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G Schackert

Publications and source records attributed to G Schackert.

At least 37 records · Page 2Linked to original sources
PubMed2001

Surgical management of single and multiple brain metastases: results of a retrospective study.

BACKGROUND: Advancement in diagnosis and treatment of various cancer entities led to an increasing incidence of brain metastases in the last decades. Surgical excision of single and multiple brain metastases is one of the central treatment options beside radiotherapy, radiosurgery and chemotherapy. To evaluate the benefit of surgery with/without whole-brain radiation therapy (WBRT) in single brain metastases and the influence of image guidance for brain metastases resection, 104 patients were retrospectively evaluated for post-operative outcome. PATIENTS AND METHODS: Between January 1994 and December 1999 150 patients were surgically treated for brain metastases at the Department of Neurosurgery at the Technical University of Dresden. Outcome could be evaluated in 104 patients with respect to special treatment strategies and survival time (69 patients with single and 35 patients with multiple lesions). RESULTS: Most metastases originated from primary lung and breast tumours. Karnofsky performance score improved on average by 10 after surgery. The extent of the extracerebral tumour burden was the main influence on survival time. Patients' age below 70 years was combined with prolonged survival time (median survival time, MST: 4.5 months vs. 7 months). Patients with solitary cerebral metastasis had a MST of 16 months, whereas patients with singular lesions had a MST of 7 and 4 months, depending on the extent of the extracerebral tumour growth. Additional post-operative WBRT with 30 Gy was combined with an increase in MST in patients with single brain metastasis (surgery + WBRT: MST 13 months; surgery only: MST 8 months). In addition, the rate of recurrent cerebral tumour growth was distinctly higher in the non-WBRT group. Neuronavigation did not significantly improve post-operative survival time. In 80% of patients extracerebral tumour growth limited patients' survival. CONCLUSION: Surgery is an initial treatment option in patients with single and multiple brain metastases especially with large tumours (> 3 cm). Post-operative WBRT seems to prolong survival time in patients with single brain metastasis by decreasing local and distant tumour recurrence. Neuronavigational devices permit a targeted approach. Multiple processes can be extirpated in one session without prolonging the hospitalisation time for the patient. However, neuronavigational devices cannot assure complete tumour resection.

Aged↗
PubMed2001

Therapeutic anti-angiogenesis for malignant brain tumors.

Malignant brain tumors, especially malignant gliomas, have a poor prognosis, a fact which has remained unchanged over the last decades despite the employment of multimodal therapeutic approaches. Malignant gliomas are among the most vascularized tumors known and the amount of vascularization has been correlated to their prognosis. Since tumor growth is dependent on concomitant vascularization, recent experimental studies have focused on the use of anti-angiogenic molecules as a novel strategy in brain tumor therapy. Angiogenesis inhibitors target at proliferating endothelial cells and suppress the formation of a sufficient vascular bed. Inhibitors such as TNP-470, suramin and angiostatin have shown their therapeutic potential in experimental studies. In a clinical setting, they could be applied for the treatment of multiple tumors or postsurgically as an adjuvant therapy to prevent recurrence. This article discusses presently available anti-angiogenic agents, emphasizing on substances already in clinical trials.

Angiogenesis Inhibitors↗
PubMed2001

Lack of association between endoglin intron 7 insertion polymorphism and intracranial aneurysms in a white population: evidence of racial/ethnic differences.

BACKGROUND AND PURPOSE: Endoglin is a component of the transforming growth factor-beta receptor complex and is predominantly expressed on cell surfaces of endothelial cells. A polymorphism of the endoglin gene has previously been found to be associated with the occurrence of intracranial aneurysms in a Japanese population. In our study, we investigated whether this polymorphism is associated with the development of cerebral aneurysm in a white population. METHODS: The study population consisted of 121 white patients who had been treated for intracranial aneurysms, 124 healthy white blood donors, and 15 Japanese volunteers. Exon 7 of the endoglin gene and adjacent intronic sequences were amplified by polymerase chain reaction and analyzed by using an automated laser fluorescence detection system. RESULTS: A well-known insertion polymorphism (5'-TCCCCC-3', starting 23 bp distal from the 3' end of exon 7) was identified. The allele frequencies of the polymorphism were 35 (14.5%) of 242 alleles in the aneurysm group and 35 (14.1%) of 248 alleles in the white control group, which does not represent a statistically significant difference (P>0.85). The sequence of the polymorphism is complementary to that reported in the previously mentioned Japanese study. However, the 2 polymorphisms are identical. Under this assumption, the allele frequencies differ significantly among the Japanese controls in that particular study and the white controls in our study (27.8% versus 14.1%, respectively; P=0.0003). CONCLUSIONS: The genetic polymorphism in the vicinity of 3' end of exon 7 in the endoglin gene was not significantly associated with the occurrence of intracranial aneurysms in the white population. There are ethnic-related differences of allele frequencies between our white controls and the previously reported Japanese controls.

Adult↗
PubMed2000

Molecular analysis of the PTEN, TP53 and CDKN2A tumor suppressor genes in long-term survivors of glioblastoma multiforme.

Despite multimodal therapy, glioblastoma multiforme (GBM) is associated with a poor prognosis with a median survival of less than 1 year. However, a small number of patients with GBM shows survival times of several years. Although clinical features like age and performance status at diagnosis are well known prognostic parameters, molecular markers for prognosis of overall survival are still lacking. Therefore, we compared 2 age- and gender-matched groups of GBM patients with different post-operative time to tumor progression (TTP), defined as 'short-term' for TTP of less than 6 months (n = 21), and 'long-term' for TTP of more than 24 months (n = 21) for genetic alterations of the PTEN, CDKN2A and TP53 genes as well as overexpression of the EGFR, p53 and Mdm2 proteins. For the GBMs with 'short-term' TTP vs. 'long-term' TTP, the studies revealed PTEN mutations in 4/21 vs. 2/21, TP53 mutations in 5/21 vs. 8/21, homozygous deletion of the CDKN2A gene in 5/21 vs. 6/21, overexpression of EGFR in 7/20 vs. 10/20, accumulation of p53 protein in 9/20 vs. 7/20 and of Mdm2 protein in 0/20 vs. 1/20 cases studied. Taken together, our data indicate that mutations of the PTEN and TP53 tumor suppressor genes, homozygous deletion of the CDKN2A gene as well as overexpression of the EGFR, p53 and Mdm2 proteins lack prognostic significance for overall survival time in patients with GBMs.

Adult↗
PubMed2000

Frequent loss of heterozygosity at the 19p13.3 locus without LKB1/STK11 mutations in human carcinoma metastases to the brain.

Inactivating germline mutations of the novel putative tumor-suppressor gene LKB1/STK11 at 19p13.3 have been shown to cause Peutz-Jeghers syndrome (PJS), an autosomal dominantly inherited disease characterized by a predisposition to mucocutaneous pigmentations, as well as various benign and malignant neoplasms. To elucidate the role of LKB1/STK11 in the carcinogenesis of primary and secondary human brain tumors, a total of 309 tumors were analyzed for loss of heterozygosity (LOH) at microsatellite loci D19S886, DI9S878, and D19S565. Low LOH rates were observed for glioma (17.3%, n = 139), meningioma (5.3%, n = 57), schwannoma (0%, n = 21), pituitary adenoma (18.8%, n = 16), primary CNS lymphoma, neuroblastoma, plasmocytoma, medulloblastoma, germinoma, and papilloma of the choroid plexus (6.6%, n = 15). In contrast, brain metastases exhibited a mean LOH frequency of 42.6% (n = 61), with breast (56.3%) and lung cancer metastases (58.3%) being most frequently affected. Genomic DNA sequencing of the complete coding region of LKB1/STK11 was performed in all brain metastases exhibiting LOH (n = 26); no mutation was revealed, but we did find a germline mutation in a PJS patient. Despite high LOH fiequencies at the 19p13.3 locus in carcinoma metastases to the brain and occasional mutations reported for certain primary carcinomas, there are no mutations in LKB1/STK11. This fact suggests that alterations of LKB1/STK11 occur relatively early in tumorigenesis and are rarely involved in the development of carcinoma metastases. Based on these findings, the genes adjacent to LKB1/STK11 may be relevant for the development of metastases to the brain from certain carcinomas.

AMP-Activated Protein Kinase Kinases↗
PubMed2000

Electroencephalogram silence ratio for early outcome prognosis in severe head trauma.

OBJECTIVE: To introduce the electroencephalogram silence-ratio (ESR) as a variable derived from mathematically processed electroencephalogram for early outcome prognosis in patients with severe head trauma and to comparatively assess sensitivity, specificity and predictive value vs. somatosensory evoked potentials and brainstem auditory evoked potentials. DESIGN: Prospective, interventional study. SETTING: Intensive care unit of a university hospital. PATIENTS: A total of 32 adults with severe acute head trauma (Glasgow Coma Scale score < or = 8). METHODS AND MAIN RESULTS: In all patients, electroencephalographic recording was continuously performed by frontomastoid electrode montage for 24-96 hrs after admission to the ICU. The data were subsequently computed by fast Fourier analysis and the ESR (intervals of suppression as periods >240 msecs during which the electroencephalographic voltage did not exceed 5 microV) was displayed and recorded on a computer for further evaluation. Somatosensory evoked potentials and brainstem auditory evoked potentials were elicited during the first 2 days after admission. Outcome evaluation was performed 6 months after trauma using the Glasgow Outcome Scale and the Rappaport Disability Rating Scale. After careful artifact exclusion, the ESR depicted the highest sensitivity, specificity, and positive predictive value compared with evoked potentials. Even a highly significant correlation between outcome and ESR was found (p < .0001). CONCLUSION: The ESR is a valuable variable showing a high reliability with respect to outcome prediction in severe head trauma with a higher predictive value than short latency somatosensory evoked potentials. Evidence exists that the ESR provides at least partial information regarding adequate cerebral oxygen delivery.

Activities of Daily Living↗
PubMed2000

Functional recovery despite prolonged bilateral loss of somatosensory evoked potentials: report on two patients.

A bilateral loss of short latency somatosensory evoked potentials (SSEPs) after head trauma or non-traumatic brain damage is normally associated with a deleterious neurological outcome. An adequate recovery in reported in two deeply comatose patients with head trauma or severe hypertensive encephalopathy despite prolonged bilateral loss of SSEPs over days, found in repeated recordings. Hence, a bilateral loss of SSEPs should not be considered alone for prediction of outcome in cerebral injury.

Adult↗
PubMed1999

Expression of TRAIL and its receptors in human brain tumors.

Recently, TRAIL has been demonstrated to selectively induce apoptosis in transformed cell lines, and subsequently four receptors (TRAIL-R1-TRAIL-R4) have been identified. The ability to transduce death signals is restricted to TRAIL-R1/TRAIL-R2. In contrast, TRAIL-R3/TRAIL-R4 are unable to activate apoptotic pathways and have therefore been suggested to act as "decoys" protecting normal tissues from cell death. However, the biological role of the TRAIL system remains incompletely understood. We analyzed the expression of TRAIL and its receptors in a panel of human brain tumors (n = 34) and in four glioma cell lines in comparison to normal brain tissue. Constant co-expression of TRAIL and of receptors TRAIL-R1, TRAIL-R2, and TRAIL-R3 in different tumor entities as well as in normal brain indicates that additional mechanisms might modulate the previously proposed "decoy" model. Furthermore, in contrast to previous reports, we demonstrate TRAIL and TRAIL-R2 to be present on a transcriptional level in normal brain tissue. Exceptional expression of TRAIL-R4 transcripts does not suggest a significant regulatory role of this receptor in the human brain and its tumors.

Alternative Splicing↗
PubMed1999

Human hypersensitivity angiitis: an uncommon cause of death after trauma.

INTRODUCTION: The article demonstrates, using a case report, that death following an accident may have rarely encountered causes that are not a direct result of trauma and that can only be detected by autopsy. CASE: An unconscious woman aged 57 years was admitted to hospital. Despite immediate surgery for intracranial haemorrhage diagnosed by means of cranial computed tomography, the patient died showing clinical symptoms of circulatory depression after a brief period of stabilisation. The autopsy established myocardial infarction with hypersensitivity angiitis as the cause of death. CONCLUSION: In this case, the authors hold the opinion that the intravenous application of antibiotics during the patient's stay in hospital resulted in hypersensitivity angiitis. The factors causing hypersensitivity angiitis, the morphological picture (clinical, histological) and therapeutic measures are described.

Anti-Bacterial Agents↗
PubMed1999

An easy and safe method to store and disinfect explanted skull bone.

In our department extensive decompression craniectomies became the treatment of choice for patients with massive cerebral oedema following either trauma or acute cerebral infarction. The remarkable survival rates of this neurosurgical technique created the problem of adequate vault defect reconstruction. To evaluate the biological safety of using stored autologous skull flaps for this purpose, we compared three different disinfection methods. Skull bone fragments stored at -21 degrees C for different periods of time were artificially contaminated with clinically relevant strains of Serratia marcescens, Enterococcus faecium and Staphylococcus aureus. As potential methods for disinfection we tested immersion in 3% H2O2, boiling in normal saline for 15 and 30 minutes and a special process of steam disinfection at a temperature of 75 degrees C for 20 minutes. We were able to demonstrate that only steam disinfection completely eliminated the bacterial strains tested. Refrigeration plus steam disinfection of autologous skull bone prior to re-implantation seems to offer reliable safety for its use for defect closure. It is available at reasonable cost in many hospitals and does not require a bone bank.

Bone Transplantation↗
PubMed1999

The biology of melanoma brain metastasis.

Brain metastases are clinically diagnosed in the majority of patients with metastatic melanoma. The prognosis for patients with melanoma brain metastasis is poor with a median survival time of 6 months after diagnosis. Development of better therapies requires a better understanding of the biology of melanoma brain metastasis. The development of a relevant in vivo model offers this possibility. The intracarotid injection of different murine or human melanoma cells into syngeneic or nude mice produces metastases in different regions of the brain. This site-specific metastasis is not due to patterns of initial cell arrest, motility, or invasiveness, but rather to the ability of melanoma cells to proliferate in the brain parenchyma or the meninges. The blood-brain barrier is intact in metastases that are smaller than 0.25 mm in diameter. Although in larger metastases the blood-brain barrier is leaky, the lesions are resistant to many chemotherapeutic drugs. We have also analyzed the malignant behavior of several melanoma cell lines isolated from brain or visceral metastases of patients. The cells from brain metastases showed a slower growth rate and exhibited lower metastatic potential than cells from visceral metastases, indicating that brain metastases do not necessarily represent the end stage in the metastatic cascade. Rather, brain metastases are likely to originate from a unique subpopulation of cells within the primary neoplasm.

Animals↗
PubMed1999

Cushing's disease in a 7-month-old girl due to a tumor producing adrenocorticotropic hormone and thyreotropin-secreting hormone.

We present the case of a 7-month-old baby with Cushing's disease due to an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma combined with cells producing thyreotropin-secreting hormone (TSH). In MRI scans, a contrast-enhancing lesion was seen inside the pituitary fossa, and it extended into the suprasellar region. On the assumption of a pituitary adenoma, surgery was performed. Corresponding with biochemical findings, histopathological evaluation revealed an ACTH- and TSH-producing tumor. Genetic analysis did not demonstrate an alteration at codon 201 (Arg) and 227 (Glu). To our knowledge, this is the first case described in a child of this age.

Adenoma↗
PubMed1999

Loss of heterozygosity accumulation in primary breast carcinomas and additionally in corresponding distant metastases is associated with poor outcome.

The occurrence of distant metastases is the most feared manifestation of breast cancer, often occurring years after the primary surgery and associated with poor survival. The dominant metastatic clone is characterized by an accumulation of genetic alterations, but it is not actually known at what stage of the metastatic cascade these alterations have occurred. We investigated allelic losses during breast cancer progression in a series of 17 primary breast carcinomas and 22 corresponding brain, liver, lung, and bone metastases (mean metastasis-free interval, 31 months) by analyzing 19 microsatellite markers on seven breast cancer- or metastasis-related chromosomal regions and correlated the incidence of combined loss of heterozygosity (LOH) with metastasis-free and postmetastatic survival. We found that, in comparison with the corresponding primary tumor, additional LOH events are frequently found in metastases and that the incidence of combined LOH in the primary tumor, plus the occurrence of additional LOH events in the distant metastases, correlated significantly with decreased postmetastatic survival. Combined LOH of the three breast cancer-related chromosomal regions alone or in combination with allelic loss at the p53 gene region seems to have a specific influence on the aggressive behavior of metastases. We hypothesize that the occurrence of additional LOH events is either involved in termination of dormancy of micrometastatic tumor cells at distant organ sites or acquired during further progression of metastases.

Bone Neoplasms↗
PubMed1999

Genetic alterations of the tumor suppressor gene PTEN/MMAC1 in human brain metastases.

The high mutation rate in advanced brain tumors, recent functional studies, and the high frequency of mutations in prostate metastases all strongly suggest that PTEN/MMAC1 alterations are involved in the formation of metastases. We searched for genetic alterations in the PTEN/MMAC1 gene in 56 consecutive brain metastases from various primary tumors by loss of heterozygosity (LOH), direct sequence analysis, and differential PCR analysis. The highest LOH rates were detected in metastases deriving from lung (67%) and breast (64%) cancers. Three (25%) of the eight detected inactivating mutations (one nonsense mutation, one splice-site mutation, one 11-bp deletion, and five homozygous deletions) were found in metastases originating from 12 different lung carcinomas, suggesting that PTEN/MMAC1 alterations may play a role in the progression of this tumor. With the exception of lung carcinomas, our findings indicate that genetic abnormalities of the PTENM/MMAC1 gene are only involved in a relatively small subset of brain metastases. However, the discrepancy between the high overall LOH rate (50%) and the low frequency of PTEN/MMAC1 mutation detection rate (14%) suggests the presence of one or more additional tumor suppressor genes on chromosome 10q.

Alleles↗
PubMed1998

Evidence that TSG101 aberrant transcripts are PCR artifacts.

Critical analysis of the data published so far concerning the TSG101 gene revealed some inconsistencies leading us to its re-evaluation in 80 breast, brain, colon, and neuroectodermal tumors and 37 normal tissue specimens. In this study, the occurrence of TSG101 cDNA aberrant transcripts was verified, but in addition we made observations that are in apparent conflict with the aberrant splicing theory supposed as the underlying mechanism for transcript formation: the location of most deletion breakpoints within exons and nonconformity of these putative splice sites with the highly conserved GT-AG rule, detection of insertions as well as nonreproducible and highly variable results in repeated RT-nested PCRs. Furthermore, we found that reamplification of full-length TSG101 cDNA products leads to the generation of deleted transcripts. In summary, for the first time we provide evidence that the acquired TSG101 transcripts are caused by PCR artifacts.

Artifacts↗
PubMed1998

Intraoperative facial nerve monitoring (IFNM) predicts facial nerve outcome after resection of vestibular schwannoma.

Intraoperative facial nerve monitoring (IFNM) is a suitable technique for intraoperative facial nerve identification and dissection, especially in large vestibular schwannomas (VS) (acoustic neuroma). To evaluate its feasibility for estimating functional nerve outcome after VS resection 60 patients underwent surgery using IFNM. Out of this group the last 40 patients were included in a prospective study evaluating the prognostic value of various IFNM parameters (proximal and distal absolute EMG amplitude, stimulation threshold, and proximal-to-distal amplitude ratio) for prediction of initial postoperative facial nerve function and recovery of function. Stimulation threshold and absolute EMG amplitude proximally at the brain stem were both predictive for postoperative nerve function. Good initial facial nerve outcome (modified House Brackmann grading, mHB degree I and degree II) was found in 15/16 patients with a proximal EMG amplitude greater than 800 microV and in 19/22 patients with proximal stimulation threshold less than 0.3 mA. Sixteen of 16 patients with proximal stimulation threshold equal to or greater than 0.3 mA had moderate-to-severe facial palsy (mHB degree III or worse). Six of six patients without evokable proximal amplitude initially had insufficient nerve function (mHB degree IV). Intraoperative decrease of the proximal amplitude was associated with an unfavourable outcome, whereas distal amplitudes usually stayed unchanged. Mean distal EMG amplitudes were also found to be decreased with poor nerve function, which may mean that the tumour had already affected the nerve. A proximal amplitude of 300 microV or less and a proximal-to-distal amplitude ratio below 1:3 were found in the absence of functional recovery in 6/8 (75%) and 5/6 (83%) patients with initial mHB degree IV, respectively. Two patients with initial mHB degree IV improved to mHB degree III despite intraoperative evidence of missing functional nerve integrity. Therefore, functional recovery cannot be predicted by IFNM in all cases of anatomical nerve preservation. We conclude that a minimum follow-up period of 1 year may still be advisable even in certain patients without evidence of intraoperative functional nerve integrity.

Adult↗
PubMed1998

Multiple intracerebral haemangioblastomas in identical twins with von Hippel-Lindau disease--a clinical and molecular study.

Von Hippel-Lindau (VHL) disease is an inherited autosomal dominant neoplastic disorder causing central nervous system haemangioblastomas. The VHL gene (3p25-3p26) is known to be a tumour suppressor gene, with its inactivation being responsible for a predisposition to tumour development. As far as we know, the present report of VHL disease manifestation in identical twins is unique. Genetic inquiry into the family background did not reveal this disease among their progenitors. For presymptomatic diagnosis of 17 presently unaffected family members, constitutional DNA of the twins was screened for VHL germline mutations, using loss of heterozygosity studies and exon-specific DNA sequencing. To determine the influence of somatic mutations of the VHL gene in tumourigenesis, DNA of five surgically removed intracerebral haemangioblastomas of the identical twins was analyzed in comparison with their constitutional DNA by DNA sequencing of the complete VHL coding region. However, no allelic losses were found for the VHL gene or for various other tumour suppressor genes (p53, BRCA1, BRCA2, DCC, and MCC). Furthermore, no mutations were found in the constitutional DNA of either twin sister or in the DNA of all five tumour lesions. Based on our observations, we conclude that in certain VHL families, presymptomatic molecular diagnosis of the disease is not feasible and requires close clinical surveillance of all individuals at risk.

Adult↗