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Table of Contents
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 42-44

Dual-imaging strategy for the resection of recurrent malignant glioma: Challenges and practical utility

Department of Surgical Oncology, Neurosurgical Oncology Services, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India

Date of Submission03-May-2020
Date of Acceptance04-Jun-2020
Date of Web Publication2-Jul-2020

Correspondence Address:
Dr. Aliasgar V Moiyadi
Department of Surgical Oncology, Neurosurgical Oncology Services, Tata Memorial Centre, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJNO.IJNO_9_20

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Recurrent high-grade gliomas constitute a significant, yet vexing burden of disease in neuro-oncological surgery. Despite evidence supporting the multiple benefits of surgery, radical resection remains difficult in many cases. One of the biggest challenges in its treatment is the difficulty in delineating progressive tumor from the treatment-related changes, namely scarring of prior surgical treatment, pseudoprogression, and radiation-induced gliosis. Neurosurgeons dealing with recurrent gliomas should be familiar with the various adjuncts available. Considering the relative benefits and limitations of each of these techniques, a combined modality approach may be most appropriate in such cases. We describe a case of a recurrent glioma operated using three-dimensional intraoperative ultrasound and 5-Aminolevulinic acid illustrating the role of a dual-imaging approach for malignant gliomas.

Keywords: Amino-levulinic acid, fluorescence-guided surgery, intraoperative ultrasound, recurrent glioma

How to cite this article:
Shaikh ST, Shetty PM, Moiyadi AV. Dual-imaging strategy for the resection of recurrent malignant glioma: Challenges and practical utility. Int J Neurooncol 2020;3:42-4

How to cite this URL:
Shaikh ST, Shetty PM, Moiyadi AV. Dual-imaging strategy for the resection of recurrent malignant glioma: Challenges and practical utility. Int J Neurooncol [serial online] 2020 [cited 2022 Jun 27];3:42-4. Available from: https://www.Internationaljneurooncology.com/text.asp?2020/3/1/42/288796

  Introduction Top

Radical resection of recurrent gliomas can be a challenging task. Various adjuncts have been used for optimizing glioma surgery. Intraoperative magnetic resonance imaging (iMRI) is the gold standard but may not always be available given its high cost, whereas intraoperative ultrasound (iUS) is cost-effective and has been shown to have comparable efficacy.[1] Fluorescence-guided resections (FGR) using 5-Aminolevulinic acid (5-ALA) have been established in both the upfront and recurrent setting.[2],[3] FGR is a surface-imaging (visualizes fluorescence on the surface of the cavity) tool, while iUS/iMRI provide cross-sectional imaging (depth of tumor involvement); and hence, the two modalities can provide complementary information.

  Case Report Top

A 50-year-old man presented to our department with complaints of headache since two weeks. Two-and-a-half years ago, he had been operated for a right frontal tumor (Oligodendroglioma WHO Grade II) and received focal radiotherapy (54 Gy). He had an uneventful disease-free period until present. The magnetic resonance imaging (MRI) showed a well-defined enhancing mass in the right frontal lobe (tumor bed) with an area of T2 signal abnormalities around it (suggestive of edema) [Figure 1]a. Following a multidisciplinary tumor board discussion, he was planned for surgery using iUS (Sonowand, M/s SONOWAND, Trondheim, Norway) and ALA (Gliolan, MEDAC GmbH, Germany) administered @ 20 mg/kg dissolved in water per oral 3 h before induction. The previous craniotomy flap was reopened. Before opening the dura, a three-dimensional iUS was acquired [Figure 2]a. Although the underlying lesion was identified, the quality of the images was suboptimal due to artifacts (secondary to scarring and calcification). On opening the dura, dense adhesions were encountered and separated. The tumor was visible on the surface as a reddish, friable variegated tissue but interface with normal tissue was blurred [Figure 3]a. On switching to blue light (Blue 400, Pentero, Carl Zeiss, Oberkochen, Germany), the friable area fluoresced bright red, whereas the central necrotic area and gritty calcified area showed no fluorescence [Figure 3]b. Tumor dissection was started in the friable, strongly fluorescing area at the interface with the surrounding nonfluorescing gliotic brain (which appeared normal in white light also). Toward the anterolateral quadrant, the grossly abnormal and calcified component was included in the resection specimen [Figure 3]c. Switching between white and blue light alternately, circumferential dissection was performed. At the depth, frontal horn of the lateral ventricle was reached. The ependyma was involved and resected with the tumor. On switching to blue light, faint but definite diffuse fluorescence was observed in the entire tumor bed in the paraventricular deep gray matter [Figure 3]d. A repeat iUS was obtained, and this confirmed the diffuse hyperechoic lesion in the resection cavity wall [Figure 2]b. As this component was infiltrating into the caudate nucleus, it was decided to terminate the resection at this point. The patient was observed postoperatively for 48 h in a dark recovery room and MRI done thereafter showed complete excision of the contrast-enhancing part with residual T2 changes [Figure 1]b. He had an uneventful recovery and was discharged on day 5. Histopathology was suggestive of anaplastic oligodendroglioma WHO Grade III with Mib index of 40%–50%, and he was planned for adjuvant temozolomide therapy.
Figure 1: (a) Preoperative (left) magnetic resonance imaging (T2 weighted image and Post contrast) showing the enhancing lesion in right frontal lobe with surrounding areas of edema. (b) Postoperative (center and right) magnetic resonance imaging (T2 weighted image and Post contrast) showing complete excision of the contrast-enhancing component with residual diffuse T2 changes

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Figure 2: (a) Left (preresection) US scan showing the lobulated tumor (white arrow) with extremely hyperechoic areas causing posterior black shadow artefact (white open arrowhead). Diffuse infiltrating component depicted as white star. Ventricle depicted as white circle. (b) Right (post-resection) US showing the resection cavity (white arrow). Ventricle depicted as white circle. The diffuse-infiltrating tumor (white star) can now be appreciated better

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Figure 3: Pictorial representation of the intraoperative findings showing the various regions of the tumor and tumor-brain interface preoperatively under. (a) White light (note the difficulty in discriminating the viable tumor component). (b) BLUE 400 nm light (strongly fluorescing viable tumor seen distinctly). (c) Diagrammatic representation (depicting the heterogeneity). (d) After resection under BLUE 400 nm light (diffuse residual fluorescence seen)

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  Discussion Top

The role of surgery in recurrent gliomas has been debated extensively, though evidence suggests it improves survival or provides better functional outcomes.[4] The key factors contributing to the benefit of resurgery include the extent of resection, longer (6-month) interval from prior therapies, and a good Karnofsky performance score.[5] Surgery provides symptomatic relief in carefully selected cases,[6] but may not be beneficial in tumors involving the ependyma and periventricular zone.[7]

Recurrent glioma boundaries may be obscured due to prior surgical intervention and more diffuse spread. A combination of adjuncts can be used intraoperatively to define the anatomical extent (iMRI and navigated iUS), pathological characterization (5-ALA), and functional status (Intraoperative Neurological Monitoring [IONM]). Ultrasound may be hampered due to artifacts as in our case and can lead to suboptimal identification of tumor in the recurrent setting. Few of these shortcomings can be overcome with the help of 5-ALA, which is proven to improve resection rates of high-grade gliomas (primary or recurrent).[8] A prospective, multi-center, phase II study found positive predictive value to be beyond 90%, especially for areas which appeared pathological and were strongly fluorescent.[3] Strongly fluorescing areas usually denote viable tumor and very rarely false-positive cases are seen due to inflammatory cells. Diffuse ependymal fluorescence can often be seen but can be nonspecific as we have reported earlier.[9] However, false negatives can still occur due to posttreatment changes such as necrosis and calcification within the tumor. In our case [Figure 3], the heterogeneity within the same tumor (with similar white light features) was well depicted. Even after apparently resecting the gross tumor (under white light), there was persistent fluorescence in the cavity walls. In recurrent gliomas, the infiltrating edge is known to have islands of strongly fluorescing tumor as opposed to primary tumors where the edge is usually weakly fluorescing.[3] This shows that recurrent gliomas are more infiltrative and resection of these areas should only be attempted if reinforced by IONM.[10] Another point to note is that the absence of fluorescence has a poor negative predictive value in primary as well as recurrent high-grade glioma surgery. These nonfluorescing tumors are likely to be visualized by the help of iUS. Thus, many of the short comings of iUS like poor imaging (due to artifacts or tumor calcification) and characterization of the post resection status may be overcome by the use of ALA fluorescence. Conversely, shortcomings of ALA such as lack of anatomical two-dimensional perspective and false negatives may be resolved with concurrent application of iUS. However, both fail to convey functional status and this is where IONM plays an important role. Nonetheless, good clinical judgement remains imperative to interpret information and optimize surgical outcomes.

  Conclusion Top

Navigable iUS and FGR are useful intraoperative techniques in challenging recurrent tumor resection. They provide complementary information for a comprehensive estimate of tumor extent and can improve intraoperative surgical decision-making along with functional monitoring.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Unsgaard G, Selbekk T, Brostrup Müller T, Ommedal S, Torp SH, Myhr G, et al. Ability of navigated 3D ultrasound to delineate gliomas and metastases-comparison of image interpretations with histopathology. Acta Neurochir (Wien) 2005;147:1259-69.  Back to cited text no. 1
Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: A randomised controlled multicentre phase III trial. Lancet Oncol 2006;7:392-401.  Back to cited text no. 2
Nabavi A, Thurm H, Zountsas B, Pietsch T, Lanfermann H, Pichlmeier U, et al. Five-aminolevulinic acid for fluorescence-guided resection of recurrent malignant gliomas: A phase ii study. Neurosurgery 2009;65:1070-6.  Back to cited text no. 3
Hervey-Jumper SL, Berger MS. Reoperation for recurrent high-grade glioma: A current perspective of the literature. Neurosurgery 2014;75:491-9.  Back to cited text no. 4
Zhao YH, Wang ZF, Pan ZY, Péus D, Delgado-Fernandez J, Pallud J, et al. A meta-analysis of survival outcomes following reoperation in recurrent glioblastoma: Time to consider the timing of reoperation. Front Neurol 2019;10:286.  Back to cited text no. 5
Moiyadi AV, Shetty PM. Surgery for recurrent malignant gliomas: Feasibility and perioperative outcomes. Neurol India 2012;60:185-90.  Back to cited text no. 6
  [Full text]  
Park CK, Kim JH, Nam DH, Kim CY, Chung SB, Kim YH, et al. A practical scoring system to determine whether to proceed with surgical resection in recurrent glioblastoma. Neuro Oncol 2013;15:1096-101.  Back to cited text no. 7
Gandhi S, Tayebi Meybodi A, Belykh E, Cavallo C, Zhao X, Syed MP, et al. Survival outcomes among patients with high-grade glioma treated with 5-aminolevulinic acid-guided surgery: A systematic review and meta-analysis. Front Oncol 2019;9:620.  Back to cited text no. 8
Moiyadi AV, Shetty P, Sridhar E. Periventricular glioblastomas and ependymal involvement interrogated using intraoperative fluorescence-a pathological correlative study. Br J Neurosurg 2017;31:107-12.  Back to cited text no. 9
Chohan MO, Berger MS. 5-Aminolevulinic acid fluorescence guided surgery for recurrent high-grade gliomas. J Neurooncol 2019;141:517-22.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]


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