Biomedical subjects

Philip H Gutin

Publications and source records attributed to Philip H Gutin.

At least 19 recordsLinked to original sources

PubMed2007

Tracking normalization of brain tumor vasculature by magnetic imaging and proangiogenic biomarkers.

Clinical assessment of the response to antiangiogenic therapy has been cumbersome. A study in this issue of Cancer Cell demonstrates that a combination of magnetic resonance imaging (MRI) for quantification of normalized vessels with measurements of circulating levels of proangiogenic factors, including FGF2, SDF1, and viable circulating endothelial cells, provides an effective means to evaluate the response of recurrent glioblastoma to a prototypical pan-VEGF receptor tyrosine kinase inhibitor, AZD2171.

Angiogenesis Inhibitors↗

PubMed2006

Hypofractionated stereotactic radiotherapy using intensity-modulated radiotherapy in patients with one or two brain metastases.

PURPOSE: A small fraction of patients with 1-2 brain metastases will not be suitable candidates to either surgical resection or stereotactic radiosurgery (SRS) due to either their location or their size. The objective of this study was to determine the local control, survival, patterns of relapse and the incidence of brain injury following a course of hypofractionated stereotactic radiotherapy while avoiding upfront whole brain radiation therapy (WBRT) in this subgroup of patients. METHODS: A Gill-Thomas removable head frame system was used for immobilization. Brain LAB software with dynamic multileaf collimator hardware was used to design and deliver an intensity-modulated radiation therapy treatment plan. A dose of 600 cGy was prescribed to the 100% isodose line that would encompass the lesion with a 3-mm margin. A total dose of 3,000 cGy was delivered in 5 fractions using 2 fractions per week. The patients were followed with neurological examination and serial MRI images done every 3 months following the procedure. RESULTS: Twenty patients have been treated using this fractionation schedule since April 2004. The 1-year local control at the site of original disease is 70%. The complete response, partial response and stable disease at the last follow-up were 15, 30 and 45%, respectively. Two patients had local recurrence at the site of original disease, while 5 had evidence of leptomeningeal disease. Two additional patients developed new brain metastases, resulting in a 1-year brain relapse-free survival of 36% following this approach. The median overall survival was 8.5 months. Three patients (15%) developed steroid dependency lasting 3 months or longer following the procedure. Four patients (20%) needed WBRT as salvage following this approach. CONCLUSIONS: The preliminary results of hypofractionated SRS are comparable to both surgery and SRS data for solitary brain metastases in terms of local control and overall survival with acceptable morbidity in this cohort of unfavorable patients.

Adult↗

PubMed2006

Effect of brain tumor neovasculature defined by rCBV on BOLD fMRI activation volume in the primary motor cortex.

We utilized blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) and MR perfusion imaging methods to study the influence of brain tumor neovascularity on the BOLD fMRI activation volume in the primary motor cortex (PMC). The results from 57 brain tumor cases demonstrated that, for grade IV gliomas only, decreases in the BOLD fMRI activation volumes within the ipsilateral PMC, when compared with that observed in the contralateral PMC, correlated with increases in the relative regional cerebral blood volume (rCBV) in the PMC. In addition, relative increases in the activation volumes, corresponding to decreases in the rCBV, exhibited a linear dependence on the distance between the grade IV glioma and PMC. These findings lend support to the hypothesis that decreases in the fMRI activation volumes adjacent to a GBM may, in part, be due to the increased contribution of aberrant tumor neovascularity, with the resultant de-coupling of blood flow from neuronal activity. The nature of the relationship between the resulting activation volumes and adjacent tumor characteristics is complex, but is found to be dependent on the tumor grade and type, as well as the distance of the tumor to the PMC.

Adult↗

PubMed2006

Intensity-modulated radiotherapy in high-grade gliomas: clinical and dosimetric results.

PURPOSE: To report preliminary clinical and dosimetric data from intensity-modulated radiotherapy (IMRT) for malignant gliomas. METHODS AND MATERIALS: Fifty-eight consecutive high-grade gliomas were treated between January 2001 and December 2003 with dynamic multileaf collimator IMRT, planned with the inverse approach. A dose of 59.4-60 Gy at 1.8-2.0 Gy per fraction was delivered. A total of three to five noncoplanar beams were used to cover at least 95% of the target volume with the prescription isodose line. Glioblastoma accounted for 70% of the cases, and anaplastic oligodendroglioma histology (pure or mixed) was seen in 15% of the cases. Surgery consisted of biopsy only in 26% of the patients, and 80% received adjuvant chemotherapy. RESULTS: With a median follow-up of 24 months, 85% of the patients have relapsed. The median progression-free survival time for anaplastic astrocytoma and glioblastoma histology was 5.6 and 2.5 months, respectively. The overall survival time for anaplastic glioma and glioblastoma was 36 and 9 months, respectively. Ninety-six percent of the recurrences were local. No Grade IV/V late neurologic toxicities were noted. A comparative dosimetric analysis revealed that regardless of tumor location, IMRT did not significantly improve target coverage compared with three-dimensional planning. However, IMRT resulted in a decreased maximum dose to the spinal cord, optic nerves, and eye by 16%, 7%, and 15%, respectively, owing to its improved dose conformality. The mean brainstem dose also decreased by 7%. Intensity-modulated radiotherapy delivered with a limited number of beams did not result in an increased dose to the normal brain. CONCLUSIONS: It is unlikely that IMRT will improve local control in high-grade gliomas without further dose escalation compared with conventional radiotherapy. However, it might result in decreased late toxicities associated with radiotherapy.

Adult↗

PubMed2006

Use of diffusion weighted magnetic resonance imaging in predicting early postoperative outcome of new neurological deficits after brain tumor resection.

OBJECTIVE: To study risk factors for the development of postoperative neurological deficits after brain tumor resection and to define prognostic factors for recovery. METHODS: We prospectively studied 82 brain tumor patients undergoing tumor resection. Pre- and postoperative neurological examination, functional and performance status, cancer treatment, cardiovascular risk factors, seizure history, and blood pressure and oxygen saturation were recorded perioperatively. Postoperative magnetic resonance imaging scans were obtained within 72 hours of surgery, and the radiologist was blinded to the patient's status. Abnormalities on magnetic resonance diffusion weighted images were classified as new if they extended beyond the tumor cavity margins and were absent before surgery. RESULTS: Of the 80 assessable patients, 24 had a new or increased postoperative deficit by at least one point on the National Institutes of Health Stroke Scale. Presence of preoperative neurological deficits predicted development of postoperative deficits, whereas a new diffusion weighted imaging lesion after craniotomy predicted incomplete recovery of a new postoperative deficit. CONCLUSION: Postoperative diffusion magnetic resonance imaging is useful in predicting early functional recovery from new deficits after brain tumor surgery.

Brain Neoplasms↗

PubMed2006

Reorganization of the cortical control of movement due to radiation necrosis. Case report.

The authors report a case of reorganization of the cortical control of movement caused by radiation necrosis based on an analysis of functional magnetic resonance (fMR) imaging data acquired during a finger-tapping paradigm. Radiation necrosis in this patient extended from the parietal lobe anteriorly to the primary motor cortex (PMC), and fMR imaging demonstrated an increase in activation in the ipsilateral supplementary motor area. This is similar to the consequences of invasion by glial tumors into the PMC.

Brain Neoplasms↗

PubMed2005

Migration and differentiation of neural precursors derived from human embryonic stem cells in the rat brain.

Human embryonic stem (hES) cells provide a potentially unlimited cell source for regenerative medicine. Recently, differentiation strategies were developed to direct hES cells towards neural fates in vitro. However, the interaction of hES cell progeny with the adult brain environment remains unexplored. Here we report that hES cell-derived neural precursors differentiate into neurons, astrocytes and oligodendrocytes in the normal and lesioned brain of young adult rats and migrate extensively along white matter tracts. The differentiation and migration behavior of hES cell progeny was region specific. The hES cell-derived neural precursors integrated into the endogenous precursor pool in the subventricular zone, a site of persistent neurogenesis. Like adult neural stem cells, hES cell-derived precursors traveled along the rostral migratory stream to the olfactory bulb, where they contributed to neurogenesis. We found no evidence of cell fusion, suggesting that hES cell progeny are capable of responding appropriately to host cues in the subventricular zone.

Animals↗

PubMed2005

Diffusion-tensor MR tractography of somatotopic organization of corticospinal tracts in the internal capsule: initial anatomic results in contradistinction to prior reports.

The goal of this study was to use diffusion-tensor magnetic resonance (MR) imaging to define the location and organization of corticospinal tracts (CSTs) in the posterior limb of the internal capsule (PLIC). The Institutional Review Board approved the study, and informed consent was obtained from all subjects. Eight volunteers and two patients with brain tumor were imaged at 3 T. All CSTs were found to lie in a compact area in one part of the PLIC: If the PLIC is divided into four equal quarters from anterior to posterior, the CST was shown to be in the third quarter. Seventeen of 20 CSTs were organized somatotopically, with hand fibers anterolateral to foot fibers, not anteromedial as is currently believed. In three of 20, hand and foot fibers were intermixed. Classically, it was thought that the CST was located in the anterior third of the PLIC. The present data confirm recent results that the CST is located more posteriorly. In the majority of cases, however, the CST is organized somatotopically.

Adult↗

PubMed2005

Brachytherapy for brain tumors.

Over the past several decades neurooncologists have attempted to find an adjuvant treatment that prolongs survival for patients with malignant brain tumors. Brachytherapy, radiotherapy delivered by placing radioactive sources directly into the tumor, was initially thought to be the solution to this problem. Initial single institution studies showed very promising results; however, this technique has failed to show a significant survival advantage in two randomized studies. Despite this, brachytherapy continues to be used in a number of centers throughout the world for the treatment of various types of brain tumors including low-grade gliomas, anaplastic astrocytomas, glioblastomas, meningiomas and metastases. This article reviews brachytherapy's rationale, radiobiology, complications, indications, and results from numerous studies that have focused on its application for brain tumors with emphasis on its application for glial tumors.

Animals↗

PubMed2005

Isolated primary intracerebral mycetoma: presenting as a mass lesion in a patient with prostate cancer and multiple myeloma.

We report a patient with a history of prostate cancer and multiple myeloma, with a solitary indolent intracerebral mass lesion without any constitutional symptoms and minimal neurologic symptoms. The radiographic appearance of the lesion was that of a tumor but resection revealed a mycetoma, consistent with Aspergillus. A brief review of the literature discusses the rarity, presentation, diagnosis, and management of primary intracerebral mycetomas.

Aged↗

PubMed2005

Surgery of brain metastases--is there still a place for it?

The role of surgery in the treatment of metastatic brain tumors has always been a source of controversy. It was only in the early 1990s that two randomized prospective trials demonstrated that surgery plus radiation therapy improved survival in patients with single metastatic brain tumors vs. radiation therapy alone. This paper reviews these articles as well as other evidence outlining management options for multiple brain metastases. An attempt has been made to better define the role of surgery in brain metastases. The prognostic factors for brain metastases after surgery are also reviewed and the data comparing stereotactic radiosurgery to surgery is examined. A short description of surgical planning, operative techniques and tools, followed by a discussion on complication avoidance before, during, and after surgery is included.

Brain Neoplasms↗

PubMed2005

Diagnosis and treatment of atypical and anaplastic meningiomas: a review.

Atypical and anaplastic meningiomas are uncommon tumors with a poorer prognosis than benign meningiomas. We reviewed the current literature and attempted to integrate and summarize available information to determine a logical approach to these tumors. Both tumors are rare and are often integrated with benign meningiomas when treatments are evaluated. In addition, because there has not been one histopathological classification scheme for atypical and anaplastic meningiomas in the past, there are numerous inconsistencies in the literature. Malignant progression with accumulation of mutations in a benign meningioma can result in an atypical and/or anaplastic meningioma. Both tumors are difficult to manage and have high recurrence and poor survival rates. The extent of tumor resection and histological grade are the key determinants for recurrence. In addition, metastases are unusual, but they do occur. We also review the evidence available that has resulted in the current World Health Organization classification. Radiation therapy can be used as an adjunctive treatment after both total and subtotal resection. In addition, the role of stereotactic radiosurgery is increasing, along with a possible role for brachytherapy. There are no effective chemotherapeutic agents available. A treatment algorithm is suggested.

Algorithms↗

PubMed2005

Meningioma resection in the elderly: nationwide inpatient sample, 1998-2002.

OBJECTIVE: Morbidity and mortality rates reported for meningioma resection in the elderly vary widely. Thus, it is difficult for neurosurgeons to compare the risks and benefits of operating on elderly patients against opting for radiosurgery or watchful waiting. To address this issue, we studied the effect of advanced age on outcome after meningioma resection using the Nationwide Inpatient Sample. METHODS: We identified all patients over the age of 20 in the Nationwide Inpatient Sample database who underwent surgical resection of a meningioma between 1998 and 2002 and were admitted from home. Primary outcomes were in-hospital mortality, adverse outcome (defined as death or discharge to a facility other than home), and length of hospitalization. Multivariate models were constructed to assess the effect of elderly age on the primary outcomes, adjusting for patient demographics, comorbid medical conditions, and hospital surgical volume. RESULTS: There were 8861 patients in the Nationwide Inpatient Sample database who underwent resection of meningioma during the study period; 26.0% were age 70 or older. Each of the primary outcomes demonstrated a marked effect of advancing age. The in-hospital mortality rate was higher in the elderly than in the nonelderly (4.0% versus 1.1%, P < 0.001), as was the rate of discharge to a facility other than home (53.2% versus 16.6%, P < 0.001). Elderly patients also had a longer mean length of stay (7.2 versus 5.1 d P < 0.001). CONCLUSION: The association between elderly age and adverse outcome after meningioma resection suggests a note of caution before proceeding to surgery with these patients.

Adult↗

PubMed2005

Discordance between functional magnetic resonance imaging during silent speech tasks and intraoperative speech arrest.

OBJECT: The goal of this study was to investigate discordance between the location of speech arrest during awake cortical mapping, a common intraoperative indicator of hemispheric dominance, and silent speech functional magnetic resonance (fMR) imaging maps of frontal language function. METHODS: Twenty-one cases were reviewed retrospectively. Images of silent speech fMR imaging activation were coregistered to anatomical MR images obtained for neuronavigation. These were compared with the intraoperative cortical photographs and the behavioral results of electrocorticography during awake craniotomy. An fMR imaging control study of three healthy volunteers was then conducted to characterize the differences between silent and vocalized speech fMR imaging protocols used for neurosurgical planning. CONCLUSIONS: Results of fMR imaging showed consistent and predominant activation of the inferior frontal gyrus (IFG) during silent speech tasks. During intraoperative mapping, however, 16 patients arrested in the precentral gyrus (PRG), well posterior to the fMR imaging activity. Of those 16, 14 arrested only in the PRG and not in the IFG as silent speech fMR imaging predicted. The control fMR imaging study showed that vocalized speech fMR imaging shifts the location of the fMR imaging prediction to include the motor strip and may be more appropriate for neurosurgical planning.

Brain Mapping↗

PubMed2005

The effect of prior surgery on blood oxygen level-dependent functional MR imaging in the preoperative assessment of brain tumors.

BACKGROUND AND PURPOSE: Blood oxygen level-dependent functional MR imaging (BOLD fMRI) is a clinically useful technique for preoperative mapping of eloquent cortices in patients with brain tumors. The purpose of this study was to determine the effect on BOLD fMRI accuracy of susceptibility artifacts caused by prior surgery by comparing volumes of activation in the primary motor cortex (PMC) of patients with and without prior brain surgery. METHODS: The volumes of fMRI activation of the PMC were measured for the tumor and nontumor sides in patients with (n = 13) and without (n = 30) prior neurosurgery. Statistical comparisons of the volumes were performed by using paired t tests and linear regression analysis. The location and degree of susceptibility artifact were subjectively assessed. RESULTS: No significant difference was found between the mean tumor and nontumor volumes of fMRI activations in patients without prior surgery (P = .51). In patients who had prior surgery, the volume of activation was significantly smaller on the side of the prior operation when compared with the contralateral side (P = .001). The volume of activation on the side of the tumor was also significantly smaller in the patients with prior surgery compared with those without prior surgery (P < .001). Nevertheless, the PMC was identified in all cases, and its location was confirmed intraoperatively. CONCLUSION: Prior surgery is associated with a decrease in the volume of fMRI activation in patients with prior surgery; however, by examining the T2 images, an astute radiologist can recognize this phenomenon, draw the appropriate conclusions, and correctly identify the PMC.

Adult↗

PubMed2004

Intensity-modulated stereotactic radiotherapy of paraspinal tumors: a preliminary report.

OBJECTIVE: Radioresistant paraspinal tumors may benefit from conformal treatment techniques such as intensity-modulated radiotherapy (IMRT). Local tumor control and long-term palliation for both primary and metastatic tumors may be achieved with IMRT while reducing the risk of spinal cord toxicity associated with conventional radiotherapy techniques. In this article, we report our initial clinical experience in treating 16 paraspinal tumors with IMRT in which the planning target volume was 2 mm or greater from the spinal cord. METHODS: IMRT was administered by using a linear accelerator mounted with a multileaf collimator. Two immobilization body frames developed at Memorial Sloan-Kettering Cancer Center were used for patients with and without spinal implants. During a 30-month period, 16 patients underwent IMRT for metastatic and primary tumors. Eleven patients were treated for symptomatic recurrences after undergoing surgery and prior external beam radiotherapy, and one patient was treated after undergoing radiotherapy for a metastatic pancreatic gastrinoma with overlapping ports to the spine. Four patients with primary tumors were treated after primary resection that resulted in positive histological margins. Twelve patients were symptomatic with pain, functional radiculopathy, or both. Tumoral doses were determined on the basis of the relative radiosensitivity of tumors. Patients with metastatic tumors were administered a median tumoral dose of 20 Gy in four to five fractions and a spinal cord maximum dose of 6.0 Gy in addition to the full tolerance dose administered in previous radiation treatments. The primary tumors were delivered a median dose of 70 Gy in 33 to 37 fractions and a spinal cord maximum dose of 16 Gy. The median tumoral volume was 7.8 cm(3). RESULTS: Of the 15 patients who underwent radiographic follow-up, 13 demonstrated either no interval growth or a reduction in tumor size in a median follow-up period of 12 months (range, 2-23 mo). Two patients, one with a thoracic chondrosarcoma and one with a chordoma, showed tumor progression 1 year after undergoing IMRT. Pain symptoms improved in 11 of 11 patients, and 4 of 4 patients had significant improvement in their functionally significant radiculopathy and/or plexopathy. Pain relief was durable in all patients except the two with tumor progression. No patient showed signs or symptoms of radiation-induced myelopathy, radiculopathy, or plexopathy, including 12 patients with a median follow-up of 18 months. CONCLUSION: IMRT was effective for treating pain and improving functional radiculopathy in patients with metastatic and primary tumors. Although long-term tumor control is not established in this study, high-dose tumoral irradiation can be performed without causing radiation myelopathy in more than 1 year of follow-up.

Adult↗

PubMed2004

Isolated translocation of Wernicke's area to the right hemisphere in a 62-year-man with a temporo-parietal glioma.

We describe a case of translocation of temporo-parietal language function (Wernicke's area) to the contralateral hemisphere in a right-handed patient with a left temporo-parietal glioma. This translocation was identified by functional MR imaging (fMRI) and validated by direct cortical stimulation during gross-total resection. The current case exemplifies how preoperative fMRI can identify unexpected language organization as a result of tumor growth, affording surgery to patients who may otherwise be deemed inoperable.

Brain Neoplasms↗

PubMed2003

Comparison of conscious sedation and general anesthesia for motor mapping and resection of tumors located near motor cortex.

OBJECT: The surgical treatment of tumors located near eloquent cortex carries a high risk of inducing worsening neurological deficits. Intraoperative electrocorticography techniques have been developed to help identify these areas at the time of surgery in an effort to minimize such risks. The optimal anesthetic technique for conducting these procedures, however, has never been determined. METHODS: The authors conducted a retrospective study to compare patients who underwent intraoperative motor mapping between September 2000 and May 2002. Demographic and neurophysiological monitoring data were collected from the hospital records. Patients were divided into two groups based on the anesthetic technique used for surgery: in Group 1 general anesthesia was used, and in Group 2 conscious sedation. Group 1 comprised 24 patients (mean age 47 years) with 16 right- and eight left-sided lesions. Group 2 consisted of 21 patients (mean age 46 years) with 18 right- and three left-sided lesions. Pathological diagnoses were similar between the two groups. Motor stimulation was elicited in 12 patients (50%) in Group 1 and in 21 patients (100%) in Group 2 (p < 0.001). In addition, the mean stimulation amplitude required was significantly higher (13 mA) in patients in whom conscious sedation was used as opposed to general anesthesia (5 mA, p < 0.0001). Electrographic evidence of seizures was seen in 29% of Group 1 compared with 10% of Group 2 patients (p > 0.05). CONCLUSIONS: The use of conscious sedation as an anesthetic technique for motor mapping not only improves the chances of achieving successful stimulation and identification of motor cortex in relationship to the lesion, but it also allows for repetitive monitoring of the patient's motor function during resection of the lesion.

Adenocarcinoma↗