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.

Dura resection in combination with en bloc spondylectomy for primary malignant tumors of the spine.

STUDY DESIGN: Resection of a primary malignant tumor of the bone with wide surgical margins has become the golden standard in oncological surgery. In the case of a spinal tumor with tumor invasion of the spinal canal, a wide resection could necessitate resection and subsequent replacement of part of the dura. SUMMARY OF BACKGROUND DATA: Dura replacement is a consequent surgical step in the treatment of primary malignant tumors of the spine. METHODS: We present the case of a 27-year-old male with a tumor of the dorsal elements of D6. After paraplegic symptoms, a laminectomy of D5 to D7 was performed and histologic examination revealed the presence of an osteosarcoma. After neoadjuvant polychemotherapy, a wide resection of the dorsal elements from D4 to D7 combined with a resection of the dorsal part of the dura was planned. Replacement of the dura was performed with Lyodura (B. Braun Melsungen AG, Melsungen, Germany). The spine was stabilized with an ISOLA instrumentation (Depuy International Ltd., Leeds, England). For wound closure, a pedicled latissimus dorsi flap and split skin graft were necessary. In a second step, ventral spondylodesis with Texas Scottish Rite Hospital instrumentation (Sofamor Danek, Memphis, TN) was performed. RESULTS: One hundred sixteen months after surgery the patient is alive without evidence of disease, is pain free, and has returned to his profession and life without any restrictions.

Paragangliomas of the temporal bone: results of different treatment modalities in 53 patients.

BACKGROUND: The authors retrospectively compared the results of three different treatment modalities (surgery, conventional radiotherapy and gamma knife radiosurgery) in patients with paragangliomas of the temporal bone, in order to determine the optimal current treatment concept. METHOD: Between 1978 and August 2001, 53 patients (12 men and 41 women; mean age, 58.3 years; range, 17 to 84 years) with paragangliomas of the temporal bone were treated at the neurosurgery and ENT departments of the University of Vienna. According to the Fisch classification, 6 patients had class B tumours, 20 had class C, and 27 patients had class D tumours. Thirty-two patients (mean age, 57.0 years; 6 B, 14 C, 12 D) underwent surgery. In 17 cases the tumour was embolised prior to surgery. Nine patients (mean age, 73.9 years; 6 C, 3 D) received primary radiotherapy (median total dose, 46.8 Gy). Six patients (mean age, 73.5 years; 6 D) underwent primary radiosurgery (median centre dose 24, Gy) and 6 patients (6 D) admitted from other departments with recurrent tumours adjuvant radiosurgery (median centre dose, 25.5 Gy). FINDINGS: In 20 of the surgical cases (62.5%) complete tumour resection was achieved and the patients required no further treatment over a mean follow-up period of 9.1 years. Of the 12 patients with incomplete tumour resection, 9 (5 C, 4 D) received postoperative adjuvant radiotherapy and three patients (3 D) adjuvant radiosurgery. In 15 (83.4%) of the 18 patients who underwent radiotherapy the tumours showed no signs of progression and the patients remained clinically unchanged over a mean period of 9.4 years. Three patients (16,6%) experienced progression of their tumour within an average period of 2.8 years. In the 15 patients who underwent primary radiosurgery, an objective 100% tumour control rate with no evidence of progression of disease was observed. INTERPRETATION: The results indicate that the most effective current treatment option for patients with paragangliomas of the temporal bone is a single-stage radical tumour resection, performed in advanced tumours as an interdisciplinary neuro-otosurgical procedure. For subtotally resected or non-resectable tumours, gamma knife radiosurgery has proved to be a safe and effective treatment modality.

Stereotactic radiosurgery for brain metastases from colorectal cancer.

PURPOSE: The development of brain metastases represents an ominous event for patients with colorectal cancer. We evaluated results following stereotactic radiosurgery (SR) for patients with metastatic colorectal cancer to identify efficacy of SR and prognostic factors for survival. METHODS: This is a retrospective study of 60 brain metastases from colorectal cancer in 35 consecutive patients who underwent SR from January 1993 to December 1996. Thirteen patients also underwent additional whole-brain radiation therapy (WBRT). The median dose delivered to the tumor margin was 20 Gray (range 16-28 Gy), in most cases the tumor enclosing the 50% isodose (range 40-60%). Patients were classified into two groups: SR with and SR without WBRT. Univariate and multivariate testing was performed to determine significant prognostic factors. RESULTS: The median survival time was 6 months after SR and 40 months after diagnosis of primary tumor. A Karnofsky performance scale >70 was a significantly favorable prognostic factor in uni- and multivariate testing. Post-SR imaging was evaluated in 32 patients and in 54 cerebral lesions. Local tumor control was revealed in 94% of patients and 96% of treated tumors. Two patients developed local recurrences, and remote brain disease was revealed in five. No patient experienced a new focal neurologic deficit due to SR. The addition of WBRT to SR did not improve survival and local tumor control rates. Distant control rate was borderline in univariate analysis and significantly improved for patients who received additional WBRT in multivariate analysis. CONCLUSION: SR for brain metastases from colorectal cancer results in a high local tumor control rate of 94% associated with few complications and therefore provides patients with a higher quality of their remaining life.

Efficiency of gamma knife radiosurgery in the treatment of glomus jugulare tumors.

This study was performed to assess the impact of gamma knife radiosurgery (RS) in the treatment of glomus jugulare tumors. Between February 1993 and February 1999, thirteen patients (9 women, 4 men; mean age 63.5 years, range 29 to 79 years) underwent stereotactic radiosurgery for glomus jugulare tumors with the Leksell Gamma Knife at the Neurosurgical Department of the University of Vienna. Four patients, mean age 74.5 years, range 67 to 79 years, underwent radiosurgery as the only treatment. Nine patients received radiosurgery as adjuvant therapy after previous treatment had failed: surgical resection in 9 patients and additional fractionated external beam radiation in two of these patients. Pretreatment evaluation included the staging of all tumors according to the Fisch Classification: De1 (7), De2 (1), Di1 (4) and Di2 (1). The mean follow-up period was 4.2 years, range 0.7 to 6.7 years. Ten patients, 77 %, were treated prior to 1997, the mean follow-up period being 5 years. Six patients showed no clinical changes, while six experienced an improvement of their clinical symptoms and neurological deficits. One patient was lost to follow-up. Radiation-induced transient cranial nerve neuropathies were observed in two patients. Serial MRI scans revealed tumor control in all patients, with unaltered tumor size in 10 and shrinkage in three patients. The results indicate that RS is an attractive treatment option for glomus jugulare tumors and will occupy an increasingly important role in the management of these tumors in selected patients.

Gamma knife radiosurgery of acoustic neurinomas.

The authors report on their series of 40 patients with 41 acoustic neurinomas (ACNs), including one patient with bilateral acoustic neurinomas suffering from neurofibromatosis type 2 (NF II) who were treated with the gamma knife unit at their institution between August 1992 and October 1995. Of these 41 tumours, 21 ACNs had been operated on before (1 to 4 times), 20 ACNs were exclusively treated by gamma knife radiosurgery (GKRS). The maximal axial tumour diameter ranged from 6 to 33 mm (median: 25 mm), the maximal transverse tumour diameter ranged from 7 mm to 36 mm (median: 16 mm). The dose distributed to the tumour margin was 10 to 17 Gy (median: 12 Gy) by enclosing the tumour with the 40% to 95% isodose line (median: 50% isodose line) and using 1 to 12 isocenters (median: 5 isocenters). Central loss of contrast enhancement was observed in 78% of the patients within six to 12 months after radiosurgery. Thirty-two patients were observed over a minimum follow up period of at least 36 months, 9 patients were lost to follow up as they died of unrelated causes or refused further check-ups. Within the follow up period of up to seven years, magnetic resonance imaging (MRI) control scans revealed the tumour diameter stable or decreased in 29 cases and increased in three tumours. Of 14 patients with useful hearing before treatment, 9 patients were examined in addition to pure tone audiogramm by measurement of brainstem auditory evoked potentials (BAEPs) one to four years after radiosurgery. None of these patients showed a postoperative loss of the cochlea function. According to slight alterations of the cochlea function (cochlea summating action potential), pure tone audiometry of those patients revealed only slight changes of the hearing level (HL) within a maximum range of +/-15 Decibel (dB). The hearing threshold improved in two, was stable in four and deteriorated in three patients, respectively. We observed postradiosurgical aggravation of a pre-existing facial weakness in two out of 13 patients, a new occurrence of facial palsy was seen in two cases (four years after treatment), one of them was previously operated on and both suffered from cystic degeneration with mass effect. Tinnitus improved in six out of 13 patients, deteriorated in two and never appeared as a new permanent sequela. Trigeminal hypaesthesia did also not appear as a new permanent symptom, improved in three out of 9, and deteriorated in one out of 9 patients. Vertigo increased in six out of 23, was stable in 8 and decreased in nine out of 23 patients each. GKRS proves to be a safe and highly satisfactory therapeutical option or addition to open surgery, especially for radiologically verified regrowing residual ACNs, but also as primary treatment in selected patients. A high rate of tumour control can be achieved with an acceptable rate of neurological deficits.

An intramural macrocyst of an acoustic neurinoma rupturing after gamma knife radiosurgery: a case report.

We want to describe the rare case when an intramural macrocyst within an acoustic neurinoma (ACN) treated by gamma knife radiosurgery (GKRS) ruptured, followed by an impressive decrease of tumor volume and improvement of neurological symptoms. In a 59-year-old female patient, a large ACN with a hugh intramural macrocyst was diagnosed. As she refused open surgery, we performed GKRS covering the tumor margin and the cyst with 11 Gy. Seven months after treatment symptoms worsened slightly. Magnetic resonance imaging (MRI) revealed no significant change of tumor volume. One year after GKRS she felt a sensation behind her treated ear, followed by an immediate improvement of all her symptoms. Trigeminal hypaesthesia and vertigo disappeared, tinnitus ameliorated. A control MRI showed the cystic compartment no longer, the solid part shrunk within the following six years. Within the whole follow-up period hearing was stable. To our knowledge this is the first report of a macrocyst within an ACN to rupture after GKRS.

Gamma knife radiosurgery of recurrent central neurocytomas: a preliminary report.

OBJECTIVES: A series of three recurrent central neurocytomas treated by gamma knife radiosurgery (GKRS), which were initially totally resected, are described. Up to now, no reports exist on this treatment modality for this rare tumour entity. METHODS: Three male patients, aged between 20 and 25 years, presented with large intraventricular tumours. Total tumour removal was achieved by a single surgical procedure (one patient) or two operations (two patients). Neuropathological investigation showed a central neurocytoma, immunohistochemically all three tumours expressed a neuronal antigenic profile typical for neurocytomas, and the MIB-1 proliferation index ranged from 2.4% to 8.7%. Each patient experienced a tumour recurrence after 5 to 6 years. The recurrence was multifocal in two and a singular tumour mass in one patient. Gamma knife radiosurgery was performed. The tumours were enclosed within the 30% to 60% isodoseline, and delivered a tumour marginal dose of 9.6 to 16 Gy. During the follow up period, the patients were tested clinically and the volume of the tumours was measured on MRI. RESULTS: Within follow up periods of 1 to 5 years, control MRI showed a significant decrease of the tumour mass in all cases. None of the patients developed new neurological symptoms after GKRS. Two patients returned to work in their previous employment, whereas one patient remained permanently disabled due to a pre-existing visual impairment and abducens palsy. CONCLUSION: GKRS proved to be a useful tool in the treatment of recurrent central neurocytomas. Tumour control and even tumour shrinkage can be achieved with a single procedure and a low risk of morbidity.

Treatment of dural arteriovenous fistulae (dAVF's) at the superior sagittal sinus (SSS) using embolisation combined with micro- or radiosurgery.

DAVF's at the SSS are extremely rare and usually present with intracranial haemorrhage (ICH) or a progressive neurological deficit. Due to their midline location and multiple arterial supply, endovascular treatment alone often fails in eliminating the fistula. Therefore, endovascular, combined with neurosurgical and/or radiosurgical treatment is often needed to cure the patient. We summarized our experience with three male patients over a ten-year period who suffered from dAVF's involving the middle and posterior third of the SSS. Two of them presented with an ICH during the clinical course. Despite multiple transarterial embolisations, complete fistula occlusion could not be achieved in any of them. Nevertheless, neurological symptoms improved in all cases. One patient refused further treatment and died six years later due to an ICH. Another patient was finally cured by microsurgical coagulation of the fistula. In the remaining patient stereotactic radiosurgery (SRS) was performed after nearly complete endovascular occlusion. We strongly recommend microsurgery and/or radiosurgery as adjunctive measures, if embolisation alone fails to eliminate these dangerous fistulae.

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.

Gamma knife radiosurgery of skull base meningiomas.

BACKGROUND: The standard surgical treatment of meningiomas is total resection of the tumour. The complete removal of skull base meningiomas can be difficult because of the proximity of cranial nerves. Stereotactic radiosurgery (SRS) is an effective therapy, either for adjuvant treatment in case of subtotal or partial tumour resection, or as solitary treatment in asymptomatic meningiomas. METHOD: Between September 1992 and October 1995. SRS using the Leksell Gamma Knife was performed on 46 patients (f:m 35:15), ranging in age from 35 to 81 years, with skull base meningiomas at the Neurosurgical Department of the University of Vienna. According to the indication of gamma knife radiosurgery (GKRS) the patients (n = 46) were divided into two subgroups. Group I (combined procedure: subtotal resection followed by GKRS as a planned procedure or because of a recurrent meningioma), group II (GKRS as the primary treatment). Histological examination of tumour tissue was available for 31 patients (67%) after surgery covering 25 benign (81%) and 6 malignant (19%) meningioma subtypes. FINDINGS: The overall tumour control rate after a mean follow-up period of 48 months (ranging from 36 to 76 months) was 96% (97.5% in benign and 83% in malignant meningiomas). Group I displayed a 96.7% tumour control rate, followed by group II with 93.3% respectively. Neurological follow-up showed an improvement in 33% stable clinical course in 58%) and a persistent deterioration of clinical symptoms in 9%. Remarkable neurological improvement after GKRS was observed in group II (47%), whereas in group I (26%) the amelioration of symptoms was less pronounced. INTERPRETATION: GKRS in meningiomas is a safe and effective treatment. A good tumour control and low morbidity rate was achieved in both groups (I, II) of our series, either as a primary or adjunctive therapeutic approach. The planned combination of microsurgery and GKRS extends the therapeutic spectrum in the treatment of meningiomas. Reduction of tumour volume, increasing the distance to the optical pathways and the knowledge of the actual growing tendency by histological evaluation of the tumour minimises the risk of morbidity and local regrowth. Small and sharply demarcated tumours are in general ideal candidates for single high dose-GKRS, even after failed surgery and radiation therapy, and in special cases also in larger tumour sizes with an adapted/reduced margin dose.

Local tumor control and morbidity after one to three fractions of stereotactic external beam irradiation for uveal melanoma.

BACKGROUND AND PURPOSE: To evaluate prospectively local tumor control and morbidity after 1-3 fractions of stereotactic external beam irradiation (SEBI) in patients with uveal melanoma, unsuitable for ruthenium-106 brachytherapy or local resection. MATERIAL AND METHODS: This phase I/II study includes 62 selected patients with uveal melanoma. The mean initial tumor height was 7.8+/-2.8 mm. With the Leskell gamma knife SEBI, 41 patients (66%) were irradiated with two equal fractions of 35, 30 or 25 Gy/fraction, 14 patients (22%) were treated with three fractions of 15 Gy each, and seven patients (11%) with small tumor volumes below 400 mm(3) were treated with one fraction of 45 Gy. The mean total dose was 54+/-8 Gy. The minimal follow-up period was 12 months, and the median follow-up was 28.3 months. Data on radiation-induced side-effects were analyzed with the Cox proportional hazards model for possible risk factors. RESULTS: Local tumor control was achieved in 98% and tumor height reduction in 97%. The mean relative tumor volume reductions were 44, 60 and 72% after 12, 24 and 36 months, respectively. Seven patients developed metastases (11%). Secondary enucleation was performed in eight eyes (13%). Morbidity was significant in tumors exceeding 8 mm in initial height; it was comparable and acceptable in those smaller. In the stepwise multiple Cox model, tumor localization, height and volume, planning target volume (PTV), total dose and patient age were identified as the strongest risk factors for radiation-induced lens opacities, secondary glaucoma, uveitis, eyelash loss and exudative retinal detachment. In this model, the high-dose volume irradiated with more than 10 Gy/fraction was the strongest risk factor for radiation-induced uveitis. CONCLUSIONS: Stereotactic external photon beam irradiation and a total dose of 45-70 Gy delivered in one to three fractions are highly effective at achieving local tumor control in uveal melanoma. Further clinical studies using smaller fraction doses, and consequent smaller high-dose volumes, are justified to optimize dose and fractionation. Fractionated stereotactic irradiation has a challenging potential as an eye-preserving treatment in uveal melanoma.

Prognostic factor analysis for multiple brain metastases after gamma knife radiosurgery: results in 97 patients.

Stereotactic radiosurgery (SR) is being used with increasing frequency in the treatment of brain metastases. This study provides data from a clinical experience with radiosurgery in the treatment of cases with multiple metastases and identifies parameters that may be useful in the proper selection and therapy of these patients. From January 1993 to April 1997, 97 patients (43 women and 54 men; median age 58 years) suffering from multiple brain metastases (median 3; range 2-4) in MRI scans, received SR with the Gamma Knife. The median dose at the tumor margin was 20 Gy (range 17-30 Gy). Median tumor volume was 3900 cmm (range 100-10,000). Different forms of hemiparesis, focal and generalized seizures, cognitive deficit, headache, dizziness and ataxia had been the predominant neurological symptoms. Major histologies included lung carcinoma (44%), breast cancer (21%), renal cell carcinoma (10%), colorectal cancer (8%), and melanoma (7%). The median survival time was 6 months after SR. The actual one-year survival rate was 26%. In univariate and multivariate analysis, a higher Karnofsky performance rating and absence of extracranial metastases had a significantly positive effect on survival. Local tumor control was achieved in 94% of the patients. Complications included the onset of peritumoral edema (n = 5) and necrosis (n = 1). SR induces a significant tumor remission accompanied by neurological improvement and, therefore, provides the opportunity for prolonged high quality survival. We conclude that radiosurgical treatment of multiple brain metastases leads to an equivalent rate of survival when compared to the historic experience of patients treated with whole brain radiotherapy. Patients presenting initially with a higher Karnofsky performance rating and without extracranial metastases had a median survival time of nine months. Each such case should therefore be evaluated based on these factors to determine an optimal treatment regimen.

Fractionated stereotactic radiotherapy with linear accelerator for uveal melanoma--preliminary Vienna results.

PURPOSE: To study local tumor control and radiogenic side-effects after fractionated stereotactic radiotherapy for uveal melanoma. PATIENTS AND METHODS: Between June 1997 and February 1998, 21 patients suffering from uveal melanomas have been treated with stereotactic 6 MeV LINAC (Saturne 43, General Electric, France) in conjunction with a stereotactic frame system (BrainLAB, Germany). Immobilization of the eye was ensured with an optical fixation system which was proven reliable. During radiotherapy, movements of the irradiated eye were controlled on a monitor and documented by video recording. All patients co-operated very well with the optical fixation system. In 1164 measurements, the median value of horizontal deviation of the diseased eye during treatment was 0.3 mm (range: 0 to 1.3 mm). Median vertical deviation was 0.2 mm (range: 0 to 1.2 mm). For all patients, mean tumor prominence before treatment was 6.0 +/- 2.2 mm. In 20 patients, the total dose of 70 Gy (at 80%) was delivered in 5 fractions within 10 days. In one patient with a ciliary body tumor, the total dose of 70 Gy was divided into 7 fractions for better sparing of the anterior eye segment. RESULTS: After a follow-up of at least 6 months, local tumor control was seen in all eyes. Mean tumor thickness reduction after 3, 6 and 9 months was 7%, 13% and 31%, respectively. Up to now, only mild subacute side-effects located in the anterior eye segment have been noticed. CONCLUSION: Optical fixation of the eye allows high precision stereotactic radiotherapy with small safety margins. Fractionated stereotactic radiotherapy and 70 Gy total dose delivered in 5 fractions seems to be appropriate for local tumor control in uveal melanoma. Further long-term studies with extended number of patients will be necessary to conclude on the use of linac-based fractionated stereotactic radiotherapy for uveal melanoma.

Expression of BCL-2 oncoprotein on tumor cells and tumor-infiltrating lymphocytes (TIL) in meningiomas.

The Expression of the antiapoptotic oncoprotein BCL-2 and its correlation to tumor grade in 62 meningiomas (48 classic, 9 atypical, and 5 anaplastic) using single and double immunohistochemistry was investigated. BCL-2 expression was found in two different cell populations identified as lymphocytes (BCL-2+CD3+) and tumor cells (BCL+/CD3-). Tumor-infiltrating lymphocytes (TIL) (CD3+) were found within classic (9.5% of cells), atypical (2.4% of cells), and anaplastic (1.8% of cells) meningiomas. In classic meningiomas, 66.5% of TIL were BCL-2-positive, in atypical meningiomas 79.2%, and in anaplastic meningiomas 37.9%. In 33 (68.8%) of the classic meningiomas, medium to high counts of BCL-2+ tumor cells were detected. Atypical meningiomas showed nearly equal percentages of high (two patients), medium (five patients), and low (two patients) BCL-2+ tumor cell counts, whereas anaplastic meningiomas showed only medium (two patients) and low (three patients) BCL-2 tumor cell counts or were BCL-2-negative (one patient). In summary, a significant inverse correlation between the number of BCL-2-positive tumor cells and tumor grade in meningiomas was found. These findings support the hypothesis of cell survival prolongation by the antiapoptotic ability of BCL-2 proto-oncogenes and demonstrate the prognostic relevance of BCL-2 immunoreactivity in meningiomas.

Radio-opaque markers for stereotactic imaging of uveal melanoma.

In in vitro and in vivo studies, episclerally sutured radio-opaque markers were evaluated as localizers for better determination of the clinical tumour volume prior to stereotactic radio-therapy of uveal melanoma. Four different types of markers were studied in vitro: tantalum marker, 2.5 mm in diameter; ring-shaped markers custom-designed in polymethyl methacrylate (PMMA), 2.6 mm and 3.0 mm in diameter; and barium-impregnated silicone rubber spheres, 2 mm in diameter. In vivo PMMA markers 3.0 mm in diameter and barium-impregnated silicone rubber spheres 2 mm in diameter were used. The best results were obtained with the barium-impregnated silicone rubber spheres both in vitro and in vivo. For the CT-delineation of selected uveal melanomas with either a flat discoid shape or flat tumour extensions or when adjacent serous retinal detachment is present, small episclerally sutured barium-impregnated silicone rubber spheres are useful as localizers for determining the clinical tumour volume.

Gamma-knife radiosurgery for brain metastases of renal cell carcinoma: results in 23 patients.

From Jan. 1993 to Sept. 1995 23 patients suffering from brain metastases from renal cell carcinoma were treated with the Leksell Gamma Knife at the University of Vienna. At the time of diagnosis 13 patients had single and 10 patients presented with multiple metastatic lesions with a total of 44 metastases in MRI scans. Median tumour volume was 5500 cmm (range 100-24000 cmm). Predominant neurological symptoms and signs were different forms of hemiparesis, focal and generalized seizures, cognitive deficit, headache, dizziness, ataxia and CN XII paresis. Fourteen patients received Gamma Knife Radiosurgery (GKRS) with a median dose of 22 Gy (range 8-30 Gy) at the tumour margin. Nine patients underwent a combined treatment of a radiosurgical boost with a median dose of 18 Gy (range 10-22 Gy) at the tumour margin followed by Whole Brain Radiotherapy (total dose 30 Gy/2 weeks). In 20 patients tumour volume reduction up to 30% of the primary tumour volume was found after 4 weeks, evaluated on CT or MRI. A total remission was seen in 4 cases 3 months after GKRS. We achieved a local tumour control of 96%. Rapid neurological improvement after GKRS was seen in 17 patients. The median survival time was 11 months; the one-year actual survival in this unselected group was 48%. Five long term survivors were still alive, 18 patients had subsequently died, 15 of them of general tumour progression. GKRS induces a significant tumour remission accompanied by rapid neurological improvement and therefore provides the opportunity for extended high quality survival. Neither local tumour control was improved nor CNS relapse free survival was prolonged significantly by additional WBRT.

Shuttle dose at the Vienna Leksell Gamma Knife.

The aim of this study was to determine the shuttle dose for all collimator helmets (4, 8, 14 and 18 mm) of the Gamma Knife, model B, in Vienna, Austria. The additional dose accumulated during the transport of the patient in and out of the treatment position should be considered in the dose planning procedure of multicentre treatment regimens and in fractionated stereotactic Gamma Knife radiotherapy. The GafChromic film study was basically used to determine the shuttle dose of all four collimator helmets. In addition, measurements with an ionization chamber (18 and 14 mm collimator--and, for the 18 mm collimator helmet, TLD dosimetry--were performed in order to confirm the GafChromic film data. The shuttle dose ranged between 99.6 and 183.5 mGy, depending mainly on the size of the collimator and the irradiated isocentres at the half-life activity of Co-60 in a brand new Gamma unit. Our film-generated data were in good correlation with the dose levels obtained with the ionization chamber and the TLD dosimetry, showing a dose difference of less than 0.8%. Since it was possible to verify the shuttle dose even for the 4 and 8 mm collimator helmets, we consider it a non-negligible factor and would advocate the inclusion of the shuttle dose in radiosurgical dose planning.

Beneficial gamma-knife radiosurgery in a patient with Nelson's syndrome.

A 50-year-old female patient with Cushing's disease had undergone transsphenoidal removal of the pituitary adenoma and conventional radiotherapy in 1988. Since no remission was achieved, she underwent bilateral adrenalectomy in May 1989. During out-patient follow-up, she developed signs and symptoms due to invasive Adrenocorticotrophic hormone (ACTH)-producing macroadenoma (Nelson's syndrome) in 1994. ACTH levels at that time were 3400 ng/l. Near-total surgical resection of a 2.0 x 2.5 pituitary tumour which slightly extended laterally into the cavernous sinus was achieved by subfrontal approach in June 1994. However, she rapidly developed a recurrence of her complaints, with a visual field defect inferior-nasal of the left eye, and a second operation was carried out in November 1994. Culture of the tumour's cells revealed significant inhibition of ACTH production by bromocriptine. Adjuvant treatment with this drug therefore was started in November 1994. Because of the rapid recurrence it was decided to treat her with gamma-knife radiosurgery. The dose that was given in January 1995 was 12 Gy to the border and 40 Gy into the centre of the tumour. During a follow-up of more than 2 years, no recurrence, but even a minor reduction of tumour mass was observed by magnetic resonance imaging (MRI). Plasma ACTH levels decreased gradually to levels between 200 and 400 ng/l, and ophthalmologic complaints disappeared. It is concluded that gamma-knife radiosurgery may be a good alternative for patients with Nelson's syndrome who have rapidly recurring disease.