Resection Of Malignant Gliomas Research Articles

Photodynamic diagnosis and fluorescence-guided resection of malignant gliomas: a report of 15 cases

To study the usefulness of the intraoperative photodynamic diagnosis (PDD) and fluorescence-guided resection of malignant gliomas. Fifteen consecutive patients with malignant gliomas received doses of hematoporphyrin derivative (HPD, 2 mg/kg body weight) 48 hours before induction of anesthesia. After the tumors recognized by bare eyes they were removed routinely. The fluorescence around 690 nm excited by laser beam (wavelength 632.5 nm) was detected by laser electronic spectrum analyzer and then fluorescing tissue was removed whenever it was considered safel. Tissue samples derived from the walls of tumor cavities after resection and PDD were sent for histological examination. Compared with the result of the histological examination, the sensitivity and specificity of PDD were calculated and recorded. Early postoperative MRI or CT were done to determine the extend of the resection of the tumors. Surgical mortality and morbidity were also recorded. Intraoperatively, in all of 15 cases tumor areas with HPD fluorescence could be recognized by laser electronic spectrum analyzer. On the basis of 106 tissue samples derived from 15 tumors, a sensitivity of 90.6%, a specificity of 96.8% and an accuracy of 94.3% of PDD were achieved. In 2 cases the resection of residual tumor were performed after finding left tumors by PDD. Complete resection of contrast-enhancing tumor was accomplished in 9 patients (60%). Residual intraoperative tissue fluorescence left unresected for safety reasons predicted residual enhancement on MR images in 5 of the 6 remaining patients. No perioperative deaths and one case of morbidity were encountered. Intraoperative photodynamic diagnosis following resection of malignant gliomas can detect residual tumor tissue with high accuracy. Photodynamic diagnosis and fluorescence-guided resection of malignant gliomas have a positive role in improving the radicality of malignant glioma resection.

Stereotaxic implantation of 5‐fluorouracil‐releasing microspheres in malignant glioma

The authors developed a new method of drug delivery into the brain using implantable, biodegradable microspheres. The strategy was evaluated initially to provide localized and sustained delivery of the radiosensitizer 5-fluorouracil (5-FU) after patients underwent surgical resection of malignant glioma. In this study, the microspheres were implanted by stereotaxy into deeply situated and inoperable brain tumors. Ten patients with newly diagnosed, inoperable, malignant gliomas were included in the study, and 1 dose of 5-FU was studied (132 mg). After histologic confirmation, a suspension of poly(D-L lactide-co-glycolide) 5-FU-loaded microspheres was implanted by stereotaxy into the tumor in one or several trajectories with one to seven deposits per trajectory. External beam radiation (59.4 grays) was started before postoperative Day 7. Patients were followed by clinical examination, computed tomography scanning, magnetic resonance imaging, and 5-FU assays in blood and cerebrospinal fluid (CSF). The number of trajectories was adapted to the size and shape of the tumor. Microsphere implantation was tolerated well, except in four patients who received a single trajectory and experienced a transitory worsening of preexisting neurologic symptoms. There were no episodes of edema or hematologic complications. 5-FU was detected in CSF and blood in some patients at very low concentrations. The median overall survival was 40 weeks, with 2 patients who had longer survival (71 weeks and 89 weeks, respectively). In this study, the authors demonstrated that biodegradable microspheres could be implanted by stereotaxy and were efficient systems for drug delivery into brain tumors. This method may have future applications in the treatment of patients other malignancies.

Treatment of relapsed malignant glioma with an adenoviral vector containing the herpes simplex thymidine kinase gene followed by ganciclovir

Between November 1998 and December 2001, we treated 14 patients with advanced recurrent high-grade gliomas with a total dose of 4.6 × 108, 4.6 × 109, 4.6 × 1010, or 4.6 × 1011 viral particles (VP) of a replication-incompetent adenoviral vector harboring the herpes simplex virus thymidine kinase gene driven by the adenoviral major late promoter (IG.Ad.MLPI.TK), followed by ganciclovir (GCV) treatment. The VP-to-infectious-unit ratio was 40. The vector was administered by 50 intraoperative wound-bed injections of 0.2 ml each (total volume 10 ml). The study's primary objective was to determine the safety of this treatment and establish the maximum tolerated dose (MTD). Injection of all doses of IG.Ad.MLPI.TK followed by GCV was safely tolerated and MTD was not reached. All patients had recurrence or progression of the tumor 1–24 months (median 3.5 months) after gene therapy. The overall median survival was 4 months. Four patients survived longer than 1 year following gene therapy. One patient is still alive, with histologically confirmed progression of the tumor, 29 months after treatment. Ten patients died within 8 months of treatment, all from progression of the tumor. In 5 patients residual and measurable tumor was visible on the direct (<48 h) postoperative MRI. No objective radiological response was documented on subsequent MRI. None of the patients came to autopsy. In conclusion, the administration of 4.6 × 1011 VP of IG.Ad.MLPI.TK by 50 injections into the wound bed following resection of recurrent malignant glioma, followed by GCV treatment, was well tolerated.

Optimizing outcomes with maximal surgical resection of malignant gliomas.

Aggressive surgical resection of malignant gliomas is a controversial issue in neurosurgery. Studies with rigorous methodology that fully address this issue have only recently become available. The controversy regarding the role of maximal surgical resection of malignant gliomas is reviewed. The authors discuss surgical techniques and adjunctive technologies that can be utilized to assist in resection of these lesions. Using current microneurosurgical techniques, it is possible to resect malignant gliomas in gross total fashion. An aggressive approach in which 98% or more of the tumor mass is resected results in a statistically significant survival advantage. An aggressive surgical procedure for malignant gliomas can result in increased survival duration for selected groups of patients.

Gliadel therapy given for first resection of malignant glioma: a single centre study of the potential use of Gliadel

The results of a recently concluded phase III study have shown that Gliadel therapy (biodegradable polymer impregnated with 3.85% BCNU placed into the surgical cavity) significantly prolongs survival and time to relapse in patients having initial resective surgery for malignant glioma followed by radiotherapy. The indications and exclusion criteria for patients in this study were well defined. To determine the relative frequencies of Gliadel 'eligible' and 'ineligible' patients, and differences in prognostic variables between these two cohorts, we conducted a review of all Edinburgh patients with an initial diagnosis of malignant glioma managed throughout the period of patient accrual into the phase III Gliadel study (Edinburgh was one of 38 contributing centres). Independent predictors of outcome were taken from the MRC prognostic index. Analysis was done on an intention to treat basis. Only 25% of patients (14/56) with malignant glioma managed over this period were eligible for the Gliadel study and all were recruited. The patients in the study group were younger (median 51 v. 59 years, p = 0.085); in better clinical grade (median Karnofsky score 85 v. 80, p = 0.038); more likely to have resective surgery (86% v. 38%, p = 0.0001); more likely to have postoperative radiotherapy (93% v. 55%, p = 0.0001) and more likely to survive longer, even though one half of the Gliadel cohort received placebo, (66 v. 19 weeks, p = 0.06) than those not eligible. If the future use of Gliadel is limited to the eligibility criteria used in the phase III trial about 20% (95% confidence intervals 13 - 34%) of patients with newly diagnosed malignant glioma will receive this therapy.

B301 2色レーザー誘起蛍光法を用いた脳腫瘍計測法の開発

In the neurosurgery of brain tumor, patients' life after surgery crucially depends on completeness of malignant glioma resection. It is, therefore, quite necessary to construct real-time monitoring system of brain tumor. In this study, proposed is the novel optical measurement method of brain tumor demarcation. It has been well known that some phosphorescence luminophor dyes used in PDT can emit fluorescence. In addition, it has been recently reported that auto-fluorescence can be observed even in brain white matter tissue; moreover its intensity locally decreases in tumor region. Using phosphorescence and auto-fluorescence images, Dual Emission Laser-Induced Fluorescence technique was experimentally applied to the brain tumor detection. Consequently, it was confirmed that the contrast between tumor and normal region could be enhanced. Undesirable fluorescence variation, which was dependent on illumination intensity distribution and brain surface shape, could be reduced. The present method was clarified to be effective to brain tumor monitoring and quantitative delimitation.

Delayed hydrocephalus after resection of supratentorial malignant gliomas.

To report our experience with 12 patients who developed delayed hydrocephalus after resection of supratentorial malignant gliomas. The charts of all affected patients were analysed retrospectively for clinical presentation, time interval between initial operation and occurrence of hydrocephalus, neuroradiological findings, constituents of cerebrospinal fluid (CSF), surgical treatment, and outcome. After initial good recovery following tumour resection all patients deteriorated secondarily due to development of hydrocephalus which was not encountered in the first postoperative CT-scans. Incidence is 3.4% overall and is 8.3% if exclusively calculated for frontal gliomas but increases to 15.2% if specified for patients with ventricular entry during tumour resection. Development of hydrocephalus is suggested to be due to proteinic precipitation since analysis of CSF revealed marked elevation of proteins in all patients. Whereas shunting of mere hydrocephalus yields satisfactory results outcome in cases of multiloculated hydrocephalus necessitating placement of multiple catheters is questionable. Development of hydrocephalus after resection of malignant gliomas is not rare. It should be considered in patients with delayed deterioration after initial improvement. Outcome in relation to hydrocephalus is favourable in cases of mere communicating hydrocephalus, occurrence of multiloculated hydrocephalus, however, heralds a poor prognosis.

Intratumoral injection of lipopolysaccharide causes regression of subcutaneously implanted mouse glioblastoma multiforme.

Anecdotal reports documented extended survival times for patients who developed infections at the site of resection of malignant gliomas. Hypothesized mechanisms for this phenomenon include immune responses triggered by lipopolysaccharide (LPS). This investigation assessed whether LPS could produce tumor regression in an in vivo model of malignant glioma. Delayed brain tumor cells (2 x 10(6)) were injected subcutaneously into female BALB/c mice. LPS (300-500 microg) was injected intratumorally or subcutaneously at a contralateral site on Days 10, 17, and 24. Control animals received phosphate-buffered saline intratumorally or subcutaneously. Mice were killed on Day 28, and tumors were removed. Mean tumor masses for control animals and the two LPS-treated groups (intratumoral or contralateral subcutaneous treatment) were compared. Histological assessments of treated and control tumors were performed. Complete or nearly total tumor regression was achieved in all 20 mice with subcutaneous delayed brain tumor cell tumors treated intratumorally with 400 microg of LPS (mean tumor mass of 0.09 +/- 0.38 g versus 2.42 +/- 2.46 g for control animals, P < 0.0001). Intratumoral administration of 300 microg of LPS or subcutaneous injection of 300 or 400 microg of LPS at a contralateral site resulted in less consistent regression of subcutaneous tumors. Administration of 500 microg of LPS resulted in tumor regression similar to that observed with lower doses but was limited by treatment-related deaths in 40% of animals. Histological assessment revealed lymphocytic infiltration of LPS-treated tumors. Intratumoral injections of LPS caused dramatic regression of subcutaneously implanted delayed brain tumor cell mouse gliomas. Investigation of this antitumoral effect may improve treatment responses for patients with malignant gliomas.

Childhood Malignant Gliomas

Learning Objectives: After reading this article, the participant should be able to: 1. Describe the clinical presentation and radiological evaluation of childhood malignant gliomas. 2. Explain the surgical indications and resection of childhood malignant gliomas. 3. Recall the role of adjuvant therapy and indications for treatment of childhood malignant gliomas. 4. Explain the different adjuvant therapies (chemotherapy, radiotherapy, and others) in the treatment of childhood malignant gliomas.

Effects of N-6 essential fatty acids on glioma invasion and growth: experimental studies with glioma spheroids in collagen gels.

Intracranial infusions of gamma-linolenic acid (GLA), an essential fatty acid, have been used as an adjuvant therapy following malignant glioma resection; however, little is known about the dose response of glioma cells to this therapy. In this in vitro study the authors address this important pharmacological question. Glioma spheroids derived from U87, U373, MOG-G-CCM, and C6 cell lines were grown in collagen gel and exposed to a range of GLA concentrations (0-1 mM) for 5 days. The diameter of glioma spheroids was measured, the apoptotic index was assessed using both the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique and cell morphological testing, and the levels of proliferating cell nuclear antigen were also measured. The dose-response patterns were similar for all four glioma spheroids. Low concentrations of GLA (<100 microM) increased both apoptosis and proliferation with a net increase in tumor growth and invasion, whereas high-dose GLA (>100 microM) significantly impaired spheroid cell growth. The proliferative effects of low-dose GLA could be a hazard in the clinical treatment of malignant glioma; however, because of the low toxicity of GLA against normal cells, local delivery of millimolar doses of GLA could significantly reduce tumor size.

Basic surgical techniques in the resection of malignant gliomas.

Although progress is being made in the imaging and medical therapy of malignant gliomas, surgery continues to play a central role in the management of these tumors. Surgery remains necessary for histological diagnosis and relief of mass effect upon adjacent neurological structures. Surgery also achieves cytoreduction of tumor mass, allowing more effective treatment of residual tumor volume. Recent technical advances have made the goal of gross total tumor resection safer and more readily achieved. Surgical techniques and adjuncts that aid the aggressive surgical resection of malignant gliomas will be reviewed.

Surgical Resection of Malignant Gliomas Defined by MRT

Surgical Resection of Malignant Gliomas Defined by MRT

Early Postoperative Magnetic Resonance Imaging after Resection of Malignant Glioma

Early Postoperative Magnetic Resonance Imaging after Resection of Malignant Glioma

Early Postoperative Magnetic Resonance Imaging after Resection of Malignant Glioma

Early Postoperative Magnetic Resonance Imaging after Resection of Malignant Glioma

Early Postoperative Magnetic Resonance Imaging after Resection of Malignant Glioma

Early Postoperative Magnetic Resonance Imaging after Resection of Malignant Glioma

Early Postoperative Magnetic Resonance Imaging after Resection of Malignant Glioma

Early Postoperative Magnetic Resonance Imaging after Resection of Malignant Glioma

Ventricular entry during resection of malignant gliomas: effect on intracranial cerebrospinal fluid tumor dissemination

The ventricular system is not infrequently entered during the course of maximum cytoreductive surgery for high-grade supratentorial gliomas. It is unclear if ventricular entry during surgery and/or proximity of the tumor to the ventricular system affects cerebrospinal fluid (CSF) tumor dissemination or the patients' overall survival rate. The authors retrospectively reviewed hospital records and neuroradiological studies of 51 patients operated on at the University of Washington between 1987 and 1991. Inclusion in this study necessitated a pathological diagnosis of malignant glioma and the availability of preoperative and postoperative computerized tomography scans or magnetic resonance images. Patients were excluded from the study if they had radiographic evidence of ventricular entry or CSF tumor dissemination prior to referral to the authors' institution. The index operation was defined as the first operation at the University of Washington or (in those patients with ventricular entry) the operation in which the ventricle was entered. Patients were followed until time of death or, in the case of survivors, until February, 1992. The effect of both ventricular entry and the proximity of the tumor to the ventricular system on CSF tumor dissemination and survival rate was assessed using statistical survival methodology. There was no significant difference in time from diagnosis to the index operation between groups compared (Mann-Whitney U-test, p > 0.40). Cerebrospinal fluid dissemination was radiographically documented in 18 patients (35%) following the index operation. This occurrence was not significantly influenced by either ventricular entry during surgery (Mantel-Cox test, p = 0.13), the proximity of the tumor to the ventricular system (p = 0.63), or these two variables combined (p = 0.28). Survival rate following the index operation was not significantly affected by ventricular entry (p = 0.66), proximity of the tumor to the ventricular system (p = 0.61), or these two variable considered in combination (p = 0.44). However, survival rate was significantly decreased once CSF tumor dissemination had occurred (Cox model, p = 0.03).

Early Postoperative Magnetic Resonance Imaging after Resection of Malignant Glioma

Early Postoperative Magnetic Resonance Imaging after Resection of Malignant Glioma

Early Postoperative Magnetic Resonance Imaging after Resection of Malignant Glioma: Objective Evaluation of Residual Tumor and Its Influence on Regrowth and Prognosis

In the vast majority of studies that address the role of surgery in the management of high-grade gliomas, the degree of tumor removal accomplished is solely based on the intraoperative perception of the neurosurgeon. Despite its fundamental importance for a comparison of different treatment modalities, little systematic effort has been made to evaluate the residual gross tumor by neuroimaging methods immediately after surgery. We report the results of a prospective study using contrast-enhanced computed tomography and magnetic resonance imaging (MRI) to monitor 60 patients after the resection of a high-grade glioma. In each case, the first scans were obtained between Days 1 and 5 after surgery, followed by serial imaging every 2 to 3 months, usually until the condition of the patient deteriorated severely or the patient died. Gadolinium-enhanced MRI proved to be extremely valuable for assessing gross residual tumor when performed during Days 1 to 3 after the resection of a preoperatively enhancing high-grade glioma. This timing avoided surgically induced contrast enhancement and minimized interpretative difficulties. In delineating residual tumor, MRI was vastly superior to computed tomography. About 80% of tumor "recurrences" emerged from definitely enhancing remnants, as revealed by early postoperative MRI. The neurosurgeon's estimation of gross tumor burden reduction could be shown to be much less accurate (by a factor of 3) than the postoperative assessment by modern neuroimaging. In our series, residual tumor enhancement was the most predictive prognostic factor of survival in patients with glioblastoma, followed by radiotherapy. Patients with a residual tumor postoperatively had a 6.595-times higher risk of death in comparison to patients without a residual tumor. Patients undergoing radiotherapy had a 0.258-times lower risk of death in comparison to patients who were not treated with radiation. Concerning survival, the prognostic significance of both variables surpassed age and performance.

Immunotherapy for malignant gliomas (author's transl)

Recently the authors investigated the therapeutic effects of specific and non-specific immunotherapies used as adjuvant therapy to surgical resection of malignant gliomas followed by 60Co radiation therapy, and obtained some results suggesting the effectiveness of these therapies. For the purpose of non-specific activation of cell-mediated immunity, the authors administered an immunopotentiator, OK-432, intramuscularly to 13 patients with intracerebral gliomas over a long period. Cell-mediated immunity of these patients before and during immunotherapy was investigated by means of various tests including delayed cutaneous hypersensitivity reactions against PPD and PHA, and lymphocyte and T-cell counts in the peripheral blood. The following methods of specific immunotherapy were used in nine patients with malignant gliomas. Resection of the tumor was first carried out and a link between the space left after the tumor resection and the lateral ventricle of the lesioned side was produced provided that no malfunction would result from this procedure. An appropriate amount of autologous lymphocytes separated from the peripheral blood of the patient was repeatedly infused through a catheter inserted into the space left after the tumor resection, either before or after 60Co irradiation therapy. When a recurrence of the glioma was found, resection of the recurrent tumor was again performed and a histopathological investigation of the tissue was carried out. The average survival period of the nine patients who received the afore-mentioned specific immunotherapy was statistically compared by the Wilcoxson test with that of twelve control patients with glioblastomas who underwent only tumor resection followed by radiation therapy. Cell-mediated immunity of patients with gliomas tended to be reinforced by non-specific immunotherapy. Successive CT scannings of the head performed on patients who received specific immunotherapy revealed that the space left after the tumor resection appeared to be a low density area poorly demarcated from the surrounding brain tissue. With the lapse of time, the low density area became clearly demarcated and remained as it was, even though a tumor recurred in the surrounding brain. Histological observation revealed that the brain tissue adjacent to a space filled with CSF was covered with a thick fibrous membrane with abundant newly developed capillaries or sinusoid-like vessels. Recurrent tumors tended to be located beneath the membrane. Numerous foci of necrosis were actually observed in association with abundant lymphocyte infiltration, suggesting that there is a possibility of immunologically competent cells wandering into the tumor tissue through the newly developed vessels. The average survival periods of patients with and without specific immunotherapy were 23 months and 10.3 months respectively. There was a statistically significant difference in the survival periods between the two groups (P<0.05).