Use of day 1 early morning cortisol to predict the need for glucocorticoid replacement after pituitary surgery.

BACKGROUND: Assessment of adrenal reserve in patients who have undergone pituitary surgery is crucial. However, there is no clear consensus with regards to the type and timing of the test that should be used in the immediate post-operative period. Recently, there has been increased interest in measuring post-operative cortisol levels. We present our data utilising day 1 post-operative early morning cortisol as a tool to assess adrenal reserve in steroid-naive patients. METHODS: A retrospective analysis of endoscopic pituitary surgery undertaken over a 2-year period. 82 patients underwent 84 surgeries in total. Patients who were already on glucocorticoids pre-operatively and patients with Cushing's disease, pituitary apoplexy and those without follow-up data were excluded, leaving a study group of 44 patients with 45 operations. A 9am day 1 post-operative cortisol value of > 400 nmol/L was taken as an indicator of adequate adrenal reserve. All the patients were reassessed at 6 weeks with a standard short synacthen test (SST) using 250 micrograms of intravenous synacthen. RESULTS: 22 out of 45 patients had a cortisol value of > 400 nmol/L on day 1 post-operatively and were discharged without glucocorticoid supplementation. Of these, only 2 patients subsequently failed the SST when reassessed at 6-8 weeks. The remaining 23 patients had a cortisol value of < 400 nmol/L on day 1 post-operatively and were discharged on hydrocortisone 10 mg twice daily. At 6-8 weeks, nine continued to show suboptimal stimulated cortisol levels whereas the remaining fourteen patients showed adequate adrenal reserve. The 9 am cortisol value had high specificity (81.8%) and positive predictive value (90.9%) for integrity of the HPA axis. Sensitivity was 58.8% and negative predictive value was 39.1%. CONCLUSION: A day 1 post-operative early morning cortisol is a useful tool to predict adrenal reserve post-pituitary surgery, enabling clinicians to avoid unnecessary blanket glucocorticoid replacement.

Gamma knife radiosurgery for the treatment of cystic cerebral metastases.

PURPOSE: To assess the role of Gamma Knife radiosurgery (GKRS) in the treatment of nonsurgical cystic brain metastasis, and to determine predictors of response to GKRS. METHODS: We reviewed a prospectively maintained database of brain metastases patients treated at our institution between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response. RESULTS: A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component. CONCLUSIONS: This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates.

Stereotactic radiosurgery for the treatment of melanoma and renal cell carcinoma brain metastases.

Renal cell carcinoma (RCC) and melanoma brain metastases have traditionally been considered radioresistant lesions when treated with conventional radiotherapeutic modalities. Radiosurgery provides high-dose radiation to a defined target volume with steep fall off in dose at lesion margins. Recent evidence suggests that stereotactic radiosurgery (SRS) is effective in improving local control and overall survival for a number of tumor subtypes including RCC and melanoma brain metastases. The purpose of this study was to compare the response rate to SRS between RCC and melanoma patients and to identify predictors of response to SRS for these 2 specific subtypes of brain metastases. We retrospectively reviewed a prospectively maintained database of all brain metastases treated with Gamma Knife SRS at the University Health Network (Toronto, Ontario) between October 2007 and June 2010, studying RCC and melanoma patients. Demographics, treatment history and dosimetry data were collected; and MRIs were reviewed for treatment response. Log rank, Cox proportional hazard ratio and Kaplan-Meier survival analysis using SPSS were performed. A total of 103 brain metastases patients (41 RCC; 62 melanoma) were included in the study. The median age, Karnofsky performance status score and Eastern Cooperative Oncology Group performance score was 52 years (range 27-81), 90 (range 70-100) and 1 (range 0-2), respectively. Thirty-four lesions received adjuvant chemotherapy and 56 received pre-SRS whole brain radiation therapy. The median follow-up, prescription dose, Radiation Therapy Oncology Group conformity index, target volume and number of shots was 6 months (range 1-41 months), 21 Gy (range 15-25 Gy), 1.93 (range 1.04-9.76), 0.4 cm3 (range 0.005-13.36 cm3) and 2 (range 1-22), respectively. Smaller tumor volume (P=0.007) and RCC pathology (P=0.04) were found to be positive predictors of response. Actuarial local control rate for RCC and melanoma combined was 89% at 6 months, 84% at 12 months, 76% at 18 months and 61% at 24 months. Local control at 12 months was 91 and 75% for RCC and melanoma, respectively. SRS is a valuable treatment option for local control of RCC and melanoma brain metastases. Smaller tumor volume and RCC pathology, predictors of response, suggest distinct differences in tumor biology and the extent of radioresponse between RCC and melanoma.

Current standards in the management of cerebral metastases.

The last 30 years have seen major changes in attitude toward patients with cerebral metastases. This paper aims to outline the major landmarks in this transition and the therapeutic strategies currently used. The controversies surrounding control of brain disease are discussed, and two emerging management trends are reviewed: tumor bed radiosurgery and salvage radiation.

Hemangiopericytoma: long-term outcome revisited. Clinical article.

OBJECT: Hemangiopericytomas are rare tumors that behave aggressively with a high rate of local recurrence and distant metastases. With the aim of determining the outcome and response to various treatment modalities, a series of 39 patients who underwent microsurgical resection for primary meningeal hemangiopericytoma over a 24-year period is presented. METHODS: Patients with hemangiopericytoma were identified from histopathology records and their medical records were analyzed retrospectively by 2 independent reviewers to collect data on surgical treatment, adjuvant therapy, postoperative course, local or distant recurrence, and follow-up. RESULTS: Of the 39 patients, 19 were male and 20 were female. Mean patient age was 44.1 years. Thirty-four tumors were intracranial and 5 were spinal. The mean follow-up period was 123 months. Twenty-eight patients developed local recurrence. The recurrence rate at 1, 5, and 15 years was 3.5%, 46%, and 92%, respectively. Extraneural metastasis occurred in 8 patients (26%) at an average of 123 months after initial surgery. Recurrences and metastases were treated by surgical excision, external beam radiation therapy (EBRT), chemotherapy, and/or stereotactic radiosurgery. Adjuvant EBRT following initial surgery was found to extend the disease-free interval from 154 months to 254 months, although it did not prevent the development of metastasis. In those patients with EBRT and complete resection, the mean recurrence-free interval was found to be 126.3 months longer (p = 0.04) and overall survival 126 months longer than without EBRT. Furthermore, adjusting for resection, patients undergoing EBRT had 0.33 times increased risk of recurrence compared with those who did not (p = 0.03). A majority of patients remained able to live independently despite revision surgery for recurrence. CONCLUSIONS: The mean follow-up of this patient series represents the longest follow-up duration published to date and demonstrates extended survival in a significant number of patients with hemangiopericytoma. Gross-total resection followed by adjuvant EBRT provides patients with the highest probability of an increased recurrence-free interval and overall survival. Prolonged survival justifies long-term follow-up and aggressive treatment of initial, recurrent, and metastatic disease.

Stability of ruptured intracranial aneurysms treated with detachable coils: is delayed follow-up angiography warranted?

The optimal strategy for monitoring the stability of ruptured intracranial aneurysms following coil embolisation is unclear. The value of delayed follow-up angiography in detecting new recurrences or progression of residual lesions visualised on earlier angiographic studies was determined in the light of the increasing use of non-invasive imaging techniques such as time of flight magnetic resonance angiography (TOF-MRA) for the evaluation of intracranial aneurysm occlusion. Ninety-seven patients with 105 ruptured aneurysms treated with detachable coils in 2005 and 2006 were included. The presence of a residual neck or aneurysm was assessed on catheter angiograms performed at 6 months and 2 years using the Raymond criteria (Class I = completely occluded, class II = small residual neck, class III = aneurysm sac filling). At 6-month follow-up, 32% of class I aneurysms progressed to class II and 6% of these aneurysms required re-treatment. A further 2-year angiogram was obtained in 59 patients with 65 aneurysms. Ninety-six per cent of class I, 100% of the class II and class III aneurysms remained unchanged at 2 years compared to 6 months. In our series, most recurrences were apparent at 6-month follow-up. The vast majority of coiled ruptured aneurysms that were class I or II at 6 months remained stable at 2-year follow-up. In the absence of a residual lesion in the early angiographic study, a further delayed catheter angiogram may not be warranted. The use of non-invasive strategies such as TOF-MRA should be considered.

Increase in apparent diffusion coefficient in normal appearing white matter following human traumatic brain injury correlates with injury severity.

Following diffuse traumatic brain injury, there may be persistent functional or psychological deficits despite the presence of normal conventional MR images. Previous experimental animal and human studies have shown diffusion abnormalities following focal brain injury. Our aim was to quantify changes in apparent diffusion coefficient (ADC) and absolute relaxation times of normal appearing white matter (NAWM) in humans following traumatic brain injury. Twenty-three patients admitted with a diagnosis of head injury (nine mild, eight moderate, and six severe) were scanned an average of 7.6 days after injury using a quantitative echo planar imaging acquisition to obtain co-registered T1, T2, and ADC parametric maps. Mean NAWM values were compared with a control group (n = 13). The patient group showed a small but significant increase in ADC in NAWM, with no significant change in T1 or T2 relaxation times. There was a correlation between injury severity and increasing ADC (p = 0.03) but no correlation with either T1 or T2, suggesting that ADC is a sensitive and independent marker of diffuse white matter tissue damage following traumatic insult. None of the patients had a reduced ADC, making ischaemia unlikely in this cohort. Pathophysiological mechanisms that may explain diffusely raised ADC include vasogenic edema, chronic ischemic phenomena, or changes in tissue cytoarchitecture or neurofilament alignment.

Primary low-grade B-cell lymphoma of mucosa-associated lymphoid tissue of the dura mimicking the presentation of an acute subdural hematoma. Case report and review of the literature.

The authors present the case of a 64-year-old woman who experienced a left hemiparesis. An initial diagnosis of subdural hematoma was made based on results of computerized tomography scanning. Subsequent magnetic resonance imaging indicated an extraaxial meningioma. Histological findings confirmed an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). The authors outline the natural history of central nervous system lymphomas and of MALT lymphomas in other tissues. They review seven previously reported cases and emphasize the importance of recognizing these tumors as a distinct clinicopathological entity.