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Biomedical subjects

J C Tonn

Publications and source records attributed to J C Tonn.

At least 19 recordsLinked to original sources
PubMed2006

Interstitial iodine-125 radiosurgery alone or in combination with microsurgery for pediatric patients with eloquently located low-grade glioma: a pilot study.

PURPOSE: The optimal therapeutic management of children with World Health Organization grade I and II gliomas not accessible to complete resection is poorly defined. Radical surgical resection is the first-line treatment for large hemispheric tumors, whereas interstitial iodine-125 radiosurgery (IRS) might be an attractive treatment concept for selected patients with small (tumor diameter in the range of 4 cm) and circumscribed tumors in any location of the brain. Precise high-dose application, maximal sparing of surrounding normal tissue, and the absence of long-term complications have been reported to be the hallmark of IRS. Therefore, the therapeutic impact and the risk of IRS alone or in combination with microsurgery (in case of larger tumor volumes) were prospectively examined. METHODS: Seven boys and four girls were included (mean age, 6.8 years; range, 11 months to 16 years). IRS (after stereotactic biopsy) was considered to be indicated for circumscribed tumors with a diameter in the range of 4 cm (four cases). For larger tumors, a combined microsurgical/radiosurgical approach was preferred (seven patients). Temporary iodine-125 seeds were used exclusively (tumor dose calculated to the boundary, 54 Gy; dose rate, 10 cGy/h). Tumor location was hypothalamic/suprasellar in four, lobar in three, deep (thalamus and pineal gland) in two, and within the brain stem in two children. Treatment effects of IRS were estimated according to the MacDonald criteria. RESULTS: A complete response after IRS was seen in four patients, and a partial response was seen in seven patients (median follow-up, 31.5 months). There was no perioperative morbidity after microsurgery and/or IRS, and no radiogenic complications occurred during the follow-up period. Five patients experienced an improvement in their deficits, and no deterioration in neurological/endocrine function was seen in any of the patients at the time of last follow-up evaluation. CONCLUSION: IRS alone or in combination with microsurgery (in the case of larger tumors) is a safe, effective, and minimally invasive treatment strategy for eloquently located pediatric low-grade gliomas and deserves further prospective evaluation.

Adolescent↗
PubMed2005

O-(2-[18F]fluoroethyl)-L-tyrosine PET for monitoring the effects of convection-enhanced delivery of paclitaxel in patients with recurrent glioblastoma.

PURPOSE: Convection-enhanced delivery (CED) of paclitaxel is a new locoregional approach for patients with recurrent glioblastoma. The aim of this study was to evaluate O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) in monitoring the effects of this type of direct drug delivery. METHODS: Eight patients with recurrent glioblastoma underwent CED of paclitaxel, which was infused over stereotactically placed catheters into the tumour. FET PET and MRI were performed before and 4 weeks after therapy and then at 3-month intervals to document follow-up. For quantitative evaluation, SUV(max)(tumour)/SUV(mean)(background) ratios were calculated. RESULTS: At baseline all tumours showed gadolinium enhancement and high FET uptake (SUV(max)/BG 3.2+/-0.8). Four weeks after CED, a statistically significant decrease in FET uptake was seen (SUV(max)/BG-17%; p<0.01). During follow-up, no recurrence was observed within the CED area. Two out of eight patients with extended tumours died 4 and 5 months after treatment, most probably from local complications. Temporarily stable disease with stable FET uptake was observed in six of eight patients; this was followed by progression and increasing FET uptake ratios (+46%) distant from the CED area in five of the six patients 3-13 months after CED. One patient still presents stable FET uptake 10 months after CED. MRI showed unchanged/increasing contrast enhancement and oedema without ability to reliably assess disease progression. CONCLUSION: FET PET is a valuable tool in monitoring the effects of CED of paclitaxel. In long-term follow-up, stable or decreasing FET uptake, even in contrast-enhancing lesions, is suggestive of reactive changes, whereas increasing ratios appear always to be indicative of recurrence. Therefore, FET PET is more reliable than MRI in differentiating stable disease from tumour regrowth.

Antineoplastic Agents↗
PubMed2004

Special indications in gamma knife surgery.

Pilocytic astrocytoma (PA) represent a rare indication for Gamma Knife Surgery. Mostly small remnants after surgical debulking are treated. The prognosis depends on specific variants of biological and clinical criteria. In this regard we differentiated two groups of tumors; the so-called 'typical' tumors with a histological grading of WHO Grade I, no prior fractionated radiotherapy and no cystic component and the so called 'atypical' tumors with either a malignant transformation, previous fractionated radiotherapy and/or cystic components. The outcome after GKS was much more favourable for typical PA than for atypical. In typical cases a high tumor control with a very low risk of side effects can be achieved.

Adolescent↗
PubMed2004

Microneurosurgery and radiosurgery--an attractive combination.

Microneurosurgery and radiosurgery have made tremendous progress in terms of increasing efficacy and reducing treatment related mobility. Both techniques have clear indications; however, there is still competition between the two modalities in a variety of diseases. In all instances, this rivalry should be replaced by the concept of using both methods as complementary. Skull base tumours, metastases as well as certain AVMs are good candidates for this approach.

Brain Neoplasms↗
PubMed2004

Clinical quality standards for gamma knife radiosurgery--the Munich protocol.

The clinical quality standards for outpatient gamma knife radiosurgery as developed in the German Gamma Knife Center Munich during the last ten years are described. The following aspects have been taken into account: appropriate patient selection, standardised treatment cycle, acquisition of high-quality stereotactic MR images, the integrated therapeutic concept, dose conformity and dose level, patient follow-up, quality control and scientific data analysis. Particular emphasis has been put on the importance of the interdisciplinary treatment concept by subspecialised experts. The results of the Munich concept in consideration of the described quality standards verifies that gamma knife radiosurgery is a safe and effective treatment option for well selected indications.

Ambulatory Surgical Procedures↗
PubMed2004

Results of outpatient gamma knife radiosurgery for primary therapy of acoustic neuromas.

Stereotactic radiosurgery (SRS) has been recognized as a non-invasive alternative to surgery for the treatment of acoustic neuromas. Purpose of the current study was to define the impact of outpatient gamma knife radiosurgery (GKS) for patients with unilateral sporadic acoustic neuromas treated within ten years. Follow-up images were analyzed using tumor volume measurements. 219 patients with sporadic acoustic neuromas were treated by GKS as primary therapy. Patients with NF-2 tumors were excluded. Patients were eligible for GKS up to a size limit of 12.5 cm3. The median follow up time was 6 years after radiosurgery. The local tumor control rate was high (97%). Cranial nerve morbidities were comparably low. 10% of the patients developed hearing loss after radiosurgery and one patient experienced a transient facial neuropathy (0.5%). Transient trigeminal neuropathy developed in 12 patients (5%) and was found to be dependent on the tumor size before treatment. Outpatient gamma knife radiosurgery is a safe and effective treatment method for selected patients with sporadic vestibular schwannomas.

Ambulatory Surgical Procedures↗
PubMed2003

Laminin inhibits lactotroph proliferation and is reduced in early prolactinoma development.

Laminin is a component of the extracellular matrix (ECM) that regulates cell proliferation and hormone secretion. Here we describe the effects of laminin on prolactin secretion in normal and tumor cells and analyze laminin expression pattern during prolactinoma development. Prolactin secretion and cell proliferation were inhibited by laminin in GH3 cells. In contrast, no effect was observed in normal pituitary cells. Laminin showed a dynamic expression pattern during prolactinoma development, which was: (a) strong in normal pituitaries from wild type or dopamine D2 receptor deficient mice, (b) lower in pituitary hyperplasia and (c) markedly reduced in prolactinomas from D2R -/- mice. A similar gradual decrease in laminin was found by comparing normal human pituitaries, human pituitary hyperplasia and human prolactinomas. These results show dynamic changes of laminin expression during prolactinoma formation which, due to laminin action on PRL production and cell proliferation, indicate a possible role for laminin in prolactinoma development.

Analysis of Variance↗
PubMed2003

Intralesional radioimmunotherapy in the treatment of malignant glioma: clinical and experimental findings.

In the last two decades radioimmunotherapy has been used as an additional treatment option for malignant glioma in several centers. More than 400 patients have been reported, who were treated in the framework of different studies. Most of them received labelled antibodies to tenascin, an extracellular matrix-glycoprotein, which is expressed in high amounts in malignant gliomas. We report side effects and survival time of 46 patients, treated after surgical resection and conventional radiotherapy with intralesionally injected labelled (131-Iodine) antibodies to tenascin. Despite the fact, that many treatments have been performed, little is known about the distribution properties of labelled antibodies after injection in the tumour cavity. For an optimal effect labelled antibodies should be able to reach tumour cells, which have migrated into the surrounding tissue. We investigated the propagation velocity and area of distribution of labelled antibodies and their considerably smaller fragments after the injection in C6-gliomas of Wistar rats. Propagation increased with time and was significantly greater after injection of labelled fragments than after injection of labelled antibodies. According to our results labelled fragments might be better able to reach distant tumour cells in the peritumoural tissue of malignant gliomas than labelled antibodies.

Administration, Topical↗
PubMed2003

Mechanisms of glioma cell invasion.

Invasive growth is one of the characteristics of gliomas--local infiltration into the surrounding nerve tissue decisively restricts all treatment strategies. Particularly the merit of all local treatment modalities is queried. The question whether a glioma represents a diffuse disease of the CNS or a local disturbance with unrestrained expansion tendency is still at issue. Understanding of the invasion mechanisms is of importance inasmuch as biologically reasonable and effective strategies of limiting and suppressing glioma invasion can only hence be derived. The affinity of glioma cells towards certain structures of the extracellular matrix as well as taking advantage of tumour vascularisation with regard to extension play a decisive role. Still not fully understood are tumour host interactions. Future thinking will have to take into account these interactions as well as evidence to be derived from development neurobiology and regeneration capacity of the CNS. The present review is meant to give a short overview and disclose many questions.

Animals↗
PubMed2003

Fluorescence-guided resections of malignant gliomas--an overview.

Radical resections of contrast-enhancing tumour in patients with malignant gliomas may be pertinent for survival but are often difficult to achieve due to uncertainties in distinguishing tumour margins intra-operatively. In this respect a number of novel methods are being examined which aim at enhancing resections. Among these methods, resections that exploit the accumulation of fluorescent porphyrins within malignant glioma tissue in response to exogenous administration of a metabolic percursor, 5-aminolevulinic acid, may offer particular advantages. This article summarises the clinical background and current status of 5-ALA drug development for fluorescence-guided resections of malignant gliomas and analyses the available literature with regard to possible mechanisms that govern the highly specific accumulation of fluorescent porphyrins in malignant glioma tissue in response to 5-ALA administration.

Aminolevulinic Acid↗
PubMed2002

Model systems in neurooncology.

Cell- and molecular biological techniques have had a major impact on experimental neurooncology in recent years; yet we are lacking suitable model systems. Monolayer cell cultures are rapid, reproducible and reliable systems, however, their validity is of major concern. Three dimensional culture systems, especially derived from primary biopsies, match better with the in vivo situation albeit being more tricky to handle. Animal models for glioma have to be orthotopic in order to draw any conclusions; most cell lines implanted into rodents still do not show the typical invasive phenotype. In addition, immunological phenomena have to be taken into account as well as changes of the biological features once cells have undergone the process of any transfection.

Animals↗