G. Evren Keles

The effect of extent of resection on recurrence in patients with low grade cerebral hemisphere gliomas

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.

Seizure characteristics and control following resection in 332 patients with low-grade gliomas.

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.

The effect of extent of resection on time to tumor progression and survival in patients with glioblastoma multiforme of the cerebral hemisphere

BACKGROUND We retrospectively analyzed preoperative and postoperative radiographic tumor volumes in 92 patients who underwent hemispheric glioblastoma multiforme operations (107) to determine the factors that affect time to tumor progression (TTP) and overall survival. METHODS Quantification of tumor volumes was based on a previously described method involving computerized image analysis of contrast enhancing tumor on computerized tomography or magnetic resonance imaging scans. RESULTS Among the variables analyzed, preoperative Karnofsky Performance Status (KPS) (p < 0.05), chemotherapy (p < 0.05), percent of resection (POR) (p < 0.001), and volume of residual disease (VRD) (p < 0.001) had a significant effect on TTP. Factors that affected survival were age (p < 0.05), preoperative KPS (p = 0.05), postoperative KPS (p < 0.005), POR (p < 0.0005), and VRD (p < 0.0001). Greater resections did not compromise the quality of life, and patients without any residual disease had a better postoperative KPS than those patients who received less than total resections. CONCLUSIONS The extent of tumor removal and the amount of residual tumor volume, documented on postoperative imaging studies, are highly significant factors affecting the median time to tumor progression and median survival for patients with glioblastoma multiforme of the cerebral hemisphere.

Treatment of Progressive or Recurrent Glioblastoma Multiforme in Adults with Herpes Simplex Virus Thymidine Kinase Gene Vector-Producer Cells Followed by Intravenous Ganciclovir Administration: A Phase I/II Multi-Institutional Trial

To determine the safety and evaluate the efficacy of repeated administration of virus-producing cells (GLI 328) containing the herpes simplex virus thymidine-kinase gene followed by ganciclovir treatment in adults with recurrent glioblastoma multiforme, we conducted a phase I/II multi-institutional trial. Eligible patients underwent surgical resection of tumor, followed by injections of vector producing cells (VPC) into the brain adjacent to the cavity. An Ommaya reservoir placed after surgery was used to inject a further dose of VPC seven days after surgery, followed seven days later by ganciclovir. Further gene therapy was given at 28-day intervals for up to a total of five cycles. Toxicity and anti-tumor effect were assessed. Of 30 patients who enrolled in the study, 16 experienced serious adverse events possibly related to the experimental therapy. Laboratory testing, including polymerase chain reaction analysis to detect replication-competent retrovirus in peripheral blood lymphocytes and tissues, as well as co-cultivation bioassays, were negative. Before receiving ganciclovir, 37% of the patients showed evidence of transduced peripheral blood leukocytes, but only 12% showed a persistence of transduced cells at the end of the first cycle of ganciclovir. Median survival was 8.4 months. Twenty percent of the patients (n = 6) survived more than 12 months from the date of study entry. This treatment modality is feasible and appears to have some evidence of efficacy. Toxicity may be related in part to the method of gene delivery.

Coregistration Accuracy and Detection of Brain Shift Using Intraoperative Sononavigation during Resection of Hemispheric Tumors

OBJECTIVESononavigation, which combines real-time anatomic ultrasound data with neuronavigation techniques, is a potentially valuable adjunct during the surgical excision of brain tumors. METHODSIn this study, we report our preliminary observations using this technology on 58 adult patients harboring hemispheric tumors. Data regarding coregistration accuracy was collected from various landmarks that typically do not shift as well as from tumor boundaries and the cortical surface. In a subset of patients, we evaluated the extent and direction of postresection brain displacement and its relationship with patient age, tumor histology, tumor volume, and use of mannitol. RESULTSFor all structures excluding the cortex, average coregistration accuracy measurements between ultrasound and preoperatively acquired magnetic resonance imaging scans were within the range of 2 mm. The most accurate alignments were obtained with the choroid plexus and the falx, and the least reliable structure in terms of coregistration accuracy was the cortical surface. CONCLUSIONSononavigation provides real-time information during tumor removal in alignment with the preoperative magnetic resonance imaging scans, thus enabling the surgeon to detect intraoperative hemorrhage, cyst drainage, and tumor resection, and it allows for calculation of brain shift during the use of standard navigation techniques.

DEFINITION AND DIAGNOSTIC IMPLICATIONS OF GEMISTOCYTIC ASTROCYTOMAS: A PATHOLOGICAL PERSPECTIVE

SummaryGemistocytic astrocytoma still continues to be enigmatic; both in terms of definition and prognostic implications. The major issue of contention has been the clinical relevance of this pathological entity. The currently accepted definition of gemistocytic astrocytoma requires 20% or more gemistocytes, and considers the neoplasm as a diffuse astrocytoma, which is a WHO grade II tumor. Some suggest that gemistocytic morphology should be considered as evidence of a higher grade astrocytoma. However, there is no consensus on the percentage of gemistocytes associated with a worse prognosis than otherwise expected. Given the reported cases and series, it is not clear that this morphology portends a more aggressive biology when all else is equal. There is still a need for studies with sufficient numbers of well-matched gemistocytic and non-gemistocytic astrocytic neoplasms to decide whether upgrading a tumor with ‘significant’ number of gemistocytes is justifiable. This article presents a critical review of the existing studies and a brief mention of our experience from a pathological perspective.

Intraventricular and Pineal Region Tumors

Intraventricular and pineal region tumors represent 2% of all primary central nervous system tumors but have many unique features. Because many patients present with symptomatic hydrocephalus, urgent treatment of the tumor or hydrocephalus is often needed. Both benign and malignant tumors can arise in these regions, and often radiographic imaging is non-diagnostic. Surgery remains the main therapeutic approach for these tumors but is complicated by the central location of these lesions. A successful resection of intraventricular and pineal region tumors is based on a thorough knowledge of the relevant cerebral anatomy and the deep vascular system, avoidance of functionally eloquent areas and use of limited retraction.