Variation in guideline implementation and adherence regarding severe traumatic brain injury treatment: a CENTER-TBI survey study in Europe

Guidelines may reduce practice variation and optimize patient care. We aimed to study differences in guideline use in the management of traumatic brain injury (TBI) patients and analyze reasons for guideline non-adherence. As part of a prospective, observational, multi-center European cohort study, participants from 68 centers in 20 countries were asked to complete 72-item questionnaires regarding their management of severe TBI. Six questions with multiple sub-questions focused on guideline use and implementation. Questionnaires were completed by 65 centers. Of these, 49 (75%) reported use of the Brain Trauma Foundation Guidelines for the medical management of TBI or related institutional protocols, 11 (17%) used no guidelines and 5 used other guidelines (8%). Of 54 centers reporting use of any guidelines, 41 (75%) relied on written guidelines. Four centers of the 54 (7%) reported no formal implementation efforts. Structural attention to the guidelines during daily clinical rounds was reported by 21 centers (38%). The most often reported reasons for non-adherence were ‘every patient is unique’ and the presence of extracranial injuries, both for centers that did and did not report the use of guidelines. There is substantial variability in the use and implementation of guidelines in neurotrauma centers in Europe. Further research is needed to strengthen the evidence underlying guidelines and to overcome implementation barriers

Cerebellar pilocytic astrocytoma: A treatment protocol based upon analysis of 73 cases and a review of the literature

In a retrospective study of 73 patients operated on for cerebellar pilocytic astrocytomas, results of treatment, outcome and biological behaviour of residual tumour were analysed. Complete tumour resection proven by CT or MRI scans within 1 year after surgery was achieved only in 69% of cases. In 31% of cases the surgeon's opinion on the extent of surgical resection was not borne out by the result of postoperative neuroimaging. Progression of residual tumour or tumour recurrence appeared in 19% of patients, 1 patient showed metastatic spread along the craniospinal axis, and in 1 patient malignant degeneration appeared during follow-up. Stable residual tumour or regression of residual tumour was seen in 14% of patients. Outcome after surgical treatment, which was combined with irradiation in 10 patients (14%), was favourable in 80% and unfavourable in 20% of patients. This outcome of treatment was not influenced by a second operation for progression of residual tumour or recurrent tumour. Characteristics of patients with tumour progression after the first operation did not differ from those of the whole group. There were 17 reoperations for residual or recurrent tumour, 10 of which took place within 4 years after the initial surgical treatment. Surgery-related morbidity was 15% and mortality 4%. Irradiation to residual tumour in s patients was followed by complete regression in 1 patient, progression in 4 patients and no changes in 1 patient. For the remaining 2 patients the effect of irradiation on the residual tumour is unknown. Factors that determine the prognosis are discussed on the basis of this retrospective analysis and the data from the literature. It is concluded that optimal treatment for a cerebellar pilocytic astrocytoma does not consist solely in surgery with the aim of total tumour removal and careful tumour handling in order to avoid spread of tumour cells and subsequent metastases and additional radiation therapy in strictly selected cases, but also in posttreatment follow-up based on direct postoperative neuroimaging, preferably by MRI. An algorithm for postoperative follow-up management is presented

AgNOR staining may reflect the growth potential of pilocytic astrocytomas

The value of AgNOR staining as a tumor biological marker was tested in 26 children with pilocytic astrocytomas (20) and fibrillary astrocytomas (6). All patients were surgically treated and then followed up by periodic MRI or CT scans. Follow-up ranged from 8 to 84 months, with a mean of 44 months. AgNOR expression was determined by using semi-automated computer-assisted surface area measurements. AgNOR values ranged from 1.4 to 81.4 mu m(2) per cell, with a mean of 26.6 and a median of 15.2. The median value was taken as a "cut-off" score separating two groups of patients with low and high AgNOR scores. Of the 13 patients in the low scoring group, 8 had total resections without recurrence, 3 had stable residual tumors, I had regressing residual tumor after irradiation and 1 had a recurrence 5 years after neuroradiologically complete resection of a fibrillary astrocytoma. In the group with high AgNOR scores only 2 patients had total resections without recurrence; 5 had stable residual tumors and 6 had residual tumors that showed progression, all within 1 year after surgery. Among the patients with classic juvenile pilocytic astrocytomas of the cerebellum 7 had residual tumor, which progressed in 2 patients, both of whom had high AgNOR scores. Among 7 patients with optic/hypothalamic tumors the 3 with rapidly progressing tumors all had very high AgNOR scores. The determination of AgNOR expression might be helpful in selection of patients with residual tumor after surgery, who may benefit from additional chemotherapy or (stereotactic) radiation therapy

The proliferative potential of the pilocytic astrocytoma:The relation between MIB-1 labeling and clinical and neuro-radiological follow-up

The proliferative potential of 39 pilocytic and 5 low grade astrocytomas was studied in relation to the Ki-67 activity as measured by the MIB-1 Labelings Index. The results were correlated to the biological behaviour of the tumor as measured by clinical and neuro-radiological (CT- or MRI-scans) follow-up of the patient. This study was undertaken to answer the question whether MIB-1 expression reflects differences in biological behaviour of these tumors, such as rapid progression of residual tumor or stable remaining tumor. MIB-1 LI values ranged from 0 to 19% in the group of pilocytic astrocytomas (mean 4,2%) and from 0 to 15% in the 5 low grade astrocytomas (mean 4,2%). All patients were operated and 23 of them had incomplete tumor resection as proven on postoperative neuro-imaging studies. Those 23 patients could be subdivided into two groups, one without progression of residual tumor during follow-up (n = 12) and the other with tumor progression (n = 11). mean MIB-1 LI in the group with 'quiescent' tumor tended to be lower than in the group with progressive tumor: 3,3% vs. 6,6%. Residual tumors which were negative for MIB-1 staining showed fewer progressions of residual tumor compared to those being positive for MIB-1 staining, however this difference was not significant (p = 0, 15, Fisher exact test). Tumor samples of a second operation of the same patient had lower MIB-1 LI values than those of the samples taken at first operation. The proliferating potential seemed to be decreased after part of the tumor was resected. Pilocytic astrocytomas with a negative MIB-1 LI are unlikely to show progression of residual tumor after partial resection. MIB-1 staining might be an additional tool in determining the frequency and duration of follow-up and in making decisions regarding further treatment of a patient operated for a pilocytic astrocytoma with residual tumor

Glioblastoma multiforme in four siblings: a cytogenetic and molecular genetic study

The familial occurrence of gliomas, in the absence of well-defined neurological tumor syndromes such as the neurofibromatoses, is uncommon, We present a family of ten children in which the four eldest suffered from gliomas. Three of these siblings had histologically verified glioblastoma multiforme, and one patient also had an intestinal non-Hodgkin's lymphoma, but there were no stigmata or family history of a neurological tumor syndrome. Cytogenetic studies of the proband revealed a normal karyotype. Molecular genetic analysis of the proband's glioblastoma revealed two mutations in the p53 tumor suppressor gene, but these were not present in the germline DNA, mutations were not detected in the MTS1 gene in the tumors or in the germline DNA. These findings suggest that a genetic factor may be responsible for the clustering of glial tumors in this family, but it is unlikely that the genetic alteration is mutation of the p53 gene. The data are discussed in light of the literature on familial brain tumors