increased ability to kill NKG2D ligand-positive tumor targets. Despite the presence of soluble NKG2D ligands in the sera of glioblastoma patients, NKG2D downregulation was primarily caused by tumor-derived tumor growth factor-beta, suggesting that blocking of this cytokine may have therapeutic benefit.

  View details for DOI 10.1093/neuonc/nop009

  View details for Web of Science ID 000273781300003

  View details for PubMedID 20150362

  View details for PubMedCentralID PMC2940557

• Gamma interferon-mediated superinduction of B7-H1 in PTEN-deficient glioblastoma: a paradoxical mechanism of immune evasion. Neuroreport Han, S. J., Ahn, B. J., Waldron, J. S., Yang, I., Fang, S., Crane, C. A., Pieper, R. O., Parsa, A. T. 2009; 20 (18): 1597-602

  Abstract

  B7 homolog 1 (B7-H1) is a recently discovered immunoresistance protein that is regulated posttranscriptionally after PTEN loss in malignant glioma, a deadly form of brain tumor. Here, the impact of gamma-interferon-mediated activation of B7-H1 was investigated in glioblastoma patients with PTEN loss. Lymphocytes and T cells were selected for apoptosis assays after 1 : 1 coculture with autologous glioma cells. Gamma interferon treatment of PTEN-deficient tumors resulted in superinduction of B7-H1 protein that correlated with increased T-cell apoptosis, an effect dependent upon activation of the PI3-kinase pathway. The combination of PTEN loss and gamma-interferon exposure in glioblastoma patients results in an exceptionally immunoresistant phenotype that may negate adaptive immunity through induction of T-cell apoptosis.

  View details for DOI 10.1097/WNR.0b013e32833188f7

  View details for PubMedID 19875977

  View details for PubMedCentralID PMC3666317

• Non-audiofacial morbidity after Gamma Knife surgery for vestibular schwannoma NEUROSURGICAL FOCUS Sughrue, M. E., Yang, I., Han, S. J., Aranda, D., Kane, A. J., Amoils, M., Smith, Z. A., Parsa, A. T. 2009; 27 (6): E4

  Abstract

  While many studies have been published outlining morbidity following radiosurgical treatment of vestibular schwannomas, significant interpractitioner and institutional variability still exists. For this reason, the authors conducted a systematic review of the literature for non-audiofacial-related morbidity after the treatment of vestibular schwannoma with radiosurgery.The authors performed a comprehensive search of the English-language literature to identify studies that published outcome data of patients undergoing radiosurgery treatment for vestibular schwannomas. In total, 254 articles were found that described more than 50,000 patients and were analyzed for satisfying the authors' inclusion criteria. Patients from these studies were then separated into 2 cohorts based on the marginal dose of radiation: < or = 13 Gy and > 13 Gy. All tumors included in this study were < 25 mm in their largest diameter.A total of 63 articles met the criteria of the established search protocol, which combined for a total of 5631 patients. Patients receiving > 13 Gy were significantly more likely to develop trigeminal nerve neuropathy than those receiving < 13 Gy (p < 0.001). While we found no relationship between radiation dose and the rate of developing hydrocephalus (0.6% for both cohorts), patients with hydrocephalus who received doses > 13 Gy appeared to have a higher rate of symptomatic hydrocephalus requiring shunt treatment (96% [> 13 Gy] vs 56% [< or = 13 Gy], p < 0.001). The rates of vertigo or balance disturbance (1.1% [> 13 Gy] vs 1.8% [< or = 13 Gy], p = 0.001) and tinnitus (0.1% [> 13 Gy] vs 0.7% [< or = 13 Gy], p = 0.001) were significantly higher in the lower dose cohort than those in the higher dose cohort.The results of our review of the literature provide a systematic summary of the published rates of nonaudiofacial morbidity following radiosurgery for vestibular schwannoma.

  View details for DOI 10.3171/2009.9.FOCUS09198

  View details for Web of Science ID 000272301500006

  View details for PubMedID 19951057

• A systematic review of intracranial chondrosarcoma and survival. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Bloch, O. G., Jian, B. J., Yang, I., Han, S. J., Aranda, D., Ahn, B. J., Parsa, A. T. 2009; 16 (12): 1547-51

  Abstract

  Most data regarding survival in patients with chondrosarcoma are limited to case studies and small series performed at single institutions. A systematic review was performed to study the relationship between potential prognostic factors and survival. The survival rates were analyzed according to modality of treatment, treatment history, histological subtype, and histological grade. A total of 560 patients with intracranial chondrosarcoma were analyzed. Median follow-up time was 60 months. The 5-year mortality among all patients was 11.5% with median survival of 24 months. Mortality at 5 years was significantly greater for patients with tumors of higher grade, or of the mesenchymal subtype, or who had received surgical resection alone. The results of our systematic review provide useful data in predicting survival among intracranial chondrosarcoma patients.

  View details for DOI 10.1016/j.jocn.2009.05.003

  View details for PubMedID 19796952

  View details for PubMedCentralID PMC3795514

• Heat-shock protein vaccines as active immunotherapy against human gliomas. Expert review of anticancer therapy Yang, I., Han, S., Parsa, A. T. 2009; 9 (11): 1577-82

  Abstract

  Modern advances in cancer immunotherapy have led to the development of active immunotherapy that utilizes tumor-associated antigens to induce a specific immune response against the tumor. Current methods of immunotherapy implementation are based on the principle that tumor-associated antigens are capable of being processed by antigen-presenting cells and inducing an activated cytotoxic T-lymphocyte-specific immune response that targets the tumor cells. Antigen internalization and processing by antigen-presenting cells, such as dendritic cells, or macrophages results in their surface association with MHC class I molecules, which can be recognized by an antigen-specific cytotoxic T-lymphocyte adaptive immune response. With the aim of augmenting current immunotherapeutic modalities, much effort has been directed towards enhancing antigen-presenting cell activation and optimizing the processing of tumor-associated antigens and major histocompatibility molecules. The goal of these immunotherapy modifications is to ultimately improve the adaptive specific immune response in killing of tumor cells while sparing normal tissues. Immunotherapy has been actively studied and applied in glioblastomas. Preclinical animal models have shown the feasibility of an active immunotherapy approach through the utilization of tumor vaccines, and recently several clinical studies have also been initiated. Recently, endogenous heat-shock proteins have been implicated in the mediation of both the adaptive and innate immune responses. They are now being investigated as a potential modality and adjuvant to immunotherapy, and they represent a promising novel treatment for human glioblastomas.

  View details for DOI 10.1586/era.09.104

  View details for PubMedID 19895242

  View details for PubMedCentralID PMC3836274

• Hearing preservation after stereotactic radiosurgery for vestibular schwannoma: a systematic review. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Yang, I., Aranda, D., Han, S. J., Chennupati, S., Sughrue, M. E., Cheung, S. W., Pitts, L. H., Parsa, A. T. 2009; 16 (6): 742-7

  Abstract

  Radiosurgery has evolved into an effective alternative to microsurgical resection in the treatment of patients with vestibular schwannoma. We performed a systematic analysis of the literature in English on the radiosurgical treatment of vestibular schwannoma patients. A total of 254 published studies reported assessable and quantifiable outcome data of patients undergoing radiosurgery for vestibular schwannomas. American Association of Otolaryngology-Head and Neck Surgery (AAO-HNS) class A or B and Gardner-Robertson (GR) classification I or II were defined as having preserved hearing. A total of 5825 patients (74 articles) met our inclusion criteria. Practitioners who delivered an average dose of 12.5 Gy as the marginal dose reported having a higher hearing preservation rate (12.5 Gy=59% vs. >12.5 Gy=53%, p=0.0285). Age of the patient was not a significant prognostic factor for hearing preservation rates (<65 years=58% vs. >65 years=62%; p=0.4317). The average overall follow-up was 41.2 months. Our data suggest that an overall hearing preservation rate of about 57% can be expected after radiosurgical treatment, and patients treated with 12.5 Gy were more likely to have preserved hearing.

  View details for DOI 10.1016/j.jocn.2008.09.023

  View details for PubMedID 19303780

• Facial nerve preservation after vestibular schwannoma Gamma Knife radiosurgery. Journal of neuro-oncology Yang, I., Sughrue, M. E., Han, S. J., Fang, S., Aranda, D., Cheung, S. W., Pitts, L. H., Parsa, A. T. 2009; 93 (1): 41-8

  Abstract

  Facial nerve preservation is a critical measure of clinical outcome after vestibular schwannoma treatment. Gamma Knife radiosurgery has evolved into a practical treatment modality for vestibular schwannoma patients, with several reported series from a variety of centers. In this study, we report the results of an objective analysis of reported facial nerve outcomes after the treatment of vestibular schwannomas with Gamma Knife radiosurgery.A Boolean Pub Med search of the English language literature revealed a total of 23 published studies reporting assessable and quantifiable outcome data regarding facial nerve function in 2,204 patients who were treated with Gamma Knife radiosurgery for vestibular schwannoma. Inclusion criteria for articles were: (1) Facial nerve preservation rates were reported specifically for vestibular schwannoma, (2) Facial nerve functional outcome was reported using the House-Brackmann classification (HBC) for facial nerve function, (3) Tumor size was documented, and (4) Gamma Knife radiosurgery was the only radiosurgical modality used in the report. The data were then aggregated and analyzed based on radiation doses delivered, tumor volume, and patient age.An overall facial nerve preservation rate of 96.2% was found after Gamma Knife radiosurgery for vestibular schwannoma in our analysis. Patients receiving less than or equal to 13 Gy of radiation at the marginal dose had a better facial nerve preservation rate than those who received higher doses (13 Gy = 94.7%, P < 0.0001). Patients with a tumor volume less than or equal to 1.5 cm(3) also had a greater facial nerve preservation rate than patients with tumors greater than 1.5 cm(3) (1.5 cm(3) 95.5%, P < 0.0001). Superior facial nerve preservation was also noted in patients younger than or equal to 60 years of age (96.8 vs. 89.4%, P < 0.0001). The average reported follow up duration in this systematic review was 54.1 +/- 31.3 months.Our analysis of case series data aggregated from multiple centers suggests that a facial nerve preservation rate of 96.2% can be expected after Gamma knife radiosurgery for vestibular schwannoma. Younger patients with smaller tumors less than 1.5 cm(3) and treated with lower doses of radiation less than 13 Gy will likely have better facial nerve preservation rates after Gamma Knife radiosurgery for vestibular schwannoma.

  View details for DOI 10.1007/s11060-009-9842-3

  View details for PubMedID 19430881