John K. Hald

Preoperative Octreotide Treatment in Newly Diagnosed Acromegalic Patients with Macroadenomas Increases Cure Short-Term Postoperative Rates: A Prospective, Randomized Trial

CONTEXT Surgery is the primary treatment of acromegaly. However, it often fails to cure the patient. New strategies that improve surgical outcome are needed. OBJECTIVE Our objective was to investigate whether 6-month preoperative treatment with octreotide improves the surgical outcome in newly diagnosed acromegalic patients. PATIENTS During a 5-yr period (1999-2004), all newly diagnosed acromegalic patients between 18 and 80 yr of age in Norway were screened and invited to participate in the study. A total of 62 patients was included in the Preoperative Octreotide Treatment of Acromegaly study. RESEARCH DESIGN AND METHODS After a baseline evaluation, patients were randomized directly to transsphenoidal surgery (n = 30) or pretreatment with octreotide (n = 32) 20 mg im every 28th day for 6 months before transsphenoidal surgery. Cure was evaluated 3 months postoperatively primarily by IGF-I levels. RESULTS According to the IGF-I criteria, 14 of 31 (45%) pretreated patients vs. seven of 30 (23%) patients with direct surgery were cured by surgery (P = 0.11). In patients with microadenomas (< or = 10 mm), one of five (20%) pretreated vs. three of five (60%) with direct surgery were cured (P = 0.52). In patients with macroadenomas, 13 of 26 (50%) pretreated vs. four of 25 (16%) with direct surgery were cured (P = 0.017). CONCLUSIONS Six-month preoperative octreotide treatment might improve surgical cure rate in newly diagnosed acromegalic patients with macroadenomas. These results have to be confirmed in future studies.

Glioma grading by using histogram analysis of blood volume heterogeneity from MR-derived cerebral blood volume maps.

PURPOSE To retrospectively compare the diagnostic accuracy of an alternative method used to grade gliomas that is based on histogram analysis of normalized cerebral blood volume (CBV) values from the entire tumor volume (obtained with the histogram method) with that of the hot-spot method, with histologic analysis as the reference standard. MATERIALS AND METHODS The medical ethics committee approved this study, and all patients provided informed consent. Fifty-three patients (24 female, 29 male; mean age, 48 years; age range, 14-76 years) with histologically confirmed gliomas were examined with dynamic contrast material-enhanced 1.5-T magnetic resonance (MR) imaging. CBV maps were created and normalized to unaffected white matter (normalized CBV maps). Four neuroradiologists independently measured the distribution of whole-tumor normalized CBVs and analyzed this distribution by classifying the values into area-normalized bins. Glioma grading was performed by assessing the normalized peak height of the histogram distributions. Logistic regression analysis and interobserver agreement were used to compare the proposed method with a hot-spot method in which only the maximum normalized CBV was used. RESULTS For the histogram method, diagnostic accuracy was independent of the observer. Interobserver agreement was almost perfect for the histogram method (kappa = 0.923) and moderate for the hot-spot method (kappa = 0.559). For all observers, sensitivity was higher with the histogram method (90%) than with the hot-spot method (55%-76%). CONCLUSION Glioma grading based on histogram analysis of normalized CBV heterogeneity is an alternative to the established hot-spot method, as it offers increased diagnostic accuracy and interobserver agreement.

The clinical response to somatostatin analogues in acromegaly correlates to the somatostatin receptor subtype 2a protein expression of the adenoma

Objective  Reduced expression of the somatostatin receptor subtype 2 (SSTR2) has been suggested as an explanation for the poor response to octreotide in acromegaly, but studies correlating levels of SSTR2 mRNA to octreotide efficacy have been contradictory. Some studies have found better responses to somatostatin analogues in G‐protein α subunit (Gsα) mutation (gsp oncogene)‐positive adenomas. The aim of this study was to determine adenoma SSTR2a protein expression and gsp status in a large group of patients with acromegaly, and relate this to the clinical effect of octreotide.

The expression of E-cadherin in somatotroph pituitary adenomas is related to tumor size, invasiveness, and somatostatin analog response.

CONTEXT Appropriate cell-to-cell adhesion is fundamental for the epithelial phenotype of pituitary cells. Loss of the adhesion protein E-cadherin has been associated with invasiveness, metastasis, and poor prognosis in cancers of epithelial origin. In somatotroph adenomas, a variable and reduced expression of E-cadherin has been demonstrated. In addition, nuclear translocation of E-cadherin was found to correlate with pituitary tumor invasion. OBJECTIVE The objective was to examine the protein expression of E-cadherin in somatotroph pituitary adenomas in relation to adenoma size, invasiveness, and somatostatin analog (SMS) efficacy. PATIENTS AND METHODS Eighty-three patients were included, and 29 were treated preoperatively with SMS. Adenoma E-cadherin protein expression was analyzed by Western blot (61 patients) and immunohistochemistry (IHC) (80 patients) with antibodies directed against both extracellular and intracellular domains (IHC). The acute (direct surgery group) and long-term (preoperatively treated group) SMS responses were evaluated. Baseline tumor volume and invasiveness were measured on magnetic resonance imaging scans. RESULTS Membranous E-cadherin was lost in several adenomas. Nine of these were nuclear E-cadherin positive. The E-cadherin protein expression correlated negatively to tumor size and positively to acute SMS response. Low E-cadherin levels (preoperatively treated group only) and loss of membranous E-cadherin correlated to tumor invasiveness. The E-cadherin level correlated positively to tumor reduction after SMS treatment, and adenomas with nuclear E-cadherin staining had lower IGF-I reduction and tumor shrinkage. Preoperatively treated adenomas had reduced E-cadherin protein levels, but the IHC expression was unaltered. CONCLUSION Reduced E-cadherin expression may correlate to a dedifferentiated phenotype in the somatotroph pituitary adenomas.

Histogram Analysis of MR Imaging–Derived Cerebral Blood Volume Maps: Combined Glioma Grading and Identification of Low-Grade Oligodendroglial Subtypes

BACKGROUND AND PURPOSE: Inclusion of oligodendroglial tumors may confound the utility of MR based glioma grading. Our aim was, first, to assess retrospectively whether a histogram-analysis method of MR perfusion images may both grade gliomas and differentiate between low-grade oligodendroglial tumors with or without loss of heterozygosity (LOH) on 1p/19q and, second, to assess retrospectively whether low-grade oligodendroglial subtypes can be identified in a population of patients with high-grade and low-grade astrocytic and oligodendroglial tumors. MATERIALS AND METHODS: Fifty-two patients (23 women, 29 men; mean age, 52 years; range, 19–78 years) with histologically confirmed gliomas were imaged by using dynamic susceptibility contrast MR imaging at 1.5T. Relative cerebral blood volume (rCBV) maps were created, and 4 neuroradiologists defined the glioma volumes independently. Averaged over the 4 observers, a histogram-analysis method was used to assess the normalized histogram peak height of the glioma rCBV distributions. RESULTS: Of the 52 patients, 22 had oligodendroglial tumors. The histogram method was able to differentiate high-grade gliomas (HGGs) from low-grade gliomas (LGGs) (Mann-Whitney U test, P < .001) and to identify low-grade oligodendroglial subtypes (P = .009). The corresponding intraclass correlation coefficients were 0.902 and 0.801, respectively. The sensitivity and specificity in terms of differentiating low-grade oligodendroglial tumors without LOH on 1p/19q from the other tumors was 100% (6/6) and 91% (42/46), respectively. CONCLUSION: With histology as a reference, our results suggest that histogram analysis of MR imaging–derived rCBV maps can differentiate HGGs from LGGs as well as low-grade oligodendroglial subtypes with high interobserver agreement. Also, the method was able to identify low-grade oligodendroglial tumors without LOH on 1p/19q in a population of patients with astrocytic and oligodendroglial tumors.

CTA IN PATIENTS WITH ACUTE SUBARACHNOID HAEMORRHAGE: A comparative study with selective, digital angiography and blinded, independent review

Purpose: Minimal- or non-invasive methods replacing intra-arterial digital subtraction angiography (IA-DSA) would be of great importance in patients suffering from acute subarachnoid haemorrhage (SAH). The aims of this study were to compare CTA with IA-DSA in patients with acute SAH, to compare CTA interpretations with those of blinded, independent reviewers and to evaluate improvement in CTA diagnostics after 1 year of experience with CTA. Material and Method: During 2 years 162 patients with SAH underwent CTA as well as IA-DSA. Independent blinded review of 77 patients was performed for 1 year. Results: Totally 144 aneurysms were demonstrated in 119 patients at IA-DSA, while 43 patients had normal intracranial arteries. Initially 131 aneurysms were detected at CTA while 2 normal, tortuous arteries were misinterpreted as aneurysms, giving a sensitivity of 91% and a specificity of 95%. At independent blinded review the observer agreement was 87% and the kappa value 0.68. Conclusion: CTA in SAH is of great value in demonstrating vascular anatomy and the exact size of an aneurysm. However, IA-DSA is still needed for diagnostic evaluation in aneurysms smaller than 5 mm in diameter, especially in those located near bony structures.

Embolization of intracranial arteriovenous malformations and fistulas with polyvinyl alcohol particles and platinum fibre coils

SummaryIn order to reduce the recanalization rate of arteriovenous malformations and multiple dural arteriovenous fistulas, embolization was carried out with polyvinyl alcohol (PVA) particles combined with platinum fibre coils in 20 patients. The malformation was occluded more effectively than by PVA alone. Distal deposition of the emboli was obtained by improved steerable catheters (Tracker-18-unibody) and guidewires. The complication rate was lower than usually reported from studies using glue as embolic agent. It was concluded that the combination of PVA and fibre coils enhances the safety and effectiveness of embolization therapy and reduces the frequency of recanalization of intracranial AVMs.

Long-term outcome after resection of intraspinal ependymomas: report of 86 consecutive cases.

BACKGROUND: Objective: To evaluate progression-free survival, overall survival (OS) and long-term clinical outcome in a consecutive series of 86 patients with intraspinal ependymomas. METHODS: Medical charts were retrospectively reviewed. Surviving patients voluntarily participated in a clinical history and physical examination that focused on neurological function and current tumor status. RESULTS: Follow-up data are nearly 100% complete; mean follow-up time was 82 months. Eighty-five patients (99%) had surgery as a first-line treatment; 14 (17%) of these patients received adjuvant radiotherapy. Of the 85 patients who underwent primary surgery, gross total resection was performed in 60 patients (71%) and subtotal resection in 25 patients (29%). Ten-year progression-free survival rate was 75%; 5-year OS, 97%; and 10-year OS, 91%. Reduced preoperative neurological function and older age at diagnosis were significantly associated with increased risk of death. At follow-up, spontaneous regression of residual tumor after primary surgery may have occurred in 7 of 19 patients (37%). More than 75% of patients had neurological function compatible with an independent life at follow-up. Good preoperative neurological function was significantly associated with favorable outcome. It was not possible to evaluate the effect of radiotherapy on progression-free survival and OS. CONCLUSION: Gross total resection remains the optimal treatment for patients with spinal ependymoma. Patients should be monitored with a clinical examination and magnetic resonance imaging at regular intervals up to 10 years after surgery.

Automatic glioma characterization from dynamic susceptibility contrast imaging: Brain tumor segmentation using knowledge‐based fuzzy clustering

To assess whether glioma volumes from knowledge‐based fuzzy c‐means (FCM) clustering of multiple MR image classes can provide similar diagnostic efficacy values as manually defined tumor volumes when characterizing gliomas from dynamic susceptibility contrast (DSC) imaging.

Spindle cell oncocytoma of the adenohypophysis: report of a case with marked cellular atypia and recurrence despite adjuvant treatment.

Spindle cell oncocytoma (SCO) of the adenohypophysis is a recently defined pituitary tumor mimicking a non-functioning macroadenoma and composed of mitochondrion rich tumor cells, positive for S-100, vimentin, epithelial membrane antigen and galectin-3 but lacking cytokeratins, pituitary hormones, and neuroendocrine markers. Derivation from pituitary folliculostellate cells (FSCs) has been suggested based upon immunohistochemical and ultrastructural characteristics shared by SCO and FSCs. 10 cases of SCO have been reported to date; of these, 8 underwent a benign clinical course and 2 recurred. We report a case of SCO with typical histologic and immunohistochemical features in addition to marked cellular pleomorphism and nuclear atypia. It showed slow regrowth over a 30-month period of follow-up despite combined surgical and radiotherapy. Despite the benign course of most reported cases, additional experience with longer follow-up are needed to assess clinical, histopathologic, and proliferative indices and their relevance to optimal therapy for this rare pituitary tumor.