원 저 ISSN 2093-9272일산병원학술지 2017;16(2):183-187

Volume 16 Number 2 December 2017 183

신경교종 수술에서 인디고카민 항법테이프 기법

국민건강보험 일산병원 신경외과

권영섭, 양국희

Navigation-Guided Indigo Carmine (IC) Tape Demarcation

Technique for Glioma Surgery

Young Sub Kwon, Kook Hee Yang

Department of Neurosurgery, National Health Insurance Service Ilsan Hospital, Goyang, Korea

Background: The goal of low and high grade glioma surgery is maximal resection with preservation of normal brain tissues. Although neuro-navigation is widely used tool for glioma resection, intraoperative brain shifting limits its accuracy. We introduced a simple technique of navigation-guided surgery using Indigo Carmine (IC) tape to aid in maximal surgical resection of glioma andanalyzed its surgical effectiveness. Methods: We have developed IC painted tape that was inserted through small dura opening with navigation-guidance to demarcate tumor resection margin. From 2008 to 2012, total of 14 patients underwent removal of glioma using navigation-guided IC tape demarcation technique. Procedures, surgical results, and complications were discussed and analyzed.Results: Among the 14 patients, gross total resection was achieved in 9 (64%) patients, subtotal resection in 4 (21%) patients, and partial resection in 1 (7%) patient. No postoperative hematoma or infection occurred in all patients. Conclusion: IC tape demarcation technique could be helpful during glioma resection by minimizing the limitation of conventional navigation-guided surgery. We believe this simple technique is cost effective and safe, although further studies are needed to verify the clinical benefit compared to other resection techniques.

Key Words: Glioma, Neuronavigation, Indigo Carmine, Navigation

책임저자 : 양국희10444 경기도 고양시 일산동구 일산로 100

국민건강보험 일산병원 신경외과전화 : (031)900-0248, 팩스 : (031)900-0588E-mail : khyang@nhimc.or.kr

INTRODUCTION

In management of gliomas, clinical benefit of surgery is still controversial.1 Although postoperative complication is crucial in clinical course of patients after glioma surgery, maximal rese- ction is usually advocated in low grade gliomas.2 In high gliomas, however, rapid recurrences and high rate of postoperative com- plication obscure the role of maximized surgery.3 Recently, increasing reports support that maximal surgery benefits in recurrence free survival even for high grade gliomas, and con- sensus lies in maximal resection for optimal clinical outcome in surgery for gliomas.1,4,5

The tumor margin in glioma is difficult to distinguish from normal parenchyma even under high powered microscope. Cystic and necrotic tumor components can be distinguishable with normal tissues, but transitional tissue of neoplastic and normal parenchyma is poorly demarcated since they share simi- lar optical properties. Even for experienced glioma surgeons, guidance for extent of tumor is mandatory for maximal glio- ma resection.

In the past decade, numerous neurosurgical tools have been developed to overcome this issue. Neuronavigation, intraope- rative magnetic resonance imaging (iMRI), intraoperative fluo- rescence, ultrasonography, and electrophysiologic mapping have reported its benefit in glioma surgery. However, advantages and disadvantages exist in each modality and no single tool has emerged to be optimal in glioma surgery.

In this study, we introduce a simple technique of naviga- tion-guided surgery using Indigo Carmine (IC) tape to aid in maximal surgical resection of glioma and analyze the clinical results and limitation of this technique.

YS Kwon, et al. Navigation-Guided IC Tape Demarcation Technique for Glioma Surgery

184 Korean Journal of National Health Insurance Service Ilsan Hospital

Fig. 1. (A) Photograph of nylon tape of about 20 cm in length.(B) Nylon tape was painted with Indigo Carmine on its surfaces.

Fig. 2. Intraoperative photograph showing insertion of Indigo Carmine tape after small opening of the dura.

Fig. 3. Intraoperative photograph showing Indigo Carmine tapeafter wide opening of the dura before resection of glioma.

MATERIAL AND METHODS

1. Patient population

From 2008 to 2012, total of 14 patients underwent remo- val of glioma using navigation-guided IC tape demarcation technique. All patients had MRI finding with a presumed dia- gnosis of low or high grade glioma. Patients underwent preo- perative MRI which was used for intraoperative neuro-naviga- tion system (Stealth Station, Medtronic, Minneapolis, MN, USA) with gadolinium(GD) enhanced T1-weighted sequences for enhancing tumors, and fluid-attenuated inversion recovery (FLAIR) or T2-weighted sequences for non-enhancing tumors. Tumor boundaries from MR images were demarcated after agreement of surgeon and neuroradiologist. After the surgery, postoperative MRI was taken within 48 hours with same MR sequence used in intraoperative neuro-navigation. Postopera- tive resection results were evaluation with volumetric measu- rement which was done by comparing the postoperative MRI with preoperative MRI, and extent of resection was calcula- ted. For enhancing tumor, gross total resection (GTR) was designated if there were no enhancing tumor on postoperative GD enhanced T1-weighted sequence. For non-enhancing tumor, postoperative FLAIR or T2-weighted images were used. Rese- ction was designated as subtotal resection (STR) if remnant tumor was less than 20%, and partial resection (PR) if remnant was more than 20%.

2. Navigation-Guided Indigo Carmine (IC) Tape Demarcation Technique

Preoperative MR images were registered in neuronaviga- tion system and predetermined tumor margin was targeted

by the surgeon. Coronal and sagittal reconstructed images were meticulously reviewed to determine large draining veins and eloquent brain structures which should be preserved. After selection of optimal resection trajectory and depth of tumor removal, surgical procedures were initiated. After routine gene- ral endotracheal anesthesia, craniotomy was done according to the location of tumor. After the craniotomy, 4 to 6 pieces of nylon tape of about 20 cm length was prepared and painted with Indigo Carmine on its surfaces (Fig. 1 A, B). Small dura incisions of about 1 cm were made at the resection margin of the tumor. Nylon tape was attached to the tip of the naviga- tion pointer, and then inserted under navigation guidance to the trajectory of the resection margin (Fig. 2). After the inser- tion of nylon tape, dura was widely opened (Fig. 3), and tumor resection was done in usual manner until the Indigo Carmine tape was encountered.

RESULTS

Demographic, radiologic, pathologic and surgical results were summarized in Table 1. A total of 14 patients was surgi- cally treated with navigation-guided Indigo Carmine tape demar- cation technique for resection of gliomas. Mean age of patients

권영섭 외. 신경교종 수술에서 인디고카민 항법테이프 기법

Volume 16 Number 2 December 2017 185

Table 1. Summary of patient demographics, radiological, pathological and surgical results

Patient No. Sex Age Location of tumor Pathology WHO grade Extent of Resection

1 M 61 Rt temporal GBM IV GTR2 M 60 Lt frontal GBM IV GTR3 M 61 Lt frontal Gliosarcoma IV GTR4 F 74 Lt frontal GBM IV GTR5 M 41 Bilat frontal GBM IV STR6 M 53 Rt temporal Anaplastic astrocytoma III GTR7 F 39 Lt frontal Oligodendroglioma II GTR8 M 66 Lt parietal GBM IV PR9 M 69 Lt parietal Anaplastic astrocytoma III GTR10 M 53 Rt temporoparietal GBM IV GTR11 F 21 Lt frontal Diffuse astrocytoma II STR12 M 67 Lt temporoparietal GBM IV STR13 F 66 Rt frontal Oligodendroglioma II GTR14 F 50 Rt frontal GBM IV STR

GBM glioblastoma multiforme, GTR gross total resection, STR subtotal resection, PR partial resection

were 55.8 years (range 21-74 years) with 9 males and 5 fema- les. The location of tumor was frontal in 8 (57%) patients, tem- poral in 2 (14%) patients, parietal in 2 (14%) patients, and temporoparietal in 2 (14%) patients. Pathological results were glioblatoma multiforme (GBM) in 8 (50%) patients, anaplastic astrocytoma in 2 (14%) patients, oligodendroglioma in 2 (14 %) patients, diffuse astrocytoma in 1 (7%) patient, and glio- sarcoma in 1 (7%) patient., Glioma was classified as grade 4 in 9 (64%), grade 3 in 2 (14%), and grade 2 in 3 (21%) pa- tients by WHO classification of glial tumors. Among the 14 patients, GTR was achieved in 9 (64%) patients, STR in 4 (21 %) patients, and PR in 1 (7%) patient. No postoperative hema- toma or infection occurred in all patients.

DISCUSSION

Glioma is the most common primary intra-axial tumor of the central nervous system in adults. Currently, the primary treatment of malignant glioma is to reduce the tumor cells by surgical resection followed by a multimodal adjuvant regimen of radiotherapy and chemotherapy. Although there are several important prognostic factors, maximal resection of the tumor within the range of no surgery-related neurologic deficit is a very potent prognostic factor.5 These are not different even in low grade glioma.2 Therefore, optimal glioma surgery is to remove as much brain tissue harboring glioma cells as possi- ble and to preserve neuronal function. For maximal surgical resection, various methods are being used.

Image guided neurosurgery using navigation systems is an effective method to increase the accuracy of intracranial sur-

gery. However, brain shift occurs during surgery which is cau- sed by the effect of gravity applied to the brain, loss of cereb- rospinal fluid, brain swelling, and surgical procedures. Nymski et al. reported that error of frameless navigation can be as much as 3 cm in their study.6 So, accuracy of navigation system is reliable only before opening of the dura and surgical removal.

Several methods have been used to overcome these limita- tions using navigation systems. iMRI is a theoretically ideal tool that allows real-time imaging of resection margin. Senft et al. reported the benefit of iMRI for maximal surgical rese- ction for glioma.7 Of 24 patients who underwent iMRI, com- plete tumor resection was achieved in 96% of patients which was significantly more compared to non-iMRI group (68%, p=0.023). Although iMRI shows highest specificity and sensi- tivity compared with other tools, it also harbors disadvanta- ges. The cost of iMRI infrastructure takes over US $3 million, and cost effectiveness is too low considering the utilization frequency in small and medium volume hospitals. Also, image quality and time are problems of iMRI that provides only low tesla imaging where resection margins can be ambiguous, and time consuming procedures put patients in longer time of anes- thesia.

Fluorescence guided surgery with 5-aminolevulinic acid (5- ALA) is another available option to help maximal glioma sur- gery. 5-ALA produces fluorescence in high grade gliomas which can be seen intraoperatively in confocal microscope. Howe- ver, the fluorescence is only limited to enhancing tumors, and extracellular leaks into surrounding edematous tissue put sur- rounding tissue in risk of misinterpretation.

Intraoperative ultrasonography and electrophysiologic map-

YS Kwon, et al. Navigation-Guided IC Tape Demarcation Technique for Glioma Surgery

186 Korean Journal of National Health Insurance Service Ilsan Hospital

ping are other adjunctive tools that help maximal resection of glioma. Serra et al. achieved gross total removal of high grade tumors in 21 of 22 cases with high-frequency ultrasono- graphy.8 The ultrasound provides information based on diffe- rent acoustic impedances and reflection coefficients of solid, cystic, and necrotic tissues. However, information provided by ultrasound is based on differences in tissue property which usually is acknowledgeable in high powered microscope, and problem of tumor-normal transition zone may also be vague as well. Electrophysiological mapping is particularly useful when tumor lies in eloquent brain. Intraoperative monitoring such as motor and somatosensory evoked potential is widely used in surgery adjacent to motor and sensory cortex. Howe- ver, awake surgery may be needed when specific functional damage is expected where routine use of awake surgery can be cumbersome and problematic.

Although navigation-guided surgery is still the most popu- lar method in glioma resection, problem of brain shift is the main reason behind incomplete resection of glioma. Different methods to overcome this problem have been reported with considerable success. Kelly et al. placed a series of stainless steel reference balls of 1mm at tumor margin to aid in glioma resection.9 Cho et al. planted ‘Tailed Bullet’ which is metal cylinder of 5mm with string attached at the end.10 Yoshikawa et al. used tubes as ‘fence-post’ around tumor margin.11 Mar- getis et al. demonstrated injection of Indigo Carmine dye around tumor margin to serve as reference point of glioma resection.12

In our study, we have modified these techniques because these techniques required customized gadgets of steel balls, bul- lets or tubes. Indigotindisulfonate sodium (Indigo Carmine, Akorn, Inc.) is a dye frequently used in urological surgery to visualize ureteral orifices after intravenous administration. Ho- wever, we felt injected IC may be difficult to encounter during glioma resection since only small amount can be injected, and dye may be washed out or diffused on copious bleeding. So, we used IC painted tapes for reference of glioma resection so that; (1) it facilitates easy view of the resection margin like the ‘fence-post’ technique, and (2) IC dye serves as contingent guide if tape was inadvertently removed or withdrawn. Our technique resulted in GTR of 9 of 14 (64%) patients which were relatively similar to other technique, that requires custo- mized gadget. The materials for our technique are usually pre- pared in operating room.

This study has few limitations. First, the accuracy of the inserted IC tape is not verified in our study. The elasticity of the tape and loose attachment to navigation pointer tip allows chances of error at insertion process. Second, although no com- plication has occurred in our case series, insertion procedure may cause hemorrhagic complications. Tape may allow relati- vely more frictional damage to brain and vessels compared with

tube, metal bullet or syringe needle. Last, this study is only a case series with small number of cases. Controlled study with comparison to other technique is needed to clarify the true effectiveness of this technique.

Although this technique was studied with only a small num- ber of cases, we believe this simple technique can be applied with maximum cost effectiveness in small volume hospitals that do not have above-mentioned costly facilities for glioma surgery.

IC tape demarcation technique could be helpful during glio- ma resection by minimizing the limitation of conventional navigation-guided surgery. We believe this simple technique is cost effective and safe where brain shifting can be compen- sated without costly equipment. Due to small number of cases, further studies may be needed to verify the clinical benefit compared to other resection techniques.

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