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Michael J. Link, Isaac Yang, Fred G. Barker II, Amir Samii, and Philip V. Theodosopoulos

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Isaac Yang, Seunggu J. Han, Michael E. Sughrue, Tarik Tihan, and Andrew T. Parsa

Object

The tumor microenvironment in astrocytomas is composed of a variety of cell types, including infiltrative inflammatory cells that are dynamic in nature, potentially reflecting tumor biology. In this paper the authors demonstrate that characterization of the intratumoral inflammatory infiltrate can distinguish high-grade glioblastoma from low-grade pilocytic astrocytoma.

Methods

Tumor specimens from ninety-one patients with either glioblastoma or pilocytic astrocytoma were analyzed at the University of California, San Francisco. A systematic neuropathology analysis was performed. All tissue was collected at the time of the initial surgery prior to adjuvant treatment. Immune cell infiltrate not associated with necrosis or hemorrhage was analyzed on serial 4-μm sections. Analysis was performed for 10 consecutive hpfs and in 3 separate regions (total 30 × 0.237 mm2). Using immunohistochemistry for markers of infiltrating cytotoxic T cells (CD8), natural killer cells (CD56), and macrophages (CD68), the inflammatory infiltrates in these tumors were graded quantitatively and classified based on microanatomical location (perivascular vs intratumoral). Control markers included CD3, CD20, and human leukocyte antigen.

Results

Glioblastomas exhibited significantly higher perivascular (CD8) T-cell infiltration than pilocytic astrocytomas (62% vs 29%, p = 0.0005). Perivascular (49%) and intratumoral (89%; p = 0.004) CD56-positive cells were more commonly associated with glioblastoma. The CD68-positive cells also were more prevalent in the perivascular and intratumoral space in glioblastoma. In the intratumoral space, all glioblastomas exhibited CD68-positive cells compared with 86% of pilocytic astrocytomas (p = 0.0014). Perivascularly, CD68-positive infiltrate was also more prevalent in glioblastoma when compared with pilocytic astrocytoma (97% vs 86%, respectively; p = 0.0003). The CD3-positive, CD20-positive, and human leukocyte antigen-positive infiltrates did not differ between glioblastoma and pilocytic astrocytoma.

Conclusions

This analysis suggests a significantly distinct immune profile in the microenvironment of high-grade glioblastoma versus low-grade pilocytic astrocytoma. This difference in tumor microenvironment may reflect an important difference in the tumor biology of glioblastoma.

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Michael E. Sughrue, Rajwant Kaur, Martin J. Rutkowski, Ari J. Kane, Gurvinder Kaur, Isaac Yang, Lawrence H. Pitts, and Andrew T. Parsa

Object

With limited studies available, the correlation between the extent of resection and tumor recurrence in vestibular schwannomas (VSs) has not been definitively established. In this prospective study, the authors evaluated 772 patients who underwent microsurgical resection of VSs to analyze the association between total tumor resection and the tumor recurrence rate.

Methods

The authors selected all cases from a prospectively collected database of patients who underwent microsurgical resection as their initial treatment for a histopathologically confirmed VS. Recurrence-free survival was analyzed using Kaplan-Meier analysis. The authors studied the impact of possible confounders such as patient age and tumor size using stepwise Cox regression to calculate the proportional hazard ratio of recurrence while controlling for other cofounding variables.

Results

The authors analyzed data obtained in 571, 89, and 112 patients in whom gross-total, near-total, and subtotal resections, respectively, were performed. A gross-total resection was achieved in 74% of the patients, and the overall recurrence rate in these patients 8.8%. There was no significant relation between the extent of resection and the rate of tumor recurrence (p = 0.58). As expected, the extent of resection was highly correlated with patient age, tumor size, and surgical approach (p < 0.0001). Using Cox regression, the authors found that the approach used did not significantly affect tumor control when the extent of resection was controlled for.

Conclusions

While complete tumor removal is ideal, the results presented here suggest that there is no significant relationship between the extent of resection and tumor recurrence.

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Aaron J. Clark, Michael E. Ivan, Michael E. Sughrue, Isaac Yang, Derick Aranda, Seunggu J. Han, Ari J. Kane, and Andrew T. Parsa

Object

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.

Methods

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.

Results

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.

Conclusions

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.

Free access

Lara L. Cohen, Brian W. Yang, Nora P. O’Neill, Mark R. Proctor, Michael P. Glotzbecker, and Daniel J. Hedequist

OBJECTIVE

Patients with trisomy 21 (Down syndrome; DS) often have atlantoaxial instability (AAI), which, if severe, causes myelopathy and neurological deterioration. Children with DS and AAI who undergo cervical spine fusion have a high rate of nonunion requiring revision surgery. Recombinant human bone morphogenetic protein–2 (rhBMP-2) is a TGF-β growth factor that is used to induce bone formation in spine fusion. Although previous studies in the adult population have reported no reduction in pseudarthrosis rates with the use of rhBMP-2, there is a lack of literature in the pediatric DS population. This study describes the use of rhBMP-2 in children with DS and AAI during revision to treat nonunion.

METHODS

A retrospective review of a cervical spine fusion database (n = 175) was conducted. This database included all cervical spine fusions using modern instrumentation at the authors’ institution from 2002 to 2019. Patients with DS who underwent a revision utilizing rhBMP-2 were included in the study. The number of prior fusions, use of rhBMP-2 in fusions, length of stay, halo use, and surgical data were collected. Postoperative complications and length of follow-up were also recorded.

RESULTS

Eight patients (75% female) met the inclusion criteria. The average age at revision with rhBMP-2 was 11 years (range 3–19 years). All patients were diagnosed with nonunion after an initial cervical fusion. All revisions were posterior fusions of C1–2 (n = 2) or occiput to cervical (n = 6). All revisions included implant revisions, iliac crest bone grafting, and rhBMP-2 use. One patient required irrigation and debridement of an rhBMP-induced seroma. Another patient required return to the operating room to repair a dural tear. There were no neurological, infectious, airway, or implant-related complications. Revision utilizing rhBMP-2 achieved fusion in 100% (n = 8) of patients. The average length of follow-up was 42.6 months. All patients demonstrated solid fusion mass on the last radiograph.

CONCLUSIONS

This is the first case series reporting the successful use of rhBMP-2 to facilitate cervical spine fusion in patients with DS after previous nonunion. In addition, few rhBMP-2–related postoperative complications occurred.

Restricted access

Jeffrey M. Breton, Calvin G. Ludwig, Michael J. Yang, T. Jayde Nail, Ron I. Riesenburger, Penny Liu, and James T Kryzanski

OBJECTIVE

Spinal anesthesia (SA) is an alternative to general anesthesia (GA) for lumbar spine surgery, including complex instrumented fusion, although there are relatively few outcome data available. The authors discuss their experience using SA in a modern complex lumbar spine surgery practice to describe its utility and implementation.

METHODS

Data from patients receiving SA for lumbar spine surgery by one surgeon from March 2017 to December 2020 were collected via a retrospective chart review. Cases were divided into nonfusion and fusion procedure categories and analyzed for demographics and baseline medical status; pre-, intra-, and postoperative events; hospital course, including Acute Pain Service (APS) consults; and follow-up visit outcome data.

RESULTS

A total of 345 consecutive lumbar spine procedures were found, with 343 records complete for analysis, including 181 fusion and 162 nonfusion procedures and spinal levels from T11 through S1. The fusion group was significantly older (mean age 65.9 ± 12.4 vs 59.5 ± 15.4 years, p < 0.001) and had a significantly higher proportion of patients with American Society of Anesthesiologists (ASA) Physical Status Classification class III (p = 0.009) than the nonfusion group. There were no intraoperative conversions to GA, with infrequent need for a second dose of SA preoperatively (2.9%, 10/343) and rare preoperative conversion to GA (0.6%, 2/343) across fusion and nonfusion groups. Rates of complications during hospitalization were comparable to those seen in the literature. The APS was consulted for 2.9% (10/343) of procedures. An algorithm for the integration of SA into a lumbar spine surgery practice, from surgical and anesthetic perspectives, is also offered.

CONCLUSIONS

SA is a viable, safe, and effective option for lumbar spine surgery across a wide range of age and health statuses, particularly in older patients and those who want to avoid GA. The authors’ protocol, based in part on the largest set of data currently available describing complex instrumented fusion surgeries of the lumbar spine completed under SA, presents guidance and best practices to integrate SA into contemporary lumbar spine practices.

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Jacob Rahul Joseph, Michael A. DiPietro, Deepak Somashekar, Hemant A. Parmar, and Lynda J. S. Yang

Ultrasonography has previously been reported for use in the evaluation of compressive or traumatic peripheral nerve pathology and for its utility in preoperative mapping. However, these studies were not performed in infants, and they were not focused on the brachial plexus. The authors report a case in which ultrasonography was used to improve operative management of neonatal brachial plexus palsy (NBPP). An infant boy was born at term, complicated by right-sided shoulder dystocia. Initial clinical evaluation revealed proximal arm weakness consistent with an upper trunk injury. Unlike MRI or CT myelography that focus on proximal nerve roots, ultrasonography of the brachial plexus in the supraclavicular fossa was able to demonstrate a small neuroma involving the upper trunk (C-5 and C-6) and no asymmetry in movement of the diaphragm or in the appearance of the rhomboid muscle when compared with the unaffected side. However, the supra- and infraspinatus muscles were significantly asymmetrical and atrophied on the affected side. Importantly, ultrasound examination of the shoulder revealed posterior glenohumeral laxity. Instead of pursuing the primary nerve reconstruction first, timely treatment of the shoulder subluxation prevented formation of joint dysplasia and formation of a false glenoid, which is a common sequela of this condition. Because the muscles innervated by proximal branches of the cervical nerve roots/trunks were radiographically normal, subsequent nerve transfers were performed and good functional results were achieved. The authors believe this to be the first report describing the utility of ultrasonography in the surgical treatment planning in a case of NBPP. Noninvasive imaging, in addition to thorough history and physical examination, reduces the intraoperative time required to determine the extent and severity of nerve injury by allowing improved preoperative planning of the surgical strategy. Inclusion of ultrasonography as a preoperative modality may yield improved outcomes for children with NBPP.

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Isaac Yang, Michael E. Sughrue, Martin J. Rutkowski, Rajwant Kaur, Michael E. Ivan, Derick Aranda, Igor J. Barani, and Andrew T. Parsa

Object

Craniopharyngiomas have a propensity to recur after resection, potentially causing death through their aggressive local behavior in their critical site of origin. Recent data suggest that subtotal resection (STR) followed by adjuvant radiotherapy (XRT) may be an appealing substitute for gross-total resection (GTR), providing similar rates of tumor control without the morbidity associated with aggressive resection. Here, the authors summarize the published literature regarding rates of tumor control with various treatment modalities for craniopharyngiomas.

Methods

The authors performed a comprehensive search of the English language literature to identify studies publishing outcome data on patients undergoing surgery for craniopharyngioma. Rates of progression-free survival (PFS) and overall survival (OS) were determined through Kaplan-Meier analysis.

Results

There were 442 patients who underwent tumor resection. Among these patients, GTR was achieved in 256 cases (58%), STR in 101 cases (23%), and STR+XRT in 85 cases (19%). The 2- and 5-year PFS rates for the GTR group versus the STR+XRT group were 88 versus 91%, and 67 versus 69%, respectively. The 5- and 10-year OS rates for the GTR group versus the STR+XRT group were 98 versus 99%, and 98 versus 95%, respectively. There was no significant difference in PFS (log-rank test) or OS with GTR (log-rank test).

Conclusions

Given the relative rarity of craniopharyngioma, this study provides estimates of outcome for a variety of treatment combinations, as not all treatments are an option for all patients with these tumors.

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Seunggu J. Han, Isaac Yang, Jose J. Otero, Brian J. Ahn, Tarik Tihan, Michael W. McDermott, Mitchel S. Berger, Susan M. Chang, and Andrew T. Parsa

Object

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.

Methods

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.

Results

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).

Conclusions

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.

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Michael E. Sughrue, Isaac Yang, Seunggu J. Han, Derick Aranda, Ari J. Kane, Misha Amoils, Zachary A. Smith, and Andrew T. Parsa

Object

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.

Methods

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: ≤ 13 Gy and > 13 Gy. All tumors included in this study were < 25 mm in their largest diameter.

Results

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% [≤ 13 Gy], p < 0.001). The rates of vertigo or balance disturbance (1.1% [> 13 Gy] vs 1.8% [≤ 13 Gy], p = 0.001) and tinnitus (0.1% [> 13 Gy] vs 0.7% [≤ 13 Gy], p = 0.001) were significantly higher in the lower dose cohort than those in the higher dose cohort.

Conclusions

The results of our review of the literature provide a systematic summary of the published rates of nonaudiofacial morbidity following radiosurgery for vestibular schwannoma.