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Michael A. Lefkowitz, David R. Hinton, Martin H. Weiss, Steven L. Giannotta, and William T. Couldwell

The authors have retrospectively analyzed selected surgical and pathological observations made among a group of 20 patients harboring recurrent cranial base meningiomas in an attempt to reveal which factors may be important in predicting tumor recurrence. This cohort was compared with a group of 34 patients with cranial base meningiomas that underwent primary resection and in whom tumor recurrence has not been demonstrated over a median follow-up period of 33 months. Features analyzed included brain, cranial nerve, carotid artery, or muscle invasion as well as tumor cellularity, nucleolar prominence, cellular pleomorphism, and percentage of cells staining positive for the Ki-67 antigen. As expected, increased cellularity and tumor necrosis were relatively more prevalent in recurrent tumors. With regard to tumor type, atypical and anaplastic tumors were more common in the group of patients with recurrent tumor compared with the primary group (p < 0.02). As expected, increased cellularity was relatively more prominent in recurrent tumors. Invasion of muscle and bone (72%) was more frequently associated with recurrent tumors, suggesting that these characteristics may be important features of recurrent skull base meningiomas.

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Charles B. Stillerman, Thomas C. Chen, J. Diaz Day, William T. Couldwell, and Martin H. Weiss

A number of operative techniques have been described for the treatment of herniated thoracic discs. The transfacet pedicle-sparing approach allows for complete disc removal with limited spinal column disruption and soft-tissue dissection. Fifteen cadaveric spinal columns were used for evaluation of exposure, development of thoracic microdiscectomy instrumentation, and establishment of morphometric measurements. This approach was used to remove eight thoracic discs in six patients. Levels of herniation ranged from T-7 through T-11. Preoperatively, all patients had moderate to severe axial pain, and three (50%) of the six had radicular pain. Myelopathy was present in four (67%) of the six patients. Through a 4-cm opening, the ipsilateral paraspinal muscles were reflected, and a partial facetectomy was performed. The disc was then removed using specially designed microscopic instrumentation. Postoperatively, the radiculopathy resolved in all patients. Axial pain and myelopathy were completely resolved or significantly improved in all patients.

The minimal amount of bone resection and muscle dissection involved in the operation allows for: 1) decreased operative time and blood loss; 2) diminished perioperative pain; 3) shorter hospitalization time and faster return to premorbid activity; 4) avoidance of closed chest tube drainage; and 5) preservation of the integrity of the facet-pedicle complex, with potential for improvement in outcome related to axial pain. This technique appears best suited for the removal of all centrolateral discs, although it has been used successfully for treating a disc occupying nearly the entire ventral canal. The initial experience suggests that this approach may be used to safely remove appropriately selected thoracic disc herniations with good results.

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Christopher J. Aho, Charles Liu, Vladimir Zelman, William T. Couldwell, and Martin H. Weiss

Object. Microscopic Rathke cleft cysts are a common incidental autopsy finding, but some Rathke cleft cysts can become sufficiently large to cause visual impairment, hypothalamic—pituitary dysfunction, and headaches. In this study patients were evaluated pre- and postoperatively to ascertain the clinical significance of surgical intervention on endocrine and visual improvement. Factors correlated with cyst recurrence were also evaluated.

Methods. A retrospective analysis was conducted in 160 patients with Rathke cleft cysts who were treated between 1984 and 1995 and completed at least a 5-year follow-up period. Of these 160 patients, 118 initially exhibited symptoms of visual impairment or endocrine dysfunction, became symptomatic during the follow-up period, or were found to have cyst enlargement. These 118 patients underwent transsphenoidal surgery. Forty-two patients with incidental lesions that demonstrated no growth on magnetic resonance (MR) images were followed up without an operation.

Complete resection, as observed on MR images 3 months postoperatively, was obtained in 114 (97%) of 118 patients. Vision improved postoperatively in 57 (98%) of 58 patients. Hypogonadism improved in 11 (18%) of 62 patients, growth hormone deficiency resolved in 14 (18%) of 78 patients, and hypocortisolemia resolved in one (14%) of seven patients. Twenty-two patients (19%) began to exhibit symptoms of diabetes insipidus, which had not been present preoperatively. The total 5-year recurrence rate was 18% (21 of 118 patients), with 12 patients requiring a repeated operation. Surgical and pathological factors that were found to be statistically associated with recurrence were the use of a fat and/or fascial graft for closure (p < 0.01) and the presence of squamous metaplasia in the cyst wall (p < 0.01). The extent of resection of the cyst wall was not associated with an increased rate of recurrence. In 42 (69%) of 61 patients the incidental cysts did not progress on imaging studies or clinically.

Conclusions. This is the largest series of patients with symptomatic Rathke cleft cysts who received operative intervention and participated in the longest postoperative follow up reported in the literature. The high recurrence rate (18%) supports the theory that a relationship exists between a symptomatic Rathke cleft cyst and craniopharyngioma. Improvements in visual and endocrine dysfunction can be expected after surgical decompression of the optic apparatus and the hypothalamic—pituitary axis.

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Joseph C. T. Chen, Arun P. Amar, SooHo Choi, Peter Singer, William T. Couldwell, and Martin H. Weiss

Object. Transsphenoidal adenomectomy with resection of a defined pituitary adenoma has been the treatment of choice for CD for the last 30 years. Surgical resection, however, may not always result in long-term remission of CD. This is particularly important in light of the high risk of morbidity and mortality in patients in the unsuccessfully treated cushingoid state. As such, it is interesting to identify prognostic factors that may predict the likelihood of long-term remission.

Methods. The authors review their series of 174 patients who have undergone transsphenoidal procedures for CD over a period of 20 years with minimum follow-up periods of 5 years. Selection of these patients was based on clinical, imaging, and laboratory criteria that included serum cortisol levels, loss of diurnal variation in serum cortisol levels, urinary free cortisol concentration, and results of a dexamethasone suppression test, petrosal sinus sampling, and corticotroph-releasing hormone stimulation tests as indicated. All patients who met the biochemical criteria underwent transsphenoidal microsurgery.

The authors found an overall rate of remission of 74% at 5 years postoperatively. Patients in whom morning serum cortisol concentrations were lower than 3 µg/dl (83 nmol/L) on postoperative Day 3, following an overnight dexamethasone suppression test, had a 93% chance of remission at the 5-year follow-up examination. Patients with cortisol concentrations higher than this level uniformly failed to achieve long-term remission.

Conclusions. Transsphenoidal microsurgery is an effective means of control for patients with adrenocorticotrophic hormone—producing microadenomas. Clinical outcome correlated well with the size of the tumor, as measured on preoperative imaging studies, and with postoperative morning cortisol levels following an overnight dexamethasone suppression test. Postoperative cortisol levels can be used as a useful prognostic indicator of the likelihood of future recurrence following transsphenoidal adenomectomy in CD.

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Matthew S. Agam, Michelle A. Wedemeyer, Bozena Wrobel, Martin H. Weiss, John D. Carmichael, and Gabriel Zada

OBJECTIVE

Pituitary adenomas (PAs) are benign neoplasms that are frequently encountered during workup for endocrinopathy, headache, or visual loss. Transsphenoidal surgery remains the first-line approach for PA resection. The authors retrospectively assessed complication rates associated with transsphenoidal PA resection from an institutional database.

METHODS

A retrospective analysis of 1153 consecutive transsphenoidal pituitary adenoma resections performed at the Keck Hospital of USC between November 1992 and March 2017 was conducted. Microscopic transsphenoidal resection was performed in 85.3% of cases, and endoscopic transsphenoidal resection was performed in 14.7%. Analysis of perioperative complications and patient and tumor risk factors was conducted.

RESULTS

The overall median hospital stay was 3 days. There was 1 perioperative death (0.1%). Surgical complications included postoperative cerebrospinal fluid leak (2.6%), epistaxis (1.1%), postoperative hematoma (1.1%), meningitis (1.0%), cranial nerve paresis (0.8%), hydrocephalus (0.8%), vision loss (0.6%), stroke (0.3%), abdominal hematoma or infection (0.2%), carotid artery injury (0.1%), and vegetative state (0.2%). Perioperative medical complications included bacteremia/sepsis (0.5%), pneumonia (0.3%), myocardial infarction (0.3%), and deep venous thrombosis/pulmonary embolism (0.1%). Endocrine complications were the most frequent, including transient diabetes insipidus (4.3%), symptomatic hyponatremia (4.2%), new hypopituitarism (any axis) (3.6%), permanent diabetes insipidus (0.3%), and adrenal insufficiency (0.2%). There were no significant differences between microscopic and endoscopic approaches with regard to surgical complications (6.4% vs 8.8%, p = 0.247) or endocrine complications (11.4 vs 11.8%, p = 0.888). Risk factors for surgical complications included prior transsphenoidal surgery (11.4% vs 6.8%, p = 0.025), preoperative vision loss (10.3% vs 6.8%, p = 0.002), and presence of PA invasion on MRI (8.5% vs 4.4%, p = 0.007).

CONCLUSIONS

In this single tertiary center study assessing complications associated with transsphenoidal PA resection, the rate of death or major disability was 0.26%. Risk factors for complications included prior surgical treatment and PA invasion. No differences in complication rates between endoscopic and microscopic surgery were observed. When performed at experienced pituitary centers, transsphenoidal surgery for PAs may be performed with a high degree of safety.

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John S. Kuo, Cynthia Hawkins, James T. Rutka, and Martin H. Weiss

Object

The authors investigated the feasibility of using fat allografts (chemically treated to reduce the host immune response) for neurosurgical applications.

Methods

Subcutaneous fat specimens collected from New Zealand White rabbits were treated with DNAse I and sodium deoxycholate to reduce immunogenicity before subcutaneous, midscapular implantation in immunocompetent recipient rabbits. Allograft incorporation and the host-allograft response were examined at 1, 6, and 11 weeks by histopathological analysis. Control specimens of autograft and untreated fat allograft implants were examined for comparison.

Results

The host immune response was markedly reduced in the region around the chemically treated fat allografts when compared with untreated allografts, and was similar to the tolerant host response to autografts.

Conclusions

Based on their results, the authors suggest that fat allografts processed for reduced immunogenicity may be a convenient, viable alternative for neurosurgical applications.

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Steven M. Grunberg, Martin H. Weiss, Irving M. Spitz, Jamshid Ahmadi, Alfredo Sadun, Christy A. Russell, Lois Lucci, and Lani L. Stevenson

✓ The possibility that meningioma growth may be related to female sex hormone levels is suggested by several lines of evidence. Meningiomas are twice as common in women as in men, have been observed to wax and wane with pregnancy, and are positively associated with breast cancer. A physiological explanation for these phenomena is provided by the finding of steroid hormone receptors in meningiomas. However, unlike breast cancer, meningiomas are much more commonly positive for progesterone receptors than for estrogen receptors.

The authors initiated a study on long-term oral therapy of unresectable meningiomas with the antiprogesterone mifepristone (RU486). Fourteen patients received mifepristone in daily doses of 200 mg for periods ranging from 2 to 31+ months (≥ 6 months in 12 patients). Five patients have shown signs of objective response (reduced tumor measurement on computerized tomography scan or magnetic resonance image, or improved visual field examination). Three have also experienced subjective improvement (improved extraocular muscle function or relief from headache). The side effects of long-term mifepristone therapy have been mild. Fatigue was noted in 11 of the 14 patients. Other side effects included hot flashes in five patients, gynecomastia in three, partial alopecia in two, and cessation of menses in two. Long-term therapy with mifepristone is a new therapeutic option that may have efficacy in cases of unresectable benign meningioma.

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Michael L. J. Apuzzo, Martin H. Weiss, Viesturs Petersons, R. Baldwin Small, Theodore Kurze, and James S. Heiden

✓ This study was designed to define the effect of positive end expiratory pressure (PEEP) ventilation on intracranial pressure (ICP). In 25 patients with severe head trauma with and without associated pulmonary injury the following parameters were simultaneously monitored under mechanical ventilation with and without PEEP: ICP, arterial blood pressure, central venous pressure, arterial blood gases, and cardiac rate. In addition, the volume-pressure response (VPR) was evaluated in each patient to assess cerebral elastance. The results indicate a significant increase in ICP with the application of PEEP only in the 12 patients who manifested increased cerebral elastance by VPR. Half of this latter group manifested impairment of cerebral perfusion pressure to levels less than 60 mm Hg. Return to baseline ICP levels was observed with termination of PEEP. No significantly consistent changes in other parameters were noted.

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Steven M. Grunberg, Anna Marie Daniels, Helmut Muensch, John R. Daniels, Leslie Bernstein, Virginia Kortes, and Martin H. Weiss

✓ Several investigators have detected progesterone receptors in a high percentage of meningioma specimens and have noted progesterone receptors to be more common than estrogen receptors in these specimens. However, a functional significance of such hormone receptor positivity in control of meningioma growth has not been described. This paper describes a paired test of the estrogen and progesterone receptor assay as the biochemical assay and of the human tumor stem-cell clonogenic assay (HTSCCA) as the functional assay in 17 meningioma specimens. Only one (6%) of the 17 specimens was estrogen receptor-positive, while 11 (69%) of 16 specimens were progesterone receptor-positive. The HTSCCA revealed that only two (15%) of 13 specimens were sensitive to estradiol while five (31%) of 16 specimens were sensitive to progesterone. Comparison of progesterone results for the 15 specimens on which both hormone receptor assay and HTSCCA were performed revealed correlation in a majority of cases; four specimens were positive for both assays and five specimens were negative for both assays. No specimen that was negative for progesterone receptors was sensitive to progesterone by HTSCCA. These results suggest that the hormone receptor and sensitivity pattern of meningiomas may differ from that of breast cancer, and that progesterone addition or ablation may be a reasonable therapeutic approach for meningiomas.