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Walter Stummer

✓Cerebral edema contributes strongly to symptoms associated with brain tumors. Although the introduction of corticosteroids has greatly simplified treatment of patients with newly diagnosed tumors, these drugs are associated with marked side effects during the long-term treatment that is often necessary in the recurrences. Therefore, a better understanding of mechanisms related to the evolution and clearance of tumor-related edema with the aid of modern imaging and molecular methodology is clearly necessary. Recently, researchers have focused on molecular mechanisms of edema development and have demonstrated alternative routes—such as the inhibition of vascular endothelial growth factor receptor inhibitors—to be explored for treating edema. In this review the author focuses on established and current concepts regarding the pathophysiology of cerebral edema and its treatment.

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Michael Müther and Walter Stummer

5-Aminolevulinic acid (5-ALA) is a useful and well-established adjunct for glioblastoma surgery. A growing body of evidence has revealed the potential utility of 5-ALA in grade II and grade III glioma patients as well. However, reliable means of identifying in whom fluorescence will occur have not been established. The authors report the case of such an indeterminate-grade glioma highlighting two pearls of 5-ALA fluorescence in this subgroup of patients. Firstly, 5-ALA–guided tissue sampling helps to ensure that the true grade of the lesion is not underestimated. Secondly, intraoperative fluorescence can serve as a prognostic marker.

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Berndt Wowra and Walter Stummer

Object. The authors assessed the efficacy of gamma knife radiosurgery (GKS) for nonfunctioning pituitary adenomas (NPAs) by sequential quantitative determinations of tumor volume and neurological and endocrinological follow-up examinations.

Methods. Through May of 2000, 45 patients with NPA were treated by GKS. Complete neurological and endocrinological follow-up information was obtained. In 30 patients (67%), follow-up examinations included stereotactic magnetic resonance imaging involving the GammaPlan software for sequential measurements of the NPA volume. These patients constitute the basis of this study. Sequential volume measurements after GKS were compared with initial tumor volumes at the date of GKS to quantify the therapeutic result. All data were stored prospectively in a computerized database. The median dose to the tumor margin was 16 Gy (range 11–20 Gy). The mean prescription isodose was 55% (range 45–75%). All except one patient (97%) underwent surgery for NPA before GKS. Fractionated radiotherapy was not administered. Median follow up after GKS was 55 months (range 28–86 months).

The actuarial long-term recurrence-free survival was 93% with respect to a single GKS and 100% if a repeated GKS was included. Neurological side effects were not detected. The actuarial risk of radiosurgery-induced pituitary damage was calculated to be 14% after 6 years. The volumetric analysis revealed a temporary swelling of the NPA in four patients, followed by shrinkage of the lesion. This is the first time this has been observed in pituitary adenomas.

Conclusions. Postoperative GKS for residual or recurrent small fragments of NPAs is effective and safe. With regard to the issues of radioprotection and therapeutic morbidity, it seems superior to fractionated radiotherapy. Quantification of tumor reduction is a valuable tool for documenting a therapeutic response and for identifying tumor recurrence. As part of a radiosurgical standard protocol, the follow-up examination for NPAs should include tumor volumetric analysis.

Free access

Grazia Menna, Alessandro Olivi, and Giuseppe Maria Della Pepa

Free access

Grazia Menna, Alessandro Olivi, and Giuseppe Maria Della Pepa

Free access

Paul Larson, Peter Nakaji, Walter Stummer, and John Pollina

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Walter Stummer, Alexander Novotny, Herbert Stepp, Claudia Goetz, Karl Bise, and Hans Jürgen Reulen

Object. It has been established that 5-aminolevulinic acid (5-ALA) induces the accumulation of fluorescent porphyrins in glioblastoma multiforme (GBM), a phenomenon potentially exploitable to guide tumor resection. In this study the authors analyze the influence of fluorescence-guided resection on postoperative magnetic resonance (MR) imaging and survival in a series of patients who underwent surgery in the authors' department.

Methods. Fifty-two consecutive patients with GBM received oral doses of 5-ALA (20 mg/kg body weight) 3 hours before induction of anesthesia. Intraoperatively, tumor fluorescence was visualized using a modified operating microscope. Fluorescing tissue was removed whenever it was considered safely possible. Residual enhancement on early postoperative MR imaging was quantified and related to each patient's characteristics to determine which factors influenced resection. Survival was analyzed using the Kaplan—Meier method and multivariate analysis was performed in which the Karnofsky Performance Scale (KPS) score, residual fluorescence, patient age, and residual enhancement on MR images were considered.

Intraoperatively, two fluorescence qualities were perceived: solid fluorescence generally reflected coalescent tumor, whereas vague fluorescence mostly corresponded to infiltrative tumor. Complete resection of contrast-enhancing tumor was accomplished in 33 patients (63%). Residual intraoperative tissue fluorescence left unresected for safety reasons predicted residual enhancement on MR images in 18 of the 19 remaining patients. Age, residual solid fluorescence, and absence of contrast enhancement in MR imaging were independent explanatory factors for survival, whereas the KPS score was significant only in univariate analysis. No perioperative deaths and one case of permanent morbidity were encountered.

Conclusions. The observations in this study indicate the usefulness of 5-ALA—induced tumor fluorescence for guiding tumor resection. The completeness of resection, as determined intraoperatively from residual tissue fluorescence, was related to postoperative MR imaging findings and to survival in patients suffering from GBM.

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Eric Suero Molina, Johannes Wölfer, Christian Ewelt, André Ehrhardt, Benjamin Brokinkel, and Walter Stummer


Fluorescence guidance with 5–aminolevulinic acid (5-ALA) helps improve resections of malignant gliomas. However, one limitation is the low intensity of blue light for background illumination. Fluorescein has recently been reintroduced into neurosurgery, and novel microscope systems are available for visualizing this fluorochrome, which highlights all perfused tissues but has limited selectivity for tumor detection. Here, the authors investigate a combination of both fluorochromes: 5-ALA for distinguishing tumor and fluorescein for providing tissue fluorescence of adjacent brain tissue.


The authors evaluated 6 patients who harbored cerebral lesions suggestive of high-grade glioma. Patients received 5-ALA (20 mg/kg) orally 4 hours before induction of anesthesia. Low-dose fluorescein (3 mg/kg intravenous) was injected immediately after anesthesia induction. Pentero microscopes (equipped either with Yellow 560 or Blue 400 filters) were used to visualize fluorescence. To simultaneously visualize both fluorochromes, the Yellow 560 module was combined with external blue light illumination (D-light C System).


Fluorescein-induced fluorescence created a useful background for protoporphyrin IX (PPIX) fluorescence, which appeared orange to red, surrounded by greenly fluorescent normal brain and edematous tissue. Green brain-tissue fluorescence was helpful in augmenting background. Levels of blue illumination that were too strong obscured PPIX fluorescence. Unspecific extravasation of fluorescein was noted at resection margins, which did not interfere with PPIX fluorescence detection.


Dual labeling with both PPIX and fluorescein fluorescence is feasible and gives superior background information during fluorescence-guided resections. The authors believe that this technique carries potential as a next step in fluorescence-guided resections if it is completely integrated into the surgical microscope.

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G. Venkateswaraprasanna

Heading : Manas Panigrahi