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Eric W. Amundson, Matthew J. McGirt, and Alessandro Olivi

✓ The authors report on the technique and results of stereotactic biopsy for intrinsic lateral pontine and medial cerebellar lesions via a contralateral, transfrontal, extraventricular approach. Multiplanar stereotactic magnetic resonance imaging was used to plan an intraparenchymal approach, thus limiting the number of crossed pial surfaces to one and eliminating the need to cross ependymal surfaces. After the administration of a local anesthetic agent with light intravenous sedation, six patients harboring intrinsic lateral pontine lesions underwent biopsies via this intraparenchymal approach with 100% diagnostic yield and no operative morbidity. In comparison to the ipsilateral transfrontal approach, the contralateral approach laterally expands the infratentorial area accessible during biopsy to include the lateral pons and middle cerebellar peduncle. The contralateral, transfrontal, extraventricular approach is a useful, straight-forward and safe alternative to the suboccipital transcerebellar and ipsilateral, transfrontal, transtentorial routes for reaching lesions of the lateral pons and middle cerebellar peduncle.

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Kaisorn Chaichana, Scott Parker, Alessandro Olivi, and Alfredo Quiñones-Hinojosa

Object

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor in adults. Although the average survival is ~ 12 months, individual survival is heterogeneous. The ability to predict short- and long-term survivors is limited. Therefore, the aims of this study were to ascertain preoperative risk factors associated with survival, develop a preoperative prognostic grading system, and evaluate the utility of this grading system in predicting survival for patients undergoing resection of a primary intracranial GBM.

Methods

Cases involving adult patients who underwent surgery for an intracranial primary (de novo) GBM between 1997 and 2007 at The Johns Hopkins Hospital, an academic tertiary-care institution, were retrospectively reviewed. Multivariate proportional hazards regression analysis was used to identify preoperative factors associated with survival, after controlling for extent of resection and adjuvant therapies. The identified associations with survival were then used to develop a grading system based on preoperative variables. Survival as a function of time was plotted using the Kaplan-Meier method, and survival rates were compared using Log-rank analysis. Associations with p < 0.05 were considered statistically significant.

Results

Of the 393 patients in this study, 310 (79%) had died as of most recent follow-up (median time from surgery to death 11.9 months). The preoperative factors, independent of extent of resection and adjuvant therapies (carmustine wafers, temozolomide, and radiation), found to be negatively associated with survival were: age > 60 years (p < 0.0001), Karnofsky performance status score ≤ 80 (p < 0.0001), motor deficit (p = 0.02), language deficit (p = 0.001), and periventricular tumor location (p = 0.04). Patients possessing 0–1, 2, 3, and 4–5 of these variables were assigned a preoperative grade of 1, 2, 3, and 4, respectively. Patients with a preoperative grade of 1, 2, 3, and 4 had a median survival of 16.6, 10.2, 6.8, and 6.1 months, respectively.

Conclusions

The present study found that older age, poor performance status, motor deficit, language deficit, and periventricular tumor location independently predicted poorer survival in patients undergoing GBM resection. A grading system based on these factors was able to identify 4 distinct groups of patients with different survival rates. This grading system, based only on preoperative variables, may provide patients and physicians with prognostic information that may guide medical and surgical therapy before any intervention is pursued.

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Grazia Menna, Alessandro Olivi, and Giuseppe Maria Della Pepa

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Kaisorn L. Chaichana, Scott L. Parker, Alessandro Olivi, and Alfredo Quiñones-Hinojosa

Object

Seizures are a common presenting symptom and cause of morbidity for patients with malignant astrocytomas. The authors set out to determine preoperative seizure characteristics, effects of surgery on seizure control, and factors associated with prolonged seizure control in patients with malignant astrocytomas.

Methods

Cases involving adult patients who underwent primary resection of a hemispheric anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) at the Johns Hopkins Medical Institutions between 1996 and 2006 were retrospectively reviewed. Multivariate logistical regression analysis was used to identify associations with pre-operative seizures, and multivariate proportional hazards regression analyses were used to identify associations with prolonged seizure control following resection.

Results

Of the 648 patients (505 with GBM, 143 with AA) in this series, 153 (24%) presented with seizures. The factors more commonly associated with preoperative seizures were AA pathology (p = 0.03), temporal lobe involvement (p = 0.04), and cortical location (p = 0.04), while the factors less commonly associated with preoperative seizures were greater age (p = 0.03) and larger tumor size (p ≤ 0.001). Among those patients with a history of seizures, outcome 12 months after surgery was Engel Class I (seizure free) in 77%, Class II (rare seizures) in 12%, Class III (meaningful improvement) in 6%, and Class IV (no improvement) in 5%. Postoperative seizures were rare in patients without a history of preoperative seizures. The factor positively associated with prolonged seizure control was increased Karnofsky Performance Scale score (p = 0.002), while the factors negatively associated with seizure control were preoperative uncontrolled seizures (p = 0.03) and parietal lobe involvement (p = 0.005). Seizure recurrence in patients with postoperative seizure control was independently associated with tumor recurrence (p = 0.006).

Conclusions

The identification and consideration of factors associated with prolonged seizure control may help guide treatment strategies aimed at improving the quality of life for patients with malignant astrocytomas.

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Francesco Dimeco, Richard E. Clatterbuck, Khan W. Li, Edward F. McCarthy, and Alessandro Olivi

✓ The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a recently described, currently evolving clinical entity that groups together several idiopathic disorders of bone and skin formerly described under a variety of names. Among the spectrum of possible locations for the bone lesions, there is no previous report in the literature of primary involvement of the skull vault. A patient with primary involvement of the calvaria in the setting of SAPHO syndrome is described here, which, to the authors' knowledge, is the first report of such localization. The clinically and radiologically benign evolution of the different stages of the bone lesions is presented. The authors suggest that the SAPHO syndrome should be considered in the differential diagnosis of lytic, sclerotic, or hyperostotic lesions of the skull, particularly before considering invasive diagnostic procedures.

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Matthew A. Koenig, Romergryko G. Geocadin, Piotr Kulesza, Alessandro Olivi, and Henry Brem

✓ Rhabdoid meningioma (RM) is a recently described, aggressive variant of meningioma. The authors report a case of RM occurring in the resection cavity of an unrelated neurosurgical procedure, temporal lobectomy for intractable seizures. The patient presented with intractable headache 10 years after the temporal lobectomy. Imaging revealed a dura-based, uniformly enhancing lesion within the resection cavity. She underwent gross-total resection and the findings of the surgical pathological report were consistent with an RM, with a dramatically elevated MIB-1 index of approximately 50%. The patient's clinical course was complicated by severe pain and communicating hydrocephalus secondary to rapid dissemination of malignant cells throughout the CSF pathways. Despite aggressive measures, including tumor resection, ventriculoperitoneal shunt placement, and the initiation of conventional radiation therapy, the ensuing leptomeningeal carcinomatosis proved to be rapidly fatal.

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Francesco DiMeco, Khan W. Li, Betty M. Tyler, Ariel S. Wolf, Henry Brem, and Alessandro Olivi

Object. Mitoxantrone is a drug with potent in vitro activity against malignant brain tumor cell lines; however, its effectiveness as a systemic agent has been hampered by poor central nervous system penetration and dose-limiting myelosuppression. To avoid these problems, we incorporated mitoxantrone into biodegradable polymeric wafers to be used for intracranial implantation, a strategy that has been shown to be safe and successful in the treatment of malignant gliomas. The authors investigated the release kinetics, toxicity, distribution, and efficacy of mitoxantrone delivered from intracranially implanted biodegradable wafers in the treatment of 9L gliosarcoma in Fischer 344 rats.

Methods. Mitoxantrone released from the biodegradable wafer matrix reached therapeutic drug concentrations in the brain for at least 35 days. Only animals with implanted wafers of the highest drug loading dose (20% mitoxantrone by weight) showed signs of significant toxicity. In three separate efficacy experiments, animals treated with mitoxantrone-loaded biodegradable wafers had significantly improved survival compared with control animals. The combined median survival for each treatment group was the following: 0% mitoxantrone wafers, 19 days; 1%, 30 days, p < 0.0001; 5%, 34 days, p < 0.0001; and 10%, 50 days, p < 0.0001.

Conclusions. These findings establish that mitoxantrone delivered from intracranially implanted biodegradable wafers is effective in the treatment of malignant gliomas in rodents and should be considered for future clinical application in humans.

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Graeme F. Woodworth, Matthew J. McGirt, Amer Samdani, Ira Garonzik, Alessandro Olivi, and Jon D. Weingart

Object

The gold standard for stereotactic brain biopsy target localization has been frame-based stereotaxy. Recently, frameless stereotactic techniques have become increasingly utilized. Few authors have evaluated this procedure, analyzed preoperative predictors of diagnostic yield, or explored the differences in diagnostic yield and morbidity rate between the frameless and frame-based techniques.

Methods

A consecutive series of 110 frameless and 160 frame-based image-guided stereotactic biopsy procedures was reviewed. Associated variables for both techniques were reviewed and compared. All stereotactic biopsy procedures were included in a risk factor analysis of nondiagnostic biopsy sampling.

Frameless stereotaxy led to a diagnostic yield of 89%, with a total permanent morbidity rate of 6% and a mortality rate of 1%. Larger lesions were fivefold more likely to yield diagnostic tissues. Deep-seated lesions were 2.7-fold less likely to yield diagnostic tissues compared with cortical lesions. Frameless compared with frame-based stereotactic biopsy procedures showed no significant differences in diagnostic yield or transient or permanent morbidity. For cortical lesions, more than one needle trajectory was required more frequently to obtain diagnostic tissues with frame-based as opposed to frameless stereotaxy, although this factor was not associated with morbidity.

Conclusions

With regard to diagnostic yield and complication rate, the frameless stereotactic biopsy procedure was found to be comparable to or better than the frame-based method. Smaller and deep-seated lesions together were risk factors for a nondiagnostic tissue yield. Frameless stereotaxy may represent a more efficient means of obtaining biopsy specimens of cortical lesions but is otherwise similar to the frame-based technique.

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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.