Biomedical subjects

S Wolfsberger

Publications and source records attributed to S Wolfsberger.

9 recordsLinked to original sources

PubMed2005

Identification of DLK1 variants in pituitary- and neuroendocrine tumors.

In a gene chip analysis of common pituitary tumor types, one of the genes with the most impressive tissue-specific expression regulation was delta-like 1 (DLK1), which was strongly expressed in GH-secreting (GH-S) pituitary tumors. In addition to pituitary adenomas, various endocrine tumors were subjected to real-time-quantitative PCR revealing high expression of DLK1 in normal pituitary tissue, in GH-S-, in one prolactin-secreting pituitary adenoma and in pheochromocytomas. Additionally, three DLK1 gene-derived subvariants were identified. The first, lacking 204 bp--coding for epidermal growth factor-like domain 6 and parts of the juxtamembrane region--was named Secredeltin. In the other two splice variants (named Brevideltin and Brevideltinin), a stop codon is introduced due to a frame-shift, leading to truncated proteins of 204 and 213 aas, respectively.

Alternative Splicing↗

PubMed2005

The value of high-field MRI (3T) in the assessment of sellar lesions.

The aim of this study was the evaluation of the normal sellar anatomy in vitro and in vivo with high-field MRI and its application in the diagnosis of sellar pathologies in comparison to standard MRI. All high-field MR images were obtained using a 3T Bruker Medspec 30/80 Scanner with a head birdcage transmit/receive coil and an actively shielded gradient system with a maximum gradient strength of 45 mT/m. Firstly an in vitro study of the sella turcica was performed to depict normal pituitary and sellar anatomy at high field. After a pilot-study this sequence-protocol was established: A RARE sequence (TR/TE = 7790/19 ms; matrix size, 512 x 512; RARE factor = 8, FOV, 200 mm) was used for T2-weighted coronal, axial and sagittal images. A 3D gradient echo sequence with magnetization-preparation (MP-RAGE, TR/TE/TI = 33.5/7.6/800 ms, matrix size, 512 x 512; FOV, 200 mm, effective slice thickness, 1.88 mm; 3 averages) was used for acquisition of T1-weighted pre- and post-contrast images. Between January 2002 and March 200458 patients were enrolled in this study. Seven patients were examined for suspected microadenoma and in 51 patients 3T MRI was used to obtain additional information about the sellar lesion already known to be present from standard MRI. In 21 cases the accuracy of the imaging findings was assessed afterwards by comparison with intraoperative findings. The infiltration of the medial cavernous sinus wall was suspected on standard MRI on 15 sides (47%), on high-field MRI on 9 sides (28%) and could be verified by intraoperative findings on 6 sides (19%). Accordingly, sensitivity to infiltration was 83% for 3T and 67% for standard MRI. Specificity was 84% for 3T and 58% for standard MRI. Moreover, high-field MRI revealed microadenomas in 7 patients with a median diameter of 4mm (range 2-9 mm). The segments of the cranial nerves were seen as mean 4 hypointense spots (range 2-5 spots) on high-field MRI in contrast to 3 spots (range 0-4 spots) on standard MRI. This difference was considerably significant (P < 0.001, Wilcoxon rank sum test). The histopathological results revealed pituitary adenoma in 16 patients and non-adenomatous sellar pathologies such as Rathke's cleft cyst, sarcoidosis, meningeoma and metastasis in 5 patients. High-field MRI is superior to standard MRI for the prediction of invasion of adjacent structures in patients with pituitary adenomas and improves surgical planning of sellar lesion.

Adenoma↗

PubMed2004

Multiregional sampling reveals a homogenous distribution of Ki-67 proliferation rate in pituitary adenomas.

Ki-67 antigen is used as a marker of proliferative activity that is linked to growth rate, invasiveness and prognosis of pituitary adenomas. So far the distribution of Ki-67 index within an individual adenoma has not been investigated. If Ki-67 antigen expression differs significantly within an individual pituitary adenoma, a sampling error may result when assessing small fragments of adenoma tissue. Such a potential error would diminish the value of Ki-67 as a tool for postoperative patient management considerations. The aim of the present study was to assess Ki-67 proliferation rates in different regions of pituitary adenomas and to statistically analyse these data for potential regional differences within each tumor. Ki-67 proliferation index was assessed in smear preparations of 100 specimens of 26 consecutive patients operated on for pituitary adenoma in the Department of Neurosurgery, Medical University Vienna. Depending on the size and extent of the tumor, a mean of 4 tissue samples (range 2-8) was selected intraoperatively from each adenoma from endosellar, suprasellar, parasellar, and basal sellar dural locations. Overall mean cell proliferation rate measured by Ki-67 was 1.81 +/- 0.90% (range 0.33-3.43%). Histologically invasive adenomas had significantly higher mean Ki-67 proliferation index in all samples from the same tumor than non-invasive adenomas (2.01 +/- 0.91% vs. 1.11 +/- 0.59%; P = 0.024). Multiregional sampling revealed a homogenous distribution of Ki-67 index throughout an individual adenoma with no significant differences between any two different regions on t-test. Our data confirm that location of a biopsy does not influence Ki-67 index. Therefore, Ki-67 index of a single biopsy is representative for the whole individual adenoma. Thus Ki-67 index can be considered a reliable parameter for assessment of cell proliferation rate in adenoma biopsies and may be used for postoperative patient management considerations.

Adenoma↗

PubMed2004

Expression of cell proliferation markers in pituitary adenomas--correlation and clinical relevance of MIB-1 and anti-topoisomerase-IIalpha.

Pituitary adenomas represent an inhomogeneous tumor entity in terms of growth rate, invasiveness and recurrence. To improve understanding of their different biological behaviour, tumor cell proliferation markers are applied. The aim of this study was to assess proliferation rates overall and in clinico-pathological subgroups using MIB-1 and the recently introduced cell proliferation marker anti-topoisomerase-IIalpha (Topo-IIalpha). Further, we correlated the two markers, and defined the clinical value of Topo-IIalpha in pituitary adenomas as compared to MIB-1. We analyzed tumor cell proliferation rates using MIB-1 and Topo-IIalpha antibodies on samples of 260 primary pituitary adenomas. We excluded recurrent cases and cases with drug pretreatment. Median patient age at the time of surgery was 47 years (range 14-86 years), the male:female ratio was 1:1. The total cohort comprised 110 non-functioning and 150 functioning cases. Subtyping was performed according to hormonal expression as defined by WHO. Tumor size and invasiveness were noted from surgical and/or radio logical reports in 95% of cases. Overall MIB-1 index was median 1.8% (range 0.2-23.6%), Topo-IIalpha index was median 1.0% (range 0-14.4%) with a strong correlation between the two markers ( R=0.837, P<0.001). As compared to MIB-1, mean Topo-IIalpha values were significantly lower by a factor 1.8. Only MIB-1 was significantly higher in invasive as compared to non-invasive adenomas, in tumors < or =3 cm in diameter, and in the age-group 21-40. Female gender had significantly higher MIB-1 and Topo-IIalpha indices than male. Silent ACTH-cell and PRL-producing adenomas had the highest, null-cell adenomas and gonadotropinomas the lowest proliferation values, respectively. Our data show a strong correlation between MIB-1 and Topo-IIalpha indices in pituitary adenomas. Only MIB-1 but not Topo-IIalpha demonstrated significantly higher values in invasive adenomas. Therefore, MIB-1 seems more useful than Topo-IIalpha for decisions regarding postoperative patient management.

Adenoma↗

PubMed2004

Virtual endoscopy is a useful device for training and preoperative planning of transsphenoidal endoscopic pituitary surgery.

Virtual endoscopy (vE) allows simulated three-dimensional (3-D) visualisation of anatomical structures by computerised reconstruction of radiological images. The aim of this study was to evaluate the feasibility of vE and its potential benefits for endoscopic transsphenoidal pituitary surgery. vE was realised using a commercially available ray-casting software plugin of a picture archiving and communications system (PACS). For this study, the vE system was enhanced with volume segmentation, transparency and cutting tools. The data for vE were derived from high resolution computed tomography (CT) scans of 22 patients with pituitary pathology (20 pituitary adenomas, 2 Rathke's cleft cysts) preoperatively. Anatomic structures were identified on vE images and compared with the intraoperative endoscopic views. The simulated 3-D vE images were found to be comparable to the intraoperative endoscopic anatomy in terms of distortion and angle of view. vE was found to be particularly useful for the preoperative depiction of 1) the nasal anatomy and its variations for choosing the side of the approach, 2) the sphenoid sinus septae and chambers for improved intraoperative orientation, 3) the transparent 3-D simulated visualisation of the pituitary gland, tumour and adjacent anatomic structures in relation to the sphenoid sinus landmarks for planning the opening of the sellar floor. We conclude that vE harbours the potential to become a valuable tool in endoscopic pituitary surgery for training purposes and preoperative planning. Furthermore, vE may add to the safety of interventions in case of anatomic variations.

Endoscopy↗

PubMed2003

Microprolactinomas in males treated by transsphenoidal surgery.

OBJECTIVE: To support the opinion that transsphenoidal surgery can be an effective alternative to medical treatment for microprolactinomas in men. DESIGN: Clinical study with retrospective data analysis. PATIENTS AND METHODS: Of 46 men who were operated on for prolactinoma in the Department of Neurosurgery of the University of Vienna General Hospital between 1985 and 2000 a microadenoma was detected 11 times (24%). RESULTS: Median patient age was 41 years (range 32 to 54 years). Symptoms were of endocrine nature in all patients with erectile dysfunction, infertility and gynaecomastia being the initial complaints and having lasted for a median of 13 months (range 7-68 months). Preoperative median serum prolactin (PRL) was elevated to 120 ng/ml (range 41-1000 ng/ml). Radiography by MRI revealed microadenomas with a median diameter of 8 mm (range 4-10 mm). All patients were operated on via the transsphenoidal approach. Endocrine cure as defined by a serum PRL <25 ng/ml was achieved in 8 of 11 patients (73%) after a median follow-up of 7 years (range 2-13 years). In none of the 3 patients with preoperative serum PRL levels >150 ng/ml was a normoprolactinaemia obtained after surgery: 2 require further dopamine-agonist therapy after surgery, 1 after late follow-up. Surgery and medical treatment could restore potency and libido in all but 1 patient, 2 of 3 patients remain infertile. CONCLUSION: Prolactinomas in males are potentially curable by surgery if detected at an early stage. They most commonly present with insidious signs and symptoms of endocrine disturbances such as loss of libido, impotence and sterility. We stress the importance of early determination of serum prolactin and high resolution magnetic resonance tomography of the sella in male patients with hyperprolactinaemia as this may prevent the possible progression to larger tumours which are rarely curable by surgery and necessitate life-long medical therapy.

Adult↗

PubMed2002

DNA topoisomerase IIalpha expression in optic pathway gliomas of childhood.

DNA topoisomerase IIalpha (Topo IIalpha) is linked to tumour cell growth and chemoresistance. We examined immunohistochemically Topo IIalpha expression levels in a series of 36 consecutive paediatric optic pathway glioma (OPG) patients. Topo IIalpha labelling index (LI) ranged from 0.0 to 11.6 and was significantly associated with patient age, with higher levels of Topo IIalpha in children < or = 3 years (P=0.031). Topo IIalpha expression did not correlate with patient survival. Topo IIalpha LI was not significantly increased in specimens of repeat surgery. Topo IIalpha LI closely correlated with MIB-1 LI (R=0.781, P<0.001). We conclude that Topo IIalpha expression correlates with tumour cell proliferation in paediatric OPGs. Assessment of cell proliferation, however, does not assist in refining prognostic predictions. Enhanced Topo IIalpha expression in children < or = 3.0 years suggests that Topo IIalpha-interfering anticancer compounds for adjuvant treatment of OPGs may be of particular benefit to young children.

Adolescent↗

PubMed2000

Defining the role of stereotactic radiosurgery versus microsurgery in the treatment of single brain metastases.

Stereotactic radiosurgery (RS) and surgery have proved to be effective treatment modalities for brain metastasis. We followed 133 patients whose treatment for intracranial disease was either RS or a single surgical resection at the University of Vienna from August 1992 through October 1996. All patients who received additional Whole Brain Radiotherapy were included. This was a retrospective, case-control study comparing these treatment modalities. Sixty-seven patients were treated by RS and 66 patients were treated by microsurgery. The median size of the treated lesions for RS patients was 7800 mm3, and 12500 mm3 for microsurgery patients, respectively. The median dose delivered to the tumour margin for RS patients was 17 gray. The median survival for patients after RS was 12 months, and 9 months for patients after microsurgery. This difference was not statistically significant (p = 0.19). Comparison of local tumour control, defined as absence of regrowth of a treated lesion, showed that tumours following RS had a preferred local control rate (p < 0.05). Univariate and multivariate analysis showed that this fact was due to a greater response rate of "radioresistant" metastasis to RS (p < 0.005). Postradiosurgical complications included the onset of peritumoural oedema (n = 5) and radiation necrosis (n = 1). Two patients after microsurgery experienced local wound infection. One postoperative death occurred due to pulmonary embolism in this group. On the basis of our data we conclude that RS and microsurgery combined with Whole Brain Radiotherapy are comparable modalities in treating single brain metastasis. Concerning morbidity and local tumour control, in particular in cases of "radioresistant" primary tumours, RS is superior. Therefore we advocate RS except for cases of large tumours (> 3 cm in maximum diameter) and for those with mass effect.

Brain Neoplasms↗

PubMed1999

Delayed visual deterioration after surgery for pituitary adenoma.

Despite its description in the literature there remains uncertainty about the incidence, the pathophysiological basis and the best management of a delayed visual deterioration in the presence of an empty sella after surgery for pituitary adenomas. Out of a series of 501 patients with pituitary adenomas operated on at our institution between 1984 and 1996, four patients (0.8%) developed a worsening of their visual function 3 to 37 months after surgery in the absence of tumour recurrence. None of the patients had received radiotherapy. Magnetic resonance imaging (MRI) ruled out compression by tumour and showed herniation of suprasellar structures into an empty sella. In three cases re-operation by a subfrontal approach with freeing of the optic structures from tethering scar tissue led to an improvement of visual deficits. In one case a spontaneous recovery was initiated by a minor head injury. Although apparently a rare event, our cases provide evidence for the occurrence of a potentially reversible delayed deterioration of visual function after surgery for pituitary adenomas. Based on our operative findings and our outcome we recommend re-operation by a transcranial approach in patients in whom repeated ophthalmological testing does not show spontaneous improvement within a short period of time.

Adenoma↗