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Michael N. Bucci, John A. Feldenzer, William A. Phillips, Stephen S. Gebarski and Robert C. Dauser

✓ An unusual case of atlanto-axial rotational limitation secondary to an osteoid osteoma of the axis is presented. Transoral microsurgical resection followed by physical therapy improved the clinical symptoms. This case illustrates several unique problems within the cervical spine as well as the efficacy of the transoral approach to the axis.

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Studies of experimental cervical spinal cord transection

Part I: Hemodynamic changes after acute cervical spinal cord transection

Phillip A. Tibbs, Byron Young, R. G. McAllister Jr., William H. Brooks and Laddie Tackett

✓ Two distinct and sequential patterns of hemodynamic alteration were observed after acute cervical spinal cord transection in anesthetized dogs. Interruption of the cord initially caused a 45% increase in mean arterial pressure (p < 0.01), a 34% increase in systemic vascular resistance (p < 0.05), and a 92% increase in left ventricular dp/dt (p < 0.01), reflecting a generalized sympathetic response to trauma. Concomitant bradycardia and escape arrhythmias suggested relative parasympathetic hyperactivity. Resolution of the brief pressor response was followed by a second, more prolonged, period characterized by a fall in arterial pressure to 71% of control levels (p < 0.05), a 16% decrease in systemic vascular resistance, and a 58.5% decrease in left ventricular dp/dt (p < 0.01). These latter hemodynamic changes are consistent with sympathetic denervation and failure of regulatory mechanisms mediated by both alpha- and beta-adrenergic peripheral vascular and myocardial receptors.

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Philip H. Gutin, Theodore L. Phillips, William M. Wara, Steven A. Leibel, Yoshio Hosobuchi, Victor A. Levin, Keith A. Weaver and Sharon Lamb

✓ Thirty-seven patients harboring recurrent malignant primary or metastatic brain tumors were treated by 40 implantations of high-activity iodine-125 (125I) sources. All patients had been treated with irradiation and most had been treated with chemotherapeutic agents, primarily nitrosoureas. Implantations were performed using computerized tomography (CT)-directed stereotaxy; 125I sources were held in one or more afterloaded catheters that were removed after the desired dose (minimum tumor dose of 3000 to 12,000 rads) had been delivered. Patients were followed with sequential neurological examinations and CT scans. Results of 34 implantation procedures were evaluable: 18 produced documented tumor regression (response) for 4 to 13+ months; five, performed in deteriorating patients, resulted in disease stability for 4 to 12 months. The overall response rate was 68%. In 11 patients, implantation did not halt clinical deterioration.

At exploratory craniotomy 5 to 12 months after implantation, focal radiation necrosis was documented in two patients whose tumor had responded initially and then progressed, and in three patients whose disease had progressed initially (four glioblastomas, one anaplastic astrocytoma); histologically identifiable tumor was documented in two of these patients. All improved after resection of the focal necrotic mass and are still alive 10, 15, 19, 24, and 25 months after the initial implantation procedure; only one patient has evidence of tumor regrowth. The median follow-up period after implantation for the malignant glioma (anaplastic astrocytoma and glioblastoma multiforme) group is 9 months, with 48% of patients still surviving. While direct comparison with the results of chemotherapy is difficult, results obtained in this patient group with interstitial brachytherapy are probably superior to results obtained with chemotherapy.

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Dennis J. Cordato, Mark A. Davies, Lynette T. Masters, Phillip D. Cremer, Raymond S. Schwartz, William Sorby and Zoran Becvarovski

✓ The authors report the unique case of a patient with a thoracic spinal dural arteriovenous fistula (DAVF) causing remote brainstem symptoms of positional vomiting and minimal vertigo. Magnetic resonance (MR) imaging of the brain demonstrated high signal abnormality in the medulla, presumably related to venous hypertension, and spinal MR imaging revealed markedly dilated veins along the dorsal aspect of the cord. Spinal angiography confirmed the presence of a thoracic spinal DAVF. Disconnection of the DAVF from the spine resulted in a marked improvement in symptoms and resolution of the preoperative MR imaging—documented abnormalities. The authors highlight the rare syndrome of positional vomiting as a brainstem symptom and conclude that spinal DAVFs should be considered in the differential diagnosis of high signal MR imaging abnormalities localized to the brainstem.

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Phillip J. Porter, Robert A. Willinsky, William Harper and M. Christopher Wallace

✓ Despite recent studies of the natural history of cavernous malformations, there remains significant uncertainty concerning hemorrhage rates and the importance of lesion location. Controversy arises over varying definitions of “hemorrhage.” What is ultimately important to the patient is the occurrence of a neurological event, which may or may not be associated with radiologically documented hemorrhage, as well as the chance of recovery after such an event. The purpose of this study was to determine the rates of occurrence and sequelae of neurological events in 173 patients referred to our vascular malformation clinic with cavernous malformations.

All patient data were entered into a database. The mean age at presentation for the 173 patients was 37.5 years. The lesion location was deep (brainstem, cerebellar nuclei, thalamus, or basal ganglia) in 64 patients (37%) and superficial in 109 (63%). Thirty-one patients (18%) had multiple lesions. Disease presentation was due to seizures in 62 patients (36%), hemorrhage in 44 (25%), focal neurological deficit without documented hemorrhage in 35 (20%), headache alone in 11 (6%), and incidental findings in 21 patients (12%). The results obtained in the 110 patients eligible for follow-up review were used to derive information on the rates of hemorrhage and neurological events. An interval event (neurological deterioration) required both symptoms and signs. The total mean follow-up period was 46 months, the majority (65%) of which was prospective. There were 18 interval events in 427 patient-years of follow-up review, for an overall annual event rate of 4.2%. Location was the most important factor for predicting interval event occurrence, with significantly higher rates for deeply located (10.6%/year) compared with superficially located lesions (0%/year) (p = 0.0001). Of patients suffering a neurological event, only 37% had complete resolution of their deficits.

This largely prospective study indicates that deep cavernous malformations carry a worse prognosis than superficial lesions with respect to annual rates of neurological deterioration. The alarming rate of adverse clinical events occurring in patients with deep lesions is punctuated by the fact that less than one-half of them recover fully during long-term follow-up review.

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Byron Young, Edward H. Oldfield, William R. Markesbery, Dennis Haack, Phillip A. Tibbs, Paul McCombs, Hong W. Chin, Yosh Maruyama and William F. Meacham

✓ The results of a second operation for tumor removal in 24 adult patients with supratentorial glioblastoma multiforme or anaplastic astrocytoma were analyzed. The median survival time after reoperation was 14 weeks. Five of the 24 patients lived 6 months or longer after reoperation. Only three of these patients maintained a Karnofsky rating (KR) of at least 60 for 6 months or longer after reoperation.

Preoperative neurological status (KR) is the most significant determinant of survival after reoperation (p = 0.02). When the KR is at least 60, median survival after reoperation is 22 weeks. When the KR prior to reoperation is less than 60, median survival is 9 weeks. Only one of 13 patients with a KR of less than 60 prior to reoperation survived longer than 6 months after the second operation. The interval between first and second operation is significantly related to survival (p = 0.03), but when adjustment is made for the KR the interoperative interval is no longer significantly related to survival after the second operation (p = 0.39). Age, sex, and location of tumor were not significantly related to duration of survival.

This study suggests that reoperation is most likely to produce the best result when the KR is at least 60 and the interval between operations is longer than 6 months. Using these criteria, one-third of the patients could be expected to survive with a KR of at least 60 for 6 months. The study indicates that reoperation should not be carried out when the KR is less than 60.

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Patricia T. Molloy, Anthony T. Yachnis, Lucy B. Rorke, James J. Dattilo, Michael N. Needle, William S. Millar, Joel W. Goldwein, Leslie N. Sutton and Peter C. Phillips

✓ Medulloepithelioma is an uncommon childhood tumor of the central nervous system (CNS) whose histopathological appearance has been confused with medulloblastoma and other childhood primitive neuroectodermal tumors (PNETs), but which has a vastly different clinical course. The authors have reviewed the clinical features and treatment responses of eight children with these rare tumors, the largest series to date.

In this series, the medulloepitheliomas were equally distributed between supratentorial and infratentorial primary sites. Four patients underwent gross- or near-total resections, one patient's tumor was partially resected, and one patient had biopsy only. Biopsy and ablative surgery were not attempted in two children with pontine tumors. Treatment included both radiation and chemotherapy (four patients), radiation alone (one patient), chemotherapy alone (one patient), and no postoperative treatment (two patients). Six patients died with a mean survival of 10 months and two are disease free with neurological impairment. Both long-term survivors underwent gross-total resections of their tumors. Postmortem examination revealed diffuse CNS tumor dissemination in four patients.

Medulloepithelioma, often confused with less aggressive PNETs, can mimic intrinsic brainstem glioma, responds poorly to treatment, and is prone to CNS dissemination at the time of tumor progression.

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Lawrence L. Wald, Sarah J. Nelson, Mark R. Day, Susan E. Noworolski, Roland G. Henry, Steven L. Huhn, Susan Chang, Michael D. Prados, Penny K. Sneed, David A. Larson, William M. Wara, Michael McDermott, William P. Dillon, Phillip H. Gutin and Daniel B. Vigneron

✓ The utility of three-dimensional (3-D) proton magnetic resonance spectroscopy (1H-MRS) imaging for detecting metabolic changes after brain tumor therapy was assessed in a serial study of 58 total examinations of 12 patients with glioblastoma multiforme (GBM) who received brachytherapy.

Individual proton spectra from the 3-D array of spectra encompassing the lesion showed dramatic differences in spectral patterns indicative of radiation necrosis, recurrent or residual tumor, or normal brain. The 1H-MRS imaging data demonstrated significant differences between suspected residual or recurrent tumor and contrast-enhancing radiation-induced necrosis. Regions of abnormally high choline (Cho) levels, consistent with viable tumor, were detected beyond the regions of contrast enhancement for all 12 gliomas.

Changes in the serial 1H-MRS imaging data were observed, reflecting an altered metabolism following treatment. These changes included the significant reduction in Cho levels after therapy, indicating the transformation of tumor to necrotic tissue. For patients who demonstrated subsequent clinical progression, an increase in Cho levels was observed in regions that previously appeared either normal or necrotic. Several patients showed regional variations in response to brachytherapy as evaluated by 1H-MRS imaging.

This study demonstrates the potential of noninvasive 3-D 1H-MRS imaging to discriminate between the formation of contrast-enhancing radiation necrosis and residual or recurrent tumor following brachytherapy. This modality may also allow better definition of tumor extent prior to brachytherapy by detecting the presence of abnormal metabolite levels in nonenhancing regions of solid tumor.

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Douglas Kondziolka, Phillip V. Parry, L. Dade Lunsford, Hideyuki Kano, John C. Flickinger, Susan Rakfal, Yoshio Arai, Jay S. Loeffler, Stephen Rush, Jonathan P. S. Knisely, Jason Sheehan, William Friedman, Ahmad A. Tarhini, Lanie Francis, Frank Lieberman, Manmeet S. Ahluwalia, Mark E. Linskey, Michael McDermott, Paul Sperduto and Roger Stupp

Object

Estimating survival time in cancer patients is crucial for clinicians, patients, families, and payers. To provide appropriate and cost-effective care, various data sources are used to provide rational, reliable, and reproducible estimates. The accuracy of such estimates is unknown.

Methods

The authors prospectively estimated survival in 150 consecutive cancer patients (median age 62 years) with brain metastases undergoing radiosurgery. They recorded cancer type, number of brain metastases, neurological presentation, extracranial disease status, Karnofsky Performance Scale score, Recursive Partitioning Analysis class, prior whole-brain radiotherapy, and synchronous or metachronous presentation. Finally, the authors asked 18 medical, radiation, or surgical oncologists to predict survival from the time of treatment.

Results

The actual median patient survival was 10.3 months (95% CI 6.4–14). The median physician-predicted survival was 9.7 months (neurosurgeons = 11.8 months, radiation oncologists = 11.0 months, and medical oncologist = 7.2 months). For patients who died before 10 months, both neurosurgeons and radiation oncologists generally predicted survivals that were more optimistic and medical oncologists that were less so, although no group could accurately predict survivors alive at 14 months. All physicians had individual patient survival predictions that were incorrect by as much as 12–18 months, and 14 of 18 physicians had individual predictions that were in error by more than 18 months. Of the 2700 predictions, 1226 (45%) were off by more than 6 months and 488 (18%) were off by more than 12 months.

Conclusions

Although crucial, predicting the survival of cancer patients is difficult. In this study all physicians were unable to accurately predict longer-term survivors. Despite valuable clinical data and predictive scoring techniques, brain and systemic management often led to patient survivals well beyond estimated survivals.