1.Advanced T and Natural Killer Cell Therapy for Glioblastoma
Journal of Korean Neurosurgical Society 2023;66(4):356-381
Although immunotherapy has been broadly successful in the treatment of hematologic malignancies and a subset of solid tumors, its clinical outcomes for glioblastoma are still inadequate. The results could be due to neuroanatomical structures such as the bloodbrain- barrier, antigenic heterogeneity, and the highly immunosuppressive microenvironment of glioblastomas. The antitumor efficacy of endogenously activated effector cells induced by peptide or dendritic cell vaccines in particular has been insufficient to control tumors. Effector cells, such as T cells and natural killer (NK) cells can be expanded rapidly ex vivo and transferred to patients. The identification of neoantigens derived from tumor-specific mutations is expanding the list of tumor-specific antigens for glioblastoma. Moreover, recent advances in gene-editing technologies enable the effector cells to not only have multiple biological functionalities, such as cytokine production, multiple antigen recognition, and increased cell trafficking, but also relieve the immunosuppressive nature of the glioblastoma microenvironment by blocking immune inhibitory molecules, which together improve their cytotoxicity, persistence, and safety. Allogeneic chimeric antigen receptor (CAR) T cells edited to reduce graft-versushost disease and allorejection, or induced pluripotent stem cell-derived NK cells expressing CARs that use NK-specific signaling domain can be a good candidate for off-the-shelf products of glioblastoma immunotherapy. We here discuss current progress and future directions for T cell and NK cell therapy in glioblastoma.
2.Postoperative Segmental Motion up to 1 Year Following Single-Level Anterior Cervical Discectomy and Fusion: Plate versus Non-plate
Kwang-Sup SONG ; Jeongik LEE ; Dae Woong HAM ; Chan-Woo JUNG ; Hyun KANG ; Seung Won PARK ; Dong-Gune CHANG ; Youngbae B. KIM
Asian Spine Journal 2023;17(3):492-499
Methods:
In retrospectively collected data, 149 patients who underwent single-level ACDF for degenerative disease were enrolled and divided into non-plating (n=66) and plating (n=83). Interspinous motion (ISM) at the arthrodesis segment, Numeric Rating Scale (NRS) for neck pain, and Neck Disability Index (NDI) were serially evaluated at 3, 6, and 12 months postoperatively. Predictable factors for fusion, including age, sex, plating, diabetes, smoking, and type of grafts, were investigated, and fusion was defined as ISM <1 mm.
Results:
In both groups, ISM was the highest at 3 months and gradually decreased thereafter, and the plating group showed significantly lower serial ISM than the non-plating group at 12 months. The plating group had lower NRS and NDI scores than the nonplating group at 12 months, and the difference in the NRS scores was statistically significant, particularly at 3 and 6 months, although that of the NDI scores was not. In a multivariate analysis, plating was the most powerful predictor for fusion.
Conclusions
Plating significantly decreases the serial ISM compared with non-plating in single-level ACDF, and such decreased motion is correlated with decreased neck pain until 12 months postoperatively, particularly at 3 and 6 months. Given that plating was the most predictive factor for fusion, we recommend plating even in single-level ACDF for better early clinical outcomes.
3.Feasibility of Non-window Three-Dimensional– Printed Porous Titanium Cage in Posterior Lumbar Interbody Fusion: A Pilot Trial
Dae-Woong HAM ; Chan-Woo JUNG ; Dong-Gune CHANG ; Jae Jun YANG ; Kwang-Sup SONG
Clinics in Orthopedic Surgery 2023;15(6):960-967
Background:
The commercially available design of a three-dimensional (3D)–printed titanium (3D-Ti) cage can be divided into two types according to the presence of a window: a cage with a window that allows filling of bone graft materials and a non-window cage for stand-alone use. This prospective observational case series study aimed to explore the clinical feasibility of using a nonwindow type 3D-Ti cage in cases of combined window and non-window cage implantation. Furthermore, we evaluated the bone in growth patterns of non-window cages and their correlation with published fusion grading systems.
Methods:
A total of 31 consecutive patients who underwent single-level posterior lumbar interbody fusion surgery were included. Two 3D-Ti cages with different designs were inserted: a non-window cage on the left side and a window cage on the right side.Radiographic fusion was defined by the segmental angle between flexion and extension radiographs (F-E angle) and cage bridging bone (CBB) scores on computed tomography. The association between the F-E angle and osteointegration scoring system including the surface osteointegration ratio (SOR) score was analyzed.
Results:
Radiographic fusion was achieved in 27 of 31 patients (87%) at 12 months postoperatively. Among the non-window cages, 23 of 31 (74.2%) had fair SOR scores, while 19 of 31 (61.3%) window cages had fair intra-cage CBB scores. The higher the SOR score was, the smaller the flexion-extension angle (SOR 0 vs. SOR 1: 6.30° ± 2.43° vs. 1.95° ± 0.99°, p < 0.001; SOR 0 vs. SOR 2: 6.03° ± 2.43° vs. 0.99°± 0.74°, p < 0.001).
Conclusions
The clinical feasibility of using a non-window 3D-Ti cage during lumbar interbody fusion might be acceptable. Furthermore, a newly suggested fusion criterion for the use of the non-window cage, the SOR score, showed a significant association with the published fusion grading systems, demonstrating its feasibility in determining interbody fusion in lumbar spinal surgery.
4.The Essential Function of miR-5739 in Embryonic Muscle Development
Ji-Heon LEE ; Min Sup KIM ; Jin-seop LEE ; Dong Hyun LEE ; Chansol PARK ; Dong Hyuk LEE ; Eun-Young KIM ; Hyung Min CHUNG
International Journal of Stem Cells 2023;16(2):145-155
Background and Objectives:
Embryologically, mesodermal development is closely related to the development of various organs such as muscles, blood vessels, and hearts, which are the main organs that make up the body. However, treatment for mesoderm developmental disorders caused by congenital or acquired factors has so far relied on surgery and drug treatment for symptom relief, and more fundamentally, treatment for mesoderm developmental disorders is needed.
Methods:
and Results: In our study, microRNA (miRNA), which plays an important role in the mesoderm development process, was identified and the developmental function was evaluated. miRNAs consist of small nucleotides, which act as transcription factors that bind to the 3’ untranslated region and suppressed target gene expression. We constructed the human embryonic stem cell (hESC) knockout cell line and analyzed the function and characteristics of miR-5739, which plays an important role in mesoderm lineage. miR-5739 acts as a transcription factor targeting SMA, Brachyury T, Hand1, which controls muscle proliferation and differentiation, and KDR gene, which regulates vessel formation in vitro. In vivo results suggest a role in regulating muscle proliferation and differentiation. Gene ontology analysis confirmed that the miR-5739 is closely related to genes that regulate muscle and vessel proliferation and differentiation. Importantly, abnormal expression of miR-5739 was detected in somatic cells derived from patients with congenital muscle disease.
Conclusions
Our study demonstrate that miR-5739 gene function significantly affects transcriptional circuits that regu-late muscle and vascular differentiation during embryonic development.
5.Utilizing a Novel Pituitary Retractor for Early Descent of the Diaphragma Sellae during Endoscopic Transsphenoidal Pituitary Surgery
Jae-Sung PARK ; Dong-Sup CHUNG ; Wan-Soo YOON
Journal of Korean Neurosurgical Society 2022;65(1):114-122
Objective:
: Early descent of the diaphragm sellae (DS) during endoscopic endonasal transsphenoidal surgery (EETS) for pituitary macroadenoma surgery is occasionally a troublesome event by blocking the surgical field. Here we introduce an alternative technique with the new pituitary retractor and present our clinical experiences.
Methods:
: We designed a simple and rigid pituitary retractor with the least space occupation in the nasal cavity to be compatible in EETS. The pituitary retractor was held by external holder system to support the herniated DS stably. We retrospectively reviewed a clinical 22 cases of pituitary macroadenomas underwent EETS using the pituitary retractor.
Results:
: The pituitary retractor stably pushed up the herniated DS in all cases, and the surgeon proceeded the procedure with bimanual maneuver. The pituitary retractor was helpful to remove tumors around the medial cavernous sinus and behind the DS in 16 and seven cases, respectively. In four cases, the meticulous hemostasis was completed with the direct visualization by the DS elevation with this retractor. Gross total tumor resection was performed in 20/22 patients (91%). The impaired visual function and hypopituitarism were improved in 18/20 (90%) and 7/14 (50%) patients after surgery, respectively. There was no complication related with the pituitary retractor.
Conclusion
: During EETS for pituitary macroadenomas, the novel pituitary retractor reported in this study is a very useful technique when the herniated DS block the surgical field and bimanual maneuver. This pituitary retractor can help to result in the excellent surgical outcomes with minimal morbidity.
6.MRI Findings of Renal Myxoma: A Case Report and Literature Review
Sung Hyun YU ; Young Sup SHIM ; So Hyun PARK ; Seung Joon CHOI ; Dong Hae CHUNG ; Sang Jin YOON
Journal of the Korean Radiological Society 2022;83(1):162-167
Renal myxomas are very rare benign tumors. To date, a few cases have been reported in English literature, mostly in pathology and urology journals. Thus, there are few reports on the radiological findings associated with renal myxomas. We report on the imaging findings in a case of renal myxoma in a 62-year-old male. MRI demonstrated a well-defined mass in the left renal sinus, with intermediate high signal intensity on T2-weighted images and low signal intensity on T1-weighted images. The tumor showed gradual enhancement on contrast-enhanced T1-weighted images.
7.Evaluation of 3-Dimensional Exoscopes in Brain Tumor Surgery
Wan-Soo YOON ; Hyoung-Woo LHO ; Dong-Sup CHUNG
Journal of Korean Neurosurgical Society 2021;64(2):289-296
Objective:
: Though the operating microscope (OM) has been the standard optical system in neurosurgery, a new technology called three-dimensional (3D) exoscope has emerged as an alternative. Herein, two types of 3D exoscopes for brain tumor surgery are presented. In addition, the advantages and limitations compared with the OM are discussed.
Methods:
: In the present study, 3D exoscope VOMS-100 or VITOM 3D was used in 11 patients with brain tumor who underwent surgical resection; the Kinevo 900 OM was used only in emergency. After completion of all surgeries, the participants were surveyed with a questionnaire regarding video image quality on the display monitor, handling of equipment, ergonomics, educational usefulness, 3D glasses, and expectation as a substitute for the OM.
Results:
: Among 11 patients, nine patients underwent neurosurgical resection with only 3D exoscope; however, two patients required additional aid with the OM due to difficulty in hemostasis. Regarding video image quality, VITOM 3D was mostly equivalent to the OM, but VOMS-100 was not. However, both 3D exoscopes showed advantages in accessibility of instruments in the surgical field and occupied less space in the operating theater. Differences in ergonomics and educational usefulness between the exoscopes were not reported. Respondents did not experience discomfort in wearing 3D glasses and thought the exoscopes could be currently, and in the future, used as a substitute for the OM.
Conclusion
: Although many neurosurgeons are not familiar with 3D exoscopes, they have advantages compared with the OM and similar image quality. Exoscopes could be a substitute for OM in the future if some limitations are overcome.
8.Considerations for Fluoroscopic Guided Intervention in Lumbar Spine
Dong-Hyun KIM ; Kwang-Sup SONG
The Journal of the Korean Orthopaedic Association 2020;55(3):210-221
Spinal block procedures are useful methods that reduce the need for surgical treatment. In addition to their therapeutic aspects of pain relief, in many patients, they are also used for diagnostic purposes to distinguish from symptoms originating from extra-spinal areas. Therefore, these procedures are the most basic technique for orthopedic surgeons dealing with diseases from limbs and spine. On the other hand, despite the simplicity of the instruments and drugs used, the overall understanding of them and the lack of knowledge of the possible side effects and complications can cause serious harm to the patient at the beginning of the trial. Therefore, it is necessary to understand the types of drugs used in the spinal block procedures, pharmacokinetic properties, and the side effects of each drug. In addition, efforts should be made to identify their indications, as well as advantages and disadvantages of each procedure to avoid possible complications. The purpose of this review was to provide basic knowledge and skills necessary for lumbar spinal block procedures as well as provide the reader with the ability to perform themselves.
9.The Korean Society for Neuro-Oncology (KSNO) Guideline for Glioblastomas: Version 2018.01
Young Zoon KIM ; Chae Yong KIM ; Jaejoon LIM ; Kyoung Su SUNG ; Jihae LEE ; Hyuk Jin OH ; Seok Gu KANG ; Shin Hyuk KANG ; Doo Sik KONG ; Sung Hwan KIM ; Se Hyuk KIM ; Se Hoon KIM ; Yu Jung KIM ; Eui Hyun KIM ; In Ah KIM ; Ho Sung KIM ; Tae Hoon ROH ; Jae Sung PARK ; Hyun Jin PARK ; Sang Woo SONG ; Seung Ho YANG ; Wan Soo YOON ; Hong In YOON ; Soon Tae LEE ; Sea Won LEE ; Youn Soo LEE ; Chan Woo WEE ; Jong Hee CHANG ; Tae Young JUNG ; Hye Lim JUNG ; Jae Ho CHO ; Seung Hong CHOI ; Hyoung Soo CHOI ; Je Beom HONG ; Do Hoon LIM ; Dong Sup CHUNG ;
Brain Tumor Research and Treatment 2019;7(1):1-9
BACKGROUND: There has been no practical guidelines for the management of patients with central nervous system (CNS) tumors in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare guidelines for CNS tumors from February 2018. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. RESULTS: First, the maximal safe resection if feasible is recommended. After the diagnosis of a glioblastoma with neurosurgical intervention, patients aged ≤70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp's protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred)±concurrent or adjuvant temozolomide, temozolomide alone (Level III), or supportive treatment. Alternatively, patients aged >70 years with good performance should be treated by hypofractionated brain radiotherapy+concurrent and adjuvant temozolomide or Stupp's protocol or hypofractionated brain radiotherapy alone, while those with poor performance should be treated by hypofractionated brain radiotherapy alone or temozolomide chemotherapy if the patient has methylated MGMT gene promoter (Level III), or supportive treatment. CONCLUSION: The KSNO's guideline recommends that glioblastomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to the individual comprehensive condition of the patient.
Brain
;
Central Nervous System
;
Chemoradiotherapy
;
Diagnosis
;
Drug Therapy
;
Glioblastoma
;
Humans
;
Korea
;
Radiotherapy
10.The Korean Society for Neuro-Oncology (KSNO) Guideline for WHO Grade II Cerebral Gliomas in Adults: Version 2019.01
Young Zoon KIM ; Chae Yong KIM ; Chan Woo WEE ; Tae Hoon ROH ; Je Beom HONG ; Hyuk Jin OH ; Seok Gu KANG ; Shin Hyuk KANG ; Doo Sik KONG ; Sung Hwan KIM ; Se Hyuk KIM ; Se Hoon KIM ; Yu Jung KIM ; Eui Hyun KIM ; In Ah KIM ; Ho Sung KIM ; Jae Sung PARK ; Hyun Jin PARK ; Sang Woo SONG ; Kyoung Su SUNG ; Seung Ho YANG ; Wan Soo YOON ; Hong In YOON ; Jihae LEE ; Soon Tae LEE ; Sea Won LEE ; Youn Soo LEE ; Jaejoon LIM ; Jong Hee CHANG ; Tae Young JUNG ; Hye Lim JUNG ; Jae Ho CHO ; Seung Hong CHOI ; Hyoung Soo CHOI ; Do Hoon LIM ; Dong Sup CHUNG ;
Brain Tumor Research and Treatment 2019;7(2):74-84
BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has developed the guideline for glioblastoma. Subsequently, the KSNO guideline for World Health Organization (WHO) grade II cerebral glioma in adults is established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords regarding diffuse astrocytoma and oligodendroglioma of brain in adults. RESULTS: Whenever radiological feature suggests lower grade glioma, the maximal safe resection if feasible is recommended globally. After molecular and histological examinations, patients with diffuse astrocytoma, isocitrate dehydrogenase (IDH)-wildtype without molecular feature of glioblastoma should be primarily treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III) while those with molecular feature of glioblastoma should be treated following the protocol for glioblastomas. In terms of patients with diffuse astrocytoma, IDH-mutant and oligodendroglioma (IDH-mutant and 1p19q codeletion), standard brain radiotherapy and adjuvant PCV (procarbazine+lomustine+vincristine) combination chemotherapy should be considered primarily for the high-risk group while observation with regular follow up should be considered for the low-risk group. CONCLUSION: The KSNO's guideline recommends that WHO grade II gliomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors and clinical characteristics of patients.
Adult
;
Astrocytoma
;
Brain
;
Central Nervous System
;
Drug Therapy
;
Drug Therapy, Combination
;
Follow-Up Studies
;
Glioblastoma
;
Glioma
;
Humans
;
Isocitrate Dehydrogenase
;
Korea
;
Oligodendroglioma
;
Radiotherapy
;
World Health Organization

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