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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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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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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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Jay Jagannathan, Aaron S. Dumont, Daniel M. Prevedello, Christopher I. Shaffrey and John A. Jane Jr.

✓Sports-related injuries to the spine, although relatively rare compared with head injuries, contribute to significant morbidity and mortality in children. The reported incidence of traumatic cervical spine injury in pediatric athletes varies, and most studies are limited because of the low prevalence of injury. The anatomical and biomechanical differences between the immature spine of pediatric patients and the mature spine of adults that make pediatric patients more susceptible to injury include a greater mobility of the spine due to ligamentous laxity, shallow angulations of facet joints, immature development of neck musculature, and incomplete ossification of the vertebrae. As a result of these differences, 60 to 80% of all pediatric vertebral injuries occur in the cervical region. Understanding pediatric injury biomechanics in the cervical spine is important to the neurosurgeon, because coaches, parents, and athletes who place themselves in positions known to be associated with spinal cord injury (SCI) run a higher risk of such injury and paralysis. The mechanisms of SCI can be broadly subclassified into five types: axial loading, dislocation, lateral bending, rotation, and hyperflexion/hyperextension, although severe injuries often result from a combination of more than one of these subtypes. The aim of this review was to detail the characteristics and management of pediatric cervical spine injury.

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Jay Jagannathan, David O. Okonkwo, Aaron S. Dumont, Hazem Ahmed, Abbas Bahari, Daniel M. Prevedello, John A. Jane Sr. and John A. Jane Jr.

Object

The authors examine the indications for and outcomes following decompressive craniectomy in a single-center pediatric patient population with traumatic brain injury (TBI).

Methods

A retrospective review of data was performed using a prospectively acquired database of patients who underwent decompressive craniectomy at the authors' institution between January 1995 and April 2006. The patients' neuroimages were examined to evaluate the extent of intracranial injury, and the patients' records were reviewed to determine the admission Glasgow Coma Scale (GCS) score, the extent of systemic injuries, the time to craniectomy, and the indications for craniectomy. Long-term functional outcome and independence levels were evaluated using the Glasgow Outcome Scale (GOS) and a Likert patient quality-of-life rating scale.

Twenty-three craniectomies were performed in children during the study period. The mean patient age at craniectomy was 11.9 years (range 2–19 years). In all patients, the computed tomography scans obtained at presentation revealed pathological findings, with diffuse axonal injury and traumatic contusions being the most common abnormalities. The median presenting GCS score was 4.6 (range 3–9). Nineteen patients (83%) suffered from other systemic injuries. One patient (4%) died intraoperatively and six patients (26%) died postoperatively. Postoperative intracranial pressure (ICP) control was obtained in 19 patients (83%); an ICP greater than 20 mm Hg was found to have the strongest correlation with subsequent brain death (p = 0.001). The mean follow-up duration was 63 months (range 11–126 months, median 49 months). The mean GOS score at the 2-year follow-up examination was 4.2 (median 5). At the most recent follow-up examination, 13 (81%) of 16 survivors had returned to school and only three survivors (18%) were dependent on caregivers.

Conclusions

Although the mortality rate for children with severe TBI remains high, decompressive craniectomy is effective in reducing ICP and is associated with good outcomes in surviving patients.

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

✓The history of the endoscope exemplifies the manner in which technological advances influence medicine and surgery. Endoscopic systems have evolved and improved, and they currently provide detailed visualization of a variety of deep organ structures. Otorhinolaryngological surgeons have used the endoscope for more than 30 years. In the 1990s, a number of influential neurosurgeons and otorhinolaryngological surgeons began performing purely endoscopic pituitary surgery. Endoscopic transsphenoidal operations are now extending beyond the sella. The collaboration between otorhinolaryngologists and neurosurgeons has produced a new subspecialty of “endoscopic skull base surgery.” There is a great deal of progress still to be made in developing skills, instruments, and improving skull base repair. The extended skull base approaches allow surgical exposures from the olfactory groove to C-2 and to the infratemporal region and jugular fossa laterally. This article discusses the history of the endoscope, the pivotal technological advances, and the key figures in the burgeoning field of endoneurosurgery.

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Daniel M. Prevedello, Amin B. Kassam, Ricardo L. Carrau, Carl H. Snyderman, Ajith Thomas, Paul Gardner, Arlan Mintz, Lisa Vecchione and Joseph Losee

✓Teratomas are neoplasms composed of tissues from all three germ layers with varying degrees of differentiation. They are most commonly found in the sacrococcygeal and gonadal regions and rarely occur in the head and neck region. A teratoma is termed “epignathus” when it arises from the skull base or hard palate and is located in the oral cavity. The authors describe a case of a giant epignathus teratoma originating in the skull base of a neonate, extending bilaterally via two pedicles throughout the hard palate and protruding through the oral cavity. The tumor was completely resected using a transpalatal endoscopic endonasal approach. The excised tumor proved to be an immature teratoma with well-differentiated yolk sac elements. At the 1-year follow-up the patient showed no evidence of tumor recurrence and the child remains neurologically intact.

This report demonstrates the use of a transpalatal endonasal corridor in a preterm infant. This approach provided an ample corridor into the ventral skull base without the need for external excisions and/or disruption of osseous elements.

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Amin B. Kassam, Allan D. Vescan, Ricardo L. Carrau, Daniel M. Prevedello, Paul Gardner, Arlan H. Mintz, Carl H. Snyderman and Albert L. Rhoton Jr.

✓ The purpose of this study was to describe the technique used to safely identify the petrous carotid artery during expanded endonasal approaches to the skull base. A series of 20 cadaveric studies was undertaken to isolate the vidian artery and nerve and to use them as landmarks to the petrous internal carotid artery (ICA). Twenty-five consecutive paraclival endoscopic cases were also reviewed to determine the consistency of the vidian artery in vivo as an intraoperative landmark to the ICA. These data were then correlated with results from a separate study in which computed tomography scans from 44 patients were evaluated to delineate the course of the vidian canal and its relationship to the petrous ICA. In all 20 cadaveric dissections and all 25 surgical cases, the vidian artery was consistently identified and could be reliably used as a landmark to the ICA. The correlation between anatomical and clinical data in this paper supports the consistent use of the vidian artery as an important landmark to the petrous ICA.

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Amin B. Kassam, Paul A. Gardner, Carl H. Snyderman, Ricardo L. Carrau, Arlan H. Mintz and Daniel M. Prevedello

Object

Craniopharyngiomas are notoriously difficult to treat. Surgeons must weigh the risks of aggressive resection against the long-term challenges of recurrence. Because of their parasellar location, often extending well beyond the sella, these tumors challenge vision and pituitary and hypothalamic function. New techniques are needed to improve outcomes in patients with these tumors while decreasing treatment morbidity. An endoscopic expanded endonasal approach (EEA) is one such technique that warrants understanding and evaluation. The authors explain the techniques and approach used for the endoscopic endonasal resection of suprasellar craniopharyngiomas and introduce a tumor classification scheme.

Methods

The techniques and approach used for the endoscopic, endonasal resection of suprasellar craniopharyngiomas is explained, including the introduction of a tumor classification scheme. This scheme is helpful for understanding both the appropriate expanded approach as well as relevant involved anatomy.

Results

The classification scheme divides tumors according to their suprasellar extension: Type I is preinfundibular; Type II is transinfundibular (extending into the stalk); Type III is retroinfundibular, extending behind the gland and stalk, and has 2 subdivisions (IIIa, extending into the third ventricle; and IIIb, extending into the interpeduncular cistern); and Type IV is isolated to the third ventricle and/or optic recess and is not accessible via an endonasal approach.

Conclusions

The endoscopic EEA requires a thorough understanding of both sinus and skull base anatomy. Moreover, in its application for craniopharyngiomas, an understanding of tumor growth and extension with respect to the optic chiasm and infundibulum is critical to safely approach the lesion via an endonasal route.