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Chiman Jeon, Sang Duk Hong, Kyung In Woo, Ho Jun Seol, Do-Hyun Nam, Jung-Il Lee, and Doo-Sik Kong

OBJECTIVE

Orbital tumors are often surgically challenging because they require an extensive fronto-temporo-orbital zygomatic approach (FTOZ) and a multidisciplinary team approach to provide the best outcomes. Recently, minimally invasive endoscopic techniques via a transorbital superior eyelid approach (ETOA) or endoscopic endonasal approach (EEA) have been proposed as viable alternatives to transcranial approaches for orbital tumors. In this study, the authors investigated the feasibility of 360° circumferential access to orbital tumors via both ETOA and EEA.

METHODS

Between April 2014 and June 2019, 16 patients with orbital tumors underwent either ETOA or EEA at the authors’ institution. Based on the neuro-topographic “four-zone model” of the orbit with its tumor epicenter around the optic nerve in the coronal plane, ETOA (n = 10, 62.5%) was performed for tumors located predominantly superolateral to the nerve and EEA (n = 6, 37.5%) for those located predominantly inferomedial to the nerve. Eight patients (50%) presented with intraconal tumors and 8 (50%) with extraconal ones. The orbital tumors included orbital schwannoma (n = 6), cavernous hemangioma (n = 2), olfactory groove meningioma (n = 1), sphenoorbital meningioma (n = 1), chondrosarcoma (n = 1), trigeminal schwannoma (n = 1), metastatic osteosarcoma (n = 1), mature cystic teratoma (n = 1), sebaceous carcinoma (n = 1), and ethmoid sinus osteoma (n = 1). The clinical outcomes and details of surgical techniques were reviewed.

RESULTS

Gross-total resection was achieved in 12 patients (75%), near-total resection in 3 (18.8%), and subtotal resection in 1 (6.2%). Eight (88.9%) of the 9 patients with preoperative proptosis showed improvement after surgery, and 4 (66.7%) of the 6 patients with visual symptoms demonstrated improvement. Four (40%) of the 10 patients treated with ETOA experienced partial third nerve palsy immediately after surgery (3 transient and 1 persistent). There have been no postoperative CSF leaks or infections in this series.

CONCLUSIONS

Without transcranial approaches requiring temporalis muscle dissection and orbitozygomatic osteotomy, the selection of ETOA or EEA based on a concept of a four-zone model with its epicenter around the optic nerve successfully provides a minimally invasive 360° circumferential access to the entire orbit with acceptable morbidity.

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Ju-Hwi Kim, Kyung-Sub Moon, Ji-Ho Jung, Woo-Youl Jang, Tae-Young Jung, In-Young Kim, Kyung-Hwa Lee, and Shin Jung

OBJECTIVE

Indocyanine green videoangiography (ICGVA) has been used in many neurosurgical operations, including vascular and brain tumor fields. In this study, the authors applied ICGVA to intracranial meningioma surgery and evaluated it usefulness with attention to collateral venous flow.

METHODS

Forty-two patients with intracranial meningioma who underwent ICGVA during microsurgical resection were retrospectively analyzed. For ICGVA, the ICG was injected intravenously at the standard dose of 12.5 mg before and/or after tumor resection. Intravascular fluorescence from blood vessels was imaged through a microscope with a special filter and infrared excitation light to illuminate the operating field. The authors assessed the benefits of ICGVA and analyzed its findings with preoperative radiological findings on MRI.

RESULTS

ICGVA allowed real-time assessment of the patency and flow direction in very small peritumoral vessels in all cases. A safe dural incision could also be done based on information from ICGVA. The collateral venous channel due to venous obstruction of tumoral compression was found in 10 cases, and venous flow restoration after tumor resection was observed promptly after tumor resection in 4 cases. Peritumoral brain edema (PTBE) was observed on preoperative T2-weighted MRI in 19 patients. The presence of collateral venous circulation or flow restoration was significantly related to PTBE formation in multivariate analysis (p = 0.001; HR 0.027, 95% CI 0.003–0.242).

CONCLUSIONS

ICGVA, an excellent method for monitoring blood flow during meningioma resection, provides valuable information as to the presence of venous collaterals and flow restoration. Furthermore, the fact that the presence of venous collaterals was found to be associated with PTBE may directly support the venous theory as the pathogenesis of PTBE formation.

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Chiman Jeon, Chang-Ki Hong, Kyung In Woo, Sang Duk Hong, Do-Hyun Nam, Jung-Il Lee, Jung Won Choi, Ho Jun Seol, and Doo-Sik Kong

OBJECTIVE

Tumors involving Meckel’s cave remain extremely challenging because of the surrounding complex neurovascular structures and deep-seated location. The authors investigated a new minimal-access technique using the endoscopic transorbital approach (eTOA) through the superior eyelid crease to Meckel’s cave and middle cranial fossa lesions and reviewed the most useful surgical procedures and pitfalls of this approach.

METHODS

Between September 2016 and January 2018, the authors performed eTOA in 9 patients with tumors involving Meckel’s cave and the middle cranial fossa. The lesions included trigeminal schwannoma in 4 patients, meningioma in 2 patients, metastatic brain tumor in 1 patient, chondrosarcoma in 1 patient, and dermoid cyst in 1 patient. In 7 of the 9 patients, eTOA alone was performed, while the other 2 patients underwent a combined eTOA and endoscopic endonasal approach or retrosigmoid craniotomy. Data including details of surgical techniques and clinical outcomes were recorded.

RESULTS

Gross-total resection was performed in 7 of the 9 patients (77.8%). Four patients underwent extended eTOA (with lateral orbital rim osteotomy). Drilling of the trapezoid sphenoid floor, a middle fossa “peeling” technique, and full visualization of Meckel’s cave were applied to approach the lesions. Tumors were exposed and removed extradurally in 3 patients and intradurally in 6 patients. There was no postoperative CSF leak.

CONCLUSIONS

The eTOA affords a direct route to access Meckel’s cave and middle cranial fossa lesions. With experience, this novel approach can be successfully applied to selected skull base lesions. To achieve successful removal of the tumor, emphasis should be placed on the importance of adequately removing the greater sphenoid wing and vertical crest. However, because of limited working space eTOA may not be an ideal approach for posterior fossa lesions.

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Ho-Shin Gwak, Myung-Jin Park, In-Chul Park, Sang Hyeok Woo, Hyeon-Ok Jin, Chang Hun Rhee, and Hee-Won Jung

Object

Local invasiveness of malignant glioma is a major reason for the failure of current treatments including surgery and radiation therapy. Tetraarsenic oxide (As4O6 [TAO]) is a trivalent arsenic compound that has potential anticancer and antiangiogenic effects in selected cancer cell lines at a lower concentration than arsenic trioxide (As2O3 [ATO]), which has been more widely tested in vitro and in vivo. The authors tried to determine the cytotoxic concentration of TAO in malignant glioma cell lines and whether TAO would show anti-invasive effects under conditions independent of cell death or apoptosis.

Methods

The human phosphatase and tensin homolog (PTEN)-deficient malignant glioma cell lines U87MG, U251MG, and U373MG together with PTEN-functional LN428 were cultured with a range of micromolar concentrations of TAO. The invasiveness of the glioma cell lines was analyzed. The effect of TAO on matrix metalloproteinase (MMP) secretion and membrane type 1 (MT1)-MMP expression was measured using gelatin zymography and Western blot, respectively. Akt, or protein kinase B, activity, which is a downstream effector of PTEN, was assessed with a kinase assay using glycogen synthesis kinase-3β (GSK-3β) as a substrate and Western blotting of phosphorylated Akt.

Results

Tetraarsenic oxide inhibited 50% of glioma cell proliferation at 6.3–12.2 μM. Subsequent experiments were performed under the same TAO concentrations and exposure times, avoiding the direct tumoricidal effect of TAO, which was confirmed with apoptosis markers. An invasion assay revealed a dose-dependent decrease in invasiveness under the influence of TAO. Both the gelatinolytic activity of MMP-2 and MT1-MMP expression decreased in a dose-dependent manner in all cell lines, which was in accordance with the invasion assay results. The TAO decreased kinase activity of Akt on GSK-3β assay and inhibited Akt phosphorylation in a dose-dependent manner in all cell lines regardless of their PTEN status.

Conclusions

These results showed that TAO effectively inhibits proliferation of glioblastoma cell lines and also exerts an anti-invasive effect via decreased MMP-2 secretion, decreased MT1-MMP expression, and the inhibition of Akt phosphorylation under conditions devoid of cytotoxicity. Further investigations using an in vivo model are needed to evaluate the potential role of TAO as an anti-invasive agent.

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Eui Hyun Kim, Jihwan Yoo, In-Ho Jung, Ji Woong Oh, Ju-Seong Kim, Jin Sook Yoon, Ju Hyung Moon, Seok-Gu Kang, Jong Hee Chang, and Tae Hoon Roh

OBJECTIVE

The insula is a complex anatomical structure. Accessing tumors in the insula remains a challenge due to its anatomical complexity and the high chance of morbidity. The goal of this study was to evaluate the feasibility of an endoscopic transorbital approach (ETOA) to the insular region based on a cadaveric study.

METHODS

One cadaveric head was used to study the anatomy of the insula and surrounding vessels. Then, anatomical dissection was performed in 4 human cadaveric heads using a dedicated endoscopic system with the aid of neuronavigation guidance. To assess the extent of resection, CT scanning was performed before and after dissection. The insular region was directly exposed by a classic transcranial approach to check the extent of resection from the side with a classic transcranial approach.

RESULTS

The entire procedure consisted of two phases: an extradural orbital phase and an intradural sylvian phase. After eyelid incision, the sphenoid bone and orbital roof were extensively drilled out with exposure of the frontal and temporal dural layers. After making a dural window, the anterior ramus of the sylvian fissure was opened and dissected. The M2 segment of the middle cerebral artery (MCA) was identified and traced posterolaterally. A small corticectomy was performed on the posterior orbital gyrus. Through the window between the lateral lenticulostriate arteries and M2, the cortex and medulla of the insula were resected in an anteroposterior direction without violation of the M2 segment of the MCA or its major branches. When confirmed by pterional craniotomy, the sylvian fissure and the MCA were found to be anatomically preserved. After validation of the feasibility and safety based on a cadaveric study, the ETOA was successfully performed in a patient with a high-grade glioma (WHO grade III) in the right insula.

CONCLUSIONS

The transorbital route can be considered a potential option to access tumors located in the insula. Using an ETOA, the MCA and its major branches were identified and preserved while removal was performed along the long axis of the insula. In particular, lesions in the anterior part of the insula are most benefited by this approach. Because this approach was implemented in only one patient, additional discussion and further verification is required.

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Chin Su Koh, Hae-Yong Park, Jaewoo Shin, Chanho Kong, Minkyung Park, In-Seok Seo, Bonkon Koo, Hyun Ho Jung, Jin Woo Chang, and Hyung-Cheul Shin

OBJECTIVE

Artificial manipulation of animal movement could offer interesting advantages and potential applications using the animal’s inherited superior sensation and mobility. Although several behavior control models have been introduced, they generally epitomize virtual reward-based training models. In this model, rats are trained multiple times so they can recall the relationship between cues and rewards. It is well known that activation of one side of the nigrostriatal pathway (NSP) in the rat induces immediate turning toward the contralateral side. However, this NSP stimulation–induced directional movement has not been used for the purpose of animal-robot navigation. In this study, the authors aimed to electrically stimulate the NSP of conscious rats to build a command-prompt rat robot.

METHODS

Repetitive NSP stimulation at 1-second intervals was applied via implanted electrodes to induce immediate contraversive turning movements in 7 rats in open field tests in the absence of any sensory cues or rewards. The rats were manipulated to navigate from the start arm to a target zone in either the left or right arm of a T-maze. A leftward trial was followed by a rightward trial, and each rat completed a total of 10 trials. In the control group, 7 rats were tested in the same way without NSP stimulation. The time taken to navigate the maze was compared between experimental and control groups.

RESULTS

All rats in the experimental group successfully reached the target area for all 70 trials in a short period of time with a short interstimulus interval (< 0.7 seconds), but only 41% of rats in the control group reached the target area and required a longer period of time to do so. The experimental group made correct directional turning movements at the intersection zone of the T-maze, taking significantly less time than the control group. No significant difference in navigation duration for the forward movements on the start and goal arms was observed between the two groups. However, the experimental group showed quick and accurate movement at the intersection zone, which made the difference in the success rate and elapsed time of tasks.

CONCLUSIONS

The results of this study clearly indicate that a rat-robot model based on NSP stimulation can be a practical alternative to previously reported models controlled by virtual sensory cues and rewards.

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Doo-Sik Kong, Stephanie Ming Young, Chang-Ki Hong, Yoon-Duck Kim, Sang Duk Hong, Jung Won Choi, Ho Jun Seol, Jung-Il Lee, Hyung Jin Shin, Do-Hyun Nam, and Kyung In Woo

OBJECTIVE

Cranioorbital tumors are complex lesions that involve the deep orbit, floor of the frontal bone, and lesser and greater wing of the sphenoid bone. The purpose of this study was to describe the clinical and ophthalmological outcomes with an endoscopic transorbital approach (TOA) in the management of cranioorbital tumors involving the deep orbit and intracranial compartment.

METHODS

The authors performed endoscopic TOAs via the superior eyelid crease incision in 18 patients (16 TOA alone and 2 TOA combined with a simultaneous endonasal endoscopic resection) with cranioorbital tumors from September 2016 to November 2017. There were 12 patients with sphenoorbital meningiomas. Other lesions included osteosarcoma, plasmacytoma, sebaceous gland carcinoma, intraconal schwannoma, cystic teratoma, and fibrous dysplasia. Ten patients had primary lesions and 8 patients had recurrent tumors. Thirteen patients had intradural lesions, while 5 had only extradural lesions.

RESULTS

Of 18 patients, 7 patients underwent gross-total resection of the tumor and 7 patients underwent planned near-total resection of the tumor, leaving the cavernous sinus lesion. Subtotal resection was performed in 4 patients with recurrent tumors. There was no postoperative CSF leak requiring reconstruction surgery. Fourteen of 18 patients (77.8%) had preoperative proptosis on the ipsilateral side, and all 14 patients had improvement in exophthalmos; the mean proptosis reduced from 5.7 ± 2.7 mm to 1.5 ± 1.4 mm. However, some residual proptosis was evident in 9 of the 14 (64%). Ten of 18 patients (55.6%) had preoperative optic neuropathy, and 6 of them (60.0%) had improvement; the median best-corrected visual acuity improved from 20/100 to 20/40. Thirteen of 18 patients showed mild ptosis at an immediate postoperative examination, all of whom had a spontaneous and complete recovery of their ptosis during the follow-up period. Three of 7 patients showed improvement in extraocular motility after surgery.

CONCLUSIONS

Endoscopic TOA can be considered as an option in the management of cranioorbital tumors involving complex anatomical areas, with acceptable sequelae and morbidity.

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Soo Heon Kim, Cheol Ryong Ku, Minkyun Na, Jihwan Yoo, Woohyun Kim, In-Ho Jung, Kyung Won Kim, Ju Hyung Moon, Daham Kim, Eun Jig Lee, Sun Ho Kim, and Eui Hyun Kim

OBJECTIVE

Thyroid-stimulating hormone (TSH)–secreting pituitary adenoma (TSHoma) is a rare type of pituitary adenoma; thus, little is known about TSHomas. The purpose of this study was to analyze clinical characteristics and therapeutic outcomes of TSHomas based on a single-center experience. The authors also searched for reliable preoperative and early postoperative factors that could predict long-term endocrinological remission.

METHODS

The clinical, radiological, and pathological characteristics and surgical and endocrinological outcomes of 31 consecutive cases of TSHomas that were surgically treated between 2005 and 2017 were reviewed retrospectively. Preoperative factors were evaluated for their ability to predict long-term remission by comparing remission and nonremission groups. TSH and free thyroxine levels were measured at 2, 6, 12, 18, and 24 hours after surgery to determine whether they could predict long-term remission.

RESULTS

Gross-total removal of tumor was achieved in 28 patients (90.3%), and 26 patients (83.9%) achieved endocrinological remission by surgery alone based on long-term endocrinological follow-up (median 50 months, range 32–81 months). The majority of the tumors were solid (21/31, 67.7%), and en bloc resection was possible in 16 patients (51.6%). Larger tumor size and tumor invasion into cavernous sinus and sphenoid sinus were strong predictors of lower rates of endocrinological remission. Immediate postoperative TSH level at 12 hours after surgery was the strongest predictor, with a 0.62 μIU/mL cutoff. Postoperative complications included CSF rhinorrhea in one patient and epistaxis in another patient, who underwent additional surgical treatment for the complications.

CONCLUSIONS

Tumor size and extent are major prognostic factors for both extent of resection and endocrinological remission. The consistency of TSHomas was more likely to be solid, which makes extracapsular dissection more feasible. Long-term remission of TSHomas could be predicted even during the early postoperative period.

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Soo Heon Kim, Cheol Ryong Ku, Minkyun Na, Jihwan Yoo, Woohyun Kim, In-Ho Jung, Kyung Won Kim, Ju Hyung Moon, Daham Kim, Eun Jig Lee, Sun Ho Kim, and Eui Hyun Kim

OBJECTIVE

Thyroid-stimulating hormone (TSH)–secreting pituitary adenoma (TSHoma) is a rare type of pituitary adenoma; thus, little is known about TSHomas. The purpose of this study was to analyze clinical characteristics and therapeutic outcomes of TSHomas based on a single-center experience. The authors also searched for reliable preoperative and early postoperative factors that could predict long-term endocrinological remission.

METHODS

The clinical, radiological, and pathological characteristics and surgical and endocrinological outcomes of 31 consecutive cases of TSHomas that were surgically treated between 2005 and 2017 were reviewed retrospectively. Preoperative factors were evaluated for their ability to predict long-term remission by comparing remission and nonremission groups. TSH and free thyroxine levels were measured at 2, 6, 12, 18, and 24 hours after surgery to determine whether they could predict long-term remission.

RESULTS

Gross-total removal of tumor was achieved in 28 patients (90.3%), and 26 patients (83.9%) achieved endocrinological remission by surgery alone based on long-term endocrinological follow-up (median 50 months, range 32–81 months). The majority of the tumors were solid (21/31, 67.7%), and en bloc resection was possible in 16 patients (51.6%). Larger tumor size and tumor invasion into cavernous sinus and sphenoid sinus were strong predictors of lower rates of endocrinological remission. Immediate postoperative TSH level at 12 hours after surgery was the strongest predictor, with a 0.62 μIU/mL cutoff. Postoperative complications included CSF rhinorrhea in one patient and epistaxis in another patient, who underwent additional surgical treatment for the complications.

CONCLUSIONS

Tumor size and extent are major prognostic factors for both extent of resection and endocrinological remission. The consistency of TSHomas was more likely to be solid, which makes extracapsular dissection more feasible. Long-term remission of TSHomas could be predicted even during the early postoperative period.