Polyamine metabolism in gliomas

Summary Biosynthesis of the polyamines putrescine, spermidine, and spermine has been found to be activated in tissues with cellular proliferation. In the present study we have investigated polyamine levels and the activity of the first rate-limiting enzyme ornithine decarboxylase (ODC) in tumour samples obtained during operation of 202 patients with gliomas. Biochemical data were closely related to the grading of malignancy and to the morphological characteristics of each sample. Mean ODC activity was significantly higher in all gliomas as compared to peritumoural non-neoplastic brain. Furthermore, it was significantly higher (p 0.001) in anaplastic gliomas who grade III and IV (9.0 ± 9.6 nmol/g/h) than in gliomas WHO grade I and II (3.3 ± 4.2 nmol/g/h). Highest enzyme activity (58.5 nmol/g/h) was found in solid and vital parts of malignant tumours, whereas predominantly necrotic areas exhibited low ODC activity (< 1 nmol/g/h). Thus, intra- and interindividual variability of ODC activity corresponded well to histomorphological heterogeneity in high-grade gliomas. Putrescine levels also increased with rising grade of malignancy, whereas spermidine and spermine levels did not correlate with the histological grading. In conclusion, high ODC activity represents a biochemical marker of malignancy in gliomas, but low values do not prove benignity. The present study reinforces the need of further and more extensive tumour sampling closely related to follow-up investigations in the heterogeneous group of gliomas.     

Deletions in chromosome arms 3p and 11q are new prognostic markers in localized and 4s neuroblastoma.

PURPOSE: To find new nonrandom chromosomal changes in neuroblastoma (NB) with a potential to forecast the patient's outcome, alterations in chromosome arms 3p and 11q were investigated. EXPERIMENTAL DESIGN: Frequency and prognostic potential of 3p and 11q alterations in 144 NBs were analyzed using interphase fluorescence in situ hybridization with DNA probes for 3p26 and 11q23. Aberrations were defined as deletion (monosomy of a specific region) or imbalance (at least two intact and additional 3p26- or 11q23-deleted chromosomes). RESULTS: Forty-two of 144 cases (29%) displayed 11q alterations (21% deletions, 8% imbalances). Most aberrations were associated with stage 4 disease (28 of 59, 47%) but were also present in localized and 4s tumors (14 of 85, 16%; P = 0.007). Patients with 11q deletion/imbalance were significantly older at diagnosis (P < 0.001). Changes in 3p were detected in 26 of 144 (18%) samples (15% deletions, 3% imbalances). These alterations were also associated with stage 4 [20 of 59 (34%) versus 6 of 85 (7%) in stages 1-3 and 4s, P = 0.007], and the median age was increased (P < 0.001). Aberrations in both chromosomes were highly associated with each other (P < 0.001). MYCN amplification (MNA) was detected in 10% and 12% of tumors with 11q and 3p alterations, and changes in 1p36 occurred in 13% and 26% of the 3p- and 11q-aberrant tumors. MYCN amplification and 11q deletion/imbalance tended to show an inverse correlation (P = 0.07) as well as 1p and 3p deletion/imbalance (P = 0.07). Patients with 3p and 11q abnormalities in localized/4s tumors showed an inferior outcome compared with those without these alterations (P = 0.002 and P = 0.0027, respectively), in particular in MYCN single copy tumors (P < 0.0001 and P = 0.0006, respectively). CONCLUSION: Alterations in 3p and 11q are frequent nonrandom aberrations in NB and define a new high-risk subgroup in MYCN single copy stage 1-3 and 4s disease.     

AIDS-related B-cell lymphoma (ARL): correlation of prognosis with differentiation profiles assessed by immunophenotyping

This study was undertaken to analyze the differentiation profiles assessed by immunophenotyping in AIDS-related B-cell lymphoma (ARL) and their relation to the clinical course. Paraffin-embedded sections of 89 ARL cases during 1989 to 2004 were stained immunohistochemically with antibodies to CD3, CD10, CD20, CD38, CD138/Syndecan-1 (Syn-1), multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4), B-cell lymphoma protein-2 (BCL-2), BCL-6, latent membrane protein-1 (LMP-1), and Ki-67. Expression of CD10 and CD20 were associated with better overall survival (OS; P = .009 and P = .04, respectively). Expression of CD20 was associated with longer disease-free survival (DFS; P = .03), whereas expression of CD138/Syn-1 was associated with shorter DFS (P = .03). OS and DFS were worse in patients with immunophenotypic profiles related to post-germinal center (GC) differentiation (BCL-6 and CD10 negative, MUM1/IRF4 and/or CD138/Syn-1 positive) when compared with GC differentiation (P = .01). When controlled for age-adjusted International Prognostic Index (IPI), prior AIDS-defining illness (ADI), and year of ARL diagnosis, a post-GC differentiation remained significantly associated with poor OS and DFS. Expression of CD10 was associated with a preserved immunocompetence, whereas CD20 was less frequent in patients developing ARL while on highly active antiretroviral therapy (P = .04). In summary, lack of CD20 or CD10 expression and a post-germinal center signature are associated with a worse prognosis in ARL.     

Internalizing Risk Factors for College Students' Alcohol use: A Combined Person- and Variable-Centered Approach

Background: Most studies that investigate internalizing problems (i.e., depression and anxiety symptoms) and alcohol use disorders use variable-centered approaches, losing important information about differences among individuals. Objectives: To group college students by different profiles of alcohol-use risk factors using a person-centered cluster analysis in two separate samples. Methods: Questionnaires were used in both studies to assess positive expectancies regarding alcohol use, coping motives for alcohol use, and symptoms of depression and anxiety. In the first study (2012), we collected information about past month alcohol use, including frequency and binge drinking episode (n = 171). In the second study (2013), we also included measures of externalizing behaviors and negative alcohol-related consequences (n = 526). Results: In Study 1, the cluster analysis identified four groups of students who displayed different patterns of risk: a low-risk group, moderate cognitions/low internalizing cluster, a high internalizing/low coping motives group of drinkers, and a high internalizing/high coping motives cluster of drinkers. This fourth group showed high levels of depression, moderate anxiety, high positive expectancies and coping motives for alcohol use, and reported the highest frequency of alcohol use. Study 2 replicated the findings from the previous study. Three groups of individuals were identified, replicating the low-risk cluster, the moderate cognitions/low internalizing cluster, and the internalizing cluster of drinkers from Study 1. Participants in the latter cluster endorsed the highest number of negative consequences of alcohol use. Conclusions: Results from both studies highlight the importance of tailoring alcohol abuse prevention efforts to a subgroup young adult who endorse internalizing symptoms.     

High Skp2 expression characterizes high-risk neuroblastomas independent of MYCN status.

PURPOSE: Amplified MYCN oncogene defines a subgroup of neuroblastomas with poor outcome. However, a substantial number of MYCN single-copy neuroblastomas exhibits an aggressive phenotype similar to that of MYCN-amplified neuroblastomas even in the absence of high MYCN mRNA and/or protein levels. EXPERIMENTAL DESIGN: To identify shared molecular mechanisms that mediate the aggressive phenotype in MYCN-amplified and single-copy high-risk neuroblastomas, we defined genetic programs evoked by ectopically expressed MYCN in vitro and analyzed them in high-risk versus low-risk neuroblastoma tumors (n = 49) using cDNA microarrays. Candidate gene expression was validated in a separate cohort of 117 patients using quantitative PCR, and protein expression was analyzed in neuroblastoma tumors by immunoblotting and immunohistochemistry. RESULTS: We identified a genetic signature characterized by a subset of MYCN/MYC and E2F targets, including Skp2, encoding the F-box protein of the SCF(Skp2) E3-ligase, to be highly expressed in high-risk neuroblastomas independent of amplified MYCN. We validated the findings for Skp2 and analyzed its expression in relation to MYCN and E2F-1 expression in a separate cohort (n = 117) using quantitative PCR. High Skp2 expression proved to be a highly significant marker of dire prognosis independent of both MYCN status and disease stage, on the basis of multivariate analysis of event-free survival (hazard ratio, 3.54; 95% confidence interval, 1.56-8.00; P = 0.002). Skp2 protein expression was inversely correlated with expression of p27, the primary target of the SCF(Skp2) E3-ligase, in neuroblastoma tumors. CONCLUSION: Skp2 may have a key role in the progression of neuroblastomas and should make an attractive target for therapeutic approaches.     

CT-guided percutaneous aspiration of Tarlov cyst as a useful diagnostic procedure prior to operative intervention

Summary Tarlov or perineural cysts are lesions of the nerve root most often found in the sacral region. Several authors recommend surgical treatment of symptomatic Tarlov cysts. However, successful surgical treatment is dependent on appropriate patient selection.In this article, we report three cases of a sacral perineural cyst, causing sciatic pain, and emphasize the usefulness of CT-guided percutaneous aspiration as an important diagnostic and prognostic procedure prior to definitive operative treatment.     

Various surgical treatments of chronic subdural hematoma and outcome in 172 patients: is membranectomy necessary?

BACKGROUND: The initial surgical management of chronic subdural hematoma (CSDH) is still controversial, and a standard therapy does not exist. Because of the advanced age and multiple medical problems of the patients, surgical therapy is frequently associated with complications. METHODS: A retrospective study was performed on 172 patients with CSDH, comparing the efficacy of three different primary surgical methods: drainage of hematoma through two different burr-holes without membranectomy (Group A, n = 38); enlarged craniectomy with a size of about 30 mm craniotomy with partial membranectomy and drainage (Group B, n = 121); and extended craniotomy with partial membranectomy and drainage (Group C, n = 13). RESULTS: Independent of surgical method, the general outcome of the patients was good. The rate of reoperation in the group of burr-hole drainage was 16%, slightly lower than in partial membranectomy with enlarged craniectomy or extended craniotomy with 18% and 23%, respectively. In patients with coagulopathy, the rate of reoperation was 41% (16/43), significantly higher than the rate in noncoagulopathic patients 12% (15/129). CONCLUSIONS: In this study, an extended surgical approach with partial membranectomy has no advantages regarding the rate of reoperation and the outcome. As initial treatment, burr-hole drainage with irrigation of the hematoma cavity and closed-system drainage is recommended. Extended craniotomy with membranectomy is now reserved for instances of acute rebleeding with solid hematoma.     

Intracranial ependymomas: Prognostic aspects

According to the grading of brain tumors as proposed by the WHO in 1976, out of 128 ependymomas 83 tumors could be classified as grade II and 38 as grade III Only seven subependymomas were benign and could be assigned to grade I.In contrast to most series known from the literature, 73 ependymomas were located above the tentorium and only 55 in the posterior cranial fossa. The grade of malignancy rised with an increased distance from the ventricular level.Macroscopically complete exstirpations were usually possible in hemispheric ependymomas, whereas tumors arising from the floor of the fourth ventricle often allowed only a partial removal. The operative mortality in the infratentorial group was more than twice as that in the supratentorial group.Postoperative survival was predominantly dependent on the histologic grade of malignancy. The five year survival rate without recurrence was 57.4% in grade II ependymomas as compared to 24.1% in grade III ependymomas. It could be improved by postoperative radiation therapy in both groups of malignancy. The almost identical longterm results indicate that even in less malignant ependymomas new tumor growth will occur later on.     

Connective tissue reactions in subdural haematomas: Imaging with contrast-enhancement MRI

Summary The sensitivity of contrast enhanced magnetic resonance imaging (MRI) in the detection of connective tissue reactions accompanying the maturation of subdural haematomas (SDH) was studied. An outer enhancing layer between the SDH and the tabula interna of the vault was shown in 16 out of 17 cases. In early SDH this outer enhancing layer presumably is due to vascular congestion and/or increased vascular permeability. A thickening of the outer enhancing layer and/or an inner enhancing layer between the haematoma and the subarachnoid space was visible in 9 patients and represented a haematoma capsule formed by proliferating granulation tissue. In 5 SDH septations were found, 3 SDH consisted almost completely of enhancing granulation tissue. Thus, contrast enhanced MRI delivers additional information about the structure of SDH, which are useful for determining the extent of surgical treatment especially in chronic SDH.