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Mark E Shaffrey

Publications and source records attributed to Mark E Shaffrey.

15 recordsLinked to original sources
PubMed2007

Part I: spinal-cord neoplasms-intradural neoplasms.

Intradural spinal-cord tumours are an uncommon but important consideration in the differential diagnosis of patients with back pain, radicular pain, sensorimotor deficits, or sphincter dysfunction. Intradural spinal tumours can be divided into intramedullary and extramedullary spinal-cord tumours on the basis of their anatomical relation to the spinal parenchyma. The heterogeneous cell composition of the intradural compartment allows the formation of neoplasms, arising from glial cells, neurons, and cells of spinal vasculature. Additionally, developmental tumours, metastases, and intradural extension of extradural tumours are represented. In this Review, we discuss the published work on intradural spinal-cord tumours in terms of epidemiological, radiographic, and histological characteristics. Surgical and adjuvant treatment strategies are also reviewed.

Humans↗
PubMed2006

Toxicity and efficacy of protracted low dose temozolomide for the treatment of low grade gliomas.

Protracted low dose temozolomide (75 mg/m(2)/day on days 1-21 of 28 days) offers potential advantages over standard temozolomide schedules (200 mg/m(2)/day on days 1-5 of 28 days) including greater cumulative drug exposure and depletion of O(6)-alkylguanine DNA alkyltransferase levels, theoretically overcoming intrinsic chemoresistance. We retrospectively review our experience in 25 patients with pathologically proven low grade gliomas (LGG) treated with protracted low dose temozolomide to primarily quantify its toxicity and secondarily to assess efficacy. None had previously received radiation. Tumor response was graded based on changes in tumor size, steroid requirements, and clinical exam. About 243 cycles of protracted low dose temozolomide were administered. Three patients (12%) were changed to standard temozolomide dosing due to side effects, including intractable nausea (n = 2) and multiple cytopenias (n = 1). The most frequent toxicities were fatigue (76%), lymphopenia (72% [48% high grade]), constipation (56%), and nausea (52%). High grade toxicities (other than lymphopenia) included secondary malignancy, pruritus, hyponatremia, neutropenia, leukopenia, and cognitive decline (n = 1 for each). Tumor response rate was 52% and and disease control rate was 84%. Six month PFS was 92% and 12 month PFS was 72%. Response rates and PFS were independent of pathological subtype, deletion status, and indication for chemotherapy. Protracted low dose temozolomide has a distinct spectrum of toxicities compared to standard dosing but is well tolerated in most patients and may provide improved response rates compared to standard dosing. The results of larger randomized trials are needed to assess its potential advantages over other management schemes.

Adult↗
PubMed2006

Anterior stabilization of three-column thoracolumbar spinal trauma.

OBJECT: The purpose of this study was to evaluate the results obtained in patients who underwent anterior stabilization for three-column thoracolumbar fractures. METHODS: The authors retrospectively reviewed available clinical and radiographic data (1997-2006) to classify three-column thoracolumbar fractures according to the Association for the Study of Internal Fixation (AO) system, neurological status, spinal canal compromise, pre- and postoperative segmental angulation, and arthrodesis rate. The mean computed tomography-measured preoperative spinal canal compromise was 48.3% (range 8-92%), and the mean vertebral body height loss was 39.4%. The mean preoperative kyphotic deformity of 14.9 degrees improved to 4.6 degrees at the final follow-up examination. Although this angulation had increased a mean of 1.8 degrees during the follow-up period, the extent of correction was still significant compared with the preoperative angulation (p < 0.01). There were no cases of vascular complication or neurological deterioration. CONCLUSIONS: Contemporary anterior spinal reconstruction techniques can allow certain types of unstable three-column thoracolumbar fractures to be treated via an anterior approach alone. Compared with traditional posterior approaches, the anterior route spares lumbar motion segments and obviates the need for harvesting of the iliac crest.

Adolescent↗
PubMed2005

Metastasis to nervous system: spinal epidural and intramedullary metastases.

Spinal cord epidural metastasis (SEM) is a common complication of systemic cancer with an increasing incidence. Prostate, breast and lung cancer are the most common offenders. Metastasis usually arises in the posterior aspect of vertebral body with later invasion of epidural space. Pathophysiologically, vascular insufficiency is more important than direct spinal cord compression. The most common complaint is pain, and two thirds of patients with SEM have motor signs at initial diagnosis. Currently magnetic resonance imaging is the most sensitive diagnostic tool. The optimal management of SEM is still arguable, but recent advances in surgical management of SEM and higher complication rate of surgery following radiotherapy should persuade clinicians to consider de novo surgery where possible. Radiotherapy has an important role, particularly in treatment of radiosensitive tumors and in patients who are not candidates for surgery. Novel approaches such as stereotactic radiosurgery are promising; however, response to chemotherapy depends on inherent properties of primary tumor. Recurrent SEM is a substantial problem for which surgery or repeat radiotherapy may be options. Intramedullary metastasis is rare but should be considered in patients with systemic malignancy and asymmetrical presentation of myelopathic symptoms. The prognosis is usually poor and preferred modality of treatment is radiotherapy.

Epidural Neoplasms↗
PubMed2005

Functional outcomes and survival in patients with high-grade gliomas in dominant and nondominant hemispheres.

OBJECT: The goal of this study was to investigate survival and functional outcomes in patients with high-grade intracranial astrocytomas as a function of the location of the lesion in the dominant or nondominant hemisphere (DH and NDH, respectively), and to suggest management strategies for such patients based on these data. METHODS: Data were collected from the Glioma Outcomes Project database, a longitudinal database of demographic, clinical, and outcome data for patients with high-grade intracranial gliomas. From the entire database of 788 patients, a subset of all 280 right-handed patients with newly diagnosed, unilateral gliomas involving potentially eloquent cortex was selected as the sample population. Two cohorts were defined based on the location of the tumor in the right or left cerebral hemisphere. All other relevant demographic and clinical data were nearly identical between the cohorts. A Kaplan-Meier analysis was conducted to assess survival, and Karnofsky Performance Scale scores assigned at 6 and 12 months postoperatively were compared as a measure of functional outcome. The analysis demonstrated no difference in survival between patients with lesions in the DH and those with tumors in the NDH. Additionally, no statistically significant difference in functional outcomes was observed between the two groups. CONCLUSIONS: Laterality of high-grade gliomas is not an independent prognostic factor for predicting survival or functional outcome. The findings in this study demonstrate that fears of increased postoperative morbidity or mortality in otherwise resectable tumors of the DH are unfounded, and the authors therefore advocate that the surgeon's decision to operate be guided by validated outcome predictors and not biased by tumor lateralization.

Actuarial Analysis↗
PubMed2005

The Ki-67 labeling index as a prognostic factor in Grade II oligoastrocytomas.

OBJECT: This study was conducted to determine whether proliferative tumor activity, as assessed using the Ki-67 immunohistochemical labeling index (LI), has prognostic utility for patients with Grade II oligoastrocytomas. METHODS: The study period spans the years 1988 to 2000. In a retrospective analysis, the authors selected cases with biopsy-proven diagnoses of Grade II oligoastrocytomas on initial presentation. The authors added new patients to this group and followed all patients prospectively at the University of Virginia Neuro-Oncology Center. Twenty-three adult patients were followed for at least 1 year (median 40.3 months). Eleven patients with Grade II tumors and initial Ki-67 LIs less than 10% had a significantly longer median time to tumor progression (TTP, 51.8 months compared with 9.9 months) and a longer median survival (93.1 months compared with 16.1 months) than 12 patients with initial Ki-67 LIs of 10% or greater. Twelve patients with Grade III oligoastrocytomas had a mean TTP that was similar to the TTP of patients with Grade II tumors and high Ki-67 LIs (mean 4 months compared with 9.9 months) and duration of survival (13.3 months compared with 16.1 months). CONCLUSIONS: Patients with a Grade II oligoastrocytoma and a Ki-67 LI of 10% or greater have a much shorter TTP and potentially a poorer disease prognosis than expected--more similar to patients with a Grade III oligoastrocytoma. These results indicate that in the future a measure of proliferative activity should be taken into consideration along with the World Health Organization grading criteria for oligoastrocytomas.

Adult↗
PubMed2004

The future of spinal arthroplasty: a biomaterial perspective.

Both total hip and knee arthroplasty have demonstrated outstanding clinical results. The functional spinal unit composed of the intervertebral disc and facet joints is at least as complex. The intricacies of the coupled motions of the functional spinal unit have made development of an artificial disc a challenge. There have been several failed attempts to create a disc replacement that recapitulates normal motion while providing significant longevity and a low incidence of complications. Better understanding of the biomechanics of the intervertebral disc complex and improvements in implant material have made successful intervertebral disc replacement a likely reality, now that several artificial discs have completed Food and Drug Administration clinical trials. In this manuscript the authors detail the biomaterials used in disc arthroplasty and discuss joint wear and the host response to wear debris.

Arthroplasty↗
PubMed2004

Brain metastases.

Explore the source record for details and available documents.

Antineoplastic Agents↗
PubMed2003

Imaging tumor angiogenesis with contrast ultrasound and microbubbles targeted to alpha(v)beta3.

BACKGROUND: Angiogenesis is a critical determinant of tumor growth and metastasis. We hypothesized that contrast-enhanced ultrasound (CEU) with microbubbles targeted to alpha(v)-integrins expressed on the neovascular endothelium could be used to image angiogenesis. METHODS AND RESULTS: Malignant gliomas were produced in 14 athymic rats by intracerebral implantation of U87MG human glioma cells. On day 14 or day 28 after implantation, CEU was performed with microbubbles targeted to alpha(v)beta3 by surface conjugation of echistatin. CEU perfusion imaging with nontargeted microbubbles was used to derive tumor microvascular blood volume and blood velocity. Vascular alpha(v)-integrin expression was assessed by immunohistochemistry, and microbubble adhesion was characterized by confocal microscopy. Mean tumor size increased markedly from 14 to 28 days (2+/-1 versus 35+/-14 mm2, P<0.001). Tumor blood volume increased by approximately 35% from day 14 to day 28, whereas microvascular blood velocity decreased, especially at the central portions of the tumors. On confocal microscopy, alpha(v)beta3-targeted but not control microbubbles were retained preferentially within the tumor microcirculation. CEU signal from alpha(v)beta3-targeted microbubbles in tumors increased significantly from 14 to 28 days (1.7+/-0.4 versus 3.3+/-1.0 relative units, P<0.05). CEU signal from alpha(v)beta3-targeted microbubbles was greatest at the periphery of tumors, where alpha(v)-integrin expression was most prominent, and correlated well with tumor microvascular blood volume (r=0.86). CONCLUSIONS: CEU with microbubbles targeted to alpha(v)beta3 can noninvasively detect early tumor angiogenesis. This technique, when coupled with changes in blood volume and velocity, may provide insights into the biology of tumor angiogenesis and be used for diagnostic applications.

Animals↗
PubMed2003

Intraventricular gliomas.

Gliomas are the most common primary brain tumor in adults, and those within or relating to the ventricular surface represent a less common but important subcategory. The most common intraventricular gliomas include ependymomas, SEs, and SEGAs. Other less common varieties have been reported, including chordoid gliomas, glioblastoma multiforme, and mixed glial-neuronal tumors. Each type of intraventricular glioma is associated with its own unique constellation of epidemiologic, clinical, radiologic, and pathologic defining characteristics. Each tumor type has its own management considerations and nuances with unique prognostic indicators and outcomes. The outcome for certain intraventricular gliomas (especially ependymomas) remains relatively poor. Future advancements in surgical technique are likely to have only a modest impact on improvement of outcome. Translational research aiming to advance the knowledge of tumor biology into new targeted cellular and molecular therapies holds tremendous promise to improve the overall outcome. Additionally, more thorough delineation of prognostic factors as well as modifications and refinements to radiation and chemotherapy may help to improve the still significantly poor outcomes for patients harboring these lesions. Future cooperative intra- and interinstitutional efforts between scientists and clinicians will hopefully culminate in an improved outlook and eventual cure for patients with gliomas.

Age Factors↗
PubMed2003

Role of resection for newly diagnosed malignant gliomas.

The surgical neuro-oncology literature testifies to the longstanding argument about the benefits (or lack thereof) of aggressive debulking of high-grade gliomas. Publications from the last decade addressing this question will be reviewed. The absence of randomized clinical trials and paucity of prospectively collected information continue to leave this issue unresolved, although most evidence continues to support a modest benefit of debulking over biopsy.

Animals↗
PubMed2002

Protein kinase C-eta regulates resistance to UV- and gamma-irradiation-induced apoptosis in glioblastoma cells by preventing caspase-9 activation.

Both increased cell proliferation and apoptosis play important roles in the malignant growth of glioblastomas. We have demonstrated recently that the differential expression of protein kinase C (PKC)-eta increases the proliferative capacity of glioblastoma cells in culture; however, specific functions for this novel PKC isozyme in the regulation of apoptosis in these tumors has not been defined. In the present study of several glioblastoma cell lines, we investigated the role of PKC-eta in preventing UV- and gamma-irradiation-induced apoptosis and in caspase-dependent signaling pathways that mediate cell death. Exposure to UV or gamma irradiation killed 80% to 100% of PKC-eta-deficient nonneoplastic human astrocytes and U-1242 MG cells, but had little effect on the PKC-eta-expressing U-251 MG and U-373 MG cells. PKC-eta appears to mediate resistance to irradiation specifically such that when PKC-eta was stably expressed in U-1242 MG cells, more than 80% of these cells developed resistance to irradiation-induced apoptosis. Reducing PKC-eta expression by transient and stable expression of antisense PKC-eta in wild-type U-251 MG cells results in increased sensitivity to UV irradiation in a fashion similar to U-1242 MG cells and nonneoplastic astrocytes. Irradiation of PKC-eta-deficient glioblastoma cells resulted in the activation of caspase-9 and caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and a substantial increase in subdiploid DNA content that did not occur in PKC-eta-expressing tumor cells. A specific inhibitor (Ac-DEVD-CHO) of caspase-3 blocked apoptosis in PKC-eta-deficient U-1242 MG cells. The data demonstrate that resistance to UV and gamma irradiation in glioblastoma cell lines is modified significantly by PKC-eta expression and that PKC-eta appears to block the apoptotic cascade at caspase-9 activation.

Apoptosis↗