AB015. Efficacy and safety of boron neutron capture therapy in managing metastatic spinal tumors: experimental findings.

BACKGROUND: Boron neutron capture therapy (BNCT) is a unique cancer treatment modality that enables precise targeting of tumors at the cellular level. Based on the success observed in nuclear reactors, BNCT now holds promise as a therapeutic approach for treating invasive brain tumors or head and neck cancers. Metastatic spinal tumors have been treated with multidisciplinary interventions such as surgical resection and radiation therapy. Despite recent advantages of radiation therapy, it remains challenging to achieve better quality of life and activity of daily living. The purpose of this study was to evaluate the efficacy and safety of BNCT in metastatic spinal tumor using a mouse model. METHODS: For the in vitro, neutron and photon irradiation was applied to A549 human lung adenocarcinoma cells. The cells were irradiated neutrons with or without p-boronophenylalanine (BPA) 10 µg Boron/mL for a 24-h exposure before neutron irradiation. The difference of biological effect between neutrons and photons was evaluated by colony forming assay. For in vivo, the tumor-bearing mice were intravenously administered BPA (250 mg/kg), followed by measuring biodistribution of boron using inductively coupled plasma atomic emission spectroscopy (ICP-AES). For in vivo BNCT, the mice were randomly assigned to untreated (n=10), neutron irradiation only (n=9), and BNCT groups (n=10). Overall survival and hindlimb function were analyzed. Histopathological examination was also performed to assess the influences of neutron irradiation. RESULTS: Neutron irradiation showed a stronger cell-killing effect than that exhibited by photon irradiation in vitro. For in vivo biodistribution, the highest boron accumulation in the tumor was seen at 2.5-h time point (10.5 µg B/g), with a tumor to normal spinal cord and blood ratios were 3.6 and 2.9, respectively. For the in vivo BNCT, BNCT had significantly prolonged survival (vs. untreated, P=0.002; vs. neutron only, P=0.01, respectively, log-rank test) and preserved mice hindlimb function compared to the other groups (vs. untreated, P<0.001; vs. neutron only, P=0.005, respectively, MANOVA). No adverse events and apparent histopathological changes were observed among three groups. CONCLUSIONS: These findings indicate that BNCT may represent a novel therapeutic option in the management of metastatic spinal tumors.

Endoscopic Transsphenoidal Drainage for Rathke Cleft Cyst With Sellar Xanthogranuloma - Successful Cyst Drainage and Prevention of Postoperative Cerebrospinal Fluid Leakage: 2-Dimensional Operative Video.

The etiology of sellar xanthogranuloma (SXG) remains unclear,1-5 and the surgical strategy for treating SXG is debatable. In this study, we present the surgical case of a symptomatic SXG associated with Rathke cleft cyst. The intraoperative decision to prevent postoperative cerebrospinal fluid (CSF) leakage and secure the drainage route is discussed. A 72-year-old woman presented with severe headaches, visual loss, and gradual enlargement of a cystic lesion on magnetic resonance imaging. The cyst compressed the chiasm upward. The cyst wall was partially thickened and contained a solid mass that was weakly enhanced after gadolinium administration. The endoscopic transsphenoidal cyst was drained, the solid tumor was partially removed for histological diagnosis, and the wide drainage orifice was secured. Intraoperatively, the cyst wall was widely open, but CSF leaked during manipulation of the solid tumor. The sellar floor was partially reconstructed by a multilayer technique to prevent postoperative CSF leakage. The wide cyst drainage route to the sphenoid sinus was also secured. Histologic diagnosis revealed SXG with ciliated columnar epithelium. No postoperative CSF leakage occurred, and the cyst continued to shrink. The patient's visual acuity improved, and pituitary function was preserved. If a CSF leak is identified intraoperatively in a case of secondary SXG associated with Rathke cleft cyst, a cystic fenestration with partial sellar reconstruction may reduce the likelihood of postoperative CSF leakage and ensure continuous drainage. Institutional Review Board approval was not required; The patient consented to the surgery and the publication of her images and surgical video.

[Defining the Role of Radiotherapy in Meningioma Treatment].

The debate regarding the role and clinical impact of radiotherapy for meningiomas remains underdeveloped due to insufficient evidence. However, following recent revisions in the WHO classification and the integration of molecular diagnostics, there has been a substantial shift in the stratification of recurrence risks. Nevertheless, the specific circumstances under which radiotherapy proves crucial remain unclear. As risk stratification becomes more refined, the effectiveness of radiotherapy in treating high-risk meningiomas continues to be a contentious issue. Concurrently, there is vigorous discussion regarding the management of 'brain invasion in otherwise benign'(BIOB)meningiomas. The incorporation of PET imaging alongside MRI for defining radiation targets is increasingly acknowledged as advantageous. Boron neutron capture therapy(BNCT), which specifically targets the biological characteristics of tumor cells in invasive regions, is also gaining significant traction as a promising therapeutic approach for meningiomas with infiltrative components.

The safety of perioperative antiplatelet continuation without selection biases in microsurgical decompression surgery for single level lumbar spinal stenosis and lumbar disc herniotomy.

PURPOSE: Each institution or physician has to decide on an individual basis whether to continue or discontinue antiplatelet (AP) therapy before spinal surgery. The purpose of this study was to determine if perioperative AP continuation is safe during single-level microsurgical decompression (MSD) for treating lumbar spinal stenosis (LSS) and lumbar disc hernia (LDH) without selection bias. METHODS: Patients who underwent single-level MSD for LSS and LDH between April 2018 to December 2022 at our institute were included in this retrospective study. We collected data regarding baseline characteristics, medical history/comorbidities, epidural hematoma (EDH) volume, reoperation for EDH, differences between preoperative and one-day postoperative blood cell counts (ΔRBC), hemoglobin (ΔHGB), and hematocrits (ΔHCT), and perioperative thromboembolic complications. Patients were divided into two groups: the AP continuation group received AP treatment before surgery and the control group did not receive antiplatelet medication before surgery. Propensity scores for receiving AP agents were calculated, with one-to-one matching of estimated propensity scores to adjust for patient baseline characteristics and past histories. Reoperation for EDH, EDH volume, ΔRBC, ΔHGB, ΔHCT, and perioperative thromboembolic complications were compared between the groups. RESULTS: The 303 enrolled patients included 41 patients in the AP continuation group. After propensity score matching, the rate of reoperation for EDH, the EDH volume, ΔRBC, ΔHGB, ΔHCT, and perioperative thromboembolic complication rates were not significantly different between the groups. CONCLUSION: Perioperative AP continuation is safe for single-level lumbar MSD, even without biases.

Boron neutron capture therapy delays the decline in neurological function in a mouse model of metastatic spinal tumors.

Metastatic spinal tumors are increasingly prevalent due to advancements in cancer treatment, leading to prolonged survival rates. This rising prevalence highlights the need for developing more effective therapeutic approaches to address this malignancy. Boron neutron capture therapy (BNCT) offers a promising solution by delivering targeted doses to tumors while minimizing damage to normal tissue. In this study, we evaluated the efficacy and safety of BNCT as a potential therapeutic option for spine metastases in mouse models induced by A549 human lung adenocarcinoma cells. The animal models were randomly allocated into three groups: untreated (n = 10), neutron irradiation only (n = 9), and BNCT (n = 10). Each mouse was administered 4-borono-L-phenylalanine (250 mg/kg) intravenously, followed by measurement of boron concentrations 2.5 h later. Overall survival, neurological function of the hindlimb, and any adverse events were assessed post irradiation. The tumor-to-normal spinal cord and blood boron concentration ratios were 3.6 and 2.9, respectively, with no significant difference observed between the normal and compressed spinal cord tissues. The BNCT group exhibited significantly prolonged survival rates compared with the other groups (vs. untreated, p = 0.0015; vs. neutron-only, p = 0.0104, log-rank test). Furthermore, the BNCT group demonstrated preserved neurological function relative to the other groups (vs. untreated, p = 0.0004; vs. neutron-only, p = 0.0051, multivariate analysis of variance). No adverse events were observed post irradiation. These findings indicate that BNCT holds promise as a novel treatment modality for metastatic spinal tumors.

Postoperative Airway Management after Anterior Cervical Spine Surgery: Retrospective Neurosurgical Multicenter Study.

Airway complications that occur after anterior cervical spine surgery pose a life-threatening risk, which encompasses complications including prolonged intubation, unplanned reintubation, and/or necessity of tracheostomy. The present study aimed to identify the surgical risks associated with postoperative airway complications in neurosurgical training institutes. A retrospective, multicenter, observational review of data from 365 patients, who underwent anterior cervical spine surgery between 2018 and 2022, at three such institutes was carried out. Postoperative airway complication was defined as either the need for prolonged intubation on the day of surgery or the need for unplanned reintubation. The perioperative medical information was obtained from their medical records. The average age of the cohort was over 60 years, with males comprising approximately 70%. Almost all surgeries predominantly involved anterior cervical discectomy and fusion or anterior cervical corpectomy and fusion, with most surgeries occurring at the level of C5/6. In total, 363 of 365 patients (99.5%) were extubated immediately after surgery, and the remaining two patients were kept under intubation because of the risk of airway complications. Of the 363 patients who underwent extubation immediately after surgery, two (0.55%) required reintubation because of postoperative airway complications. Patients who experienced airway complications were notably older and exhibited a significantly lower body mass index. The results of this study suggested that older and frailer individuals are at an elevated risk for postoperative airway complications, with immediate postoperative extubation generally being safe but requiring careful judgment in specific cases.

Translational research of boron neutron capture therapy for spinal cord gliomas using rat model.

Boron neutron capture therapy (BNCT) is a type of targeted particle radiation therapy with potential applications at the cellular level. Spinal cord gliomas (SCGs) present a substantial challenge owing to their poor prognosis and the lack of effective postoperative treatments. This study evaluated the efficacy of BNCT in a rat SCGs model employing the Basso, Beattie, and Bresnahan (BBB) scale to assess postoperative locomotor activity. We confirmed the presence of adequate in vitro boron concentrations in F98 rat glioma and 9L rat gliosarcoma cells exposed to boronophenylalanine (BPA) and in vivo tumor boron concentration 2.5 h after intravenous BPA administration. In vivo neutron irradiation significantly enhanced survival in the BNCT group when compared with that in the untreated group, with a minimal BBB scale reduction in all sham-operated groups. These findings highlight the potential of BNCT as a promising treatment option for SCGs.

[Usefulness of Preoperative Simulation: Skull Base Approach].

Preoperative simulation images creates an accurate visualization of a surgical field. The anatomical relationship of the cranial nerves, arteries, brainstem, and related bony protrusions is important in skull base surgery. However, an operator's intention is unclear for a less experienced neurosurgeon. Three-dimensional(3D)fusion images of computed tomography and magnetic resonance imaging created using a workstation aids precise surgical planning and safety management. Since the simulation images allows to perform virtual surgery, a déjà vu effect for the surgeon can be obtained. Additionally, since 3D surgical images can be used for preoperative consideration and postoperative verification, discussion among the team members is effective from the perspective of surgical education for residents and medical students. Significance of preoperative simulation images will increase eventually.

Lumbar disc herniation: Epidemiology, clinical and radiologic diagnosis WFNS spine committee recommendations.

Objective: To formulate the most current, evidence-based recommendations regarding the epidemiology, clinical diagnosis, and radiographic diagnosis of lumbar herniated disk (LDH). Methods: A systematic literature search in PubMed, MEDLINE, and CENTRAL was performed from 2012 to 2022 using the search terms "herniated lumbar disc", "epidemiology", "prevention" "clinical diagnosis", and "radiological diagnosis". Screening criteria resulted in 17, 16, and 90 studies respectively that were analyzed regarding epidemiology, clinical diagnosis, and radiographic diagnosis of LDH. Using the Delphi method and two rounds of voting at two separate international meetings, ten members of the WFNS (World Federation of Neurosurgical Societies) Spine Committee generated eleven final consensus statements. Results: The lifetime risk for symptomatic LDH is 1-3%; of these, 60-90% resolve spontaneously. Risk factors for LDH include genetic and environmental factors, strenuous activity, and smoking. LDH is more common in males and in 30-50 year olds. A set of clinical tests, including manual muscle testing, sensory testing, Lasegue sign, and crossed Lasegue sign are recommended to diagnose LDH. Magnetic resonance imaging (MRI) is the gold standard for confirming suspected LDH. Conclusions: These eleven final consensus statements provide current, evidence-based guidelines on the epidemiology, clinical diagnosis, and radiographic diagnosis of LDH for practicing spine surgeons worldwide.

Comparison of outcomes with/without preoperative embolization for meningiomas with diluted N-butyl-2-cyanoacrylate.

BACKGROUND: Preoperative embolization for meningiomas is controversial regarding its effectiveness in reducing intraoperative blood loss and operative time. In contrast, some reports have documented improved surgical outcomes in large meningiomas. In this study, we retrospectively compared the outcomes of craniotomy for meningiomas with/without preoperative embolization with diluted N-butyl-2-cyanoacrylate (NBCA) primarily in a single institution. METHODS: Data (World Health Organization grade, Simpson grade, maximum tumor diameter, intraoperative bleeding, operative time, history of hypertension, and time from embolization to craniotomy) of patients with initial intracranial meningiomas were compared with or without preoperative embolization from January 2015 to April 2022. RESULTS: The embolization group consisted of 56 patients and the nonembolization group included 76 patients. Diluted NBCA (13% concentration for all patients) was used in 51 of 56 patients (91.1%) who underwent transarterial embolization. Permanent neurological complications occurred in 2 (3.6%) patients. Intraoperative bleeding was significantly lower in the embolization group for a maximum tumor diameter ≥40 mm (155 vs. 305 ml, respectively, p < 0.01). In the nonembolization group, for a maximum tumor diameter ≥30 mm, patients with hypertension had more intraoperative bleeding than non-hypertensive ones. CONCLUSIONS: Despite its limitations, the present results showed that, under certain conditions, preoperative embolization for intracranial meningiomas caused less intraoperative bleeding. The safety of treatment was comparable with that reported in the Japan Registry of NeuroEndovascular Therapy 3 (JR-NET3) with a complication rate of 3.7% for preoperative embolization of meningiomas, despite the treatment focused on the liquid embolization material.

A Case of Symptomatic Multiple Tarlov Cysts Treated with Microsurgical Wrapping Technique -Efficacy and Limitation of Surgical Procedure.

Tarlov cysts (TCs) rarely cause clinical symptoms, such as leg pain, buttock pain, and bladder/bowel dysfunction. Surgery is considered when these symptoms persist despite medical treatments. Among several surgical procedures, microsurgical wrapping (MSW) is a relatively novel, simple technique with few complications, including cerebrospinal fluid leakage. Herein, we report a case of multiple TCs treated with MSW and present the mechanism of symptoms generated by TC and the procedure's limitations. A 58-year-old man complained of severe right leg and buttock pain for 3 months and was admitted to our hospital. His symptoms aggravated with sitting and standing and improved with the prone position. Spinal magnetic resonance imaging (MRI) demonstrated multiple sacral cysts containing intense cerebrospinal fluid. The cysts connect to the right S3 and S4 nerve roots. He was treated conservatively with medications; however, his symptoms were not improved. Therefore, MSW was performed for TCs connected to the S3 and S4 roots. The postoperative course was uneventful, and cerebrospinal fluid leakage did not occur. MRI performed 1 year after the operation demonstrated no recurrence of the TCs, and his leg pain was completely relieved; however, the buttock pain remained. MSW for TCs is effective for symptoms of adjacent nerve root compression; however, repairing the damaged nerve root in TCs is sometimes difficult. This may be a limitation of present surgical interventions because these symptoms may be difficult to treat even with other interventions.

Factors influencing slippage after microsurgical single level lumbar spinal decompression surgery - Are the psoas and multifidus muscles involved?

PURPOSE: Patients with lumbar spinal stenosis (LSS) require microsurgical decompression (MSD) surgery; however, MSD is often associated with postoperative instability at the operated level. Paraspinal muscles support the spinal column; lately, paraspinal volume has been used as a good indicator of sarcopenia. This study aimed to determine preoperative radiological factors, including paraspinal muscle volume, associated with postoperative slippage progression after MSD in LSS patients. METHODS: Patients undergoing single-level (L3/4 or L4/5) MSD for symptomatic LSS and followed-up for ≥ 5 years in our institute were reviewed retrospectively to measure preoperative imaging parameters focused on the operated level. Paraspinal muscle volumes (psoas muscle index [PMI] and multifidus muscle index [MFMI]) defined using the total cross-sectional area of each muscle/L3 vertebral body area in the preoperative lumbar axial CT) were calculated. Postoperative slippage in the form of static translation (ST) ≥ 2 mm was assessed on the last follow-up X-ray. RESULTS: We included 95 patients with average age and follow-up periods of 69 ± 8.2 years and 7.51 ± 2.58 years, respectively. PMI and MFMI were significantly correlated with age and significantly larger in male patients. Female sex, preoperative ST, dynamic translation, sagittal rotation angle, facet angle, pelvic incidence, lumbar lordosis, and PMI were correlated with long-term postoperative worsening of ST. However, as per multivariate analysis, no independent factor was associated with postoperative slippage progression. CONCLUSION: Lower preoperative psoas muscle volume in LSS patients is an important predictive factor of postoperative slippage progression at the operated level after MSD. The predictors for postoperative slippage progression are multifactorial; however, a well-structured postoperative exercise regimen involving psoas muscle strengthening may be beneficial in LSS patients after MSD.

Transcriptomic and epigenetic dissection of spinal ependymoma (SP-EPN) identifies clinically relevant subtypes enriched for tumors with and without NF2 mutation.

Ependymomas encompass multiple clinically relevant tumor types based on localization and molecular profiles. Tumors of the methylation class "spinal ependymoma" (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, their developmental origin is ill-defined, molecular data are scarce, and the potential heterogeneity within SP-EPN remains unexplored. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations, but neither types and frequency of these alterations nor their clinical relevance have been described in a large, epigenetically defined series. Transcriptomic (n = 72), epigenetic (n = 225), genetic (n = 134), and clinical data (n = 112) were integrated for a detailed molecular overview on SP-EPN. Additionally, we mapped SP-EPN transcriptomes to developmental atlases of the developing and adult spinal cord to uncover potential developmental origins of these tumors. The integration of transcriptomic ependymoma data with single-cell atlases of the spinal cord revealed that SP-EPN display the highest similarities to mature adult ependymal cells. Unsupervised hierarchical clustering of transcriptomic data together with integrated analysis of methylation profiles identified two molecular SP-EPN subtypes. Subtype A tumors primarily carried previously known germline or sporadic NF2 mutations together with 22q loss (bi-allelic NF2 loss), resulting in decreased NF2 expression. Furthermore, they more often presented as multilocular disease and demonstrated a significantly reduced progression-free survival as compared to SP-EP subtype B. In contrast, subtype B predominantly contained samples without NF2 mutation detected in sequencing together with 22q loss (monoallelic NF2 loss). These tumors showed regular NF2 expression but more extensive global copy number alterations. Based on integrated molecular profiling of a large multi-center cohort, we identified two distinct SP-EPN subtypes with important implications for genetic counseling, patient surveillance, and drug development priorities.

Surgical Outcomes and Medical Costs Associated with Spinal Cord Tumors: Comparison of Extramedullary and Intramedullary Tumors.

OBJECTIVE: This study aimed to clarify the differences in the perioperative data of patients with extramedullary and intramedullary tumors and estimate the impact of surgery on medical costs. METHODS: This single-center retrospective study included consecutive patients who underwent spinal tumor resection between September 2020 and December 2022. The perioperative medical information and medical costs for individual patients were obtained from their medical records. RESULTS: Thirty-two patients with extramedullary spinal cord tumors and 18 with intramedullary spinal cord tumors were included in the study. The 2 groups had no difference in surgery-related or major systemic complications. However, the operation time and the length of hospital stay were significantly longer and activities of daily living at discharge tended to worsen in the intramedullary tumor group compared to those in the extramedullary tumor group. As a result, the discharge outcome was significantly different between the 2 groups. The total medical costs for intramedullary tumors were approximately 1.43 times higher than those for extramedullary tumors. Further, a better functional outcome at discharge can save medical costs, regardless of extramedullary or intramedullary tumors. CONCLUSIONS: Surgery for intramedullary tumors can be performed with similar perioperative risks as for extramedullary tumors. However, intramedullary tumors are associated with concerns, such as prolonged hospitalization and worsening of activities of daily living at discharge, which ultimately result in higher medical costs.

Epidemiology and Comparative Analysis of Outcomes of Intramedullary Spinal Cord Tumor Between Pediatric and Adult Patients.

STUDY DESIGN: This was as clinical retrospective study. OBJECTIVES: We sought to evaluate the characteristics of Pediatric intramedullary spinal cord tumors (PISCTs) and to identify differences between pediatric and adult intramedullary spinal cord tumors. SUMMARY OF BACKGROUND DATA: PISCTs represent a rare clinical entity with limited evidence-base in the literature. METHODS: This study is a subanalysis of the retrospective multicenter observational study authorized by the Neurospinal Society of Japan, including consecutive patients with spinal intramedullary tumors treated surgically at 58 institutions between 2009 and 2020. Data on 1080 intramedullary spinal cord tumors were obtained, consisting of 91 pediatric and 939 adult patients. Survival was compared using Cox hazard regression while clinical differences were evaluated using multivariable logistic regression that controlled for confounders. RESULTS: Pediatric patients had a shorter overall, and progression-free, survival than adults. Pediatric patients with ISCTs were likely to have scoliosis [odds ratio (OR) = 6.49, 95% CI: 2.26-18.7], short preoperative symptom duration (OR = 0.99, 95% CI: 0.98-0.99), lower incidence of paresthesia (OR = 0.41, 95% CI: 0.22-0.77), higher incidence of paresis (OR = 2.10, 95% CI: 1.01-4.35), histopathology of astrocytoma (OR = 2.97, 95% CI: 1.19-7.43), and postoperative functional deterioration upon discharge (OR = 2.83, 95% CI: 1.43-5.58). Age was not a statistically significant prognostic factor of overall survival among the pediatric cohort. CONCLUSION: We found that the clinical characteristics of ISCTs differed between pediatric and adult patients. In terms of histopathological types, astrocytoma was most common in pediatric patients. ISCT occurring at an early age may not be an indicator for poor prognosis.

Shorter survival time of adolescents and young adult patients than older adults with spinal cord glioblastoma: a multicenter study.

OBJECTIVE: Cancers in adolescents and young adults (AYAs) (age 15-39 years) often present with unique characteristics and poor outcomes. To date, spinal cord glioblastoma, a rare tumor, remains poorly understood across all age groups, including AYAs. This comparative study aimed to investigate the clinical characteristics and outcomes of spinal cord glioblastoma in AYAs and older adults (age 40-74 years), given the limited availability of studies focusing on AYAs. METHODS: Data from the Neurospinal Society of Japan's retrospective intramedullary tumor registry (2009-2020) were analyzed. Patients were dichotomized on the basis of age into AYAs and older adults. Univariate and multivariate Cox proportional hazards regression models were utilized to explore risk factors for overall survival (OS). RESULTS: A total of 32 patients were included in the study, with a median (range) age of 43 (15-74) years. Of these, 14 (43.8%) were AYAs and 18 (56.2%) were older adults. The median OS was 11.0 months in AYAs and 32.0 months in older adults, and the 1-year OS rates were 42.9% and 66.7%, respectively, with AYAs having a significantly worse prognosis (p = 0.017). AYAs had worse preoperative Karnofsky Performance Status (KPS) than older patients (p = 0.037). Furthermore, AYAs had larger intramedullary tumors on admission (p = 0.027) and a significantly higher frequency of intracranial dissemination during the clinical course (p = 0.048). However, there were no significant differences in the degrees of surgical removal or postoperative radiochemotherapy between groups. The Cox proportional hazards regression model showed that AYAs (HR 3.53, 95% CI 1.17-10.64), intracranial dissemination (HR 4.30, 95% CI 1.29-14.36), and no radiation therapy (HR 57.34, 95% CI 6.73-488.39) were risk factors for mortality for patients of all ages. Worse preoperative KPS did not predict mortality in AYAs but did in older adults. The high incidence of intracranial dissemination may play an important role in the poor prognosis of AYAs, but further studies are needed. CONCLUSIONS: The clinical characteristics of AYAs with spinal cord glioblastoma differ from those of older adults. The prognosis of AYAs was clearly worse than that of older adults. The devastating clinical course of spinal glioblastoma in AYAs was in line with those of other cancers in this age group.

Expression and distribution of hypoxia-inducible factor-1α and vascular endothelial growth factor in comparison between radiation necrosis and tumor tissue in metastatic brain tumor: A case report.

We report the case of a 70-year-old woman with metastatic brain tumors who underwent surgical removal of the tumor and radiation necrosis. The patient had a history of colon cancer and had undergone surgical removal of a left occipital tumor. Histopathological evaluation revealed a metastatic brain tumor. The tumor recurred six months after surgical removal, followed by whole-brain radiotherapy, and the patient underwent stereotactic radiosurgery. Six months later, the perifocal edema had increased, and the patient became symptomatic. The diagnosis was radiation necrosis and corticosteroids were initially effective. However, radiation necrosis became uncontrollable, and the patient underwent removal of necrotic tissue two years after stereotactic radiosurgery. Pathological findings predominantly showed necrotic tissue with some tumor cells. Since the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were expressed around the necrotic tissue, the main cause of the edema was determined as radiation necrosis. Differences in the expression levels and distribution of HIF-1α and VEGF were observed between treatment-naïve and recurrent tumor tissue and radiation necrosis. This difference suggests the possibility of different mechanisms for edema formation due to the tumor itself and radiation necrosis. Although distinguishing radiation necrosis from recurrent tumors using MRI remains challenging, the pathophysiological mechanism of perifocal edema might be crucial for differentiating radiation necrosis from recurrent tumors.

Increasing C-reactive protein levels in a patient with glioblastoma with lymph node metastasis: a case report.

BACKGROUND: Glioblastoma usually recurs locally and extracranial metastases are rare. Most patients with extracranial metastases experience recurrence of the primary intracranial tumor. Lymph node metastases are often detected based on lymphadenopathy or symptoms caused by other metastatic sites. CASE PRESENTATION: Herein, we report a case of glioblastoma with lymph node metastasis in which the patient was asymptomatic but exhibited gradually increasing C-reactive protein levels prior to becoming febrile 9 months after the initial C-reactive protein increase. Diagnosis of lymph node metastasis that was delayed because the patient had a fever of unknown origin, no signs of infection, and the primary intracranial tumor did not recur. Chest computed tomography indicated supraclavicular, mediastinal, and hilar lymphadenopathy, and biopsy identified lymph node metastasis of glioblastoma. This is the fifth reported case of lymph node metastasis without intracranial recurrence. CONCLUSIONS: C-reactive protein levels may be a diagnostic marker for lymph node metastasis in patients with glioblastoma. Further evaluation is needed to elucidate the role of CRP in glioblastoma with lymph node metastasis.

Actin Alpha 2, Smooth Muscle (ACTA2) Is Involved in the Migratory Potential of Malignant Gliomas, and Its Increased Expression at Recurrence Is a Significant Adverse Prognostic Factor.

Malignant glioma is a highly invasive tumor, and elucidating the glioma invasion mechanism is essential for developing novel therapies. We aimed to highlight actin alpha 2, smooth muscle (ACTA2) as potential biomarkers of brain invasion and distant recurrence in malignant gliomas. Using the human malignant glioma cell line, U251MG, we generated ACTA2 knockdown (KD) cells treated with small interfering RNA, and the cell motility and proliferation of the ACTA2 KD group were analyzed. Furthermore, tumor samples from 12 glioma patients who underwent reoperation at the time of tumor recurrence were utilized to measure ACTA2 expression in the tumors before and after recurrence. Thereafter, we examined how ACTA2 expression correlates with the time to tumor recurrence and the mode of recurrence. The results showed that the ACTA2 KD group demonstrated a decline in the mean motion distance and proliferative capacity compared to the control group. In the clinical glioma samples, ACTA2 expression was remarkably increased in recurrent samples compared to the primary samples from the same patients, and the higher the change in ACTCA2 expression from the start to relapse, the shorter the progression-free survival. In conclusion, ACTA2 may be involved in distant recurrence in clinical gliomas.

Occult neurohypophyseal germinoma discovered during the course of long-term diabetes insipidus: illustrative case.

BACKGROUND: The authors report a case of occult neurohypophyseal germinoma detected in a patient with long-term diabetes insipidus. Central diabetes insipidus is the initial symptom in 95% of cases of neurohypophyseal germinoma. In occult neurohypophyseal germinomas, no abnormalities are seen on magnetic resonance imaging (MRI) at the onset of symptoms. It can take several months or even years for these changes to be detected on MRI. OBSERVATIONS: A 20-year-old male was diagnosed with central diabetes insipidus at the age of 17 years, and gonadal and adrenal corticosteroid insufficiency was noted at the age of 19 years. Head MRI showed an enlarged and enhanced pituitary stalk. He was referred to our department for a suspected neoplastic lesion. Endoscopic transsphenoidal biopsy indicated a pure germinoma. He was treated with chemotherapy and radiotherapy and then was discharged. LESSONS: In this case, new imaging findings appeared 19 months after the onset of diabetes insipidus, and the pathological diagnosis was made after almost 24 months. Because the patient had a history of growth hormone deficiency and had a positive test result for diabetes insipidus, occult neurohypophyseal germinoma was suspected, and periodic contrast-enhanced MRI monitoring was deemed essential.