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Introduction: Intensive care patients commonly suffer from hyperglycemia. Evidence is growing that strictly maintaining normoglycemia by intensive insulin therapy (IIT) ameliorates outcome in these patients. Whether or not this also holds true for patients with sepsis and septic shock is the issue of this post-hoc analysis of the database (2,748 patients) of 2 recent prospective clinical trials.Material and Methods: A total of 950 patients suffering from sepsis were identified and of these 462 fulfilled the diagnostic criteria of septic shock upon admission to the intensive care unit (ICU). Patients were treated by either IIT [mean glycemia 5.88 mmol/l (106 mg/dl)] or conventional glucose management [mean glycemia 8.44 mmol/l (152 mg/dl)].Results: Under IIT the mortality of patients treated for more than 3 days in the ICU was lowered by 7.6% (p=0.03) in septic patients and by 8.7% (p=0.08) in septic shock patients. Polyneuropathy occurred less frequently under IIT compared to conventional glucose management (sepsis -9.8%, septic shock -14%; p<0.001). The incidence of acute renal failure was not affected by either treatment regimen (sepsis -3.3%, septic shock -3.1%; p<0.25). Intensive insulin therapy was associated with an increased risk of hypoglycemia (sepsis +16.7%, septic shock +18.8; p<0.0001) which did not, however, directly affect morbidity nor mortality.Conclusions: These data suggest that IIT improves outcome of patients with sepsis or septic shock. Hypoglycemia is a frequent complication, but its clinical relevance remains to be defined. [ABSTRACT FROM AUTHOR]

Background: Pituitary metastases are rare and commonly described in case reports or small case series. Due to its rarity this entity is not subject to standardized treatment guidelines, there is debate about typical initial symptoms that may lead to finding the correct diagnosis and information about the clinical course is also sparse. Methods: We have conducted a retrospective analysis of patients with pituitary metastases who were surgically treated via a transsphenoidal procedure at our institution between 2006 and 2014. Underlying primary disease, clinical and surgical course as well as adjuvant radiotherapy and follow-up data are presented. Results: 14 patients met the inclusion criteria (8 female, 6 male). Mean age was 61.5 years. Most patients became symptomatic with visual symptoms-both visual deterioration and/or diplopia (n = 13)-and anterior lobe insufficiency (n = 8). Surprisingly diabetes insipidus was only seen in three patients. All patients underwent transsphenoidal surgery initially, four patients had to undergo surgery for residual tumor or recurrence, two of them via a transcranial route. Breast cancer was the most common entity (n = 6), followed by prostate cancer (n = 3), nsclc (n = 2) and melanoma, thyroid cancer and renal cancer in one case each. Postoperative MRI showed gross total resection in four cases and residual disease in eight cases (subtotal resection, partial resection and biopsy), two patients files were incomplete regarding MRI-results. All patients underwent adjuvant radiotherapy. Survival after the initial diagnosis of cancer was 36 and 16 months after diagnosis of pituitary metastases. Conclusion: Our results indicate that transsphenoidal surgery is a safe method to resect pituitary metastases and that the extend of resection does not have an influence on survival time. Our results also indicate that diabetes insipidus may not be the most common initial symptom of pituitary metastases and lack thereof should not lead to making a wrong diagnosis and delaying appropriate therapy. [ABSTRACT FROM AUTHOR]

Intracranial germinomas are fairly rare tumors occurring mostly in children or young adults with a comparatively good prognosis. Radiation is the preferred treatment of choice for this diagnosis. It has been thoroughly studied to what extent radiation doses and fields can be limited in order to avoid side effects in these young patients. The role of chemotherapy remains unclear, whereas surgery is limited to biopsy for proof of histology. Regarding the good overall survival rate, quality of life is a significant aspect to consider in these patients. We present a single institution analysis of patients with intracranial germinoma and analyze the long-term outcome with special regard to quality of life. Thirty-three patients with intracranial germinomas were analyzed by chart review, telephone interview, and neurological assessment. Additionally, a survey on quality of life was performed. The 10-year overall survival rate was 82.1 % at a mean follow-up of 141 (22-306) months. Three quarters (76 %) of the patients reached a favorable neurological outcome on the Modified Rankin Scale (mRS 0-2). However, the self-reported quality of life was significantly worse in germinoma patients compared with a healthy control group ( p < 0.001). Surgical resection of the tumor led to no improvement regarding overall survival, neurological outcome, and quality of life. In terms of cognitive functioning, patients with tumor resection were significantly more impaired than biopsied patients ( p = 0.04). Although germinomas are efficiently treatable tumors, the restrictions in quality of life in these often young patients are considerable, including financial difficulties. There seems no justification for tumor resection in newly diagnosed cases suspicious for germinoma as the cognitive outcome is worse than in biopsied patients, and there is no effect on overall survival. [ABSTRACT FROM AUTHOR]

There is a lack of relevant prognostic and predictive factors in neurooncology besides mutation of isocitrate dehydrogenase 1, codeletion of 1p/19q and promoter hypermethylation of O -methylguanine- DNA- methyltransferase. More importantly, there is limited translation of these factors into clinical practice. The cancer genome atlas data and also clinical correlative analyses suggest a pivotal role for the epidermal growth factor receptor /protein kinase B/mammalian target of rapamycin (mTOR) pathway in both biology and the clinical course of gliomas. However, attempts to stratify gliomas by activating alterations in this pathway have failed thus far. The tumors of 40 patients with WHO grade II gliomas without immediate postoperative genotoxic treatment and known progression and survival status at a median follow-up of 12.2 years were analyzed for expression of the mTOR complex 2 downstream target N-myc downstream regulated gene (NDRG)1 using immunohistochemistry. Baseline characteristics for NDRG1 absent/low versus moderate/high patients were similar. Time to reintervention was significantly longer in the NDRG1 group ( P = 0.026). NDRG1 may become a novel biomarker to guide the decision which WHO°II glioma patients may be followed without postsurgical intervention and which patients should receive genotoxic treatment early on. Validation of this hypothesis will be possible with the observational arm of the RTOG 9802 and the pretreatment step of the EORTC 22033/26032 trials. [ABSTRACT FROM AUTHOR]

Current treatment strategies in patients with newly-diagnosed glioblastoma include surgical resection with post-operative radiotherapy and concomitant/adjuvant temozolomide (the 'Stupp protocol') or resection with implantation of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers in the surgical cavity followed by radiotherapy. In clinical practice, patients with malignant glioma treated with BCNU wafer often also receive adjuvant temozolomide. However, current treatment guidelines are unclear on whether and how these treatment practices can be combined, and no prospective phase 3 study has assessed the safety and efficacy of combining BCNU wafers with temozolomide and radiation in high-grade malignant glioma. The rationale for multimodal therapy comprising surgical resection with adjunct local BCNU wafers followed by radiotherapy and temozolomide is based on complementary and synergistic mechanisms of action between BCNU and temozolomide in preclinical studies; a shared primary resistance pathway, methylguanine-DNA methyltransferase (MGMT); and the opportunity to overcome resistance through MGMT depletion to boost cytotoxic activity. A comprehensive review of the literature identified 19 retrospective and prospective studies investigating the use of this multimodal strategy. Median overall survival in 14 studies of newly-diagnosed patients suggested a modest improvement versus resection followed by Stupp protocol or resection with BCNU wafers, with an acceptable and manageable safety profile. [ABSTRACT FROM AUTHOR]

This article reports on the case of a multiple trauma patient, who was admitted to the intensive care unit with haemorrhagic shock and severe hypoxaemia. Following posttraumatic septic shock the patient developed quadriplegia 3 weeks after admittance. After having excluded any traumatic and cerebral origins, an analysis of the cerebrospinal fluid was performed and revealed a"dissociation albuminocytologique". This finding in association with limb quadriplegia led to the diagnosis of Guillain-Barré syndrome. Therapy with high-dose i.v. immunoglobulins led to a complete recovery. [ABSTRACT FROM AUTHOR]

Objectives: T2' values reflect the presence of deoxyhaemoglobin related to high local oxygen extraction. We assessed the feasibility of T2' imaging to display regions with high metabolic activity in brain gliomas.Methods: MRI was performed in 25 patients (12 female; median age 46 years; range 2-69) with brain gliomas with additional T2 and T2* sequences. T2' maps were derived from T2 and T2*. Dynamic susceptibility weighted contrast (DSC) perfusion was performed in 12/25 patients. Images were visually assessed by two readers and five ROIs were evaluated for each patient. Pearson correlation, Mann-Whitney and Kruskal-Wallis tests were applied for statistical analysis.Results: Three patients were not further evaluated because of artefacts. Mean values of high-grade (III-IV) gliomas showed significantly lower T2' values than low-grade (II) gliomas (p < 0.001). An inverse relationship was observed between rCBV and sqr (T2') (r = -0.463, p < 0.001). No correlation was observed between T2' and rCBV for grade II tumours (r = 0.038; p = 0.875).Conclusions: High-grade tumours revealed lower T2' values, presumably because of higher oxygen consumption in proliferating tissue. Our results indicate that T2' imaging can be used as an alternative to DSC perfusion in the detection of subtle deviations in tumour metabolism. [ABSTRACT FROM AUTHOR]

In recent years further forms of local treatment for primary brain tumors have been developed in addition to resection and radiation. There are basically three principles for local therapy, intralesional therapy for primary or recurrent non-resectable tumors as well as intracavitary and pericavitary therapy following microscopic surgical complete resection. Local therapy procedures are complex and suffer from special difficulties in the evaluation of their effectiveness by imaging techniques, because they are inevitably accompanied by alterations in the imaging, barrier disturbances and contrast medium uptake. [ABSTRACT FROM AUTHOR]

Background: Arginine vasopressin (AVP) and terlipressin (TP) are increasingly used as adjunct vasopressors in the treatment of septic shock. Despite important pharmacological differences between the two drugs (e.g., receptor selectivity, effective half-life) the use of either substance is determined mainly by local availability and institutional inventory. We briefly describe the pathophysiology and pharmacology of septic shock relevant to the treatment with vasopressin analogues. In addition, differences in pharmacokinetics and pharmacodynamics between AVP and TP are discussed.Discussion: The current literature suggests that neither AVP nor TP should be administered in high doses in patients with septic shock. Furthermore, increasing evidence indicates that early administration of vasopressin analogues may improve outcome as compared to a last-resort treatment. Low-dose infusion of AVP (0.6-2.4 U/h) has been demonstrated to be a safe adjunct in the management of septic shock. The V2 agonistic effects of AVP may exert favorable effects on hepatosplanchnic, renal, pulmonary, and coronary perfusion. However, the higher V1 receptor selectivity of TP may prove more potent in restoring arterial blood pressure and avoiding rebound hypotension, while carrying the risk of sustained global and regional vasoconstriction after bolus injection.Conclusions: Evidence from experimental studies and initial clinical reports suggests that continuous low-dose infusion of TP may stabilize hemodynamics in septic shock with reduced side effects. However, randomized, controlled trials are necessary to determine the role of bolus or continuous infusion of TP in the treatment of septic shock before this approach can be recommended for routine clinical use. [ABSTRACT FROM AUTHOR]

Tumor cells with stem cell-like properties can be cultured from human glioblastomas by using conditions that select for the expansion of neural stem cells. We generated cell lines from glioblastoma specimens with the goal to obtain model systems for glioma stem cell biology. Unsupervised analysis of the expression profiles of nine cell lines established under neural stem cell conditions yielded two distinct clusters. Four cell lines were characterized by the expression of neurodevelopmental genes. They showed a multipotent differentiation profile along neuronal, astroglial and oligodendroglial lineages, grew spherically in vitro, expressed CD133 and formed highly invasive tumors in vivo. The other five cell lines shared expression signatures enriched for extracellular matrix-related genes, had a more restricted differentiation capacity, contained no or fewer CD133+ cells, grew semiadherent or adherent in vitro and displayed reduced tumorigenicity and invasion in vivo. Our findings show that stable, multipotent glioblastoma cell lines with a full stem-like phenotype express neurodevelopmental genes as a distinctive feature, which may offer therapeutic targeting opportunities. The generation of another distinct cluster of cell lines showing similarly homogeneous profiling but restricted stem cell properties suggests that different phenotypes exist, each of which may lead to the typical appearance of glioblastoma.Oncogene (2008) 27, 2897–2909; doi:10.1038/sj.onc.1210949; published online 26 November 2007 [ABSTRACT FROM AUTHOR]

Zippa Mountain pluton is a Mesozoic concentrically-zoned intrusion, located within the Canadian Cordillera of British Columbia. An extensive phase of K-feldspar bearing syenite grades towards its margins to mela-syenite and clinopyroxenite. This simple pattern of petrological zonation is overprinted by localised occurrences of silica-undersaturated, peralkaline rock types. High-purity wollastonite skarns occur within and peripheral to the intrusion and result from extensive interaction between intrusion-related fluids and Permian limestone/marble, at shallow crustal levels. Field, chemical and isotopic studies provide insights into interaction between a parental syenitic magma and these country rocks. To achieve this, petrological studies of four of the skarn bodies present have been combined with chemical and isotopic data from the pluton, and from drill core through the skarn into the pluton, to reconstruct the stages in the development of wollastonite skarn and progressive magma-country rock interaction. Derivation of peralkaline compositions from the syenitic magma requires either a loss of Si and Al, or addition of Na and/or K. Our studies preclude the addition of alkali elements but highlight extensive Si-infiltration into the limestone, while the conversion of marble to grossular-andradite skarn, indicates Al-infiltration. Fluid egress resulted in de-silicification/de-alumination of the Zippa Mountain magmas, and increased peralkalinity; wollastonite and garnet-bearing skarn formed as a by-product. Hence, the development of peralkaline rock compositions at Zippa Mountain required a parental syenitic magma, and reaction and/or interaction with calcareous country rocks. [ABSTRACT FROM AUTHOR]

Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective. Adjuvant systemic chemotherapy increases survival of primary malignant glioma patients beyond 12–18 months. The only interstitial chemotherapy treatment approved for malignant glioma is Gliadel® wafer containing carmustine (BCNU) placed in the resection cavity at surgery. Analysis of a large trial by Westphal and colleagues (n = 240) showed a 29% risk reduction ( P = 0.03) in the BCNU wafer-treated group over the course of the 30-month trial. Long-term follow-up of these patients was undertaken to determine the survival benefit at 2 and 3 years. Methods. Survival proportions for the placebo and treatment groups over the 56-month study were estimated by the Kaplan-Meier method. Multiple-regression analyses using the Cox proportional hazards model included prognostic factors of age, KPS, and tumor type. A secondary analysis was conducted for 207 GBM patients. Results. Of the 59 patients available for long-term follow-up, 11 were alive at 56 months: 9 had received BCNU wafers and 2 had received placebo wafers. Median survival of patients treated with BCNU wafers was 13.8 months vs 11.6 months in placebo-treated patients ( P = 0.017) with a hazard ratio of 0.73 ( P = 0.018), representing a 27% significant risk reduction. This survival advantage was maintained at 1, 2, and 3 years and was statistically significant ( P = 0.01) at 3 years. Two of 207 GBM patients remained alive at the end of the follow-up period, both in the BCNU wafer-treated group. Conclusion. Malignant glioma patients treated with BCNU wafers at the time of initial surgery in combination with radiation therapy demonstrated a survival advantage at 2 and 3 years follow-up compared with placebo. [ABSTRACT FROM AUTHOR]

Adrenomedullin (AM) is an endogenous vasodilatory peptide hormone, which plays a key role in the regulation and preservation of cardiovascular and pulmonary functions. Clinical and experimental studies have demonstrated that AM represents an alternative therapeutic option in the treatment of pulmonary hypertension. In addition, AM proved to be useful in the treatment of cardiovascular dysfunctions, such as arterial hypertension and congestive heart failure following myocardial infarction. Recent research has also shown that AM plays a pivotal role in the development of sepsis-associated hemodynamic and microcirculatory disorders. Experimental studies also suggest that infusion of exogenous AM might be a rational approach to prevent and treat hypodynamic septic shock. The objectives of this review article are to characterize the regulative properties of AM and to discuss clinical and experimental studies which allow to judge the role of AM in the setting of cardiovascular dysfunction and sepsis. [ABSTRACT FROM AUTHOR]

Aneurysms originating from perforatoring branches of the midbasilar artery are extremely rare. Rupture of such an aneurysm resulted in a subarachnoid hemorrhage with a prepontine clot in a 44 year old male who presented with an acute confusional state. After coil embolization had failed, the partially thrombosed aneurysm was wrapped and coagulated via a combined supra-/infratentorial subtemporal presigmoid approach in prone position. The postoperative course was complicated by a tension pneumatocephalus and liquorrhea. Additional aneurysms of the anterior communicating artery and right middle cerebral artery were clipped several months later. The patient recovered well, and except for slight gait ataxia no other deficit remained. [ABSTRACT FROM AUTHOR]

Copyright of Der Schmerz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background. Placement of ventricular catheters is a routine procedure in neurosurgery. Ventricle puncture is done using a flexible ventricular catheter stabilised by a solid steel mandrin in order to improve stability during brain penetration. A correct catheter placement is confirmed after removing the solid steel mandrin by observation of cerebrospinal fluid (CSF) flow out of the flexible catheter. Incorrect placement makes further punctures necessary. The newly developed device allows CSF flow observation during the puncture procedure and in addition precise intracranial pressure (ICP) measurement. Method. The developed mandrin is hollow with a blunt tip. On one side 4–5 small holes with a diameter of 0.8 mm are drilled corresponding exactly with the holes in the ventricular catheter, allowing CSF to pass into the hollow mandrin as soon as the ventricle is reached. By connecting a small translucent tube at the distal portion of the hollow mandrin ICP can be measured without loss of CSF. The system has been used in 15 patients with subarachnoid haemorrhage (SAH) or intraventricular haemeorrhage (IVH) and subsequent hydrocephalus. Findings. The new system improved the external ventricular drainage implantation procedure. In all 15 patients catheter placement was correct. ICP measurement was easy to perform immediately at ventricle puncture. In 4 patients at puncture no spontaneous CSF flow was observed, therefore by connecting a syringe and gentle aspiration of CSF correct placement was confirmed in this unexpected low pressure hydrocephalus. Otherwise by using the conventional technique further punctures would have been necessary. Conclusions. Advantages of the new technique are less puncture procedures with a lower risk of damage to neural structures and reduced risk of intracranial haemorrhages. Implantation of the ventricular catheter to far into the brain can be monitored and this complication can be overcome. Using the connected pressure monitoring tube an exact measurement of the opening intracranial pressure can be obtained performed without losing CSF. [ABSTRACT FROM AUTHOR]

Vasopressin and terlipressin are increasingly used as alternative non-adrenergic vasopressors for hemodynamic support of septic patients with arterial hypotension. Despite excellent vasopressive effects, vasopressin analogues may potentially impair macro-hemodynamics, oxygen transport and microvascular blood flow. Due to those unwanted side-effects, vasopressin and terlipressin may potentially compromise organ function and possibly foster the development of multiple organ failure. This review article discusses the results of clinical and experimental studies to judge the effects of vasopressin and terlipressin on microcirculation, oxygen supply, metabolism and organ function in patients with sepsis or systemic inflammatory response syndrome (SIRS). Although vasopressin analogues are emerging as promising alternatives to treat catecholamine-refractory hypotension, there is no evidence that vasopressin receptor agonists improve outcome. To date, vasopressin and terlipressin can, therefore, not be recommended for routine clinical use. [ABSTRACT FROM AUTHOR]

Highlights the 12th European Congress of Neurosurgery in Lisbon, Portugal. Techniques in the treatment of arteriovenous malformation and aneurysms; Ethical aspects of selection for admission to intensive treatment and for withdrawal of treatment of patients with a severe head injury; Gene expression profiles of human gliomas and their clinical significance as tumor classifiers; Limits of skull base surgery for tumors; Use of intraoperative fluorescence as a guide to the resection of a malignant glioma; Development of oncolytic virus therapy; Management of spinal cord tumors with emphasis on the distinction between glial and vascular types.

Summary ¶Background. Orthotopic in vivo models for the experimental treatment of malignant gliomas have become indispensable to evaluate the efficacy of novel therapeutic regimens. Recently, a guide screw system was introduced which is implanted into the cranium of small rodents where it facilitates fast, repeated and exactly reproducible intracerebral injections, avoiding time consuming stereotactic procedures. Here we report our experience with this system, and describe several modifications which we introduced to improve its reliability and to simplify its application. Findings. The most important modification made was the optimization of the guide screw implantation site, which needs to be adapted to the age of the mice. Other improvements were the fixation of the guide screw to the cranium of the mice using a two component adhesive. This avoids the tendency, when daily intratumoural injections are performed over several weeks, for the screw to loosen, making precise injections impossible. The injection procedure, initially described as a free-hand approach, was improved by mounting the syringe to a Greenberg retractor. This provided additional stability and speeded up the process. Applying this modified technique, we were able to achieve reproducible results with regard to engraftment rate, tumour growth, and intratumoural treatment in immunocompromized mice. Interpretation. We introduced several major and some minor improvements to make working with the guide screw system more reliable, faster and more comfortable. Daily injections over a period of three weeks using this system are feasible and well tolerated by mice. [ABSTRACT FROM AUTHOR]

Background: In order to minimize maternal trauma from current techniques for temporary fetoscopic tracheal occlusion, we tried to develop a percutaneous fetoscopic technique in sheep.Methods: In nine ewes between 77 and 128 days of gestation, the amniotic cavity was entered percutaneously. Each fetus was positioned and the feasibility of fetal laryngoscopy and percutaneous fetoscopic tracheal balloon occlusion was assessed.Results: Percutaneous intraamniotic access, fetal positioning, oropharyngeal sheath insertion, and fetoscopic laryngoscopy were achieved in all nine fetal sheep. Following some technical modifications to the working channel of the fetoscope, percutaneous fetoscopic tracheal balloon occlusion was successfully achieved in the last seven sheep.Conclusion: Percutaneous fetoscopic balloon occlusion of the fetal trachea can effectively and safely be achieved in sheep. Because intraamniotic spatial relationships, fetal position, and umbilical cord length are technically less favorable in sheep, our operative techniques might be feasible in humans even if difficult intraamniotic conditions are encountered. [ABSTRACT FROM AUTHOR]

Background: In order to minimize maternal trauma from open fetal surgery for prenatal coverage of fetal myelomeningoceles in humans, we assessed the feasibility of a percutaneous fetoscopic approach in sheep.Methods: In seven ewes between 90 and 100 days of gestation, the amniotic cavity was entered percutaneously. Each fetus was postured and a full-thickness skin lesion was created in the lumbosacral region. Then, the feasibility of covering this lesion with a patch and fetal skin by standard endoscopic suturing techniques (n = 3) or robot assistance (n = 4) was assessed.Results: Percutaneous fetoscopic patch and skin coverage of the full-thickness skin lesion was achieved in six of the seven fetal sheep. Five fetuses survived gestation and were delivered healthy.Conclusions: Percutaneous fetoscopic posturing and patch coverage of lumbosacral full-thickness skin lesions can effectively and safely be achieved in sheep. This approach promises to provide a substantial reduction of maternal trauma from fetal surgery for myelomeningoceles. [ABSTRACT FROM AUTHOR]

Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary. Introduction: The case of a 38-year old man with a histologically benign choroid plexus papilloma arising within the fourth ventricle with en plaque growth around the brain stem and medulla is described in detail. Up to this point this particular growth pattern has not been published and is a rare presentation for this tumour. Clinical Presentation: The patient presented with a 1.5 year history of headache, nausea, and vomiting in the morning. Additional symptoms like blurred vision and gait ataxia lead to hospital admission. MRI demonstrated a homogeneously contrast-enhancing tumour completely filling the fourth ventricle and subsequent obstructive hydrocephalus. In addition Gd enhancement encasing the brain stem, the lower aspect of the medulla and the conus medullaris was seen suggesting a disseminated ependymoma or medulloblastoma. Intervention: An extensive resection of the tumour in the fourth ventricle and CP angle was performed. Infiltrative growth into the structures of the left CP angle and into the rhomboid fossa hampered complete removal. Surprisingly histological examination revealed a well-differentiated papillary choroid plexus papilloma without signs of anaplasia. On follow up imaging the Gd enhancement encasing the pons vanished completely. A growing cyst adjacent to a small tumour residuum left behind on the floor of the fourth ventricle led to re-operation after 8 months with complete removal. Discussion: This case presents several biological, neuroradiological and surgical aspects which make it noteworthy and we hope that the informations provided add to the understanding of these tumours, expand the differential diagnostic thinking of lesions which present with diffuse arachnoid Gd enhancement upon first presentation. [ABSTRACT FROM AUTHOR]

Summary We have previously identified thromboxane synthase as an important regulator of glioma cell migration. Inhibitors of this enzyme abrogate cell motility and induce apoptosis. However, the formation rate of thromboxanes is indirectly dependent on the activity of cyclo-oxygenase, which represents the rate-limiting step in the synthesis of prostaglandins and thromboxanes. In this study we have analyzed the expression of COX-1 and COX-2 in glioma cell lines and biopsies of glial tumors. In normal glia no expression of both COX isoforms was present, however, reactive astrocytes and glial tumors of all grades demonstrated expression of both COX-1 and COX-2. In contrast to inhibitors of thromboxane synthase, selective and non-selective cyclo-oxygenase inhibitors did not block cell motility. Specific COX-2 inhibitors resulted in growth inhibition and induction of intracellular DNA fragmentation indicative of apoptotic cell death. Treatment of glioma cells with thromboxane synthase inhibitors had a synergistic effect on induction of apoptosis by camptothecin, whereas COX inhibitors had not. Furthermore, combined treatment using COX-2 inhibitors and specific thromboxane synthase inhibitors did not show a synergistic increase of apoptosis. These data indicate that COX inhibitors and thromboxane synthase inhibitors influence apoptosis in glioma cells through different pathways. We hypothesize that, in contrast to the COX-2 inhibitors, thromboxane synthase inhibitors block the invasive phenotype of glioma cells and therefore increase the pro-apoptotic disposition of the cells and increase the susceptibility to induced apoptosis. This effect may be independent of prostaglandin synthesis controlled by cyclo-oxygenases. [ABSTRACT FROM AUTHOR]

Summary Background. Only less than half of the patients with malignant gliomas respond to a continuous high dose Tamoxifen (TAM) and/or Carboplatin (CP)-treatment. Therefore, a method for predicting the efficacy of TAM-treatment would be desirable. Methods. Paralleling a clinical study, the predictive value of in vitro-sensitivity testing of TAM and TAM's metabolite 4-OH-TAM in primary cultures of tumour explants from 15 of a total of 50 patients was examined. Additionally, the influence of TAM, 4-OH-TAM, and CP on the proliferation of established glioblastoma cell lines and of those explanted from athymic nude mice and re-established in cell culture was investigated. Human glioblastomas xenotransplanted subcutaneously into athymic nude mice and subsequently treated with TAM and/or CP were examined in a parallel in vivo-study. Findings. TAM-chemosensitivity-testing of glioblastomas failed to predict the clinical response to TAM-treatment in our patients and did not correlate with the in vivo-TAM-response of tumours xenotransplanted into nude mice. TAM's and 4-OH-TAM's ability to inhibit growth of various glioblastoma cell lines in vitro in very similar concentrations was shown to be a consistent phenomenon which seems to be independent of the in vivo response in either patients or mice as previous hosts. However, CP's antiproliferative effect on glioblastomas in vivo was paralleled by respective in vitro results. Whereas TAM showed to mediate its in vitro antiproliferative effect by inducing apoptosis in most cell lines examined, CP-treatment lead to necrosis of cells. Interpretation. Combining the results obtained from our human and mouse studies, it has to be postulated that host factors other than the sensitivity to TAM of the individual cell, determine the efficacy of TAM-treatment in vivo. [ABSTRACT FROM AUTHOR]

The treatment of malignant glioma remains problematic. Surgical removal followed by external beam irradiation represents a standard treatment that has demonstrated a prolonged time to progression and survival. However, the capacity to locally invade normal brain invariably leads to formation of a recurrent tumor most often immediately adjacent to the site of resection. This clinical everyday experience prompts the hypothesis that improved local control of the tumor may translate into a delayed time to progression and possibly survival, specifically because systemic chemotherapy for most of these tumors has failed to significantly improve survival. Local treatment strategies including chemotherapy, gene therapy, and immunotherapy are rapidly developing and progressing to clinical trials. Several theoretical considerations suggest that these approaches may be promising in the treatment of brain tumors. [ABSTRACT FROM AUTHOR]

Provides information on the department of neurosurgery at the University Hospital Eppendorf in Hamburg, Germany. Full administrative independence in 1996; Formative years in the 1930s; Reputation built by Henning Brutt during the department's formative years; General surgeons' opposition to the construction of a neurosurgical unit; Department's struggle for adequate space.

Summary¶ Overexpression or untimely expression of wild-type or mutated protein growth factors and their receptors is associated with the biology of malignant gliomas and other types of cancer. It may result in unchecked tumour cell proliferation, migration/invasion into normal tissue, tumour angiogenesis, escape from immune surveillance, and decreased apoptotic cell death, i.e. after treatment with cytotoxic agents. This often involves activation of growth factor receptors either by simultaneous production of growth factors and corresponding receptors on the same or adjacent tumour cells or by constitutive receptor activation due to mutations. In several instances, the cellular genes encoding these growth factors and receptors are homologous to transforming genes/oncogenes from tumourigenic retroviruses and have thus been regarded as cellular proto-oncogenes. In recent years much progress has been made towards a better understanding of the function of these molecules and how they lead to the aggressive phenotype of malignant gliomas and its inherent resistance to adjuvant therapies. This, still insufficient, knowledge is a prerequisite for the development of novel therapies for this non-curable disease. The aim of this review is to address relevant growth factor receptor systems with emphasis on their particular role in glioma biology. [ABSTRACT FROM AUTHOR]

Intracranial lesions may compromise structures critical for motor performance, and mapping of the cortex, especially of the motor hand area, is important to reduce postoperative morbidity. We investigated nine patients with parietal lobe tumours and used functional MRI sensitized to changes in blood oxygenation to define the different motor areas, especially the primary sensorimotor cortex, in relation to the localization of the tumour. Activation was determined by pixel-by-pixel correlation of the signal intensity time course with a reference waveform equivalent to the stimulus protocol. All subjects showed significant activation of the primary sensorimotor cortex while performing a finger opposition task with the affected and unaffected side. In five patients the finger opposition task additionally activated the ipsilateral sensorimotor cortex and the supplementary motor area (SMA). Extension and flexion of the foot, additionally performed in two patients, also activated the sensorimotor cortex, in one case within the perifocal oedema of the tumour. Tumour localization near the central sulcus induced displacement of the sensorimotor cortex as compared to the unaffected side in all patients with a relevant mass effect. The results of our study demonstrate that functional MRI at 1.5 T with a clinically used tomograph can reproducibly localize critical brain regions in patients with intracranial lesions. [ABSTRACT FROM AUTHOR]

Glial tumours often show high degrees of local invasion that lead to local recurrence of the disease. Extracellular matrix components as well as soluble factors may play a critical role in this poorly understood process. Cyst fluid from human brain tumours may accumulate such autocrine produced factors and may represent a source were those factors may be easily obtained and studied. We have studied the effect of cyst fluids harvested from 17 glial tumours, 3 meningiomas, and three metastases on the motility of established human glioma cell lines. Both cyst fluids of high grade and low grade gliomas contained varying degrees of motility enhancing activity. No such activity was identified in cyst fluids obtained from meningiomas. The relation of mitogenic and motogenic activity in three selected cyst fluids was analysed using a quantitative monolayer migration assay. Quantitative analysis of cyst fluid effects on both proliferation and migration indicate that tumour cyst fluids contain factors that strongly stimulate cell migration and that maximum stimulation of migration did not occur at concentrations optimal for cell proliferation. Our findings indicate that glial tumours in fact produce and secrete soluble factors that may contribute to their dissemination in brain tissue. [ABSTRACT FROM AUTHOR]

We present the results of a series of 105 patients with cerebral arteriovenous malformations (AVMs) who were treated by a combined protocol including endovascular occlusive measures and open surgical resection. 25 patients were treated only by surgical intervention, 72 patients underwent preoperative endovascular embolization and 8 patients were treated only by embolization, seven of which were only treated for palliation. After superselective angiography the vascular territories suitable for endovascular or microsurgical approach were defined, and in most cases these territories were complementary to each other. In 56 cases, only one embolization was necessary and due to an advantageous co-localization of the departments the whole combined endovascular/neurosurgical procedure was done in one anesthesia. If several endovascular sessions were necessary (16 patients), the resection was mostly carried out immediately after the last neuroradiological session in the same anesthesia with total time of such combined procedure now averaging about 7 hours. According to the proposed grading system by Spetzler we treated 25 grade 1, 24 grade 2, 40 grade 3, 11 grade 4, and 5 grade 5 lesions. The overall success rate defined as complete resection without additional permanent neurological deficit was 89.6% (87 out of 97 surgical cases). The benefits of such combined approach to cerebral AVMs become apparent in shortened and safer surgical procedures as well as in a low complication rate. [ABSTRACT FROM AUTHOR]

We report a series of 26 patients affected by a Chiari I malformation treated at our department between 1987 and 1993. All patients underwent pre- and postoperative evaluation by magnetic resonance imaging (MRI). Sequential perioperative motor evoked potential (MEP) recordings were performed in 8 patients. The preoperative symptoms can be divided into four subgroups: cephalgias (84.6%), cranial nerve deficits (69.2%), motor deficits (76.9%), sensory deficits (73%). Twenty-five out of 26 patients underwent craniovertebral decompression, 1 a transoral anterior decompression. One patient died 2 months after surgery because of progressive pulmonary failure. We registered following postoperative complications: transient hypoglossal palsy (1 case), vertigo (2 cases), meningitis (1 case), minor CSF leaks (3 cases). Cephalgias subsided in 17 and improved in 4 out of 22 patients. Cranial nerve deficits improved in 8 and were stabilized in 7 out of 18 patients. A limited recovery of trigeminal function was possibly due to nuclear lesions. Five patients whose vestibular disturbances were not relieved by surgery were put on a course of carbazepine. Vertigo resolved in one case and in two others improved. While hypesthesia improved after decompression, the other sensory deficits were stabilized in 5% of the patients. Spasticity improved in 12 out of 18 patients, but weakness only in 7 out of 17 patients. Motor disturbances ewre always detected by MEP-recording. MEP-characteristics were not specific, resembling those of patients with other intra-, extramedullary myelopathies. Functional recovery was not matched by an improvement of the MEP parameters. MEP may be used as a tool for survellance of patients whose clinical findings are not progressive and are not at first surgical candidates. [ABSTRACT FROM AUTHOR]

Human malignant gliomas are frequently associated with loss of gonosomes and chromosomes 13, 17, and 22. Their progression from anaplastic glioma to glioblastoma is marked by additional loss of chromosome 10. In addition, structural and numerical aberrations of chromosome 7 are frequently found. We report on the karyotypes of a series of 20 human gliomas of which 11 were analysed as established cell lines; 9 cases were investigated in early culture, 5 of which later also became established lines. In addition to the frequently reported overrepresentation of chromosome 7, four cell lines with polysomy for chromosome 22 were seen. A high incidence of structural chromosomal aberrations was present in early cultures as well as in cell lines after various in vitro passages. We found that the general characteristics of karyotypic aberrations found in early cultures or direct preparations of dispersed tumour material were reflected in the pattern of aberrations present in cell lines at much later time points. Thus it appears as if no systematic changes can be attributed to long-term cultures. Suspicious losses of chromosomes 14, 18, and 19 or gain of chromosome 22 indicate that individual cases may have originated due to other mechanisms than the ones already hypothesized, i.e., different suppressor genes or amplification of genes other than the EGF-R-gene. None of the established cell lines had a genomic rearrangement of c-erbB 1, c-erbB 2 or of the p 53 gene. [ABSTRACT FROM AUTHOR]

The evaluation of tumours located in the posterior part of the third ventricle or pineal region is achieved best by magnet resonance imaging (MRI). It shows the exact localization and extent, the involvement of neighbouring structures like thalamus or quadrigeminal plate and the displacement of the large veins, the internal cerebral veins, the vein of Galen and the veins of Rosenthal. If only CT is available, angiography shoud be performed prior to operation to identify the course of the veins. In children with a pineal region tumour the 'tumour markers' AFP and β-HCG should be determined before operation. We approach the rare tumours entirely located within the posterior part of the third ventricle by the posterior interhemispheric transcallosal route with the patient in prone position with the head elevated. The same approach is used for pineal region tumours extending above the internal cerebral veins. Tumours arising from the posterior thalamus extending into the thalamus and ventricle as well, are better approached by the posterior transcortical transventricular route since the lateral view is rather limited by the midline approach. The most frequent tumours in the pineal region are approached if they are located below the internal veins by the infratentorial, supracerebellar route in the sitting position. A total of 60 cases are evaluted. If AFP and/or β-HCG are positive a highly malignant nongerminomatous germ-cell tumour must be suspected. We recommend initial chemotherapy with a combination of Vinblastine, Ifosfamide and Cis-platin without biopsy to avoid tumour seeding. After the 'markers' are normalized operative removal of the residual tumour and radiotherapy should be carried out. In a series of 13 children operated on for pineal region tumours a rigid neuropsychological and endocrine evaluation was perfomed with encouraging results. During the last 10 years we have performed 49 open operations and 11 stereotactic biopsies. 40% of the patients were children under the age of 18. 40% of the tumours in childhood and 60% in adults were benign. In childhood 24% were germinomas and 20% non-germinomatous germ cell tumours. The indications for stereotactic biopsy and for open operation after biobsy are discussed. [ABSTRACT FROM AUTHOR]

Five cultured human glioma cell lines were investigated for their reaction to prostaglandin (PG) D 2 and E 2. In all cases a suppressive effect on DNA synthesis as assessed byH-thymidine incorporation was seen with all test substances as early as six hours after the addition of the compounds in doses of usually 10 M. A dose response curve was generated in four cases and showed an estimated ED 50 of about 5 · 10 M. The effect was most pronounced at 12 hours after which the cultures began to recover except those which had been incubated with PGD 2. In those cultures which had been exposed to PGD 2 virtually no thymidine incorporation was seen after 24 hours and as long as 72 hours. In another set of experiments, the effect of PGD 2, PGE 2, two synthetic PGD 2 analogues, with a chlorine substitution in position 9 (DACl) or with a fluoride substitution in position 9 (DAF) and a synthetic prostacyclin-analogue (Iloprost) was investigated after single and repeated addition of the compounds. A second administration after 12 hours of incubation did not result in a further decrease inH-thymidine incorporation like that observed during that first incubation period. In general the cells recovered after 24 hours total incubation time except those which had received PGD 2 or repeated doses of PGE 2. Only in those cells which had been treated with PGD 2, an almost complete blockade ofH-thymidine incorporation was seen even after the single administration. Parallel evaluation of the cells by flow cytometry showed effects on cell cycle distribution at different times of the incubation. After 12 hours cells began to accumulate in G2/M at levels of approximately twice control, the effect being the least pronounced for PGD 2. For this compound we observed a threefold increase in cells in the S phase. After 24 hours the cell cycle distribution had normalized for all compounds except PGD 2 where the 'arrest' of cells in G2/M persisted to be about 2-3-fold control level until the end of the experiment. Our data suggest, that also in cultured human glioma cells, prostaglandins are effective in suppressing cellular DNA synthesis. Although the effect of PGD 2 can be achieved to some extent by PGE 2 and the analogues which are more stable to dehydrogenases and the metabolic conversion into other biologically active homologues, PGD 2 appears to have a unique quality of action, becoming apparent 24 hours after administration. [ABSTRACT FROM AUTHOR]

Equilibrium binding assays of EGF were performed on confluent cultures of 12 human meningiomas at early passage. In all meningeomas complete binding curves were obtained and the resulting ED 50 values ranged between 0.5 and 6.3 nM. In four cases (ED 50 values ranging from 1.5 nM to 3.0 nM) where saturation analysis was performed, the sites were saturable at similar levels (7nM). In five cases additional experiments were undertaken to evaluate the biological response of cultured cells to EGF as assessed byH-thymidine incorporation. In all cases EGF was a potent stimulus and increasedH-thymidine incorporation by 2.5 to 6-fold. Functionally intact EGF receptors appear to be a regular feature of meningiomas in cell culture and appear not to be related to histological classification. [ABSTRACT FROM AUTHOR]

Cell suspensions of ACTH cell adenomas of 10 patients with Nelson's syndrome were investigated for in-vitro secretion of ACTH. Two incubation systems, one using incubation beakers and the other a superfusion system, were employed. The cells were tested for their reactivity to lysine-vasopressin (LVP), cortisol, and combinations of both. LVP regularly provoked a rapid significant increase of ACTH secretion. The effect of cortisol was heterogeneous. Paradoxical initial stimulatory effects of cortisol were observed. There was a suppressive effect in some patients, which correlates to low proliferative activity in histological evaluation. In both systems a low secretory activity coincided with high proliferative activity in vivo. [ABSTRACT FROM AUTHOR]

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