Academic Appointments


Professional Education


  • Fellowship, University of California, San Francisco, Neuro-Oncology (2017)
  • Residency, University of California, San Francisco, Neurological Surgery (2016)
  • M.D., University of California, San Francisco, Medicine (2010)
  • B.S., University of California, Los Angeles, Neuroscience (2005)

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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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