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Matthew J. McGirt, Shlomi Constantini, and George I. Jallo

Object

Postoperative progressive spinal deformity often complicates functional outcome after resection of pediatric intramedullary spinal cord tumors (IMSCTs). The authors propose a preoperative grading scale that correlates with the postoperative development of progressive spinal deformity requiring subsequent fusion.

Methods

The data obtained in 164 patients who underwent resection of an IMSCT at a single institution were retrospectively collected and analyzed to determine the development of progressive spinal deformity requiring fusion. A grading scale (range of scores I–V) was created based on the presence or absence of 4 preoperative variables: preoperative scoliosis, involvement of the thorocolumbar junction, age < 13 years, and number of surgeries for an IMSCT. The grading scale was then retrospectively applied to this series of 164 children to assess the correlation of variables with subsequent spinal deformity.

Results

Nine patients presented with Grade I status, 41 patients with Grade II, 58 patients with Grade III, 44 patients with Grade IV, and 12 patients with Grade V. Overall, 44 patients (27%) developed progressive spinal deformity requiring fusion at a mean follow-up of 5 years after surgery. A higher preoperative grade was associated with an increasing need for subsequent fusion for progressive spinal deformity (Grade I [0%], Grade II [5%], Grade III [26%], Grade IV [40%], and Grade V status [75%]).

Conclusions

Application of this grading scheme to a series of resected pediatric IMSCTs has demonstrated its correlation with the incidence of postoperative progressive spinal deformity requiring fusion. The application of a standardized grading scheme will assist in the process of surgical decision making and postoperative evaluation.

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Daniel M. Sciubba, Clarke Nelson, Beryl Gok, Matthew J. McGirt, Gregory S. McLoughlin, Joseph C. Noggle, Jean Paul Wolinsky, Timothy F. Witham, Ali Bydon, and Ziya L. Gokaslan

Object

Resection of sacral tumors has been shown to improve survival, since the oncological prognosis is commonly correlated with the extent of local tumor control. However, extensive soft-tissue resection in close proximity to the rectum may predispose patients to wound complications and infection. To identify potential risk factors, a review of clinical outcomes for sacral tumor resections over the past 5 years at a single institution was completed, paying special attention to procedure-related complications.

Methods

Between 2002 and 2007, 46 patients with sacral tumors were treated with surgery. Demographic data, details of surgery, type of tumor, and patient characteristics associated with surgical site infections (SSIs) were collected; these data included presence of the following variables: diabetes, obesity, smoking, steroid use, previous surgery, previous radiation, cerebrospinal fluid leak, number of spinal levels exposed, instrumentation, number of surgeons scrubbed in to the procedure, serum albumin level, and combined anterior-posterior approach. Logistic regression analysis was implemented to find an association of such variables with the presence of SSI.

Results

A total of 46 patients were treated for sacral tumor resections; 20 were male (43%) and 26 were female (57%), with an average age of 46 years (range 11–83 years). Histopathological findings included the following: chordoma in 19 (41%), ependymoma in 5 (11%), rectal adenocarcinoma in 5 (11%), giant cell tumor in 4 (9%), and other in 13 (28%). There were 18 cases of wound infection (39%), and 2 cases of repeat surgery for tumor recurrence (1 chordoma and 1 giant cell tumor). Factors associated with increased likelihood of infection included previous lumbosacral surgery (p = 0.0184; odds ratio [OR] 7.955) and number of surgeons scrubbed in to the operation (p = 0.0332; OR 4.018). Increasing age (p = 0.0864; OR 1.031), presence of complex soft-tissue reconstruction (p = 0.118; OR 3.789), and bowel and bladder dysfunction (p = 0.119; OR 2.667) demonstrated a trend toward increased risk of SSI.

Conclusions

Patients undergoing sacral tumor surgery may be at greater risk for developing wound complications due to the extensive soft-tissue resections often required, especially with the increased potential for contamination from the neighboring rectum. In this study, it appears that previous lumbosacral surgery, number of surgeons scrubbed in, patient age, bowel and bladder dysfunction, and complex tissue reconstruction may predict those patients more prone to developing postoperative SSIs.

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Matthew J. McGirt, Beril Gok, Starane Shepherd, Joseph Noggle, Giannina L. Garcés Ambrossi, Ali Bydon, and Ziya L. Gokaslan

Object

Hyperglycemia has been shown to potentiate ischemic injury of the spinal cord by quenching vasodilators and potentiating tissue acidosis and free radical production. Steroid-induced hyperglycemia is a common event in the surgical management of metastatic epidural spinal cord compression (MESCC). The goal in this study was to determine whether experimentally induced hyperglycemia accelerates neurological decline in an established animal model of MESCC.

Methods

Sixteen Fischer 344 rats underwent a transabdominal approach for implantation of a CRL-1666 breast adenocarcinoma cell line within the vertebral body of L-6. After 72 hours of recovery from tumor implantation, the animals received intraperitoneal injections every 12 hours of either 2 g/kg dextrose in 5 ml 0.09% saline (hyperglycemia, 8 rats) or 5 ml 0.09% saline alone (normoglycemia, 8 rats). Weights were taken daily, and the hindlimb function was tested daily after tumor implantation by using the Basso-Beattie-Bresnahan (BBB) scale (score range 1–21). Animals were killed at time of paralysis (BBB Score < 7), and the volume of epidural tumor growth within the spinal canal was measured. To determine the degree of hyperglycemia induced by this dextrose regimen, a surrogate group of 10 Fischer 344 rats underwent intraperitoneal injections of 2 g/kg dextrose (5 rats) or 0.09% saline (5 rats) every 12 hours, and serum glucose levels were assessed 1, 3, 6, 8, 10, and 12 hours after injections for 24 hours.

Results

Dextrose versus saline injections resulted in elevated mean serum glucose at 3 (259 vs 103 μg/dl), 6 (219 vs 102 μg/dl), 8 (169 vs 102 μg/dl), and 10 hours (118 vs 99 μg/dl) after injection, returning to normal levels by 12 hours (96 vs 103 μg/dl) just prior to subsequent injection. All rats had normal hindlimb function for the first 8 days after tumor implantation. Hyperglycemic versus normoglycemic rats demonstrated a worsened median BBB score by postimplantation Day 9 (Score 20 vs 21, p = 0.023) through Day 16 (Score 8 vs 12, p = 0.047). Epidural tumor volume demonstrated a near-linear growth rate across both groups; however, hyperglycemic rats developed paralysis earlier (median 15.5 vs 17.5 days, p = 0.0035), with significantly less epidural tumor volume (2.75 ± 0.38 cm3 vs 4 ± 0.41 cm3, p < 0.001) at time of paralysis.

Conclusions

In a rat model of metastatic epidural spinal cord compression, rats maintained in a hyperglycemic state experienced accelerated time to paralysis. Also, less epidural tumor volume was required to cause paralysis in hyperglycemic rats. These results suggest that hyperglycemic states may contribute to decreased spinal cord tolerance to compression resulting from MESCC. Clinical studies evaluating the effect of aggressive glucose control in patients with MESCC may be warranted.

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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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Sophia F. Shakur, Matthew J. McGirt, Michael W. Johnson, Peter C. Burger, Edward Ahn, Benjamin S. Carson, and George I. Jallo

Object

Angiocentric glioma was recently recognized as a distinct clinicopathological entity in the 2007 World Health Organization Classification of Tumours of the Central Nervous System. The authors present the first 3 pediatric cases of angiocentric glioma encountered at their institution and review the literature of reported cases to elucidate the characteristics and outcomes of pediatric patients with this novel tumor.

Methods

The children in the 3 cases of angiocentric glioma were 10, 10, and 13 years old. Two presented with intractable seizures and 1 with worsening headache and several months of decreasing visual acuity. Twenty-five cases, including the 3 first described in the present paper, were culled from the literature.

Results

In all 3 cases, MR imaging demonstrated a superficial, nonenhancing, T2-hyperintense lesion in the left temporal lobe. Histologically, the tumors were composed of monomorphous cells with a strikingly perivascular orientation that were variably reactive for glial fibrillary acidic protein and epithelial membrane antigen. Surgical treatment resulted in gross-total resection in all 3 cases. By 24, 9, and 6 months after surgery, all 3 patients remained seizure free without focal neurological deficits.

Conclusions

Among 25 cases of angiocentric glioma, seizure was the most common symptom at presentation. Magnetic resonance imaging demonstrated supratentorial, nonenhancing, T1-hypointense, T2-hyperintense lesions. Gross-total resection of this lesion yields excellent results.

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Daniel M. Sciubba, Rory J. Petteys, Giannina L. Garces-Ambrossi, Joseph C. Noggle, Matthew J. McGirt, Jean-Paul Wolinsky, Timothy F. Witham, and Ziya L. Gokaslan

Sacral tumors pose significant challenges to the managing physician from diagnostic and therapeutic perspectives. Although these tumors are often diagnosed at an advanced stage, patients may benefit from good clinical outcomes if an aggressive multidisciplinary approach is used. In this review, the epidemiology, clinical presentation, imaging characteristics, treatment options, and published outcomes are discussed. Special attention is given to the specific anatomical constraints that make tumors in this region of the spine more difficult to effectively manage than those in the mobile portions of the spine.

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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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Ziya L. Gokaslan and Matthew J. McGirt

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Matthew J. McGirt, Giannina L. Garces Ambrossi, Judy Huang, and Rafael J. Tamargo

Object

Vasospasm is the major cause of disability and death after aneurysmal subarachnoid hemorrhage (aSAH). Although the results of 2 randomized clinical trials demonstrated that statin decreases the incidence of symptomatic cerebral vasospasm after aSAH, retrospective studies have failed to confirm this. The authors conducted a prospective observational study to determine whether a standardized regimen of simvastatin would reduce the incidence of cerebral vasospasm and improve neurological outcomes in patients with aSAH.

Methods

Since 1991, all patients with aSAH admitted to the authors' institution have been prospectively followed up with standardized outcomes recording. Starting in September 2005, all patients admitted with aSAH were given enteral simvastatin (80 mg/day for 14 days) in addition to the standard care. The incidence of symptomatic cerebral vasospasm, length of hospitalization, in-hospital mortality rate, and discharge Glasgow Outcome Scale scores in these 170 patients were compared to data obtained in 170 consecutive patients who underwent treatment in our unit prior to the introduction of statin therapy.

Results

The 5-year study period included 340 consecutively treated patients (170 who received statins and 170 who did not). Patients who received simvastatin therapy were more frequently male (29 vs 20%) and had a smaller median aneurysm diameter (6 vs 7 mm). Baseline characteristics were otherwise similar between the cohorts. There were no differences in the incidence of symptomatic vasospasm (25.3 vs 30.5%; p = 0.277), in-hospital mortality rate (18 vs 15%; p = 0.468), length of hospitalization (21 ± 15 vs 19 ± 12 days; p = 0.281), or poor outcome at discharge (Glasgow Outcome Scale Scores 1–2: 21.7 vs 18.2%; p = 0.416) between the simvastatin and nonstatin cohorts. There were no statin-related complications.

Conclusions

The uniform introduction of simvastatin did not reduce the incidence of symptomatic cerebral vasospasm, death, or poor outcome in patients with aSAH. Simvastatin was well tolerated, but its benefit may be less than has been previously reported.