Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study

Stummer, Walter; Tonn, Jörg‐Christian; Mehdorn, H. Maximilian; Nestler, Ulf; Franz, Kea; Goetz, Claudia; Bink, Andrea; Pichlmeier, Uwe

doi:10.3171/2010.3.jns097

Cited by 265 publications

(182 citation statements)

References 13 publications

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“…One of the greatest barriers to achieving optimal surgical results in infiltrative tumors is the difficulty in distinguishing tumor from normal brain (5)(6)(7). Failure to discern where the border of the lesion ends and viable, minimally infiltrated brain begins increases the likelihood of inadequate resection and neurological damage.…”

mentioning

confidence: 99%

“…Although maximal surgical resection with the goal of gross total tumor resection is desirable, in practice, delineation of resection margins is difficult because tumors can closely resemble healthy brain, often infiltrate brain tissue, and may be immediately adjacent to critical functional brain tissue. Aggressive resection can increase the risk for postoperative neurological deficits (7). For example, brain tumors located near critical brain areas subserving primary motor, sensory, or language functions are difficult to resect maximally while avoiding postoperative neurological deficits (8).…”

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confidence: 99%

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Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors

Eberlin

Norton²,

Orringer³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

263

234

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The main goal of brain tumor surgery is to maximize tumor resection while preserving brain function. However, existing imaging and surgical techniques do not offer the molecular information needed to delineate tumor boundaries. We have developed a system to rapidly analyze and classify brain tumors based on lipid information acquired by desorption electrospray ionization mass spectrometry (DESI-MS). In this study, a classifier was built to discriminate gliomas and meningiomas based on 36 glioma and 19 meningioma samples. The classifier was tested and results were validated for intraoperative use by analyzing and diagnosing tissue sections from 32 surgical specimens obtained from five research subjects who underwent brain tumor resection. The samples analyzed included oligodendroglioma, astrocytoma, and meningioma tumors of different histological grades and tumor cell concentrations. The molecular diagnosis derived from mass-spectrometry imaging corresponded to histopathology diagnosis with very few exceptions. Our work demonstrates that DESI-MS technology has the potential to identify the histology type of brain tumors. It provides information on glioma grade and, most importantly, may help define tumor margins by measuring the tumor cell concentration in a specimen. Results for stereotactically registered samples were correlated to preoperative MRI through neuronavigation, and visualized over segmented 3D MRI tumor volume reconstruction. Our findings demonstrate the potential of ambient mass spectrometry to guide brain tumor surgery by providing rapid diagnosis, and tumor margin assessment in near-real time.

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mentioning

confidence: 99%

mentioning

confidence: 99%

Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors

Eberlin

Norton²,

Orringer³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

263

234

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“…Alternatively, 5‐aminolevulinic acid (5‐ALA), a bio‐precursor of protoporphyrin IX (PPIX), has gained considerable attentions in recent years, and PDT with ALA‐derived endogenous porphyrins has already shown promising clinical results in the treatment of several superficial disorders of the skin (such as actinic keratosis, a skin condition that will further develop into cancer) and internal hollow organs 5. 5‐ALA is an endogenous amino acid, which is usually synthesized from glycine and succinyl CoA in mitochondria.…”

Section: Introductionmentioning

confidence: 99%

A Nanosystem Capable of Releasing a Photosensitizer Bioprecursor under Two‐Photon Irradiation for Photodynamic Therapy

Zeng

Zhang

et al. 2015

Advanced Science

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The applications of photodynamic therapy (PDT) are usually limited by photosensitizers' side effects and singlet oxygen's short half‐life. Herein, a mitochondria‐targeted nanosystem is demonstrated to enhance the PDT efficacy by releasing a bio‐precursor of photosensitizer under two‐photon irradiation. A phototriggerable coumarin derivative is first synthesized by linking 5‐aminolevulinic acid (5‐ALA, the bio‐precursor) to coumarin; and the nanosystem (CD‐ALA‐TPP) is then fabricated by covalently incorporating this coumarin derivative and a mitochondria‐targeting compound triphenylphosphonium (TPP) onto carbon dots (CDs). Upon cellular internalization, the nanosystem preferentially accumulates in mitochondria; and under one‐ or two‐photon irradiation, it releases 5‐ALA molecules that are then metabolized into protoporphyrin IX in mitochondria through a series of biosynthesis processes. The subsequent red light irradiation induces this endogenously synthesized photosensitizer to generate singlet oxygen, thereby causing oxidant damage to mitochondria and then the apoptosis of the cells. Analysis via 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyltetrazolium bromide (MTT) assays indicate that the novel PDT system exhibits enhanced cytotoxicity toward cancer cells. This study may offer a new strategy for designing PDT systems with high efficacy and low side effects.

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“…21,34,43 Similarly, post hoc analysis of the 5-ALA study 41 showed a 4.9-month survival difference between patients who underwent gross-total resection (GTR) and those who underwent STR, even though the difference in residual tumor volume was marginal (0 vs 0.7 cm 3 for GTR and STR, respectively). 42 Delivering an optimal oncological result in patients with tumors adjacent to motor eloquent areas thus requires the ability to resect tumor tissue down to very low MTs (1-2 mA).…”

Section: The Need For Refinement Of Mapping Techniquementioning

confidence: 99%

Intraoperative monopolar mapping during 5-ALA–guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome

Schucht¹,

Seidel²,

Beck³

et al. 2014

FOC

102

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Object Resection of glioblastoma adjacent to motor cortex or subcortical motor pathways carries a high risk of both incomplete resection and postoperative motor deficits. Although the strategy of maximum safe resection is widely accepted, the rates of complete resection of enhancing tumor (CRET) and the exact causes for motor deficits (mechanical vs vascular) are not always known. The authors report the results of their concept of combining monopolar mapping and 5-aminolevulinic acid (5-ALA)–guided surgery in patients with glioblastoma adjacent to eloquent tissue. Methods The authors prospectively studied 72 consecutive patients who underwent 5-ALA–guided surgery for a glioblastoma adjacent to the corticospinal tract (CST; < 10 mm) with continuous dynamic monopolar motor mapping (short-train interstimulus interval 4.0 msec, pulse duration 500 μsec) coupled to an acoustic motor evoked potential (MEP) alarm. The extent of resection was determined based on early (< 48 hours) postoperative MRI findings. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. Results Five patients were excluded because of nonadherence to protocol; thus, 67 patients were evaluated. The lowest motor threshold reached during individual surgery was as follows (motor threshold, number of patients): > 20 mA, n = 8; 11–20 mA, n = 13; 6–10 mA, n = 10; 4–5 mA, n = 13; and 1–3 mA, n = 23. Motor deterioration at postsurgical Day 1 and at discharge occurred in 30% (n = 20) and 10% (n = 7) of patients, respectively. At 3 months, 3 patients (4%) had a persisting postoperative motor deficit, 2 caused by vascular injury and 1 by mechanical injury. The rates of intra- and postoperative seizures were 1% and 0%, respectively. Complete resection of enhancing tumor was achieved in 73% of patients (49/67) despite proximity to the CST. Conclusions A rather high rate of CRET can be achieved in glioblastomas in motor eloquent areas via a combination of 5-ALA for tumor identification and intraoperative mapping for distinguishing between presumed and actual motor eloquent tissues. Continuous dynamic mapping was found to be a very ergonomic technique that localizes the motor tissue early and reliably.

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Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study

Abstract: Extended resections performed using a tool such as 5-ALA-derived tumor fluorescence, carries the risk of temporary impairment of neurological function. However, risks are higher in patients with deficits unresponsive to steroids.

Cited by 265 publications

References 13 publications

Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors

Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors

A Nanosystem Capable of Releasing a Photosensitizer Bioprecursor under Two‐Photon Irradiation for Photodynamic Therapy

Intraoperative monopolar mapping during 5-ALA–guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome

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