Gamma Knife Stereotactic Radiosurgery for the treatment of chordomas and chondrosarcomas.

INTRODUCTION: Primary chordomas and chondrosarcomas of the skull base are difficult tumours to treat successfully. Despite advances in surgical techniques, a gross total resection is often impossible to achieve. In addition, some patients may be deemed unsuitable or not wish to undergo extensive surgery for these conditions. This study examines the role of Gamma Knife Stereotactic Radiosurgery (GKRS) in the treatment of these difficult cases. METHODS: All patients harbouring either a chordoma or chondrosarcoma treated at the National Centre for Stereotactic Radiosurgery, Royal Hallamshire Hospital, Sheffield, UK, between 1985 and 2018, were reviewed with regard to their clinical presentations, pre- and post-treatment imaging, GKRS prescriptions and outcomes. RESULTS: In total, 24 patients with a mean tumour volume of 13 cm3 in the chordoma group (n=15) and 12 cm3 in the chondrosarcoma group (n=9) underwent GKRS. The 5- and 10-year overall survival rates for the chordoma group were 67% and 53% respectively, while for the chondrosarcoma group, they were 78% at both time points. The tumour control rates at 5 and 10 years in the chordoma group were 67% and 49% and for the chondrosarcoma group 78% at both time points. Patients with tumour volumes of less than 7 cm3 before GKRS treatment demonstrated a statistically significant longer overall survival rate (p=0.03). CONCLUSIONS: GKRS offers a comparable option to proton beam therapy for the treatment of these tumours. Early intervention for tumour volumes of less than 7 cm3 gives the best long-term survival rates.

A Retrospective Analysis of the Role of Single-Session Gamma Knife Stereotactic Radiosurgery in Sporadic Vestibular Schwannomas with Tumor Volumes Greater Than 10 cm3: Is It Worth Stretching the Boundaries?

OBJECTIVE: To evaluate the role of single-session Gamma Knife stereotactic radiosurgery (GK-SRS) in the treatment of vestibular schwannomas (VSs) with volumes of greater 10 cm3. METHODS: A retrospective analysis was performed of 103 patients treated with single-session GK-SRS between 1993 and 2011 with a mean follow-up of 6.2 years ± 4.4 SD. Treatment, clinical and outcome details were recorded and assessed. RESULTS: Eighty-one (78.6%) patients achieved radiological control with slow progression in a further 5 (4.9%) patients, who did not require further treatment. Linear measurements did not correlate well with volume, which can predict outcome following treatment more precisely. 2.9% of patients developed a new facial paresis, 5.8% trigeminal numbness and 2.9% facial pain. In all, 26 (25.2%) patients who were tested preserved some level of hearing following treatment. CONCLUSIONS: The overall radiological control rate in this study was 78.6%, while tumor volumes less than 20 cm3 can be safely treated with single-stage GK-SRS with an expected control rate of 83.2% without unacceptable morbidity rates. GK-SRS can be utilized as a first-line treatment option in patients with large-volume VSs especially in whom surgery is unattractive.

[RADIOSURGERY OF INTRACEREBRAL CAVERNOMAS--CURRENT INTERNATIONAL TRENDS]. / AZ INTRACEREBRALIS CAVERNOMÁK SUGÁRSEBÉSZETE--HOL TART MA A VILÁG?

Although still a controversial management option, radio-surgery of intracranial cavernomas has become increasingly popular world-wide during the last decade. Microsurgery is a safe and effective treatment for symptomatic hemispheric cavernomas. However, the indication for microsurgical resection of deep eloquent cavernomas is relatively limited even in experienced hands. The importance of radiosurgery has recently been appreciated in parallel with increasing positive experiences both in terms of effectiveness and safety, especially for cases high risk for surgical resection, in the brainstem, thalamus and basal ganglia. While radiosurgery was earlier indicated mainly for surgically inaccessible lesions that had bled multiple times, a more proactive policy has recently become more accepted. In our opinion preventive treatment with the low morbidity radiosurgery serves the patients' interest especially for deep eloquent lesions that had bled not more than once, due to the cumulative morbidity of repeated hemorrhages. Despite our increasing knowledge on natural history, there is currently no available treatment algorithm for cavernomas. Arguments for all three treatment modalities (observation, microsurgery and radiosurgery) are established, but their indication criteria are yet to be defined. It is time to organize a prospective population based data collection in Hungary, which appears to be the most realistic way to clarify indication criteria.

[RADIOSURGERY OF INTRACEREBRAL CAVERNOMAS--CURRENT HUNGARIAN PRACTICE]. / AZ INTRACEREBRALIS CAVERNOMÁK SUGÁRSEBESZETE--HOL TART MAGYARORSZÁG?

BACKGROUND AND PURPOSE: Radiosurgery is an increasingly popular treatment option especially for deep eloquent intracerebral cavernomas that are often too risky for surgical removal, but their re-bleed carries significant risk for persisting neurological deficit. Gamma-radiation based radiosurgery has been being available since 2007 in Hungary in Debrecen. Our aim is to summarize our experience accumulated during the first five years of treatment and to compare it to the international experience. PATIENT SELECTION AND METHODS: We retrospectively analyzed 51 cavernomas in 45 patients treated between 2008 and 2012 in terms of localization, natural history, and the effect of radiosurgery on re-bleed risk and epilepsy, and its side effects. RESULTS: We treated 26.5% deep eloquent (brainstem, thalamic/basal ganglia) and 72.5% superficial hemispheric cavernomas. The median presentation age was 25 years (13-60) for deep, and 45 years (6-67) for superficial cavernomas. They were treated median of 1 year after presentation. 64.5% of deep cavernomas bled before treatment, the annual risk of first hemorrhage was 2%/lesion, re-bleed risk 21.7%, with 44% persisting morbidity. 13.5% of superficial cavernomas bled prior to treatment, the risk of first bleed was 0.3%, there was no re-bleed, and 35% caused epilepsy. We used GammaART-6000TM rotating gamma system for treatment, marginal dose was 14 Gy (10-16), and treatment volume 1.38-1.53 cm3. Re-bleed risk of deep eloquent lesions fell to 4% during the first two years after treatment and to 0% thereafter, and no hemorrhage occurred from superficial lesions after treatment. Persisting morbidity in deep lesions came from adverse radiation effect in 7% and from re-bleed in 7%, and there was no persisting side effect in superficial cavernomas. 87.5% of cases of epilepsy resistant to medical therapy improved. Radiological regression was found in 37.5% and progression in 2% after treatment. CONCLUSIONS: Radiosurgery of cavernomas is safe and effective. Early preventive treatment for deep cavernomas carrying high surgical risk is justified. Moreover, for superficial lesions that are surgically easily accessible radiosurgery also appears to be an attractive alternative.

Prognosis in human glioblastoma based on expression of ligand growth hormone-releasing hormone, pituitary-type growth hormone-releasing hormone receptor, its splicing variant receptors, EGF receptor and PTEN genes.

PURPOSE: Glioblastoma (GB) is the most frequent brain tumor. Despite recent improvement in therapeutic strategies, the prognosis of GB remains poor. Growth hormone-releasing hormone (GHRH) may act as a growth factor; antagonists of GHRH have been successfully applied for experimental treatment of different types of tumors. The expression profile of GHRH receptor, its main splice variant SV1 and GHRH have not been investigated in human GB tissue samples. METHODS: We examined the expression of GHRH, full-length pituitary-type GHRH receptor (pGHRHR), its functional splice variant SV1 and non-functional SV2 by RT-PCR in 23 human GB specimens. Epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog gene (PTEN) expression levels were also evaluated by quantitative RT-PCR. Correlations between clinico-pathological parameters and gene expressions were analyzed. RESULTS: Expression of GHRH was found to be positive in 61.9 % of samples. pGHRH receptor was not expressed in our sample set, while SV1 could be detected in 17.4 % and SV2 in 8.6 % of the GB tissues. In 65.2 and 78.3 % of samples, significant EGFR over-expression or PTEN under-representation could be detected, respectively. In 47.8 % of cases, EGFR up-regulation and PTEN down-regulation occurred together. Survival was significantly poorer in tumors lacking GHRH expression. This worse prognosis in GHRH negative group remained significant even if SV1 was also expressed. CONCLUSION: Our study shows that GHRH and SV1 genes expressed in human GB samples and their expression patterns are associated with poorer prognosis.

Real time analysis of brain tissue by direct combination of ultrasonic surgical aspiration and sonic spray mass spectrometry.

Direct combination of cavitron ultrasonic surgical aspirator (CUSA) and sonic spray ionization mass spectrometry is presented. A commercially available ultrasonic surgical device was coupled to a Venturi easy ambient sonic-spray ionization (V-EASI) source by directly introducing liquified tissue debris into the Venturi air jet pump. The Venturi air jet pump was found to efficiently nebulize the suspended tissue material for gas phase ion production. The ionization mechanism involving solely pneumatic spraying was associated with that of sonic spray ionization. Positive and negative ionization spectra were obtained from brain and liver samples reflecting the primary application areas of the surgical device. Mass spectra were found to feature predominantly complex lipid-type constituents of tissues in both ion polarity modes. Multiply charged peptide anions were also detected. The influence of instrumental settings was characterized in detail. Venturi pump geometry and flow parameters were found to be critically important in ionization efficiency. Standard solutions of phospholipids and peptides were analyzed in order to test the dynamic range, sensitivity, and suppression effects. The spectra of the intact tissue specimens were found to be highly specific to the histological tissue type. The principal component analysis (PCA) and linear discriminant analysis (LDA) based data analysis method was developed for real-time tissue identification in a surgical environment. The method has been successfully tested on post-mortem and ex vivo human samples including astrocytomas, meningeomas, metastatic brain tumors, and healthy brain tissue.

The prandial insulin sensitivity-modifying effect of vagal stimulation in rats.

The effect of left cervical vagal nerve stimulation was studied on insulin sensitivity to test the proposed permissive insulin-sensitizing role of hepatic vagal parasympathetic efferent pathways in fasted and fed anesthetized rats. In fed animals, electrical stimulation (square impulses: 25 V, 5 Hz, 0.5 milliseconds over 15 minutes) of the vagal nerve induced hyperglycemia and an increase in plasma insulin immunoreactivity. Atropine (1.0 mg/kg intravenously) induced insulin resistance estimated by rapid insulin sensitivity testing. This was amplified when the vagal nerve was stimulated. The insulin-resistant state developed by fasting was not modified by either treatment with atropine or electrical stimulation. We conclude that both parasympathetic cholinergic and noncholinergic vagal efferents modulate postprandial neurogenic insulin sensitivity adjustments.