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Edward F. Chang, Gabriel Zada, Sang Kim, Kathleen R. Lamborn, Alfredo Quinones-Hinojosa, J. Blake Tyrrell, Charles B. Wilson and Sandeep Kunwar

Object

Long-term outcomes following surgery for nonfunctional pituitary adenomas (NFPAs) are unclear. The role of adjuvant radiation therapy is therefore controversial because it is associated with higher tumor control but also carries known long-term morbidity. The authors' aim was to determine predictors of recurrence and overall survival and to define patient subgroups that may benefit from radiotherapy.

Methods

The authors performed a retrospective cohort analysis of 663 patients who underwent surgery between 1975 and 1995 for treatment of primary NFPAs. The main outcome measures were disease progression after surgery, defined by clinical and/or imaging criteria, and all-cause mortality.

Results

Over a median clinical follow-up of 8.4 years, there were 64 (9.7%) recurrences after treatment, with a median time to recurrence of 5.6 years. The 5-, 10-, and 15-year recurrence-free probabilities were 0.93, 0.87, and 0.81, respectively. Multivariate Cox proportional hazard regression analysis identified the following predictors as associated with increased recurrence: cavernous sinus invasion (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5–6.4; p < 0.001) and subtotal resection (STR) without radiotherapy (HR 3.6, 95% CI 1.4–14; p = 0.01). Using time-to-event estimates to adjust for differences in follow-up between groups, radiotherapy was found to reduce tumor recurrence in only those patients who received an STR (p < 0.001, log-rank test) but not gross-total resection (GTR; p = 0.63, log-rank test). Median follow-up for overall survival was 14.0 years. The 5-, 10-, 15- and 20-year overall survival estimates were 0.91, 0.81, 0.69, and 0.55, respectively. Within the study cohort and in age- and sex-adjusted comparison with the general US population, increased relative mortality was observed in patients who underwent radiotherapy or STR.

Conclusions

Cavernous sinus invasion is an important prognostic variable for long-term control of NFPAs. Radiotherapy results in long-term tumor control for patients who undergo STR but does not affect recurrence rates and may increase the risk of death after GTR. Given the risks associated with radiotherapy, there is no role for its routine application in patients who have undergone GTR of their NFPA. In all patients, long-term monitoring is required.

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Nader Sanai, Alfredo Quinones-Hinojosa, Nalin M. Gupta, Victor Perry, Peter P. Sun, Charles B. Wilson and Michael T. Lawton

Object

Longer life expectancies and differences in the underlying disease in children with aneurysms raise important issues concerning the choice of microsurgical or endovascular therapy. The authors reviewed their experience at one institution regarding patients treated between 1977 and 2003, focusing on the issue of treatment durability.

Methods

Forty-three aneurysms in 32 pediatric patients were identified. The patients ranged in age from 2 months to 18 years (mean 11.7 years). Only seven patients (22%) presented with subarachnoid hemorrhage, and in nine patients (28%) significant medical comorbidities were present. Aneurysm locations included the internal carotid artery (13 lesions), middle cerebral artery (11 lesions), and the basilar artery/vertebrobasilar junction (six lesions). Of the 43 lesions, 17 (40%) were giant aneurysms and 22 (51%) exhibited fusiform/dolichoectatic morphological features. Thirteen patients underwent microsurgery, 16 endovascular treatment, and three observation. Complete aneurysm obliteration rates were 94 and 82% in the microsurgical and endovascular groups, respectively. There were no deaths in either group, and neurological morbidity rates were comparable. Over time, 14% of endovascularly treated aneurysms recurred, and in 19% of these patients de novo aneurysms developed (mean follow-up duration 5.7 years). In contrast, there were no recurrences in the microsurgically treated aneurysms and only one de novo aneurysm (6%).

Conclusions

Both microsurgical and endovascular therapies can be conducted safely to treat pediatric aneurysms. Microsurgery may be more efficacious in completely eliminating the aneurysm and its effects more durable over the extended lifetime of these patients. Parental biases toward nonoperative therapy should be thoroughly addressed before ultimately selecting a treatment strategy.

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G. Edward Vates, Mitchel S. Berger and Charles B. Wilson

Object. Pituitary abscess is a rare but serious intrasellar infection. To better determine the salient signs and symptoms that help in making the diagnosis, and to determine the most appropriate treatment, the authors reviewed their experience in a series of 24 patients treated at the University of California at San Francisco.

Methods. Nine of the patients were female and 15 were male, and their mean age was 41.2 years (range 12–71 years). Surprisingly, most patients in our series presented with complaints and physical findings consistent with a pituitary mass, but rarely with evidence of a serious infection. Headache, endocrine abnormalities, and visual changes were the most common clinical indicators; fever, peripheral leukocytosis, and meningismus were present in 33% or fewer of the patients. Imaging tests demonstrated a pituitary mass in all patients, but the features evident on computerized tomography and magnetic resonance studies did not distinguish pituitary abscesses from other, more common intrasellar lesions. Because of the ambiguous clinical features and imaging findings, most abscesses were not diagnosed before treatment; rather, the diagnosis was made during surgical exploration of the sella turcica, when the surgeon encountered a cystic mass containing pus. There were only two deaths in this series (8.3%). Patients presenting with headache and visual changes noted improvement in almost all cases; patients with endocrine dysfunction generally did not recover normal pituitary function, but were easily treated with hormone replacement therapy.

Conclusions. Antibiotic therapy is suggested for patients who have symptoms of sepsis, or for patients in whom specific organisms are identified from cultures obtained during surgery. The transsphenoidal approach is recommended over open craniotomy for surgical drainage.

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Charles S. Cobbs and Charles B. Wilson

✓ The authors present a rare entity, an intrasellar cavernous hemangioma that on neuroimages mimicked a nonfunctioning pituitary macroadenoma in a patient with a known orbital hemangioma. Such lesions can grow extraaxially within the dural sinuses, particularly the cavernous sinus, and present like tumors. A better understanding of the neuroimaging, clinical, and anatomical features of these lesions may prevent difficulties in management.

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Andrew K. Metzger, Gayatry Mohapatra, Yuriko A. Minn, Andrew W. Bollen, Kathleen Lamborn, Frederic M. Waldman, Charles B. Wilson and Burt G. Feuerstein

Object. This study was conducted to determine whether comparative genomic hybridization (CGH) is a more sensitive method for detecting genetic aberrations than other tests currently in use.

Methods. The authors used CGH to examine 40 primary and 13 recurrent adenomas obtained from 52 patients for loss and gain of genetic material. Copy number aberrations (CNAs) were detected in 25 (48%) of the 52 patients studied. The chromosomes affected were, in order of decreasing frequency, 11, 7, X, 1, 8, 13, 5, 14, 2, 6, 9, 10, 12, 3, 18, 21, 4, 16, 15, 19, 22, and Y. Endocrinologically active adenomas were more likely to contain (p = 0.009) and had a greater number (p = 0.003) of CNAs. Of 26 adenomas with CNAs, 18 showed multiple aberrations involving entire chromosomes or chromosome arms. The most frequent CNA involving a chromosome subregion, which was present in four (8%) of 53 adenomas, was the loss of all chromosome 11 material except for a preserved common segment containing 11q13. Immunoperoxidase staining did not detect cyclin D1 expression in those four cases, making cyclin D1 an unlikely target of this rearrangement.

Conclusions. These findings indicate that genetic abnormalities are present in pituitary adenomas at a higher rate than previously reported, are associated with endocrinological activity, and often involve several chromosomes. Rearrangement at 11q13 may inactivate a tumor suppressor gene or activate an oncogene that is important in the initiation or progression of sporadic pituitary adenomas.

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Fred G. Barker II, Michael D. Prados, Susan M. Chang, Philip H. Gutin, Kathleen R. Lamborn, David A. Larson, Mary K. Malec, Michael W. McDermott, Penny K. Sneed, William M. Wara and Charles B. Wilson

✓ To determine the value of radiographically assessed response to radiation therapy as a predictor of survival in patients with glioblastoma multiforme (GBM), the authors studied a cohort of 301 patients who were initially treated according to uniform clinical protocols. All patients had newly diagnosed supratentorial GBM and underwent the maximum safe resection followed by external-beam radiation treatment (60 Gy in standard daily fractions or 70.4 Gy in twice-daily fractions of 160 cGy). The radiation response and survival rates were assessable in 222 patients. The extent of resection and the immediate response to radiation therapy were highly correlated with survival, both in a univariate analysis and after correction for age and Karnofsky performance scale (KPS) score in a multivariate Cox model (p < 0.001 for radiation response and p = 0.04 for extent of resection). A subgroup analysis suggested that neuroimaging obtained within 3 days after surgery served as a better baseline for assessment of radiation response than images obtained later. Imaging obtained within 3 days after completion of a course of radiation therapy also provided valid radiation response scores. The impact of the radiographically assessed radiation response on survival time was comparable to that of age or KPS score. This information is easily obtained early in the course of the disease, may be of value for individual patients, and may also have implications for the design and analysis of trials of adjuvant therapy for GBM, including volume-dependent therapies such as radiosurgery or brachytherapy.

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Charles B. Wilson

✓ The author reviews the molecular genetics, pathology, and cell kinetics of meningiomas and the role that regional multiplicity in the dura mater may play in their recurrence. Malignant and radiation-induced meningiomas are discussed, with summaries of series of 60 patients with frankly malignant lesions treated over a period of 22 years at the University of California, San Francisco, and of 10 patients with meningiomas induced by high-dose radiation therapy. Reviewing a 23-year series of 140 patients with subtotally removed meningiomas who were treated postoperatively with radiation, the author recommends that, with meticulous technique, irradiation is effective in preventing the regrowth of subtotally removed benign meningiomas and of all malignant meningiomas. Adoption of both the microscopical cytological grading system proposed by Jääskeläinen's group in Helsinki and the classification of operations proposed by Donald Simpson is also recommended. Wide removal of dura adjacent to meningioma reduces the risk of recurrence, and determination of the bromodeoxyuridine labeling index provides a valid basis for planning treatment and follow-up evaluations. Increased awareness is necessary for early recognition of radiation-induced meningiomas in patients at risk for developing such tumors. For meningiomas in such sites as the parasellar region and the posterior fossa, conservative removal of tumor followed by irradiation is advocated in preference to a radical operation that may cause neurological injury without being curative.