PubMed Health⌕ Search

Biomedical subjects

Andreas M Stark

Publications and source records attributed to Andreas M Stark.

17 recordsLinked to original sources
PubMed2006

Glioblastoma--the consequences of advanced patient age on treatment and survival.

Glioblastoma is the most common primary brain tumor. Recent evidence suggests that aggressive treatment is also effective in elderly patients. However, large patient series are missing. The aim of this retrospective study was to determine prognostic factors in a large series (n=345) of elderly patients surgically treated for newly diagnosed glioblastoma (WHO grade IV) at a single institution between 1991 and 2002. U-tests (Mann Whitney), chi-square tests, log-rank tests/Kaplan-Meier plots and Cox regression models were used for statistical analysis. Based on the maximum difference in median survival, a threshold of 60 years was used to separate younger from older patients. In total, 185 patients (53.6%) were over 60 years old. In these individuals, total tumor resection, radiotherapy and reoperation for tumor recurrence were identified as independent prognostic factors. When total surgical resection was combined with radiotherapy and reoperation, Kaplan-Meier analysis revealed a median survival of up to 64 weeks in elderly patients. Our data indicate that total tumor resection, radiotherapy and reoperation should also be considered in selected elderly patients. Age alone should not generally exclude elderly individuals from aggressive treatment.

Adult↗
PubMed2006

Differential expression of matrix metalloproteinases in brain- and bone-seeking clones of metastatic MDA-MB-231 breast cancer cells.

Matrix Metalloproteinases (MMPs) play a crucial role in breast cancer metastasis. We examined the mRNA and protein expression of several MMPs in brain- and bone-seeking clones of MDA-MB-231 breast cancer cells, their transcriptional regulation and their functional role in the metastatic process. MMP mRNA expression was examined using real-time reverse transcription polymerase chain reaction. Protein expression was examined using enzyme linked immunosorbent essay (ELISA). The inducibility of mRNA and protein expression was tested with TPA (phorbol 12-myristate 13-acetate; 50 microM); epidermal growth factor and transforming growth factor beta (20 ng/ml both). Migration and invasion assays were performed with the QCM 96-Well Migration/Invasion Assay (8 microm; Chemicon) over 24 h with or without specific MMPs inhibitors (MMP Inhibitor I Mix (5 microM); MMP-2/MMP-9 Inhibitor III (50 microM); EMD Biosciences). We found significantly higher mRNA expression of MMP-1 and -9 in brain-seeking 231-clones in comparison to -bone and -parental cells. In contrast, the mRNA expression of MMP-3 and -14 was comparable in all cells lines examined and MMP-13 expression was lower in both selective metastatic lines. MMP-2 and -8 were not expressed. ELISA revealed a higher amount of total as well as active MMP-1 and -9 in brain-seeking cells. TPA stimulation showed that MMP-1 and -9 transcription was inducible on the mRNA and protein level in 231-parental but not in 231-brain or -bone. 231-brain showed the highest migration and invasive capacity which could be decreased by the application of MMP-1 and/or MMP-9 inhibitor. Our results indicate functional importance of MMP-1 and -9 overexpression in brain metastasis in an in vitro model.

Bone Neoplasms↗
PubMed2006

Matrix-degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas.

Brain tumors, in particular glioblastomas, have a high morbidity and mortality, mainly due to their invasive nature. A prerequisite for this invasiveness is cell migration based on increased expression of proteases digesting the extracellular matrix. Brevican, an important extracellular proteoglycan that is upregulated in glioblastomas, can be degraded by certain proteases. We demonstrate that in human glioblastomas secretory proteases like ADAMTS4 and ADAMTS5 (aggrecanases 1 and 2; ADAMTS = a disintegrin and metalloproteinase with thrombospondin motifs) are expressed on the mRNA and protein levels in considerable amounts. Real-time RT-PCR shows a higher levels of ADAMTS4 and 5 expressions in glioblastomas in situ, compared to cultured human glioblastoma cells. The upregulation of these proteases in vivo by cytokines may explain this difference. In vitro, transforming growth factor-beta induces ADAMTS4, but less ADAMTS5, and interleukin-1beta ADAMTS5, but not ADAMTS4. As demonstrated by immunohistochemistry and confocal microscopy in situ, ADAMTS5 expression is confined to proliferating glioblastoma cells of surgical tumor sections and with lower intensity to astroglial cells in normal brain sections, as opposed to brevican. In vitro, glioblastoma-derived ADAMTS5 degrades recombinant human brevican to several smaller fragments. Our results show that ADAMTS4 and 5 are upregulated on proliferating glioblastoma cells and these proteases may contribute to their invasive potential.

ADAM Proteins↗
PubMed2006

Chronic recurrent subarachnoid hemorrhage from a trigeminal nerve malignant peripheral nerve sheath tumor: case report.

OBJECTIVE: Clinically significant intratumoral or peritumoral bleeding from trigeminal nerve tumors is very rare. CLINICAL PRESENTATION: We report the case of a 59-year-old man who presented with recurrent subarachnoid hemorrhage from a left trigeminal nerve malignant peripheral nerve sheath tumor. He presented with decreased consciousness, left facial hypesthesia, and left facial weakness. Trigeminal neuralgia was present for 18 months. Cranial computed tomographic and magnetic resonance imaging scans revealed a left parapontine mass with cystic changes and intratumoral bleeding. Furthermore, signs of hemosiderosis of the subarachnoid space were noted. Lumbar puncture revealed fresh bleeding. Angiography detected no aneurysm or other causes of bleeding. The patient became fully alert within hours, the facial weakness improved within a few days. There was no evidence of vasospasm or persisting hydrocephalus. He underwent left-sided suboccipital craniotomy for macroscopically total tumor removal. INTERVENTION: The patient underwent total tumor removal via a left suboccipital approach. Intraoperatively, evidence of recurrent intratumoral bleeding was noted. Histological examination revealed a malignant peripheral nerve sheath tumor (World Health Organization Grade III). Postoperatively, the hypesthesia improved significantly. The patient was transferred to radiotherapy for external beam radiation. CONCLUSIONS: This is the first report regarding a malignant peripheral nerve sheath tumor of the trigeminal nerve that caused clinically significant subarachnoid hemorrhage caused by intratumoral bleeding.

Chronic Disease↗
PubMed2005

Management of tectal glioma in childhood.

Tectal glioma is a topographical diagnosis including tumors of different histology, mainly low-grade astrocytomas. Clinical symptoms are usually associated with increased intracranial pressure. This report discusses the management of this rare tumor in children. Clinical charts of 12 children with tectal glioma treated in our department between 1976 and 2001 were retrospectively reviewed. The mean age at the time of diagnosis was 6.75 years (range, 4 weeks to 16 years). The duration between first symptoms and the diagnosis of tectal glioma was in the range of 2 days to 9 years. Ten patients presented with symptoms associated with increased intracranial pressure, one patient presented with ataxia, and in one case tectal glioma was an incidental finding. First-line therapy was endoscopic third ventriculostomy in 5 cases (42%), ventriculoperitoneal shunting in 6 cases (50%), and combined partial tumor resection and shunting in one case. Histology was obtained in 5 cases (low-grade astrocytoma, n = 4; ependymoma, n = 1). All patients had good neurologic function at the end of follow-up. Tectal glioma represents a distinct subgroup of brainstem tumors associated with a good (or favorable) prognosis. Effective treatment for hydrocephalus is essential; the tumor should be monitored by regular clinical examination and magnetic resonance imaging. Biopsy is warranted in cases with tumor progression.

Adolescent↗
PubMed2005

Glioblastoma multiforme-report of 267 cases treated at a single institution.

OBJECTIVE: Glioblastoma multiforme (GBM) is the most common and most malignant primary brain tumor in adults. We present 267 cases treated at a single institution and discuss clinical characteristics and prognostic factors with regard to the neurosurgical literature. METHODS: Included in this study were 267 patients who underwent craniotomy for newly diagnosed GBM between 1990 and 2001 at our department. Clinical charts and radiographic images were reviewed. Association to patient survival was estimated using log-rank test. RESULTS: Median patient age was 61 years (mean, 59.5; range, 22-86 years), the male-female ratio was 1.2:1. In 35 cases (13.1%) the tumor was multicentric. Most of the tumors were classified as primary GBM (87.6%). During follow-up,72 patients (26.4%) underwent recraniotomy for GBM recurrence and 3 patients (1.1%) developed spinal drop metastases. Overall median survival was 47 weeks (range, 5-305 weeks). The following parameters were significantly associated with prolonged survival: (1) age 61 years or younger, P < .001; (2) Karnofsky performance scale score of 70 or more, P < .001; (3) radiotherapy with a total dose of at least 54 Gy, P < .001; (4) chemotherapy, P < .001; (5) total tumor resection, P = .014; (6) recraniotomy for GBM recurrence, P = .012. CONCLUSIONS: Glioblastoma multiforme remains an important cause of morbidity and mortality from intracranial tumors. The overall prognosis is dismal, although interdisciplinary therapy can significantly prolong survival and allows a small subgroup of patients to survive 3 years or more.

Adult↗
PubMed2005

Breast cancer metastasis to the central nervous system.

Clinically symptomatic metastases to the central nervous system (CNS) occur in approximately 10 to 15% of patients with metastatic beast cancer. CNS metastases are traditionally viewed as a late complication of systemic disease, for which few effective treatment options exist. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment. The blood:brain barrier and the unique brain microenvironment are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. New research approaches using cell lines that reliably and preferentially metastasize in vivo to the brain have been reported. Using such model systems, as well as in vitro analogs of blood-brain barrier penetration and tissue-based studies, new molecular leads into this disease are unfolding.

Antibodies, Monoclonal↗
PubMed2004

Surgical treatment for brain metastases: prognostic factors and survival in 177 patients.

Brain metastases are an increasingly frequent complication of cancer. Advances in diagnosis and treatment have led to wider indications for surgery. We present a single-institution series of 177 patients and discuss our results with regard to the literature. Special focus is on patients with advanced age, multiple brain metastases, extracranial metastases, and brain metastasis recurrence. All patients underwent craniotomy for the resection of solid tumor brain metastases between 1994 and 2001 in our department. Perioperative morbidity and mortality as well as survival were evaluated. The median patient age was 59 years (range 32-86 years). In 177 patients, 348 brain metastases were detected, of which 68.0% were supratentorial and 32.0% were infratentorial. According to univariate analysis, the following parameters were significantly associated with prolonged patient survival: (1) age <70 years, (2) one to three intracranial metastases, (3) favorable postoperative performance, (4) resection of all intracranial lesions, and (5) recraniotomy for brain metastasis recurrence. In contrast, the presence of extracranial metastases, metachronous diagnosis, and solitary brain metastases had no influence on survival. As expected, younger age and limited number of brain metastases (up to three) are favorable prognostic factors. Remarkably, the presence of extracranial metastases had no influence on patient survival.

Adult↗
PubMed2004

Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases.

PURPOSE: Brain metastases are an increasingly common complication in breast cancer patients. The Metastasis Suppressor Genes (MSG) Nm23, KISS1, KAI1, BRMS1, and Mkk4 have been associated with the metastatic potential of breast cancer in vitro and in vivo. METHODS: The mRNA expression of Nm23, KISS1, KAI1, BRMS1, and Mkk4 in fresh frozen tissue samples of brain metastases from ductal invasive breast cancer specimens was examined in relation to primary tumors. In a first step, mRNA expression screening was carried out using a semi-quantitative RT-PCR approach, in a second step quantitative real-time RT-PCR was performed on selected specimens. By immunohistochemical staining, gene products were visualized on the protein level. RESULTS: Semi-quantitative RT-PCR revealed reduced mRNA expression of Nm23, KISS1, KAI1, BRMS, and Mkk4 in brain metastases. Results for KISS1, KAI1, BRMS, and Mkk4 were confirmed by real-time RT-PCR. In detail, mRNA expression reduction in breast cancer brain metastases was tenfold. Expression of MSG could be confirmed by immunohistochemical staining on protein level. CONCLUSIONS: Our investigations revealed significantly reduced mRNA expression of metastases suppressor genes KISS1, KAI1, BRMS1, and Mkk4 in breast cancer brain metastasis. Particularly, in the case of KISS1 and Mkk4, an important role for future treatment of patients with breast cancer brain metastatic lesions can be assumed.

Antigens, CD↗
PubMed2003

Accidental intrathecal mercury application.

The authors present a case of accidental intrathecal mercury application. A 69-year-old white woman was admitted to our department with suspected meningitis following surgery for spinal stenosis at another hospital. Postoperatively, she had developed a cerebro-spinal fluid (CSF) fistula with a subcutaneous cavity. Local wound irritation had been suspected and, unfortunately, mercury-containing disinfectant was injected into the cavity. Within 24 h the patient demonstrated acute neurological deterioration due to meningitis and encephalitis and was admitted to our clinic with suspected meningitis due to postoperative CSF fistula. Lumbar puncture revealed desinfectant-stained, non-bloody CSF, while lumbar MRI demonstrated the large lumbar subcutaneous cavity. Additionally, CSF fistula was visualized on MRI. Laboratory examination revealed extremely high mercury levels in CSF, blood and urine. Treatment consisted in insertion of a lumbar drainage to wash out the mercury. The patient underwent medical detoxication using chelating agents (DMPS: RS-2,3-dimercapto-1-propansulfonacid, DMSA: meso-2,3-dimercaptosuccinatacid). Surgery was performed in order to close the cavity and the fistula. Postoperatively, the patient was admitted to the intensive care unit and remained intubated for 3 days. Within 4 weeks after surgery, she demonstrated good recovery. Eighteen months after intoxication, polyneuropathy and slight neuropsychological deficiencies were detectable.

Aged↗
PubMed2003

Skull metastases: clinical features, differential diagnosis, and review of the literature.

BACKGROUND: Most metastatic skull lesions are asymptomatic, although they can cause severe disability due to compression of dural sinuses and cranial nerves. The authors present current cases of calvarial and skull base metastases. Clinical features are compared to those of primary skull tumors and tumor-like lesions. METHODS: We retrospectively reviewed the charts and radiographic images of 38 patients who underwent surgery for a skull lesion at our department between 1991 and 2001. The literature on skull metastases was reviewed. RESULTS: In 12 cases, histologic examination revealed skull metastases. Eleven patients were known to suffer from cancer at the time of presentation. However, in 5 cases metastatic lesions were the first evidence of disseminated disease. Radical resection was possible in 9 cases. Removal and reconstruction of the infiltrated dura mater was necessary in 5 patients, whereas reconstruction of the bone was required in 8 patients. In comparison to 18 cases with primary skull tumors, patients with skull metastases presented less frequently with a neurologic deficit (3/12 vs. 9/18), reported a shorter history of symptoms (median 2 months vs. 24 months), and were older (median 70 years vs. 51 years). CONCLUSION: Patients presenting with skull metastases are often in an advanced stage of disease, although surgery can relieve symptoms quickly and effectively with low morbidity. In particular, patients with signs of dura infiltration and related neurologic deficit should be offered neurosurgical therapy.

Adolescent↗
PubMed2003

Cerebral edema leading to decompressive craniectomy: an assessment of the preceding clinical and neuromonitoring trends.

The aim of this study was to examine the pre-operative clinical and neuromonitoring courses in patients with a decompressive craniectomy to assess and to compare clinical and neuromonitoring signs indicating extensive cerebral edema. We conducted a retrospective analysis of the clinical signs and courses of simultaneous monitoring of intracranial pressure (ICP) and cerebral oxygenation (PtiO2) in 26 consecutive patients who were sedated and treated with a decompressive craniectomy due to extensive cerebral edema after aneurysmal subarachnoid hemorrhage (SAH) (n = 20) or severe head injury (SHI) (n = 6). Pathological monitoring trends always preceded clinical deterioration. In 18 of 26 patients extensive cerebral edema was indicated solely by increasing ICP > 20 mmHg or decreasing PtiO2 < 10 mmHg or both. Anisocoria occurred in only 8 of 26 patients. As opposed to SHI patients, 9 of 20 SAH patients showed decreasing PtiO2 as first warning sign clearly before neurological deterioration or ICP increase. This series shows the utility of combined ICP and PtiO2 monitoring in patients who develop extensive cerebral edema. Pathological monitoring trends indicate deterioration prior to clinical signs which offers a wider therapeutical window. PtiO2 monitoring appears to be particularly valuable after aneurysmal SAH as adjunct to ICP monitoring and CT imaging.

Adolescent↗
PubMedDate not supplied

Protein expression of Fas, Fas ligand, Bcl-2 and TGFbeta2 and correlation with survival in initial and recurrent human gliomas.

Several studies have recently demonstrated that human gliomas express Fas, Fas ligand (FasL), Bcl-2 and TGFbeta2 at some degree. These factors are considered to interact with apoptotic processes and to have immuno-reactive potential. Their role for tumor evasion from the immune surveillance is currently under examination. To date, there is only limited information about the definite expression patterns of these four factors in human gliomas, particularly in pilocytic astrocytoma (PA) and recurrent tumors. We analyzed 75 human gliomas for the immunohistochemical expression of Fas, FasL, Bcl-2, and TGFbeta2: (1) 25 PAs (WHO grade I), (2) 25 primary glioblastomas (WHO grade IV), and (3) 25 paired initial and recurrent glioblastomas (WHO grade IV), respectively. Co-expression of all four factors was present in the majority of specimens, i.e. in 72% (18/25) of PAs and 88% (47/50) of primary glioblastomas. Pilocytic astrocytomas showed significantly higher scores of TGFbeta2 expression (p < 0.05) and significantly lower Fas, Fas ligand and Bcl-2 scores (p < 0.05) than glioblastomas. There were no significant expression differences in initial versus recurrent glioblastoma specimens. Likewise, no significant correlation was observed between protein expression and clinical parameters, i.e. total survival time or progression free survival time, as documented by Kaplan-Meier method and log rank-test. In conclusion, Fas, FasL, Bcl-2 and TGFbeta2 are differently expressed in PAs versus glioblastomas. These factors, however, are not associated with patient prognosis. The broad co-expression of these factors may enable new therapeutic approaches in the future.

Adolescent↗