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Biomedical subjects

E Alexander

Publications and source records attributed to E Alexander.

At least 37 records · Page 2Linked to original sources
PubMed1999

Craniotomy for tumor treatment in an intraoperative magnetic resonance imaging unit.

OBJECTIVE: The complex three-dimensional anatomic features of the brain and its vulnerability to surgical intervention make the surgical treatment of intracranial tumors challenging. We evaluated the surgical treatment of supratentorial tumors using intraoperative magnetic resonance imaging (MRI), which provides real-time guidance, allows localization of intracranial tumors and their margins, and facilitates continuous assessment of surgical progress. METHODS: Sixty patients underwent craniotomies for tumor treatment in the General Electric intraoperative MRI unit at the Brigham and Women's Hospital (Boston, MA) during a 1-year period. The patients selected were those with intracranial tumors that were considered difficult to resect because of their locations or previous incomplete operations. Twenty-nine low-grade and 19 high-grade gliomas, 8 metastatic lesions, 2 meningiomas, 1 pineoblastoma, and 1 astroblastoma were resected. RESULTS: Tumors were accurately localized and targeted, and the extent of resection, as well as any intraoperative complications, could be immediately assessed during surgery. Marked brain shifting occurred during the procedures, and repeated intraoperative imaging allowed surgical accommodation for this shifting. In more than one-third of the cases, intraoperative imaging showed residual tumor when resection appeared complete on the basis of surgical observation alone. CONCLUSION: Intraoperative MRI is a revolutionary tool for the surgical treatment of brain tumors, providing observation of the procedure as it is being performed. With intraoperative MRI, tumor resection is safer, the extent of resection can be directly evaluated, and intraoperative complications can be noted if they occur. Outcomes after resection depend on minimizing injury to normal brain tissue and achieving maximal tumor resection. The use of intraoperative MRI directly affects these factors.

Adult↗
PubMed1999

World War II: a neurosurgeon in New Guinea.

During World War II, many doctors joined the military after completing their medical training. Civilian careers were put on hold until after the war was over. In 1942, Eben Alexander, Jr., joined the Air Force, then the United States Army, and served 4 years, much of it overseas, as a "3131C" neurosurgeon.

History, 20th Century↗
PubMed1999

Intraoperative MR imaging guidance for intracranial neurosurgery: experience with the first 200 cases.

PURPOSE: To review preliminary experience with an open-bore magnetic resonance (MR) imaging system for guidance in intracranial surgical procedures. MATERIALS AND METHODS: A vertically oriented, open-configuration 0.5-T MR imager was housed in a sterile procedure room. Receive and transmit surface coils were wrapped around the patient's head, and images were displayed on monitors mounted in the gap of the magnet and visible to surgeons. During 2 years, 200 intracranial procedures were performed. RESULTS: There were 111 craniotomies, 68 biopsies, 12 intracranial cyst evaluations, four subdural drainages, and five transsphenoidal pituitary resections performed with the intraoperative MR unit. In each case, the intraoperative MR system yielded satisfactory results by allowing the radiologist to guide surgeons toward lesions and to assist in treatment. In two patients, hyperacute hemorrhage was noted and removed. The duration of the procedure and the complication rate were similar to those of conventional surgery. CONCLUSION: Intraoperative MR imaging was successfully implemented for a variety of intracranial procedures and provided continuous visual feedback, which can be helpful in all stages of neurosurgical intervention without affecting the duration of the procedure or the incidence of complications. This system has potential advantages over conventional frame-based and frameless stereotactic procedures with respect to the safety and effectiveness of neurosurgical interventions.

Adolescent↗
PubMed1999

Treatment of patients with primary glioblastoma multiforme with standard postoperative radiotherapy and radiosurgical boost: prognostic factors and long-term outcome.

OBJECT: To assess the value of stereotactic radiosurgery (SRS) as adjunct therapy in patients suffering from glioblastoma multiforme (GBM), the authors analyzed their experience with 78 patients. METHODS: Between June 1988 and January 1995, 78 patients underwent SRS as part of their initial treatment for GBM. All patients had undergone initial surgery or biopsy confirming the diagnosis of GBM and received conventional external beam radiotherapy. Stereotactic radiosurgery was performed using a dedicated 6-MV stereotactic linear accelerator. Thirteen patients were alive at the time of analysis with a median follow-up period of 40.8 months. The median length of actuarial survival for all patients was 19.9 months. Twelve- and 24-month survival rates were 88.5% and 35.9%, respectively. Patient age and Radiation Therapy Oncology Group (RTOG) class were significant prognostic indicators according to univariate analysis (p < 0.05). Twenty-three patients aged younger than 40 years had a median survival time of 48.6 months compared with 55 older patients who had 18.2 months (p < 0.001). Patients in this series fell into RTOG Classes III (27 patients), IV (29 patients), or V (22 patients). Class III patients had a median survival time of 29.5 months following diagnosis; this was significantly longer than median survival times for Classes IV and V, which were 19.2 and 18.2 months, respectively (p = 0.001). Only patient age (< 40 years) was a significant prognostic factor according to multivariate analysis. Acute complications were unusual and limited to exacerbation of existing symptoms. There were no new neuropathies secondary to SRS. Thirty-nine patients (50%) underwent reoperation for symptomatic necrosis or recurrent tumor. The rate of reoperation at 24 months following SRS was 54.8%. CONCLUSIONS: The addition of a radiosurgery boost appears to confer a survival advantage to selected patients.

Actuarial Analysis↗
PubMed1999

The role of radiosurgery for glial neoplasms.

Malignant gliomas are one of the most serious challenges in clinical neurosurgery. Despite advances in surgical and radiation techniques, chemotherapy, and other systemic antineoplastic regimens, such as gene therapy and immunotherapy, patients who suffer from malignant gliomas often succumb to their disease. Although some success has been made with forms of enhanced surgical guidance and localized radiotherapy, current techniques are unable to eradicate the infiltrative glioma cells.

Brain Neoplasms↗
PubMed1999

The case for radiosurgery.

Brain metastases represent a significant health-care problem, with almost 200,000 patient in the Unite States annually suffering from symptomatic parenchymal lesions. Lung, breast, melanoma, renal, and gastrointestinal cancers contribute the majority of lesions that come to clinical attention. Although median survival once brain metastases are diagnosed is less than a year, timely therapy can restore neurological function and can often prevent further neurological complications of cancer for the duration of a patient's survival. Important prognostic features associated with improved survival include the absence of extracranial disease progression, young age, a high pretreatment neurological status, one to three versus more than three lesions, and a long interval from primary disease diagnosis to the development of brain metastases. The need to aggressively treat brain metastases effectively is becoming increasingly important, however, as advances in the treatment of systemic disease result in an increasing number of patients developing brain metastases in the setting of limited systemic disease. For many such patients, surgery provides the best therapy, but results are still not encouraging because even patients with the best prognostic indicators often die within 18 to 24 months. Until Superior treatment modalities are developed, the judicious use of available techniques for treatment of patients with limited systemic disease provides the best opportunities for palliation and extended survival. Perhaps the most significant development in the treatment of patients with brain metastases during the last decade is the increasing use of radiosurgery. For patients with a single lesion, local control and survival rates of radiosurgery compare well with those produced with surgical resection. Radiosurgery remains an important treatment modality and, when used promptly, can reverse neurological deficits, often for the remainder of a patients life. There is compelling evidence to suggest that aggressive local therapy (surgery or radiosurgery) for patients with a single brain metastasis produces superior survival and quality of life compared with treatment with whole brain radiotherapy alone. However, surgery should be restricted to the minority of patients for whom brain metastases represents the life-threatening site of their disease. For an asymptomatic or mildly symptomatic patient with a lesion smaller than 3 cm in diameter, radiosurgery is an excellent alternative to surgery. Although radiosurgery is a noninvasive procedure, the same selection criteria should be considered as for those patients undergoing surgical resection.

Brain Neoplasms↗
PubMed1998

Initial clinical results of LINAC-based stereotactic radiosurgery and stereotactic radiotherapy for pituitary adenomas.

PURPOSE: To retrospectively evaluate the initial clinical results of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) for pituitary adenomas with regard to tumor and hormonal control and adverse effects of the treatment. SUBJECTS AND METHODS: Forty-eight patients with pituitary adenoma who underwent SRS or SRT between September 1989 and September 1995 were analyzed. Of these, 18 received SRS and 30 received SRT. The median tumor volumes were 1.9 cm3 for SRS and 5.7 cm3 for SRT. Eleven of the SRS and 18 of the SRT patients were hormonally active at the time of the initial diagnosis. Four of the SRS and none of the SRT patients had a history of prior radiation therapy. Both SRS and SRT were performed using a dedicated stereotactic 6-MV linear accelerator (LINAC). The dose and normalization used for the SRS varied from 1000 cGy at 85% of the isodose line to 1500 cGy at 65% of the isodose line. For SRT patients, a total dose of 4500 cGy at 90% or 95% of the isodose line was delivered in 25 fractions of 180 cGy daily doses. RESULTS: Disease control-The three year tumor control rate was 91.1% (100% for SRS and 85.3% for SRT). Normalization of the hormonal abnormality was achieved in 47% of the 48 patients (33% for SRS and 54% for SRT). The average time required for normalization was 8.5 months for SRS and 18 months for SRT. Adverse effects-The 3-year rate of freedom from central nervous system adverse effects was 89.7% (72.2% for SRS and 100% for SRT). Three patients who received SRS for a tumor in the cavernous sinus developed a ring enhancement in the temporal lobe as shown by follow-up magnetic resonance imaging. Two of these cases were irreversible and were considered to be radiation necrosis. None of the 48 patients developed new neurocognitive or visual disorders attributable to the irradiation. The incidence of endocrinological adverse effects were similar in the two groups, resulting in 3-year rates of freedom from newly initiated hormonal replacement of 78.4% (77.1% for SRS and 79.9% for SRT). CONCLUSION: Considering the relatively high incidence of morbidity observed in the SRS group, we recommend SRT as the primary method of radiation therapy for pituitary tumors. When treating a lesion in the cavernous sinus with SRS, special attention should be paid to dose distribution in the adjacent brain parenchyma. Longer follow-up is necessary before drawing any conclusions about the advantages of these techniques over conventional external beam radiation therapy.

Adenoma↗
PubMed1998

Survival results from a phase I study of etanidazole (SR2508) and radiotherapy in patients with malignant glioma.

PURPOSE: To report the survival results from a previous Phase I study of etanidazole (ETA) and radiotherapy in patients with glioblastoma multiforme (GBM n = 50) or anaplastic astrocytoma (AA n = 19) and examine survival according to age, Karnofsky performance status (KPS), and implant status. PATIENTS AND METHODS: In a previous Phase I study, 70 previously untreated patients (median age 49) with malignant gliomas were accrued. One patient was excluded from analysis because pathology was unverifiable. All had KPS > or = 70. Prior to initiation of treatment, patients were stratified according to whether they were candidates for interstitial implantation. The implant patients (IMP n = 14) received accelerated fractionation radiotherapy (XRT) 2 Gy BID (6 hours apart) to 40 Gy in 2 weeks with ETA 2 gm/m2 x 6 doses, a 2 week break, and then interstitial implant for an additional 50 Gy (4-7 days) with a continuous infusion of ETA over 90-96 hours. There were 55 patients treated on two sequentially conducted non-implant arms. These patients started with accelerated fractionation XRT 2 Gy BID (6 hours apart) to 40 Gy in 2 weeks with ETA 2 gm/m2 x 4-5 doses/week. Non-IMP1 arm (n = 41) received a 2-week break before standard fractionated boost XRT of 2 Gy/day for 2 weeks to a total dose of 60 Gy with ETA. Non-IMP2 arm (n = 14) did not have the 2-week break. All patients had plasma pharmacokinetic monitoring of ETA. Subsequent follow-up study provided information regarding long-term survival status of this group of patients. The Phase I toxicity evaluation was conducted according to the RTOG toxicity scale and was found well tolerated in both groups. Overall actuarial survival was plotted for all patients, by histologic group, and by implant status. Subset analyses of GBM patients by age (< or = 49 or > 49 years), KPS (< or = 80 or > 80) and implant versus non-implant were also performed. RESULTS: Median survival of GBM patients was 1.1 years and that of anaplastic astrocytoma patients was 3.1 years (p = 0.0001). In GBM patients, KPS > 80, implanted patients, and age < or = 49 were factors found not to be associated with a statistically improved survival. CONCLUSION: The results of survival in this Phase I etanidazole study of patients with anaplastic astrocytoma are comparable to the results from other studies using bromodeoxyuridine, iododeoxyuridine, or procarbazine, lomustine (CCNU), and vincristine. The use of etanidazole with accelerated radiotherapy does not appear to improve survival in patients with glioblastoma multiforme compared to those treated with conventional therapies.

Adult↗
PubMed1998

Experimentation with a transcranial magnetic stimulation system for functional brain mapping.

We describe functional brain mapping experiments using a transcranial magnetic stimulation (TMS) device. This device, when placed on a subject's scalp, stimulates the underlying neurons by generating focused magnetic field pulses. A brain mapping is then generated by measuring responses of different motor and sensory functions to this stimulation. The key process in generating this mapping is the association of the 3-D positions and orientations of the TMS probe on the scalp to a 3-D brain reconstruction such as is feasible with a magnetic resonance image (MRI). We have developed a registration system which not only generates functional brain maps using such a device, but also provides real-time feedback to guide the technician in placing the probe at appropriate points on the head to achieve the desired map resolution. Functional areas we have mapped are the motor and visual cortex. Validation experiments focus on repeatability tests for mapping the same subjects several times. Applications of the technique include neuroanatomy research, surgical planning and guidance, treatment and disease monitoring, and therapeutic procedures.

Brain Mapping↗
PubMed1998

Visual hemifield mapping using transcranial magnetic stimulation coregistered with cortical surfaces derived from magnetic resonance images.

The perception of a visual stimulus can be inhibited by occipital transcranial magnetic stimulation. This visual suppression effect has been attributed to disruption in the cortical gray matter of primary visual cortex or in the fiber tracts leading to V1 from the thalamus. However, others have suggested that the visual suppression effect is caused by disruption in secondary visual cortex. Here the authors used a figure-eight coil, which produces a focal magnetic field, and a Quadropulse stimulator to produce visual suppression contralateral to the stimulated hemisphere in five normal volunteer subjects. The authors coregistered the stimulation sites with magnetic resonance images in these same subjects using optical digitization. The stimulation sites were mapped onto the surface of the occipital lobes in three-dimensional reconstructions of the cortical surface to show the distribution of the visual suppression effect. The results were consistent with disruption of secondary visual cortical areas.

Adult↗
PubMed1998

Results of linear accelerator-based radiosurgery for intracranial meningiomas.

OBJECTIVE: We report the outcomes of patients treated with linear accelerator-based radiosurgery for intracranial meningiomas at our institution. METHODS: We reviewed 127 patients with 155 meningiomas treated with stereotactic radiosurgery (SRS) at the study institutions between October 1988 and December 1995. RESULTS: There were 86 female and 41 male patients (median age, 61.5 yr; range, 19.9-87.9 yr). The median follow-up period was 31 months (range, 1.2-79.8 mo). The median tumor volume was 4.1 cc (range, 0.16-51.2 cc), and the median marginal dose was 15 Gy (range, 9-20 Gy). The tumor locations were as follows: convexity, 31 tumors; parasagittal/falcine, 39 tumors; cranial base, 82 tumors; and ventricular/pineal, 3 tumors. There were 106 benign, 26 atypical, and 18 malignant meningiomas and 5 cases of meningiomatosis. SRS was performed on 48 lesions as the initial treatment and on 107 lesions as adjunct therapy. Freedom from progression was observed in 107 patients (84.3%) at a median time of 22.9 months (range, 1.2-79.8 mo). Twenty patients (15.7%) had disease progression (16 marginal [12.6%] and 4 local [3.1%]) at a median time of 19.6 months (range, 4.1-69.3 mo); the median time for freedom from progression for the benign, atypical, and malignant meningiomas was 20.9, 24.4, and 13.9 months, respectively. Actuarial tumor control for the patients with benign meningiomas was 100, 92.9, 89.3, 89.3, and 89.3% at 1, 2, 3, 4, and 5 years, respectively. Six patients (4.7%) had permanent complications attributable to SRS (median time, 10.3 mo; range, 4.3-18.0 mo); 13 patients died as a result of causes related to the meningiomas (median, 17.5 mo; range, 4.3-37.3 mo). The 1-, 2-, 3-, 4-, and 5-year survival probability for the entire group of patients was 90.3, 82.6, 73.6, 70.5, and 68.2%, respectively; for patients with benign meningiomas, excluding death resulting from intercurrent disease, the survival probability was 97.6, 94.8, 91.0, 91.0, and 91.0%, respectively. The 1-, 2-, 3-, and 4-year survival probability for the patients with atypical and malignant meningiomas was 91.7, 83.3, 83.3, and 83.3% and 92.3, 64.6, 43.1, and 21.5%, respectively. CONCLUSION: Even though complications from SRS are expected more frequently with large tumors near critical structures, SRS is a safe and effective means of treating selected meningiomas.

Adult↗
PubMed1998

Dual-isotope single-photon emission computerized tomography scanning in patients with glioblastoma multiforme: association with patient survival and histopathological characteristics of tumor after high-dose radiotherapy.

OBJECT: The study was conducted to determine the association between dual-isotope single-photon emission computerized tomography (SPECT) scanning and histopathological findings of tumor recurrence and survival in patients treated with high-dose radiotherapy for glioblastoma multiforme. METHODS: Studies in which SPECT with 201Tl and 99mTc-hexamethypropyleneamine oxime (HMPAO) were used were performed 1 day before reoperation in 47 patients with glioblastoma multiforme who had previously been treated by surgery and high-dose radiotherapy. Maximum uptake of 201Tl in the lesion was expressed as a ratio to that in the contralateral scalp, and uptake of 99mTc-HMPAO was expressed as a ratio to that in the cerebellar cortex. Patients were stratified into groups based on the maximum radioisotope uptake values in their tumor beds. The significance of differences in patient gender, histological characteristics of tissue at reoperation, and SPECT uptake group with respect to 1-year survival was elucidated by using the chi-square statistic. Comparisons of patient ages and time to tumor recurrence as functions of 1-year survival were made using the t-test. Survival data at 1 year were presented according to the Kaplan-Meier method, and the significance of potential differences was evaluated using the log-rank method. The effects of different variables (tumor type, time to recurrence, and SPECT grouping) on long-term survival were evaluated using Cox proportional models that controlled for age and gender. All patients in Group I (201Tl ratio < 2 and 99mTc-HMPAO ratio < 0.5) showed radiation changes in their biopsy specimens: they had an 83.3% 1-year survival rate. Group II patients (201Tl ratio < 2 and 99mTc-HMPAO ratio of > or = 0.5 or 201Tl ratio between 2 and 3.5 regardless of 99mTc-HMPAO ratio) had predominantly infiltrating tumor (66.6%); they had a 29.2% 1-year survival rate. Almost all of the patients in Group III (201Tl ratio > 3.5 and 99mTc-HMPAO ratio > or = 0.5) had solid tumor (88.2%) and they had a 6.7% 1-year survival rate. Histological data were associated with 1-year survival (p < 0.01): however, SPECT grouping was more closely associated with 1-year survival (p < 0.001) and was the only variable significantly associated with long-term survival (p < 0.005). CONCLUSIONS: Dual-isotope SPECT data correlate with histopathological findings made at reoperation and with survival in patients with malignant gliomas after surgical and high-dose radiation therapy.

Adolescent↗
PubMed1997

Prostate pathology case study seminar.

Great strides have been made in the past decade in our understanding of the pathology of the prostate. Diagnostic criteria have been proposed, debated, and refined for a number of entities, including prostatic intraepithelial neoplasia, atypical adenomatous hyperplasia, basal cell proliferations, postatrophic hyperplasia, verumontanum mucosal gland hyperplasia, and numerous new variants of prostatic adenocarcinoma such as ductal adenocarcinoma, mucinous carcinoma, signet ring cell carcinoma, and lymphoepithelioma-like carcinoma. This report presents a series of case studies in prostate pathology which illustrate some of the contemporary issues which confront the pathologist and urologist.

Adenocarcinoma↗