Tumors in the cerebellopontine angle in children: warning of a high probability of malignancy.

Phi, Ji Hoon,Wang, Kyu-Chang,Kim, In-One,Cheon, Jung-Eun,Choi, Jung Won,Cho, Byung-Kyu,Kim, Seung-Ki M. Nijhoff ; Kluwer Academic Publishers 2013 Journal of neuro-oncology Vol.112 No.3

<P>Cerebellopontine angle (CPA) tumors are uncommon in children, and the pathological spectrum is different from that of adults. In this study, we reviewed the pathological diagnosis of pediatric patients with a CPA tumor to determine the pattern in this age group. In a cohort of 267 patients with posterior fossa tumor, tumor locations were determined with preoperative magnetic resonance imaging (MRI). The pathological diagnosis, imaging characteristic, and treatment outcomes of patients with CPA tumors was reviewed and analyzed. Twenty-six patients (9.7 %) had a tumor in the CPA. The pathological spectrum was wide, from malignant intrinsic brain tumors to benign extra-axial tumors and sarcomatous lesions. Eighteen patients (69 %) had malignant tumors. The pathological nature was strongly linked to patient age. The mean age of malignant tumor group was significantly younger than that of benign tumor group. MRI findings that favored malignant histology included a plastic feature of the tumor, multiple signal voids, encasement of major arteries, widening of lateral recess, focal cerebellar edema, and hydrocephalus. The presence of seeding in the neuraxis also indicated malignant pathology. Especially, increased density on precontrast computed tomography was a strong predictor of malignant pathology. Malignant CPA tumors showed high surgical morbidity rate and grim long-term prognosis. Patient age and tumor location are the two most important clues for the diagnosis of any brain tumor. Unlike in adult patients, clinicians should expect a high probability of malignant histology for pediatric CPA tumors, especially in infants and young children.</P>

Sacrococcygeal Teratoma : A Tumor at the Center of Embryogenesis

Phi, Ji Hoon The Korean Neurosurgical Society 2021 Journal of Korean neurosurgical society Vol.64 No.3

Sacrococcygeal teratoma (SCT) is an extragonadal germ cell tumor (GCT) that develops in the fetal and neonatal periods. SCT is a type I GCT in which only teratoma and yolk sac tumors arise from extragonadal sites. SCT is the most common type I GCT and is believed to originate through epigenetic reprogramming of early primordial germ cells migrating from the yolk sac to the gonadal ridges. Fetal SCT diagnosed in utero presents many obstetrical problems. For high-risk fetuses, fetal interventions (devascularization and debulking) are under development. Most patients with SCT are operated on after birth. Complete surgical resection is the key for tumor control, and the anatomical location of the tumor determines the surgical approaches. Incomplete resection and malignant histology are risk factors for recurrence. Approximately 10-15% of patients have a tumor recurrence, which is frequently of malignant histology. Long-term surveillance with monitoring of serum alpha fetoprotein and magnetic resonance imaging is required. Survivors of SCT may suffer anorectal, urological, and sexual sequelae later in their life, and comprehensive evaluation and care are required.

Overcoming Chemoresistance of Pediatric Ependymoma by Inhibition of STAT3 Signaling

Phi, Ji Hoon,Choi, Seung-Ah,Kim, Seung-Ki,Wang, Kyu-Chang,Lee, Ji Yeoun,Kim, Dong Gyu Neoplasia Press 2015 Translational oncology Vol.8 No.5

<P>The long-term clinical outcome of pediatric intracranial epepdymoma is poor with a high rate of recurrence. One of the main reasons for this poor outcome is the tumor’s inherent resistance to chemotherapy. Signal transducer and activator of transcription 3 (STAT3) is overactive in many human cancers, and inhibition of STAT3 signaling is an emerging area of interest in oncology. In this study, the possibility of STAT3 inhibition as a treatment was investigated in pediatric intracranial ependymoma tissues and cell lines. STAT3 activation status was checked in ependymoma tissues. The responses to conventional chemotherapeutic agents and a STAT3 inhibitor WP1066 in primarily cultured ependymoma cells were measured by cell viability assay. Apoptosis assays were conducted to reveal the cytotoxic mechanism of applied agents. Knockdown of STAT3 was tried to confirm the effects of STAT3 inhibition in ependymoma cells. High levels of phospho-STAT3 (p-STAT3) expression were observed in ependymoma tissue, especially in the anaplastic histology group. There was no cytotoxic effect of cisplatin, ifosfamide, and etoposide. Both brain tumor-initiating cells (BTICs) and bulk tumor cells (BCs) showed considerably decreased viability after WP1066 treatment. However, BTICs had fewer responses than BCs. No additive or synergistic effect was observed for combination therapy of WP1066 and cisplatin. WP1066 effectively abrogated p-STAT3 expression. An increased apoptosis and decreased Survivin expression were observed after WP1066 treatment. Knockdown of STAT3 also decreased cell survival, supporting the critical role of STAT3 in sustaining ependymoma cells. In this study, we observed a cytotoxic effect of STAT3 inhibitor on ependymoma BTICs and BCs. There is urgent need to develop new therapeutic agents for pediatric ependymoma. STAT3 inhibitors may be a new group of drugs for clinical application.</P>

Radiosurgical treatment of vestibular schwannomas in patients with neurofibromatosis type 2 : Tumor control and hearing preservation

Phi, Ji Hoon,Kim, Dong Gyu,Chung, Hyun-Tai,Lee, Joongyub,Paek, Sun Ha,Jung, Hee-Won Wiley Subscription Services, Inc., A Wiley Company 2009 Cancer Vol.115 No.2

<B>BACKGROUND:</B><P>The radiosurgical treatment of vestibular schwannomas in patients with neurofibromatosis type 2 (NF2) is controversial. The authors investigated the radiologically proven tumor control rate after gamma knife radiosurgery. The factors that affect tumor control and serviceable hearing preservation were analyzed.</P><B>METHODS:</B><P>Thirty-six lesions in 30 patients were included. The median lengths of the clinical and radiologic follow-ups were 48.5 months and 36.5 months, respectively. The median tumor volume was 3.2 cm<SUP>3</SUP>. The mean marginal dose was 12.1 grays (Gy) (range, 8–14 Gy) at an isodose line of 50%±0.6%. The Kaplan-Meier method and Cox proportional hazards model were used for the statistical analyses.</P><B>RESULTS:</B><P>The actuarial tumor control rate was 81%, 74%, and 66%, respectively, in the first, second, and fifth years. Five tumors required a salvage surgery because of tumor control failure. A low marginal dose and a young age at radiosurgery were associated with poor tumor control. Of the 16 tumors with which ipsilateral hearing was serviceable, the actuarial serviceable hearing preservation rates were 50%, 45%, and 33%, respectively, in the first, second, and fifth years. Better ipsilateral hearing (Gardner-Robertson grade 1, compared with grade 2) at the time of radiosurgery was associated with significantly greater serviceable hearing preservation.</P><B>CONCLUSIONS:</B><P>Gamma knife radiosurgery for vestibular schwannomas in NF2 patients provided 5-year tumor control in approximately two-thirds of patients and preserved serviceable hearing in approximately one-third. The rates of other cranial nerve deficits were low, and no secondary malignancy was observed. Radiosurgery should be included in treatment options for NF2 patients. Cancer 2009. © 2009 American Cancer Society.</P>

Clinical Pearls and Advances in Molecular Researches of Epilepsy-Associated Tumors

Phi, Ji Hoon,Kim, Seung-Ki The Korean Neurosurgical Society 2019 Journal of Korean neurosurgical society Vol.62 No.3

Brain tumors are the second most common type of structural brain lesion that causes chronic epilepsy. Patients with low-grade brain tumors often experience chronic drug-resistant epilepsy starting in childhood, which led to the concept of long-term epilepsy-associated tumors (LEATs). Dysembryoplastic neuroepithelial tumor and ganglioglioma are representative LEATs and are characterized by young age of onset, frequent temporal lobe location, benign tumor biology, and chronic epilepsy. Although highly relevant in clinical epileptology, the concept of LEATs has been criticized in the neuro-oncology field. Recent genomic and molecular studies have challenged traditional views on LEATs and low-grade gliomas. Molecular studies have revealed that low-grade gliomas can largely be divided into three groups : LEATs, pediatric-type diffuse low-grade glioma (DLGG; astrocytoma and oligodendroglioma), and adult-type DLGG. There is substantial overlap between conventional LEATs and pediatric-type DLGG in regard to clinical features, histology, and molecular characteristics. LEATs and pediatric-type DLGG are characterized by mutations in BRAF, FGFR1, and MYB/MYBL1, which converge on the RAS-RAF-MAPK pathway. Gene (mutation)-centered classification of epilepsy-associated tumors could provide new insight into these heterogeneous and diverse neoplasms and may lead to novel molecular targeted therapies for epilepsy in the near future.

Clinical Features and Treatment of Pediatric Cerebral Cavernous Malformations

Ji Hoon Phi,Seung-Ki Kim 대한신경외과학회 2024 Journal of Korean neurosurgical society Vol.67 No.3

Cerebral cavernous malformation (CCM) is a vascular anomaly commonly found in children and young adults. Common clinical presentations of pediatric patients with CCMs include headache, focal neurological deficits, and seizures. Approximately 40% of pediatric patients are asymptomatic. Understanding the natural history of CCM is crucial and hemorrhagic rates are higher in patients with an initial hemorrhagic presentation, whereas it is low in asymptomatic patients. There is a phenomenon known as temporal clustering in which a higher frequency of symptomatic hemorrhages occurs within a few years following the initial hemorrhagic event. Surgical resection remains the mainstay of treatment for pediatric CCMs. Excision of a hemosiderin-laden rim is controversial regarding its impact on epilepsy outcomes. Stereotactic radiosurgery is an alternative treatment, especially for deepseated CCMs, but its true efficacy needs to be verified in a clinical trial.

Moyamoya Syndrome : A Window of Moyamoya Disease

Phi, Ji Hoon,Wang, Kyu-Chang,Lee, Ji Yeoun,Kim, Seung-Ki The Korean Neurosurgical Society 2015 Journal of Korean neurosurgical society Vol.57 No.6

Moyamoya-like vasculopathy develops in association with various systemic diseases and conditions, which is termed moyamoya syndrome. Relatively common diseases and conditions are related to moyamoya syndrome, including neurofibromatosis type 1, Down syndrome, thyroid disease, and cranial irradiation. Moyamoya syndrome shares phenotypical characteristics with idiopathic moyamoya disease. However, they differ in other details, including clinical presentations, natural history, and treatment considerations. The study of moyamoya syndrome can provide clinicians and researchers with valuable knowledge and insight. Although it is infrequently encountered in clinical practice, moyamoya-like vasculopathy can severely complicate outcomes for patients with various underlying diseases when the clinician fails to expect or diagnose moyamoya syndrome development. Furthermore, moyamoya syndrome could be used as a doorway to more enigmatic moyamoya disease in research. More comprehensive survey and investigation are required to uncover the secrets of all the moyamoya-like phenomena.

Epilepsy Surgery in 2019 : A Time to Change

Phi, Ji Hoon,Cho, Byung-Kyu The Korean Neurosurgical Society 2019 Journal of Korean neurosurgical society Vol.62 No.3

Epilepsy has been known to humankind since antiquity. The surgical treatment of epilepsy began in the early days of neurosurgery and has developed greatly. Many surgical procedures have stood the test of time. However, clinicians treating epilepsy patients are now witnessing a huge tide of change. In 2017, the classification system for seizure and epilepsy types was revised nearly 36 years after the previous scheme was released. The actual difference between these systems may not be large, but there have been many conceptual changes, and clinicians must bid farewell to old terminology. Paradigms in drug discovery are changing, and novel anti-seizure drugs have been introduced for clinical use. In particular, drugs that target genetic changes harbor greater therapeutic potential than previous screening-based compounds. The concept of focal epilepsy has been challenged, and now epilepsy is regarded as a network disorder. With this novel concept, stereotactic electroencephalography (SEEG) is becoming increasingly popular for the evaluation of dysfunctioning neuronal networks. Minimally invasive ablative therapies using SEEG electrodes and neuromodulatory therapies such as deep brain stimulation and vagus nerve stimulation are widely applied to remedy dysfunctional epilepsy networks. The use of responsive neurostimulation is currently off-label in children with intractable epilepsy.

Intracranial Germ Cell Tumor in the Molecular Era

Phi, Ji Hoon,Wang, Kyu-Chang,Kim, Seung-Ki The Korean Neurosurgical Society 2018 Journal of Korean neurosurgical society Vol.61 No.3

Intracranial germ cell tumors (iGCTs) are a heterogeneous group of tumors with peculiar characteristics clearly distinguished from other brain tumors of neuroepithelial origin. Diverse histology, similarity to gonadal GCT, predilection to one sex, and geographic difference in incidence all present enigmas and fascinating challenges. The treatment of iGCT has advanced for germinoma to date; thus, clinical attention has shifted from survival to long-term quality of life. However, for non-germinomatous GCT, current protocols provide only modest improvement and more innovative therapies are needed. Recently, next-generation sequencing studies have revealed the genomic landscape of iGCT. Novel mutations in the KIT-RAS-MAPK and AKT-MTOR pathways were identified. More importantly, methylation profiling revealed a new method to assess the pathogenesis of iGCT. Molecular research will unleash new knowledge on the origin of iGCT and solve the many mysteries that have lingered on this peculiar neoplasm for a long time.

Transcerebellar biopsy of diffuse pontine gliomas in children: a technical note.

Phi, Ji Hoon,Chung, Hyun-Tai,Wang, Kyu-Chang,Ryu, Seul Ki,Kim, Seung-Ki Springer Verlag 2013 Child’s nervous system Vol.29 No.3

<P>The need for a surgical biopsy for diffuse pontine glioma (DPG) is increasing, and a safer and less invasive procedure is required.</P>