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Kaisorn L. Chaichana, Debraj Mukherjee, Owoicho Adogwa, Joseph S. Cheng and Matthew J. McGirt

Object

Lumbar discectomy is the most common surgical procedure performed in the US for patients experiencing back and leg pain from herniated lumbar discs. However, not all patients will benefit from lumbar discectomy. Patients with certain psychological predispositions may be especially vulnerable to poor clinical outcomes.

The goal of this study was therefore to determine the role that preoperative depression and somatic anxiety have on long-term back and leg pain, disability, and quality of life (QOL) for patients undergoing single-level lumbar discectomy.

Methods

In 67 adults undergoing discectomy for a single-level herniated lumbar disc, the authors determined quantitative measurements of leg and back pain (visual analog scale [VAS]), quality of life (36-Item Short Form Health Survey [SF-36]), and disease-specific disability (Oswestry Disability Index) preoperatively and at 6 weeks, 3, 6, and 12 months after surgery. The degree of preoperative depression and somatization was assessed using the Zung Self-Rating Depression Scale and a modified somatic perception questionnaire (MSPQ). Multivariate regression analyses were performed to assess associations between Zung Scale and MSPQ scores with achievement of a minimum clinical important difference (MCID) in each outcome measure by 12 months postoperatively.

Results

All patients completed 12 months of follow-up. Overall, a significant improvement in VAS leg pain, VAS back pain, Oswestry Disability Index, and SF-36 Physical Component Summary scores was observed by 6 weeks after surgery. Improvements in all outcomes were maintained throughout the 12-month follow-up period. Increasing preoperative depression (measured using the Zung Scale) was associated with a decreased likelihood of achieving an MCID in disability (p = 0.006) and QOL (p = 0.04) but was not associated with VAS leg pain (p = 0.96) or back pain (p = 0.85) by 12 months. Increasing preoperative somatic anxiety (measured using the MSPQ) was associated with decreased likelihood of achieving an MCID in disability (p = 0.002) and QOL (p = 0.03) but was not associated with leg pain (p = 0.64) or back pain (p = 0.77) by 12 months.

Conclusions

The Zung Scale and MSPQ are valuable tools for stratifying risk in patients who may not experience clinically relevant improvement in disability and QOL after discectomy. Efforts to address these confounding and underlying contributors of depression and heightened somatic anxiety may improve overall outcomes after lumbar discectomy.

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Debraj Mukherjee, Kaisorn L. Chaichana, Ziya L. Gokaslan, Oran Aaronson, Joseph S. Cheng and Matthew J. McGirt

Object

Malignant primary osseous spinal neoplasms are aggressive tumors that remain associated with poor outcomes despite aggressive multidisciplinary treatment measures. To date, prognosis for patients with these tumors is based on results from small single-center patient series and controlled trials. Large population-based observational studies are lacking. To assess national trends in histology-specific survival, the authors reviewed patient survival data spanning 30 years (1973–2003) from the Surveillance, Epidemiology, and End Results (SEER) registry, a US population-based cancer registry.

Methods

The SEER registry was queried to identify cases of histologically confirmed primary spinal chordoma, chondrosarcoma, osteosarcoma, or Ewing sarcoma using coding from the International Classification of Disease for Oncology, Third Edition. Association of survival with histology, metastasis status, tumor site, and year of diagnosis was assessed using Cox proportional-hazards regression analysis.

Results

A total of 1892 patients were identified with primary osseous spinal neoplasms (414 with chordomas, 579 with chondrosarcomas, 430 with osteosarcomas, and 469 with Ewing sarcomas). Chordomas presented in older patients (60 ± 17 years; p < 0.01) whereas Ewing sarcoma presented in younger patients (19 ± 11 years; p < 0.01) compared with patients with all other tumors. The relative incidence of each tumor type remained similar per decade from 1973 to 2003. African Americans comprised a significantly greater proportion of patients with osteosarcomas than other tumors (9.6% vs 3.5%, respectively; p < 0.01). Compared with the sacrum, the mobile spine was more likely to be the site of tumor location for chordomas than for all other tumors (47% vs 23%, respectively; p < 0.05). Osteosarcoma and Ewing sarcoma were 3 times more likely than chondrosarcoma and chordoma to present with metastasis (31% vs 8%, respectively). Resection was performed more frequently for chordoma (88%) and chondrosarcoma (89%) than for osteosarcoma (61%) and Ewing sarcoma (53%). Overall median survival was histology-specific (osteosarcoma, 11 months; Ewing sarcoma, 26 months; chondrosarcoma, 37 months; chordoma, 50 months) and significantly worse in patients with metastasis at presentation for all tumor types. Survival did not significantly differ as a function of site (mobile spine vs sacrum/pelvis) for any tumor type, but more recent year of diagnosis was associated with improved survival for isolated spinal Ewing sarcoma (hazard ration [HR] 0.95; p = 0.001), chondrosarcoma (HR 0.98; p = 0.009), and chordoma (HR 0.98; p = 0.10), but not osteosarcoma.

Conclusions

In this analysis of a 30-year, US population-based cancer registry (SEER), the authors provide nationally representative prognosis and survival data for patients with malignant primary spinal osseous neoplasms. Overall patient survival has improved for isolated spine tumors with advancements in care over the past 4 decades. These results may be helpful in providing historical controls for understanding the efficacy of new treatment paradigms, patient education, and guiding level of aggressiveness in treatment strategies.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010

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Kaisorn L. Chaichana, Matthew J. McGirt, John Laterra, Alessandro Olivi and Alfredo Quiñones-Hinojosa

Object

Unlike their malignant counterparts, low-grade gliomas are associated with prolonged survival. However, these tumors have a propensity to progress after resection and ultimately undergo malignant degeneration. The factors associated with recurrence and malignant degeneration remain relatively unknown. The authors set out to determine factors that were independently associated with recurrence and malignant degeneration in patients who underwent resection of a hemispheric low-grade glioma.

Methods

Adult patients who underwent craniotomy and resection of a hemispheric low-grade glioma (WHO Grade II) at the Johns Hopkins Medical Institution's academic tertiary-care institution between 1996 and 2006 were retrospectively reviewed. Multivariate proportional hazards regression analyses were used to identify associations with tumor recurrence and malignant degeneration.

Results

Of the 191 consecutive patients with low-grade gliomas in this series (89 fibrillary astrocytomas, 89 oligodendrogliomas, and 13 mixed gliomas), 83 (43%) and 44 (23%) experienced tumor recurrence and malignant degeneration at last follow-up, respectively. The 5-year progression-free and malignancy-free survival rates were 44 and 74%, respectively. Independent predictors of recurrence were duration of longest lasting symptom (relative risk [RR] 0.978, 95% CI 0.954–0.996, p = 0.01), tumor size (RR 1.328, 95% CI 1.109–1.602, p = 0.002), and preoperative contrast enhancement (RR 2.558, 95% CI 1.241–5.021, p = 0.01). Independent factors associated with malignant degeneration were fibrillary astrocytoma pathology (RR 1.800, 95% CI 1.008–4.928, p = 0.04), tumor size (RR 1.086, 95% CI 1.044–1.358, p = 0.04), and gross-total resection (RR 0.526, 95% CI 0.221–1.007, p = 0.05).

Conclusions

The identification and consideration of factors associated with recurrence and malignant progression may help guide treatment strategies aimed at delaying recurrence and preventing malignant degeneration for patients with hemispheric low-grade gliomas.

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Matthew J. McGirt, Khoi D. Than, Jon D. Weingart, Kaisorn L. Chaichana, Frank J. Attenello, Alessandro Olivi, John Laterra, Lawrence R. Kleinberg, Stuart A. Grossman, Henry Brem and Alfredo Quiñones-Hinojosa

Object

Gliadel (BCNU) wafer and concomitant temozolomide (TMZ) therapy, when used individually as adjuvant therapies, extend survival from that achieved by resection and radiation therapy (XRT) for glioblastoma multiforme (GBM). It remains unstudied whether combining Gliadel and TMZ therapy is safe or further improves survival in patients with newly diagnosed GBM. The authors reviewed their initial experience utilizing combined Gliadel, TMZ, and radiation therapy for the treatment of GBM.

Methods

All cases involving patients undergoing primary resection of GBM with or without Gliadel wafer (3.85% BCNU) implantation and adjuvant XRT over a 10-year period (1997–2006) were retrospectively reviewed. Beginning in 2004, concomitant TMZ became the standard of care at the authors' institution and all patients with Gliadel implantation also received concomitant TMZ (Stupp protocol). Overall survival and treatment-related morbidity were assessed for all patients treated with Gliadel plus concomitant TMZ (XRT + Gliadel + TMZ). Age-matched (≤ 70 years) comparison of survival and morbidity was performed between the XRT + Gliadel + TMZ (post-2003) and XRT + Gliadel (pre-2004) cohorts.

Results

Thirty-three patients were treated with XRT + Gliadel + TMZ. The median survival in this group was 20.7 months, with a 2-year survival rate of 36%. Six-month morbidity included surgical site infection in 1 case (3%), perioperative seizures in 2 cases (6%), deep-vein thrombus in 1 (3%), pulmonary embolism in 3 (9%), and cerebral edema requiring admission for intravenous dexamethasone in 1 case (3%). Myelosuppression required premature termination of TMZ in 7 patients (21%) (thrombocytopenia in 5, neutropenia in 2 cases). In patients ≤ 70 years of age, XRT + Gliadel + TMZ (30 patients, post-2003) was independently associated with improved median survival (21.3 vs 12.4 months, p = 0.005) versus XRT + Gliadel (78 patients, pre-2004), with 2-year survival of 39 versus 18%, respectively. In these patients, XRT + Gliadel + TMZ was not associated with an increase in perioperative morbidity in comparison with XRT + Gliadel.

Conclusions

In this experience, concomitant TMZ therapy in addition to Gliadel wafer implantation was associated with a median survival of nearly 21 months without increased perioperative morbidity. Temozolomide can be safely administered to patients receiving Gliadel wafers after resection of GBM.

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Matthew J. McGirt, Kaisorn L. Chaichana, Muraya Gathinji, Frank J. Attenello, Khoi Than, Alessandro Olivi, Jon D. Weingart, Henry Brem and Alf redo Quiñones-Hinojosa

Object

With recent advances in the adjuvant treatment of malignant brain astrocytomas, it is increasingly debated whether extent of resection affects survival. In this study, the authors investigate this issue after primary and revision resection of these lesions.

Methods

The authors retrospectively reviewed the cases of 1215 patients who underwent surgery for malignant brain astrocytomas (World Health Organization [WHO] Grade III or IV) at a single institution from 1996 to 2006. Patients with deep-seated or unresectable lesions were excluded. Based on MR imaging results obtained < 48 hours after surgery, gross-total resection (GTR) was defined as no residual enhancement, near-total resection (NTR) as having thin rim enhancement of the resection cavity only, and subtotal resection (STR) as having residual nodular enhancement. The independent association of extent of resection and subsequent survival was assessed via a multivariate proportional hazards regression analysis.

Results

Magnetic resonance imaging studies were available for review in 949 cases. The mean age and mean Karnofsky Performance Scale (KPS) score at time of surgery were 51 ± 16 years and 80 ± 10, respectively. Surgery consisted of primary resection in 549 patients (58%) and revision resection for tumor recurrence in 400 patients (42%). The lesion was WHO Grade IV in 700 patients (74%) and Grade III in 249 (26%); there were 167 astrocytomas and 82 mixed oligoastrocytoma. Among patients who underwent resection, GTR, NTR, and STR were achieved in 330 (35%), 388 (41%), and 231 cases (24%), respectively. Adjusting for factors associated with survival (for example, age, KPS score, Gliadel and/or temozolomide use, and subsequent resection), GTR versus NTR (p < 0.05) and NTR versus STR (p < 0.05) were independently associated with improved survival after both primary and revision resection of glioblastoma multiforme (GBM). For primary GBM resection, the median survival after GTR, NTR, and STR was 13, 11, and 8 months, respectively. After revision resection, the median survival after GTR, NTR, and STR was 11, 9, and 5 months, respectively. Adjusting for factors associated with survival for WHO Grade III astrocytoma (age, KPS score, and revision resection), GTR versus STR (p < 0.05) was associated with improved survival. Gross-total resection versus NTR was not associated with an independent survival benefit in patients with WHO Grade III astrocytomas. The median survival after primary resection of WHO Grade III (mixed oligoastrocytomas excluded) for GTR, NTR, and STR was 58, 46, and 34 months, respectively.

Conclusions

In the authors' experience with both primary and secondary resection of malignant brain astrocytomas, increasing extent of resection was associated with improved survival independent of age, degree of disability, WHO grade, or subsequent treatment modalities used. The maximum extent of resection should be safely attempted while minimizing the risk of surgically induced neurological injury.

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Daniel M. Sciubba, Kaisorn L. Chaichana, Graeme F. Woodworth, Matthew J. McGirt, Ziya L. Gokaslan and George I. Jallo

Object

The indications remain unclear for fusion at the time of cervical laminectomy for intradural tumor resection. To identify patients who may benefit from initial fusion, the authors assessed clinical, radiological/imaging, and operative factors associated with subsequent symptomatic cervical instability requiring fusion after cervical laminectomy for intradural tumor resection.

Methods

The authors reviewed 10 years of data obtained in patients who underwent cervical laminectomy without fusion for intradural tumor resection and who had normal spinal stability and alignment preoperatively. The association of pre- and intraoperative variables with the subsequent need for fusion for progressive symptomatic cervical instability was assessed using logistic regression analysis, and percentages were compared using Fisher exact tests when appropriate.

Results

Thirty-two patients (mean age 41 ± 17 years) underwent cervical laminectomy without fusion for resection of an intradural tumor (18 intramedullary and 14 extramedullary). Each increasing number of laminectomies performed was associated with a 3.1-fold increase in the likelihood of subsequent vertebral instability (odds ratio 3.114, 95% confidence interval 1.207–8.034, p = 0.02). At a mean follow-up interval of 25.2 months, 33% (4 of 12) of the patients who had undergone a ≥ 3-level laminectomy required subsequent fusion compared with 5% (1 of 20) who had undergone a ≤ 2-level laminectomy (p = 0.03). Four (36%) of 11 patients initially presenting with myelopathic motor disturbance required subsequent fusion compared with 1 (5%) of 21 presenting initially with myelopathic sensory or radicular symptoms (p = 0.02). Age, the presence of a syrinx, intramedullary tumor, C-2 laminectomy, C-7 laminectomy, and laminoplasty were not associated with subsequent symptomatic instability requiring fusion.

Conclusions

In the authors' experience with intradural cervical tumor resection, patients presenting with myelopathic motor symptoms or those undergoing a ≥ 3-level cervical laminectomy had an increased likelihood of developing subsequent symptomatic instability requiring fusion. A ≥ 3-level laminectomy with myelopathic motor symptoms may herald patients most likely to benefit from cervical fusion at the time of tumor resection.

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Matthew J. McGirt, Kaisorn L. Chaichana, April Atiba, Ali Bydon, Timothy F. Witham, Kevin C. Yao and George I. Jallo

Object

Gross-total resection of pediatric intramedullary spinal cord tumor (IMSCT) can be achieved in the majority of cases while preserving long-term neurological function. Nevertheless, postoperative progressive spinal deformity often complicates functional outcome years after surgery. The authors set out to determine whether laminoplasty in comparison with laminectomy has reduced the incidence of subsequent spinal deformity requiring fusion after IMSCT resection at their institution.

Methods

The first 144 consecutive patients undergoing resection of IMSCTs at a single institution underwent laminectomy with preservation of facet joints. The next 20 consecutive patients presenting for resection of IMSCTs underwent osteoplastic laminotomy regardless of patient or tumor characteristics. All patients were followed up with telephone interviews corroborated by medical records for the following outcomes: 1) neurological and functional status (modified McCormick Scale [MMS] score and Karnofsky Performance Scale [KPS] score); and 2) development of progressive spinal deformity requiring fusion. The incidence of progressive spinal deformity and the long-term neurological function were compared between the laminectomy and osteoplastic laminotomy cohorts. The means are expressed ± the standard deviation.

Results

Overall, the patients' mean age was 8.6 ± 5 years, and they presented with median MMS scores of 2 (interquartile range [IQR] 2–4). A > 95% resection was achieved in 125 cases (76%). There were no differences (p > 0.10) between patients treated with osteoplastic laminotomy and those treated with laminectomy in terms of the following characteristics: age; sex; duration of symptoms; location of tumor; incidence of preoperative scoliosis (Cobb angle > 10°: 7 [35%] with laminoplasty compared with 49 [34%] with laminectomy); involvement of the cervicothoracic junction (7 [35%] compared with 57 [40%]); thoracolumbar junction (4 [20%] compared with 36 [25%]); tumor size; extent of resection; radiation therapy; histopathological findings; or mean operative spinal levels (7.5 ± 2 compared with 7.5 ± 3). Nevertheless, patients who underwent osteoplastic laminotomy had better median preoperative MMS scores than those treated with laminectomy (2 [IQR 2–2] compared with 2 [IQR 2–4]; p = 0.04). A median of 3.5 years (IQR 1–7 years) after surgery, only 1 patient (5%) in the osteoplastic laminotomy cohort required fusion for progressive spinal deformity, compared with 43 (30%) in the laminectomy cohort (p = 0.027). Adjusting for the inter-cohort difference in preoperative MMS scores, osteoplastic laminotomy was associated with a 7-fold reduction in the odds of subsequent fusion for progressive spinal deformity (odds ratio 0.13, 95% confidence interval 0.02–1.00; p = 0.05). The median MMS and KPS scores were similar between patients who underwent osteoplastic laminotomy and those in whom laminectomy was performed (MMS Score 2 [IQR 2–3] for laminotomy compared with 2 [IQR 2–4] for laminectomy, p = 0.54; KPS Score 90 [IQR 70–100] for laminotomy compared with 90 [IQR 80–90] for laminectomy, p = 0.545) at a median of 3.5 years after surgery.

Conclusions

In the authors' experience, osteoplastic laminotomy for the resection of IMSCT in children was associated with a decreased incidence of progressive spinal deformity requiring fusion but did not affect long-term functional outcome. Laminoplasty used for pediatric IMSCT resection may decrease the incidence of progressive spinal deformity requiring subsequent spinal stabilization in some patients.

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Matthew J. McGirt, Kaisorn L. Chaichana, April Atiba, Frank Attenello, Kevin C. Yao and George I. Jallo

Object

With modern surgical advances, radical resection of pediatric intramedullary spinal cord tumors (IMSCTs) can be expected to preserve long-term neurological function. Nevertheless, postoperative neurological decline is not uncommon after surgery, and many patients continue to experience long-term dysesthetic symptoms. Preoperative predictors of postoperative neurological decline and sensory syndromes have not been investigated and may serve as a guide for surgical risk stratification.

Methods

Neurological function (as determined using the modified McCormick Scale [mMS]) preoperatively, postoperatively, and 3 months after surgery was retrospectively recorded from patient charts in 164 consecutive patients undergoing resection of IMSCTs. A median 4 years (interquartile range [IQR] 1–8 years) after surgery, long-term motor and sensory symptoms were assessed by telephone interviews and corroborated by subsequent medical visits in 120 available patients. This long-term assessment was retrospectively reviewed for the purposes of this study. The authors reviewed this series to assess long-term motor, sensory, and urinary outcomes and to determine independent risk factors of postoperative neurological decline and long-term sensory dysfunction.

Results

Patients were 8.6 ± 5.7 years old and presented with a median mMS of 2 (IQR 2–4). Three months after surgery, 38 patients (23%) continued to experience decreased neurological function (1 mMS point) incurred perioperatively. Increasing age (p = 0.028), unilateral symptoms (p = 0.046), and urinary dysfunction at presentation (p = 0.004) independently predicted persistent 3-month perioperative decline. At long-term follow-up (median 4 years), 39 (33%) exhibited improvements in their mMS scores, 13 (30%) had improvement in their urinary dysfunction, and 27 (30%) had resolution of their dysesthesias. Seventy-eight patients (65%) experienced long-term dysesthetic symptoms. Increasing age (p = 0.024), preoperative symptom duration > 12 months (p = 0.027), and worsened postoperative mMS score at hospital discharge (p = 0.013) independently increased the risk of long-term dysesthesias.

Conclusions

In the authors' experience, nearly one third of patients may experience improvement in motor, sensory, and urinary dysfunction years after IMSCT resection, whereas the majority will continue to experience long-term dysesthetic symptoms. Improvement in motor deficits preceded improvement in sensory syndromes, and urinary dysfunction typically resolved much longer after surgery. The risk of persistent perioperative motor decline was increased with older age, unilateral symptoms, preoperative urinary symptoms, and less severe preoperative neurological deficit. The risk of long-term dysesthesias was increased with older age, increased duration of symptoms prior to resection, and greater postoperative neurological deficit.

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Kevin C. Yao, Matthew J. McGirt, Kaisorn L. Chaichana, Shlomi Constantini and George I. Jallo

Object

Gross-total resection of pediatric intramedullary spinal cord tumors (IMSCTs) can be achieved in the majority of cases, with preservation of long-term neurological function. However, progressive spinal deformity requiring subsequent fusion occurs in many cases. It remains unknown which subgroups of patients have the greatest risk for progressive spinal deformity.

Methods

Data for 161 patients undergoing resection of IMSCTs at a single institution were retrospectively collected and analyzed with regard to the development of progressive spinal deformity requiring fusion and patient functional status (based on the modified McCormick Scale [mMS] and Karnofsky Performance Scale [KPS]) by conducting telephone interviews corroborated by medical records. The independent association of all clinical, radiographic, and operative variables to subsequent progressive spinal deformity was assessed using multivariate logistic regression analysis.

Results

Patients were a mean of 8.6 ± 5.7 years old at the time of surgery. The tumor spanned a mean of six ± three spinal levels. Preoperative scoliotic deformity was present in 56 cases (35%). Seventy-six patients (47%) had undergone a previous biopsy procedure, and 28 (17%) a prior resection. Gross-total resection (> 95%) was achieved in 122 cases (76%). A median of 9 years (range 1–21) after surgery, progressive spinal deformity requiring fusion developed in 43 patients (27%). The median functional scores at the last follow-up were worse in patients who required fusion compared with those who did not (mMS: 3 compared with 2, p = 0.006; KPS: 80 compared with 90, p = 0.04) despite similar mMS scores between the groups at 3 months postoperatively. An age less than 13 years, preoperative scoliotic deformity (Cobb angle > 10°), involvement of the thoracolumbar junction, and tumor-associated syrinx independently increased the odds of a postoperative progressive deformity requiring fusion 4.4-, 3.2-, 2.6-, and 3.4-fold, respectively (p < 0.05). Each subsequent resection increased the odds of a progressive deformity 1.8-fold (p < 0.05). Symptoms lasting less than 1 month before resection decreased the odds of spinal deformity requiring fusion ninefold (p < 0.05).

Conclusions

Progressive spinal deformity requiring fusion occurred in 27% of children undergoing resection of an IMSCT and was associated with a decreased functional status. Preoperative scoliotic deformity, an increasing number of resections, an age less than 13 years, tumor-associated syrinx, and surgery spanning the thoracolumbar junction increased the risk for progressive spinal deformity. Patients possessing one or more of these characteristics should be monitored closely for progressive spinal deformity following surgery.