G. Evren Keles

BACKGROUND: To evaluate the role of radical resection for low grade cerebral hemisphere gliomas, the authors analyzed the preoperative and postoperative radiographic tumor volumes (computed tomography hypodensity, magnetic resonance imaging-T2 signal hyperintensity) in 53 patients. METHODS: Using a previously described method of computerized image analysis, the authors evaluated whether the percent of resection and volume of residual disease, postoperatively, influenced the incidence of recurrence, time to tumor progression, and histology of the recurrent tumor. Survival was not analyzed in this study. RESULTS: No recurrence was detected, regardless of percent of resection and volume of residual disease, in patients with preoperative tumor volumes less than 10 cm2 (mean follow-up, 41.7 months). Patients with tumors measuring 10-30 cm3 had an incidence of recurrence and time to tumor progression of 13.6% and 58 months, respectively, compared with tumors measuring greater than 30 cm3, which had an incidence of recurrence and time to tumor progression of 41.2% and 30 months, respectively (P = 0.016). All patients (n = 13) who underwent a 100% resection had a recurrence-free follow-up period (mean, 54 months). In the remaining patients (n = 40), as the percent of resection decreased, the incidence of recurrence increased along with a shorter time to tumor progression (P = 0.03). Patients with a volume of residual disease of greater than 10 cm3 had a higher incidence of recurrence (46.2%) and a shorter time to tumor progression (30 months) compared with patients with a tumor volume of residual disease of less than 10 cm3 (incidence of recurrence, 14.8% and time to tumor progression, 50 months) (P = 0.002). Forty-six percent of patients with a tumor volume of residual disease of more than 10 cm3 had a recurrence of higher histologic grade, and this was significantly more frequent than patients with a volume of residual disease less than 10 cm3 (3.7%) (P = 0.0009). Age, radiotherapy, and histologic subtype had no influence on recurrence patterns. CONCLUSION: For tumors greater than 10 cm3, the authors' data suggest that a greater percent of resection and a smaller volume of residual disease conveys a significant advantage, that is, terms of incidence of recurrence and the recurrent tumor phenotype, for patients with low grade cerebral hemisphere gliomas, compared with those who have a less aggressive resection or biopsy. While this may also be the case with tumors less than 10 cm3, further follow-up is necessary to determine the effect of surgery on recurrence patterns for this subset of patients.

OBJECT: Seizures play an important role in the clinical presentation and postoperative quality of life of patients who undergo surgical resection of low-grade gliomas (LGGs). The aim of this study was to identify factors that influenced perioperative seizure characteristics and postoperative seizure control. METHODS: The authors performed a retrospective chart review of all cases involving adult patients who underwent initial surgery for LGGs at the University of California, San Francisco between 1997 and 2003. RESULTS: Three hundred and thirty-two cases were included for analysis; 269 (81%) of the 332 patients presented with >or=1 seizures (generalized alone, 33%; complex partial alone, 16%; simple partial alone, 22%; and combination, 29%). Cortical location and oligodendroglioma and oligoastrocytoma subtypes were significantly more likely to be associated with seizures compared with deeper midline locations and astrocytoma, respectively (p=0.017 and 0.001, respectively; multivariate analysis). Of the 269 patients with seizures, 132 (49%) had pharmacoresistant seizures before surgery. In these patients, seizures were more likely to be simple partial and to involve the temporal lobe, and the period from seizure onset to surgery was likely to have been longer (p=0.0005, 0.0089, and 0.006, respectively; multivariate analysis). For the cohort of patients that presented with seizures, 12-month outcome after surgery (Engel class) was as follows: seizure free (I), 67%; rare seizures (II), 17%; meaningful seizure improvement (III), 8%; and no improvement or worsening (IV), 9%. Poor seizure control was more common in patients with longer seizure history (p<0.001) and simple partial seizures (p=0.004). With respect to treatment-related variables, seizure control was far more likely to be achieved after gross-total resection than after subtotal resection/biopsy alone (odds ratio 16, 95% confidence interval 2.2-124, p=0.0064). Seizure recurrence after initial postoperative seizure control was associated with tumor progression (p=0.001). CONCLUSIONS: The majority of patients with LGG present with seizures; in approximately half of these patients, the seizures are pharmacoresistant before surgery. Postoperatively, >90% of these patients are seizure free or have meaningful improvement. A shorter history of seizures and gross-total resection appear to be associated with a favorable prognosis for seizure control.

OBJECT: The goal of this study was to perform a critical review of literature pertinent to low-grade gliomas of the cerebral hemisphere in adults and, on the basis of this review, to evaluate systematically the prognostic effect of extent of resection on survival and to determine if treatment-related guidelines could be established for patients in whom these tumors have been newly diagnosed. Quality of evidence for current treatment options, guidelines, and standards as well as methodological limitations were evaluated. METHODS: Several prognostic factors thought to affect outcome in patients with low-grade gliomas include the patient's age and neurological status, tumor volume and histological characteristics, and treatment-related variables such as timing of surgical intervention, extent of resection, postoperative tumor volume, and radiation therapy. Patient age and the histological characteristics of the lesion are generally accepted prognostic factors. Among treatment-related factors, timing and extent of resection are controversial because of the lack of randomized controlled trials addressing these issues and the difficulty in obtaining information from available studies that have methodological limitations. All English-language studies on low-grade gliomas published between January 1970 and April 2000 were reviewed. Thirty studies that included statistical analyses were further evaluated with regard to the prognostic effect of extent of resection. Of these 30 studies, those that included pediatric patients, unless adults were analyzed separately, were excluded from further study because of the favorable outcome associated with the pediatric age group. Also excluded were studies including pilocytic and gemistocytic astrocytomas, because the natural histories of these histological subtypes are significantly different from that of low-grade gliomas. Series in which there were small numbers of patients (< 75) were also excluded. Results for oligodendrogliomas are reported separately. Currently, for patients with low-grade glial tumors located in the cerebral hemisphere, the only management standard based on high-quality evidence is tissue diagnosis. All other treatment methods are practice options supported by evidence that is inconclusive or conflicting. The majority of published series that the authors identified had design-related limitations including a small study size, a small number of events (that is, deaths for survival studies), inclusion of pediatric patients, and/or inclusion of various histological types of tumors with different natural histories. Of the 30 series addressing the issue of timing and extent of surgery, almost all had additional design limitations. Methods used to determine the extent of resection were subjective and qualitative in almost all studies. Only five of the 30 series met the authors' criteria, and these studies are discussed in detail. CONCLUSIONS: Management of low-grade gliomas is controversial and practice parameters are ill defined. This is caused by limited knowledge regarding the natural history of these tumors and the lack of high-quality evidence supporting various treatment options. Although a prospective randomized study seems unlikely, both retrospective matched studies and prospective observational trials will improve the clinician's ability to understand the importance of various prognostic factors.

Neural stem cells with astrocyte-like characteristics exist in the human brain subventricular zone (SVZ), and these cells may give rise to glioblastoma multiforme (GBM). We therefore analyzed MRI features of GBMs in specific relation to the SVZ. We reviewed the preoperative and serial postoperative MR images of 53 patients with newly diagnosed GBM. The spatial relationship of the contrast-enhancing lesion (CEL) with the SVZ and cortex was determined preoperatively. Classification was as follows: group I, CEL contacting SVZ and infiltrating cortex; group II, CEL contacting SVZ but not involving cortex; group III, CEL not contacting SVZ but involving cortex; and group IV, CEL neither contacting SVZ nor infiltrating cortex. Patients with group I GBMs (n = 16) were most likely to have multifocal disease at diagnosis (9 patients, 56%, p = 0.001). In contrast, group IV GBMs (n = 14) were never multifocal. Group II (n = 14) and group III (n = 9) GBMs were multifocal in 11% and 29% of cases, respectively. Group I GBMs always had tumor recurrences noncontiguous with the initial lesion(s), while group IV GBM recurrences were always bordering the primary lesion. Group I GBMs may be most related to SVZ stem cells; these tumors were in intimate contact with the SVZ, were most likely to be multifocal at diagnosis, and recurred at great distances to the initial lesion(s). In contrast, group IV GBMs were always solitary lesions; these may arise from non-SVZ, white matter glial progenitors. Our MRI-based classification of GBMs may further our understanding of GBM histogenesis and help predict tumor recurrence pattern.

OBJECT: Intraoperative stimulation mapping of subcortical white matter tracts during the resection of gliomas has become a valuable surgical adjunct that is used to reduce morbidity associated with tumor removal. The purpose of this retrospective analysis was to assess the morbidity and functional outcome associated with this method, thus allowing the surgeon to predict the likelihood of causing a temporary or permanent motor deficit. METHODS: In this study, the authors report their experience with intraoperative stimulation mapping to locate subcortical motor pathways in 294 patients who underwent surgery for hemispheric gliomas within or adjacent to the rolandic cortex. Data were collected regarding intraoperative cortical and subcortical stimulation mapping results, along with the patient's neurological status pre- and postoperatively. For patients in whom an additional motor deficit occurred postoperatively, its evolution was examined. Of 294 patients, an additional postoperative motor deficit occurred in 60 (20.4%). Of those 60, 23 (38%) recovered to their preoperative baseline status within the 1st postoperative week. Another 12 (20%) recovered from their postoperative motor deficit by the end of the 4th postoperative week, and 11 more recovered to their baseline status by the end of the 3rd postoperative month. Thus, 46 (76.7%) of 60 patients with postoperative motor deficits regained their baseline function within the first 90 days after surgery. The remaining 14 patients (4.8% of the entire study population of 294) had a persistent motor deficit after 3 months. Patients whose subcortical pathways were identified with stimulation mapping were more prone to develop an additional (temporary or permanent) motor deficit than those in whom subcortical pathways could not be identified (27.5% compared with 13.1%, p = 0.003). This was also true when additional (permanent) motor deficits lasted more than 3 months (7.4% when subcortical pathways were found, compared with 2.1% when they were not found; p = 0.041). CONCLUSIONS: In patients with gliomas that are located within or adjacent to the rolandic cortex and, thus, the descending motor tracts, stimulation mapping of subcortical pathways enables the surgeon to identify these descending motor pathways during tumor removal and to achieve an acceptable rate of permanent morbidity in these high-risk functional areas.