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Gabriel Zada, Ning Lin, Eric Ojerholm, Shakti Ramkissoon and Edward R. Laws

Object

Cystic epithelial masses of the sellar and parasellar region may be difficult to differentiate on a clinical, imaging, or even histopathological basis. The authors review the developmental relationships and differentiating features of various epithelial lesions of the sellar region.

Methods

The authors performed a review of the literature to identify previous studies describing the etiological relationships and differentiating features of various cystic sellar lesions, including craniopharyngioma (CP), Rathke cleft cyst, xanthogranuloma, and dermoid and epidermoid cysts.

Results

There is significant evidence in the literature to support a common ectodermal origin of selected sellar and suprasellar cystic lesions, which may account for the overlap of features and transitional states observed in some cases. Research obtained from animal studies and reports of transitional cystic epithelial masses or lesions crossing over from typical to more aggressive pathological subtypes have collectively provided a solid foundation for this theory. Histological features that signify transitional entities beyond simple benign Rathke cleft cysts include squamous metaplasia, stratified squamous epithelium, and ciliated or mucinous goblet cells in squamous-papillary CPs. Several studies have identified key clinical, imaging, and histopathological features that can be used in the differentiation of these lesions.

Conclusions

The pattern of embryological formation of the hypothalamic-pituitary axis plays a major role in its propensity for developing cystic epithelial lesions. Subsequent inflammatory, metaplastic, and neoplastic processes may promote further progression along the pathological continuum, ranging from benign epithelial cysts to aggressive neoplastic cystic CPs. Selected clinical, imaging, and histopathological features can be used collectively to help differentiate these lesions and assign a formal diagnosis, thus accurately guiding further treatment.

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John A. Jane Jr., Erin Kiehna, Spencer C. Payne, Stephen V. Early and Edward R. Laws Jr.

Object

Although the transsphenoidal approach for subdiaphragmatic craniopharyngiomas has been performed for many years, there are few reports describing the role of the endoscopic transsphenoidal technique for suprasellar craniopharyngiomas. The purpose of this study was to report the outcomes of the endoscopic transsphenoidal approach for adults with craniopharyngiomas in whom the goal was gross-total resection.

Methods

Twelve patients were identified who were older than 18 years at the time of their pure endoscopic transsphenoidal surgery. Their medical records and imaging studies were retrospectively reviewed.

Results

Gross-total resection was achieved in 42% of cases when assessed by intraoperative impression alone and in 75% when assessed by the first postoperative MR imaging study. However, 83% of patients achieved at least a 95% resection when assessed by both intraoperative impression and the first postoperative MR imaging study. Permanent diabetes insipidus occurred postoperatively in 44% of patients. Six (67%) of 9 patients who had a functioning hypothalamic-pituitary axis preoperatively developed panhypopituitarism after surgery. Visual improvement or normalization occurred in 78% of patients with preoperative visual deficits. Although no patient experienced a postoperative CSF leak, 1 patient was treated for meningitis.

Conclusions

The authors have achieved a high rate of radical resection and symptomatic improvement with the endoscopic transsphenoidal technique for both subdiaphragmatic (sellar/suprasellar) and supradiaphragmatic (suprasellar) craniopharyngiomas. However, this is also associated with a high incidence of new endocrinopathy. Endoscopic assessment of tumor resection may be more sensitive for residual tumor than the first postoperative MR imaging study.

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Chirag G. Patil, Shivanand P. Lad, Laurence Katznelson and Edward R. Laws Jr.

✓ Cushing's disease is associated with brain atrophy and cognitive deficits. Excess glucocorticoids cause retraction and simplification of dendrites in the hippocampus, and this morphological change probably accounts for the hippocampal volume loss. Mechanisms by which glucocorticoids affect the brain include decreased neurogenesis and synthesis of neurotrophic factors, impaired glucose utilization, and increased actions of excitatory amino acids. In this review, the timing, pathology, and pathophysiology of the brain atrophy in Cushing's disease are discussed. The correlation of atrophy with cognitive deficits and its reversibility is also reviewed.

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Chirag G. Patil, Shivanand P. Lad, Griffith R. Harsh, Edward R. Laws Jr. and Maxwell Boakye

Object

Information about complications, patient outcomes, and mortality rate after transsphenoidal surgery (TSS) for Cushing's disease has been derived largely from single-institution series. In this study the authors report on inpatient death, morbidity, and outcomes following TSS for Cushing's disease on a national level.

Methods

All patients in the Nationwide Inpatient Sample (NIS) database who had undergone transsphenoidal resection of a pituitary tumor for Cushing's disease between 1993 and 2002 were included in the study. The number of cases per year, length of stay (LOS), and rates of inpatient complications, death, and adverse outcomes (death or discharge to institution other than home) were abstracted. Univariate and multivariate analyses were performed to determine the effects of patient and hospital characteristics on outcome measures.

Results

According to the NIS, there were an estimated 3525 cases of TSS for Cushing's disease in the US between 1993 and 2002. During this period, there was a trend toward a small increase in the number of TSSs for Cushing's disease. The in-hospital mortality rate was 0.7%, and the complication rate was 42.1%. Diabetes insipidus (15%), fluid and electrolyte abnormalities (12.5%), and neurological deficits (5.6%) were the most common complications reported. Multivariate analysis showed that complications were more likely in patients with pre-operative comorbidities. Patients older than 64 years were much more likely to have an adverse outcome (odds ratio [OR] 20.8) and a prolonged hospital stay (OR 2.2). Women were less likely than men to have an adverse outcome (OR 0.3). A single postoperative complication increased the mean LOS by 3 days, more than tripled the odds of an adverse outcome, and increased the hospital charges by more than US $7000.

Conclusions

The authors provided a national perspective on trends, inpatient complications, and outcomes after TSS for Cushing's disease in the US. Postoperative complications had a significantly negative effect on LOS, adverse outcome, and resource utilization. Advanced age and multiple preoperative comorbidities were identified as important risk factors, and their effects on patient outcomes were quantified.

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Shivanand P. Lad, Chirag G. Patil, Edward R. Laws Jr. and Laurence Katznelson

✓ Cushing's syndrome can present a complex problem of differential diagnosis. Of cases in which hypercortisolemia results from an adrenocorticotropic hormone (ACTH)–dependent process, approximately 80% are due to a pituitary adenoma (Cushing's disease [CD]), 10% are due to adrenal lesions, and the remaining 10% are secondary to ectopic ACTH secretion. For patients with CD, surgical removal of the pituitary adenoma is the treatment of choice. Thus, localization of the source of ACTH secretion is critical in guiding timely treatment decisions.

Inferior petrosal sinus sampling (IPSS) is considered to be the gold standard for confirming the origin of ACTH secretion in patients with Cushing's syndrome.

The authors present an overview of IPSS—both the technique and its interpretation—as well as a summary of recent studies. A number of other techniques are discussed including sampling from the cavernous sinus, the jugular vein, and multiple sites to aid the diagnosis and lateralization of ACTH-producing pituitary adenomas. Management is best undertaken by a comprehensive multidisciplinary team taking into account the results of all the biochemical and imaging studies available, to provide the best advice in patient treatment decisions.

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Jay Jagannathan, Daniel M. Prevedello, Vivek S. Ayer, Aaron S. Dumont, John A. Jane Jr. and Edward R. Laws

Object

In this study the authors address the efficacy and safety of frameless stereotaxy in transsphenoidal surgery.

Methods

One thousand transsphenoidal operations were performed at the authors' institution between June 2000 and July 2005. This series consists of a retrospective review of 176 patients entered in a prospectively obtained database who underwent frameless stereotactic transsphenoidal surgery in which magnetic resonance (MR) imaging, computerized tomography (CT) scanning, or fluoroscopic guidance was used. Of the 176 patients, 104 (59%) had suprasellar extension of their tumor, 70 (40%) had involvement of the visual apparatus, and 65 (37%) had cavernous sinus involvement. All patients underwent detailed pre- and postoperative neurological, endocrinological, radiographic, and ophthalmological follow-up evaluations. Records were reviewed retrospectively for intraoperative and postoperative complications related to the surgical approach.

No instances of visual deterioration, carotid artery (CA) stenosis, or stroke were observed following transsphenoidal surgery. Only one patient sustained damage to the CA intraoperatively, and this was controlled in the operating room. Five patients (3%) required an intensive care unit stay postoperatively. Intraoperative cerebrospinal fluid leakage was encountered in 112 patients (64%) and was more frequently observed in tumors with suprasellar involvement.

Conclusions

Frameless stereotaxy is a safe and effective modality for the treatment of recurrent or invasive sellar masses. All three frameless stereotaxy modalities provided accurate information regarding the anatomical midline and the trajectory to the sella turcica. The MR imaging, CT scanning, and fluoroscopic stereotaxy modalities all have unique advantages as well as specific limitations.

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Francesco Doglietto, Daniel M. Prevedello, John A. Jane Jr., Joseph Han and Edward R. Laws Jr.

Since its inception, one of the major issues in transsphenoidal surgery has been the adequate visualization of anatomical structures. As transsphenoidal surgery evolved, technical advancements improved the surgical view of the operative field and the orientation. The operating microscope replaced Cushing's headlight and Dott's lighted speculum retractor, and fluoroscopy provided intraoperative imaging. These advances led to the modern concept of micro-surgical transsphenoidal procedures in the early 1970s.

For the past 30 years the endoscope has been used for the treatment of diseases of the sinus and, more recently, in the surgical treatment of pituitary tumors. The collaboration between neurological and otorhinolaryngological surgeons has led to the development of novel surgical procedures for the treatment of various pathological conditions in the skull base.

In this paper the authors review the history of the endoscope—its technical development and its application—from the first endoscope described by Philipp Bozzini to the First World Congress of Endoscopic Skull Base Surgery held in 2005 in Pittsburgh, Pennsylvania. Specifically, in this review the history of endoscopy and its application in endonasal neurosurgery are presented.

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John A. Jane Jr., Joseph Han, Daniel M. Prevedello, Jay Jagannathan, Aaron S. Dumont and Edward R. Laws Jr.

Sellar tumors are most commonly approached through the transsphenoidal corridor, and tumor resection is most often performed using the operating microscope. More recently the endoscope has been introduced for use either as an adjunct to or in lieu of the microscope. Both the microscopic and endoscopic transsphenoidal approaches to sellar tumors allow safe and effective tumor resection. The authors describe their current endoscopic technique and elucidate the advantages and disadvantages of the pure endoscopic adenomectomy compared with the standard microscopic approach.

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Relevance of high Ki-67 in pituitary adenomas

Case report and review of the literature

Daniel M. Prevedello, Jay Jagannathan, John A. Jane Jr., M. Beatriz S. Lopes and Edward R. Laws Jr.

Pituitary adenomas are heterogeneous in growth rate, invasiveness, and recurrence. To understand the biological behavior of the individual adenoma more fully, cell proliferation markers such as monoclonal antibodies targeted against the Ki-67 antigen have been applied. The Ki-67 antigen is a protein related to cell proliferation and is expressed in cell nuclei throughout the entire cell cycle. The authors report the case of an extremely rapidly growing pituitary adenoma with cavernous sinus invasion. The lesion, which displayed a high Ki-67 labeling index (LI; 22%), was found in a 54-year-old woman who presented with diplopia and headaches. The patient underwent three transsphenoidal operations in less than 6 months and, ultimately, was treated with fractionated intensity-modulated radiation therapy. The relationships between high Ki-67 LIs and tumor recurrence, invasiveness, and growth velocity in pituitary adenomas are reviewed.

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Jay Jagannathan, Aaron S. Dumont, John A. Jane Jr. and Edward R. Laws Jr.

The diagnosis and management of pediatric sellar lesions is discussed in this paper. Craniopharyngiomas account for the majority of pediatric sellar masses, and pituitary adenomas are extremely uncommon during childhood. The diagnosis of sellar lesions involves a multidisciplinary effort, and detailed endocrinological, ophthalmological, and neurological testing is critical in the evaluation of a new sellar mass. The management of pituitary adenomas varies depending on the entity. For most tumors other than prolactinomas, transsphenoidal resection remains the mainstay of treatment. Less invasive methods, such as endoscopic transsphenoidal surgery and stereotactic radiosurgery, have shown promise as primary and adjuvant treatment modalities, respectively.