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E R Laws

Publications and source records attributed to E R Laws.

At least 55 records · Page 3Linked to original sources

Secondary gain influences the outcome of lumbar but not cervical disc surgery.

BACKGROUND: The expectation of monetary compensation has been associated with poor outcomes in lumbar discectomy, fueling a reluctance among surgeons to treat worker's compensation cases. This issue, however, has not been investigated in patients undergoing cervical disc surgery. This study analyzes the relationship between economic forms of secondary gain and surgical outcome in a group of patients with common pay scales, retirement plans, and disability programs. METHODS: All procedures were performed at the Portsmouth Naval Medical Center between 1993 and 1995; active duty military servicepersons who were treated for cervical radiculopathy were prospectively included. Clinical, demographic, and financial factors were analyzed to determine which were predictive for outcome. Financial data were used to create a compensation incentive (CI) which is proportional to the rank, years of service, potential disability, retirement eligibility, and base pay and reflects the monetary incentive of disability. The results of cervical surgery were compared to a previously reported companion population of patients treated for lumbar disc disease. A good outcome is defined as a return to active duty, whereas a referral for disability is considered a poor surgical result. RESULTS: One hundred percent follow-up was obtained for 269 patients who were treated with 307 cervical operations. Only 16% (43/269) of cervical patients received disability, whereas 24.7% (86/348) of lumbar patients obtained a poor result (p = 0.0082). Although economic forms of secondary gain were not associated with outcome in cervical disease, both the position (p = 0.002) and duration of an individual's military career were significant factors (p = 0.02). Of the medical variables tested, multilevel surgery (p = 0.03) and revision operations at the same level (p = 0.03) were associated with referral for medical discharge. CONCLUSIONS: Secondary gain in the form of economic compensation influences outcome in lumbar but not cervical disc surgery; this observation may in part account for the success of cervical surgery relative to lumbar discectomy. Social factors that are independent of the anticipation of economic compensation seem to influence the outcome of cervical disc surgery.

Adult↗

Pituitary surgery.

Surgical management of pituitary adenomas continues to be a safe and effective method for treating many patients with these lesions. The goal of overall management should be to provide the patient with the most effective means of long-term control of this benign but potentially disabling disease. Currently, surgery has a significant role. It is hoped that with advances in the understanding of pituitary pathophysiology and with advances in pharmacotherapy, surgical management may become even more focused, more precise, and more effective over time.

Adenoma↗

Estrogen receptors in prolactinomas: a clinico-pathological study.

BACKGROUND: Antiestrogens are effective in the treatment of estrogen receptor (ER) positive breast carcinoma. The use of antiestrogen therapy in pituitary adenomas, however, has not been explored. This study attempted to identify a population who may benefit from antiestrogen therapy. MATERIALS & METHODS: Prolactinomas from 29 patients (10 men, 19 women) were analyzed for ER and Ki-67 labeling index using immunohistochemistry. Nine of the 19 women were either amenorrheic or had not received exogenous estrogen for at least one year. Ten women were menstruating either spontaneously or as a result of estrogen administration. Factors including age, serum prolactin level, tumor size, evidence of tumor invasiveness and recurrence of tumor were evaluated to determine if they were predictive of ER expression. RESULTS: Tumors from 6/10 (60%) men were positive for ER. Among women who were having menses, 9/10 (90%) tumors were positive, whereas 6/9 (67%) tumors from amenorrheic women were positive. Statistical analysis revealed that none of the variables: gender, age, menstrual status, Ki-67 proliferative rate, exposure to dopamine agonists, preoperative prolactin level, tumor size, or invasiveness was predictive for the presence of the receptor. The incidence of ER, however, was significantly reduced in recurrent tumors (p = 0.03). CONCLUSIONS: ER expression is less likely in recurrent tumors. The efficacy of ER antagonists cannot be inferred by gender or estrogen exposure.

Adult↗

Vascular complications of transsphenoidal surgery.

Vascular complication of transsphenoidal surgery can lead to mortality and serious morbidity. In a series of 3,061 transsphenoidal operations for pituitary disease, 24 such complications were encountered, seven of which were fatal. The anatomic substrate for such complications is discussed, along with technical aspects of surgery and other methods for the avoidance of vascular complications.

Aneurysm, False↗

Insulin-like growth factor-1 content and pattern of expression correlates with histopathologic grade in diffusely infiltrating astrocytomas.

Studies of experimental tumorigenesis have strongly implicated signaling of the insulin-like growth factor 1 (IGF-1) as a key component in astrocytic neoplasia; however, its role in the growth of low-grade and malignant human tumors is not well understood. Correlative analyses of IGF-1, p53, and Ki-67 (MIB-1) immunohistochemistry and IGF-1 receptor (IGF-1R) mRNA expression were performed to examine the cellular pattern of IGF-1 signaling in 39 cases of astrocytoma (World Health Organization grades II-IV). Tumor cells expressing IGF-1 and IGF-1R were present in all tumor grades. The proportion of tumor cells that expressed IGF-1 correlated with both histopathologic grade and Ki-67 labeling indices, while expression of IGF-1R mRNA correlated with Ki-67 indices. In cases where stereotactic tissue sampling could be identified with a specific tumor area by neuroimaging features, the numbers of IGF-1 immunoreactive cells correlated with the tumor zones of highest cellularity and Ki-67 labeling. In glioblastomas, the localization of IGF-1 immunoreactivity was notable for several features: frequent accentuation in the perivascular tumor cells surrounding microvascular hyperplasia; increased levels in reactive astrocytes at the margins of tumor infiltration; and selective expression in microvascular cells exhibiting endothelial/pericytic hyperplasia. IGF-1R expression was particularly prominent in tumor cells adjacent to both microvascular hyperplasia and palisading necrosis. These data suggest that IGF-1 signaling occurs early in astroglial tumorigenesis in the setting of cell proliferation. The distinctive correlative patterns of IGF-1 and IGF-1R expression in glioblastomas also suggest that IGF-1 signaling has an association with the development of malignant phenotypes related to aberrant angiogenesis and invasive tumor interactions with reactive brain.

Astrocytoma↗

Frameless stereotaxy for transsphenoidal surgery.

OBJECTIVE: To evaluate the utility of performing transsphenoidal surgery with computer-assisted image guidance. METHODS: Thirty-seven patients underwent transsphenoidal surgery in which a frameless stereotactic system was used to confirm the trajectory to the sella and to locate the anatomic midline. This technique was compared with our standard method of using an image intensifier to confirm the approach (n = 43). The numbers of complications associated with the approach, the times required to set up and perform each operation, and the average costs for each group were compared. RESULTS: There were no complications attributable to inaccurate localization from the neuronavigational system. Additional setup time was necessary to calibrate and register the system; this represented a mean of 17 minutes in transsphenoidal procedures performed for the first time (n = 30), whereas reoperations required an average of 22 minutes (n = 7) (P < 0.05). The operative times, defined as time from incision to closure, were not statistically different (P = 0.38). To reduce assistant variation, a subset of this group in which the same assistant was used (n = 18) was analyzed. The additional setup time was reduced to a mean of 12 minutes (P < 0.05). The total case times were actually reduced in this group (127 versus 133 min), but this was not statistically significant (P = 0.75). Fluoroscopy was not required when frameless stereotaxy was used. The cost savings were partially offset by the cost of the preoperative computed tomographic study necessary for fiducial registration and the additional cost of setup time in the operating room. When all factors were analyzed, an additional cost to the patient of $318.00 was noted. The image guidance in axial, coronal, and sagittal planes provided by frameless stereotaxy was subjectively beneficial; it increased our confidence with the approach to the sella and intraoperative localization and was particularly helpful in reoperations where standard anatomic landmarks were distorted. CONCLUSION: Frameless stereotaxy is a technology that provides continuous, three-dimensional information for localization and surgical trajectory to the surgeon and can be applied to transsphenoidal surgery with minimal additional cost and time requirements.

Adult↗

An accurate adjustable applicator for magnetic resonance imaging-based stereotactic procedure using the Leksell G frame.

OBJECTIVE: An applicator system for the Leksell G frame was constructed to enable accurate placement of the frame for stereotactic magnetic resonance imaging (MRI) and successful stereotactic surgery. The applicator prevents inaccurate placement of the fiducial box on the patient's head and prevents contact of the frame holder with the patient's shoulder while in the MRI unit. It also helps to ensure optimal positioning of desired targets within the three-dimensional stereotactic space defined by the frame. METHODS: The applicator is made of transparent acrylic plates, which simulate the fiducial box that is attached to the frame for the preoperative stereotactic MRI study. An air cuff at the top supports the frame at any desired height and makes minute adjustments possible. Side cuffs help to keep the frame at the desired position from right to left. Indicators attached to the frame for the anterior fiducial plate prevent potential contact of the plate with the anterior posts and help avoid a poor fit caused by bending of the frame from excessive torque on the cranium fixation screws. Indicators for the MRI frame holder on the foot screws predict potential collision of the holder with the patient's shoulder before actually applying the holder on the frame. The applicator shows the range and limits of the Leksell stereotactic arc. RESULTS: This applicator system has been used effectively in more than 89 MRI-based functional stereotactic procedures. These include pallidotomy, thalamotomy, implantation of deep brain stimulators, and implantation of depth electrodes. It has functioned well and has facilitated excellent operative results in these cases. CONCLUSION: This simple frame applicator eliminates the need for reapplication of the stereotactic frame and additional imaging studies, thus providing successful and appropriate frame placement for stereotactic surgery.

Brain↗

Optimizing accuracy in magnetic resonance imaging-guided stereotaxis: a technique with validation based on the anterior commissure-posterior commissure line.

OBJECT: Some of the earliest successful frame-based stereotactic interventions directed toward the thalamus and basal ganglia depended on identifying the anterior commissure (AC) and posterior commissure (PC) in a sagittal ventriculogram and defining the intercommissural line that connects them in the midsagittal plane. The AC-PC line became the essential landmark for the localization of neuroanatomical targets in the basal ganglia and diencephalon and for relating them to stereotactic atlases. Stereotactic/functional neurosurgery has come to rely increasingly on magnetic resonance (MR) imaging guidance, and methods for accurately determining the AC-PC line on MR imaging are being developed. The goal of the present article is to present the authors' technique. METHODS: The technique described uses MR sequences that minimize geometric distortion and registration error, thereby maximizing accuracy in AC-PC line determinations from axially displayed MR data. The technique is based on the authors' experience with the Leksell G-frame but can be generalized to other MR imaging-based stereotactic systems. This methodology has been used in a series of 62 stereotactic procedures in 47 adults (55 pallidotomies and seven thalamotomies) with preliminary results that compare favorably with results reported when using microelectrode recordings. The measurements of the AC-PC line reported here also compare favorably with those based on ventriculography and computerized tomography scanning. CONCLUSIONS: The methodology reported here is critical in maintaining the accuracy and utility of MR imaging as its role in modern stereotaxy expands. Accurate parameters such as these aid in ensuring the safety, efficacy, and reproducibility of MR-guided stereotactic procedures.

Adult↗

Complications in a contemporary series of patients who underwent transsphenoidal surgery for Cushing's disease.

OBJECT: Transsphenoidal surgery is the usual treatment of choice for adrenocorticotropic hormone-secreting pituitary adenomas associated with Cushing's disease. In this paper the authors investigate the complications of transsphenoidal surgery in the treatment of a contemporary series of patients with Cushing's disease. METHODS: Between January 1992 and December 1997, 105 patients with Cushing's disease underwent transsphenoidal surgery at the University of Virginia Health Sciences Center. A retrospective analysis of the complications was conducted, and the mortality rate was found to be 0.9% and permanent morbidity was 1.8%. The overall number of complications was 14 (13.3%), which included seven complications directly related to surgery; one instance of permanent diabetes insipidus; one syndrome of inappropriate secretion of antidiuretic hormone; and five medical complications (four patients developed deep vein thrombosis and one developed pneumonia). CONCLUSIONS: Transsphenoidal surgery for Cushing's disease has a higher complication rate than that for pituitary adenomas in general. This is primarily related to a greater number of medical complications, most notably deep vein thrombosis, resulting from the generally debilitated state of most patients with Cushing's disease. In view of the high incidence of deep vein thrombosis in these patients, prophylaxis for thromboembolism during the perioperative period is recommended.

Adenoma↗

Radiosurgery for pituitary tumors and craniopharyngiomas.

Standard techniques of conventional radiation therapy have been used for many years to treat pituitary adenomas and craniopharyngiomas. These techniques are not always effective and carry with them morbidity in the form of damage to the normal pituitary gland, damage to the hypothalamus, the potential of damage to the visual system and to intellectual functions of the brain and a small but real risk of the development of secondary malignancies. In an effort to avoid these complications and to provide more effective adjunctive radiation therapy, techniques of stereotactic delivery of high-dose radiation to the pituitary region have been developed, known as radiosurgery. The history of the development of radiosurgery and its application to pituitary problems are recounted in this article, as are a number of the controversies that currently exist and need to be considered as these modalities of stereotactic radiosurgery are applied more frequently and to better effect in the future.

Brain Injuries↗

Pallidotomy improves motor responses and widens the levodopa therapeutic window in Parkinson's disease.

Stereotactic posteroventral pallidotomy (PVP) as a treatment for Parkinson's disease (PD) symptoms has been increasingly used in moderate-advanced disease. We examined the pharmacodynamic responses of PD patients to single oral levodopa doses and intravenous levodopa infusions before and after PVP surgery. Nine subjects with advanced PD received a single oral dose and ramped intravenous levodopa infusions before and 3-5 weeks after unilateral PVP. Timed motor tasks, Unified Parkinson's Disease Rating Scale (UPDRS) evaluations, and ordinal dyskinesia rating were performed after oral levodopa and during i.v. levodopa infusions. Serum prolactin and dopa levels were measured during the levodopa infusions. Overall timed motor but not motor UPDRS scores were improved after PVP in both the worst ("off") and best ("on") states. Contralateral but not ipsilateral limb dyskinesias were substantially reduced at all serum (dopa) levels after PVP. Ipsilateral and contralateral timed motor performance at low serum (dopa) levels was improved by PVP. Walking speeds at all serum (dopa) levels were not changed by PVP. Serum prolactin was reduced equally by increasing (dopa) preoperatively and postoperatively. PVP significantly and favorably altered oral and intravenous levodopa pharmacodynamics by improving bilateral limb motor function and contralateral dyskinesia but did not alter walking speed. PVP appears to widen significantly the therapeutic window for levodopa in PD.

Administration, Oral↗

Sutureless repair of major intracranial vessels with the Sundt clip-graft: technical note.

Major intracranial vessels can be damaged during tumor resection. With the availability of refined microvascular techniques, direct repair or by-pass of the damaged segment is possible. These methods, however, often require temporary occlusion of the offending vessel, can result in a less than optimal angiographic result, and are difficult to perform in a deep field. Additionally, in some patients direct repair or by-pass is not feasible because of the friability of the vessel or as a result of the large size of the tear. In these cases the Sundt clip-graft represents a valid adjunct to the armamentarium of the surgeon. Over the years, it has been used by the senior author in five patients where vascular injury occurred during the removal of brain tumors (3 meningiomas, one pituitary adenoma, and one low-grade glioma). In this report we illustrate our most recent experience with this ingenious tool. A 22-year-old man underwent resection of a recurrent left temporal lobe low-grade glioma. During resection of the tumor, a tear occurred in a branch of the middle cerebral artery. The tear was repaired using a Sundt clip-graft. A post-operative angiogram, performed five days later, showed patency of the vessel with no evidence of wall irregularities. Described 30 years age to be used primarily in aneurysm surgery, the Sundt clip-graft provides an excellent, too often forgotten, sutureless method of repairing intracranial vessels damaged during tumor removal.

Adult↗

Brain tumor survival: results from the National Cancer Data Base.

Hospital-based data reported to the National Cancer Data Base (NCDB) were available for over 60,000 patients with a primary brain tumor diagnosed from 1985-1988 and 1990-1992. The most common histologies were glioblastomas, astrocytomas and meningiomas. Five-year survival rates for these tumors were 2%, 30% and 70% respectively. Histology, age at diagnosis, behavior, and location were important variables in estimating survival. Comparisons with population-based registry data suggest that the malignant tumors are well represented in NCDB, but the benign histologies are under-reported. Survival estimates for the malignant tumors are comparable to previously reported studies. The NCDB provides recent information on brain tumor distribution and survival patterns not available in other large databases.

Adolescent↗

Glioma occurrence after sellar irradiation: case report and review.

OBJECTIVE: Tumor neogenesis is an uncommon but known consequence after therapeutic irradiation of the central nervous system. Causative agents for glioma induction remain unknown, but laboratory and clinical data suggest a possible role for radiation as a promotor. In the treatment of both pituitary adenomas and craniopharyngiomas, adjunctive conventional radiation therapy has long played a role. CLINICAL PRESENTATION: This report details two cases in which patients received standard sellar irradiation for growth hormone-secreting pituitary adenomas and later were diagnosed with gliomas, after a latency period of 11 and 18 years, respectively. Additionally, a comprehensive review of the literature with 30 reports of gliomas developing after conventional radiation for treatment of pituitary adenomas and craniopharyngiomas is presented. The mean dose for craniopharyngiomas (n = 8) was 5800 cGy, with a mean latency of 11.5 years from initial diagnosis to the eventual discovery of the gliomas. The mean dose for the treatment of pituitary adenomas (n = 24) was 5300 cGy, with a mean latency of 10.4 years. CONCLUSION: Typical features of the resulting gliomas included presentation in young patients, histologically high grades, and occurrence within the temporal lobe. A large proportion of gliomas were associated with growth hormone-secreting adenomas. This review assesses the implication of doses of conventional radiotherapy that were previously thought to be benign and concludes that although radiation-associated gliomas are uncommon, they represent a potentially devastating long-term risk. Based on this analysis, treatment of sellar tumors with conventional fractionated radiotherapy should be carefully considered and perhaps used primarily in those cases for which radiosurgery is not appropriate.

Adenoma↗

The role of preoperative adjuvant treatment in the management of esthesioneuroblastoma: the University of Virginia experience.

OBJECTIVE: Multidisciplinary management of esthesioneuroblastoma has effected markedly increased survival during the past 20 years. The potential for radical craniofacial surgery for complete en bloc resection, the availability of advanced neuroimaging modalities, and the incorporation of neoadjuvant therapy into treatment strategies for tumor remission have all contributed to this accomplishment. However, a standard protocol for the management of these lesions has not been accepted; preoperative radiation and chemotherapy have been advocated, but neither radiographic nor clinical response has been quantified. METHODS: Thirty-four consecutive patients with biopsy-proven esthesioneuroblastoma treated at one institution from 1976 to 1994 were reviewed to determine the effects of preoperative radiation therapy, with or without chemotherapy, on tumor size and long-term survival. RESULTS: In a multivariate regression analysis, advanced age was predictive of decreased disease-free survival (P=0.008), whereas advanced Kadish stage was associated with a borderline higher rate of disease-related mortality (P=0.056). Two-thirds of the patients showed a significant reduction in tumor burden with adjuvant therapy. Patients with response to neoadjuvant therapy demonstrated a significantly lower rate of disease-related mortality (P=0.050). In this series, the overall 5- and 10-year survival rates were 81.0 and 54.5%, respectively. CONCLUSION: Preoperative neoadjuvant therapy provides a valuable complement to radical craniofacial resection, leading to reduction in tumor burden. Patients experiencing reduction in tumor volume by neoadjuvant therapy demonstrate an improved prognosis.

Adolescent↗

Selective expression of estrogen receptor alpha and beta isoforms in human pituitary tumors.

The physiological effects of estrogen on the pituitary, including cellular proliferation and regulation of hormone synthesis, are mediated by the nuclear estrogen receptor (ER). The ER acts as a dimer to modulate gene transcription and contains specific functional domains encoded in different exons. Two separate, but related, forms of the receptor (ERalpha and ERbeta) exist, with distinct tissue and cell patterns of expression. Additional ER isoforms, generated by alternative messenger ribonucleic acid (mRNA) exon splicing, have been defined in several tissues and are postulated to play a role in tumorigenesis or in modulating the estrogen response. We examined 71 human pituitary adenomas of varying phenotypes and 6 normal pituitary specimens for ER mRNA forms by RT-PCR and hybridization blotting analysis. All prolactinomas (n = 14) contained ERalpha, and several contained ERbeta (5 of 14) mRNA. In comparison, 6 tumors that expressed PRL and GH expressed ERbeta (4 of 6) more frequently than ERalpha (3 of 6). ERbeta mRNA was also found more frequently in null cell (8 of 24 ERalpha and 14 of 24 ERbeta) and gonadotrope (13 of 21 ERalpha and 18 of 21 ERbeta) tumors. Additionally, ERbeta was found in 4 of 6 tumors that contained only GH, although ERalpha was not observed in this tumor type. Expression of the two ER forms within a tumor type was overlapping, but some tumors contained only 1 isoform. Expression of ERalpha mRNA splice variants also varied with cell type. All normal pituitaries contained ERalpha deletions of exon 4, 5, and 7, whereas only 2 of 6 samples contained the exon 2 deletion variant. Although the same ERalpha mRNA variants were observed among the various tumor types, the proportion of specific splice variants expressed varied. For example, most ER-positive prolactinomas expressed ERalpha variants with deletions of exon 2, 4, or 5, whereas gonadotropin tumors preferentially expressed the ERalpha exon 7 deletion variant. A novel ERbeta mRNA splice variant, missing exon 2, was observed in a majority of all ERbeta-positive tumors. Immunoblotting analysis of ERalpha and ERbeta proteins supported the mRNA results. Because ERalpha and ERbeta have different biological responses to selective ER modulators, and the ER deletion variants have biological effects distinct from those of the full-length ER, expression of these isoforms may influence the biological properties of these tumors and affect their ability to respond to estrogen and antiestrogen therapies.

Adenoma↗

Growth hormone secretagogue receptor expression in human pituitary tumors.

The GH secretagogue (GHS) receptor (GHS-R) has been characterized and cloned. It is a member of a family of seven transmembrane receptors and is closely related to the neurotensin and TRH receptors. To determine the expression of this receptor in normal anterior pituitary and in 24 human pituitary adenomas, we analyzed GHS-R messenger ribonucleic acid (mRNA) using a RT-PCR assay. We found that normal human pituitary was positive for the GHS-R signal. In addition, all GH-secreting adenomas and the one TSH-secreting adenoma demonstrated the presence of GHS-R mRNA. Three of four ACTH-secreting tumors and three of nine gonadotroph adenomas were also positive for the GHS-R mRNA. To determine the amounts of GHS-R mRNA in normal pituitary and in representative tumors, semiquantitative competitive PCR was performed. We determined that normal pituitary had approximately 750 molecules/L GHS-R mRNA. The acromegalic tumor had approximately 1.5 x 10(5) molecules/L, and the TSH-secreting tumor had approximately 7.5 x 10(3) molecules/L. Other tumor types contained considerably less, with the ACTH-secreting and gonadotroph tumors expressing 7.5 x 10(2) and 3 x 10(2) GHS-R mRNA molecules/L, respectively. These results suggest that GH- and TSH-producing adenomas express GHS-R mRNA at levels 200 and 10 times higher, respectively, than the normal pituitary, and that this receptor expression may be involved in the pathogenesis and growth of these pituitary adenomas.

Adenoma↗