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Background@#Inflammasomes are key in the initiation of inflammatory responses and serve to de-fend the organism. However, when the immune system is imbalanced, these complexes contribute to tumor progression. The purpose of this study was to investigate the effect of non-canonical inflammasomes on glioma malignancy. @*Methods@#We performed bioinformatics analysis to confirm the expression of canonical andnon-canonical inflammasome-related molecules according to the degree of malignancy through immunohistochemical examination of glioma tissues obtained with patient consent from our institution. @*Results@#Bioinformatics analysis confirmed that the expression levels of non-canonical inflam-masome-related molecules were significantly higher in tumor tissues than in normal tissues, and they also increased according to malignancy, which adversely affected the survival rate. Furthermore, in gliomas, positive correlations were found between N-form gasdermin-D, a key molecule associated with the non-canonical inflammasome, and other related molecules, including NLRP3, caspase-1, caspase-4, and caspase-5. These results were verified by immunohistochemical examination of glioma tissues, and the expression levels of these molecules also increased significantly with increasing grade.In addition, the features of pyroptosis were confirmed. @*Conclusion@#This study identified the potential of non-canonical inflammasomes as aggressiveness markers for gliomas and presented a perspective for improving glioma treatment.
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Purpose@#Glioblastoma (GBM) is one of the most lethal human tumors with a highly infiltrative phenotype. Our previous studies showed that GBM originates in the subventricular zone, and that tumor-derived mesenchymal stem-like cells (tMSLCs) promote the invasiveness of GBM tumorspheres (TSs). Here, we extend these studies in terms of ventricles using several types of GBM patient-derived cells. @*Materials and Methods@#The invasiveness of GBM TSs and ventricle spheres (VSs) were quantified via collagen-based 3D invasion assays. Gene expression profiles were obtained from microarray data. A mouse orthotopic xenograft model was used for in vivo experiments. @*Results@#After molecular and functional characterization of ventricle-derived mesenchymal stem-like cells (vMSLCs), we investigated the effects of these cells on the invasiveness of GBM TSs. We found that vMSLC-conditioned media (CM) significantly accelerated the invasiveness of GBM TSs and VSs, compared to the control and even tMSLC-CM. Transcriptome analyses revealed that vMSLC secreted significantly higher levels of several invasiveness-associated cytokines. Moreover, differentially expressed genes between vMSLCs and tMSLCs were enriched for migration, adhesion, and chemotaxis-related gene sets, providing a mechanistic basis for vMSLC-induced invasion of GBM TSs. In vivo experiments using a mouse orthotopic xenograft model confirmed vMSLCinduced increases in the invasiveness of GBM TSs. @*Conclusion@#Although vMSLCs are non-tumorigenic, this study adds to our understanding of how GBM cells acquire infiltrative features by vMSLCs, which are present in the region where GBM genesis originates.
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Background@#Rathke’s cleft cysts (RCCs) are benign tumors of the pituitary gland. Small, asymptomatic RCCs do not require surgical treatment, whereas surgical treatment is required for symptomatic RCCs. @*Methods@#We retrospectively reviewed medical records of patients with an RCC who were diagnosed and managed in our institution between April 2004 and April 2020 and generated two different cohorts: the observation (n=114) and the surgical group (n=99). Their initial MRI signal characteristics were analyzed. The natural course focusing on cyst size was observed in the observation group and postoperative visual and endocrine outcomes were evaluated in the surgical group. @*Results@#The characterization of MRI signals of cyst contents in both T1-weighted (T1W) and T2-weighted (T2W) images revealed nine combinations for our 213 patients. Among 115 patients with a high T2W signal, the cysts showed hypo-, iso-, and hyper-intensity on T1W images in 72, 39, and 44 patients, respectively; Type S-low, Type S-iso, and Type S-high. One more major group of 35 patients showed RCCs with hyperintensity on the T1W images and hypointensity on the T2W images named as Type M. In the comparison between observation and surgical groups, we identified only two major groups in which the number of patients in the surgical and observation groups was statistically different: more Type S-low in a surgical group (p<0.001) and more Type M in an observation group (p=0.007). In subgroup analysis, the range of change in the cyst size was the highest in Type S-high in the observation group (p=0.028), and intergroup differences in visual and endocrine outcomes were not evident in the surgical group. @*Conclusion@#MRI characteristics help to predict the natural course of RCCs. We identified subgroups of RCCs which are more or less likely to require surgical intervention.
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Objective@#: Pituitary adenomas frequently extend into the suprasellar space. After a suprasellar tumor is removed, the superiorly extended arachnoid becomes redundant and sinks down into the intrasellar space which often hiders visualization and accessibility to the hidden space behind the evaginated arachnoid. We introduced arachnoid remodeling by clipping technique, and evaluated its usefulness and safety during TSS. @*Methods@#: Total 223 patients who underwent arachnoid remodeling with our new clipping technique were included. Redundant arachnoid was clipped along the dural edge with multiple 2.6-mm titanium clips until the redundant arachnoid membrane no longer blocked the surgical route. To check for possible deterioration of hormonal function by this technique, we assessed anterior pituitary function of 166 patients who underwent arachnoid remodeling by clipping and compared this with those of other 429 control patients. @*Results@#: Our technique greatly enhanced the accessibility and visualization of intrasellar and parasellar spaces, both of which are generally hindered by redundant arachnoid during transsphenoidal surgery (TSS). We found no difference in anterior pituitary function between a clip-assisted arachnoid remodeling group and the control group, implying that this technique does not result in hypopituitarism. @*Conclusion@#: During TSS for pituitary adenomas with suprasellar extension, arachnoid remodeling by clipping technique is very useful and convenient for the management of the redundant arachnoid membrane to enhance visualization and surgical accessibility.
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Background@#The guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics. @*Methods@#We studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor. @*Results@#GNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively). @*Conclusion@#GNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.
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Purpose@#A critical indicator of the overall survival of patients with high-grade glioma is the successful isolation of tumor mesenchymal stem-like cells (tMSLCs), which play important roles in glioma progression. However, attempts to isolate tMSLCs from surgical specimens have not always been successful, and the reasons for this remain unclear. Considering that the amount of surgical high-grade glioma specimens varies, we hypothesized that larger surgical specimens would be better for tMSLC isolation. @*Materials and Methods@#We assessed 51 fresh, high-grade glioma specimens and divided them into two groups according to the success or failure of tMSLC isolation. The success of tMSLC isolation was confirmed by plastic adherence, presenting antigens, tri-lineage differentiation, and non-tumorigenicity. Differences in characteristics between the two groups were tested using independent two sample t-tests, chi-square tests, or Kaplan-Meier survival analysis. @*Results@#The mean specimen weights of the groups differed from each other (tMSLC-negative group: 469.9±341.9 mg, tMSLC positive group: 546.7±618.9 mg), but the difference was not statistically significant. The optimal cut-off value of specimen weight was 180 mg, and the area under the curve value was 0.599. @*Conclusion@#Our results suggested a minimum criterion for specimen collection, and found that the specimen amount was not deeply related to tMSLC detection. Collectively, our findings imply that the ability to isolate tMSLCs is determined by factors other than the specimen amount.
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Background@#The guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics. @*Methods@#We studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor. @*Results@#GNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively). @*Conclusion@#GNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.
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Purpose@#A critical indicator of the overall survival of patients with high-grade glioma is the successful isolation of tumor mesenchymal stem-like cells (tMSLCs), which play important roles in glioma progression. However, attempts to isolate tMSLCs from surgical specimens have not always been successful, and the reasons for this remain unclear. Considering that the amount of surgical high-grade glioma specimens varies, we hypothesized that larger surgical specimens would be better for tMSLC isolation. @*Materials and Methods@#We assessed 51 fresh, high-grade glioma specimens and divided them into two groups according to the success or failure of tMSLC isolation. The success of tMSLC isolation was confirmed by plastic adherence, presenting antigens, tri-lineage differentiation, and non-tumorigenicity. Differences in characteristics between the two groups were tested using independent two sample t-tests, chi-square tests, or Kaplan-Meier survival analysis. @*Results@#The mean specimen weights of the groups differed from each other (tMSLC-negative group: 469.9±341.9 mg, tMSLC positive group: 546.7±618.9 mg), but the difference was not statistically significant. The optimal cut-off value of specimen weight was 180 mg, and the area under the curve value was 0.599. @*Conclusion@#Our results suggested a minimum criterion for specimen collection, and found that the specimen amount was not deeply related to tMSLC detection. Collectively, our findings imply that the ability to isolate tMSLCs is determined by factors other than the specimen amount.
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Glioblastoma (GBM) is a disease without any definite cure. Numerous approaches have been tested in efforts to conquer this brain disease, but patients invariably experience recurrence or develop resistance to treatment. New surgical tools, carefully chosen samples, and experimental methods are enabling discoveries at single-cell resolution. The present article reviews the cell-of-origin of isocitrate dehydrogenase (IDH)-wildtype GBM, beginning with the historical background for focusing on cellular origin and introducing the cancer genesis patterned on firework. The authors also review mutations associated with the senescence process in cells of the subventricular zone (SVZ), and biological validation of somatic mutations in a mouse SVZ model. Understanding GBM would facilitate research on the origin of other cancers and may catalyze the development of new management approaches or treatments against IDH-wildtype GBM.
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Purpose@#The aim of this study is to evaluate the survival rate and prognostic factors of anaplastic gliomas according to the 2016 World Health Organization classification, including extent of resection (EOR) as measured by contrast-enhanced T1-weighted magnetic resonance imaging (MRI) and the T2-weighted MRI. @*Materials and Methods@#The records of 113 patients with anaplastic glioma who were newly diagnosed at our institute between 2000 and 2013 were retrospectively reviewed. There were 62 cases (54.9%) of anaplastic astrocytoma, isocitrate dehydrogenase (IDH) wild-type (AAw), 18 cases (16.0%) of anaplastic astrocytoma, IDH-mutant, and 33 cases (29.2%) of anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted. @*Results@#The median overall survival (OS) was 48.4 months in the whole anaplastic glioma group and 21.5 months in AAw group. In multivariate analysis, age, preoperative Karnofsky Performance Scale score, O6-methylguanine-DNA methyltransferase (MGMT) methylation status, postoperative tumor volume, and EOR measured from the T2 MRI sequence were significant prognostic factors. The EOR cut-off point for OS measured in contrast-enhanced T1-weighted MRI and T2-weighted MRI were 99.96% and 85.64%, respectively. @*Conclusions@#We found that complete resection of the contrast-enhanced portion (99.96%) and more than 85.64% resection of the non-enhanced portion of the tumor have prognostic impacts on patient survival from anaplastic glioma.
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OBJECTIVE: Silent corticotroph adenomas (SCA) are endocrine-inactive pituitary adenomas with positive immunohistochemistry staining for adrenocorticotropic hormone (ACTH). We investigated whether SCA-associated clinical profiles were more aggressive than hormonally negative adenomas (HNA). METHODS: Among 627 patients with pathologically proven endocrine-inactive pituitary adenomas between 2004 and 2013, positive immunohistochemistry revealed 55 SCAs and 411 HNAs. Surgical outcomes and radiological and endocrinological characteristics were compared. RESULTS: Strong female predominance was observed in the SCA group (p<0.001). Cavernous sinus invasion was identified in 22 (40%) SCA patients and 72 (17.6%) HNA patients (p<0.001). There were no differences in ACTH or cortisol levels between the two groups. The incidence of preoperative hypopituitarism and postoperative hormonal outcome did not differ between two groups. Total resection was achieved in 35 patients (63.7%) with SCA and 332 patients (80.8%) with HNA (p=0.007). When tumors were completely removed, recurrence rates were not statistically different between two groups (p=0.60). When complete resection was not achieved, tumors regrew from these remnants in seven patients (35.0%) with SCA and 12 patients (15.2%) with HNA (p=0.05). CONCLUSION: Total surgical resection for SCA is often challenging as these tumors frequently invade a cavernous sinus. Early remnant tumor intervention is justified, because untreated residual pituitary tumors regrow when patients were followed up for a long time. Prophylactic radiotherapy is not warranted for completely resected SCAs as tumor recurrence is uncommon.
Subject(s)
Female , Humans , ACTH-Secreting Pituitary Adenoma , Adenoma , Adrenocorticotropic Hormone , Cavernous Sinus , Corticotrophs , Hydrocortisone , Hypopituitarism , Immunohistochemistry , Incidence , Pituitary Neoplasms , Radiotherapy , RecurrenceABSTRACT
OBJECTIVE: Silent corticotroph adenomas (SCA) are endocrine-inactive pituitary adenomas with positive immunohistochemistry staining for adrenocorticotropic hormone (ACTH). We investigated whether SCA-associated clinical profiles were more aggressive than hormonally negative adenomas (HNA).METHODS: Among 627 patients with pathologically proven endocrine-inactive pituitary adenomas between 2004 and 2013, positive immunohistochemistry revealed 55 SCAs and 411 HNAs. Surgical outcomes and radiological and endocrinological characteristics were compared.RESULTS: Strong female predominance was observed in the SCA group (p<0.001). Cavernous sinus invasion was identified in 22 (40%) SCA patients and 72 (17.6%) HNA patients (p<0.001). There were no differences in ACTH or cortisol levels between the two groups. The incidence of preoperative hypopituitarism and postoperative hormonal outcome did not differ between two groups. Total resection was achieved in 35 patients (63.7%) with SCA and 332 patients (80.8%) with HNA (p=0.007). When tumors were completely removed, recurrence rates were not statistically different between two groups (p=0.60). When complete resection was not achieved, tumors regrew from these remnants in seven patients (35.0%) with SCA and 12 patients (15.2%) with HNA (p=0.05).CONCLUSION: Total surgical resection for SCA is often challenging as these tumors frequently invade a cavernous sinus. Early remnant tumor intervention is justified, because untreated residual pituitary tumors regrow when patients were followed up for a long time. Prophylactic radiotherapy is not warranted for completely resected SCAs as tumor recurrence is uncommon.
Subject(s)
Female , Humans , ACTH-Secreting Pituitary Adenoma , Adenoma , Adrenocorticotropic Hormone , Cavernous Sinus , Corticotrophs , Hydrocortisone , Hypopituitarism , Immunohistochemistry , Incidence , Pituitary Neoplasms , Radiotherapy , RecurrenceABSTRACT
A 56-year woman presented eyeball pain and blurred vision. MRI revealed a small well-delineated solid tumor in the apex of right orbit with optic nerve compression. Intraoperatively, the tumor was found very fibrous, hypervascular and adhesive to surrounding structures. The tumor was completely removed with the combination of endoscopic and microscopic technique. Patient experienced transient oculomotor nerve palsy, which completely recovered 3 months after surgery. Herein we report a rare case of angioleiomyoma in the orbital apex.
Subject(s)
Female , Humans , Adhesives , Angiomyoma , Endoscopy , Magnetic Resonance Imaging , Oculomotor Nerve Diseases , Optic Nerve , Orbit , Orbital NeoplasmsABSTRACT
We report the first case of severe fever with thrombocytopenia syndrome (SFTS) and a spontaneous acute subdural hematoma (SDH) in Korea. A 79-year-old male presented with fever and thrombocytopenia. On the third day of hospitalization, his mental changed from drowsy to semi-coma. Brain computed tomography indicated an acute subdural hemorrhage on the right convexity. He was given early decompressive craniectomy, but did not survive. Real-time reverse transcription polymerase chain reaction analysis of a blood sample indicated the presence of SFTS virus (SFTSV). This is the first reported case with intracranial hemorrhage and SFTS. This case report describes our treatment of a patient with acute SDH and an infection from a tick-borne species of Bunyaviridae.
Subject(s)
Aged , Humans , Male , Brain , Bunyaviridae , Decompressive Craniectomy , Fever , Hematoma, Subdural , Hematoma, Subdural, Acute , Hospitalization , Intracranial Hemorrhages , Korea , Orthobunyavirus , Polymerase Chain Reaction , Reverse Transcription , Thrombocytopenia , TicksABSTRACT
Among intracranial meningiomas, falcotentorial meningiomas, occurring at the junction of the falx cerebri and tentorial dural folds, are extremely rare. Because of their deep location, they are surrounded by critical structures, and have been regarded as one of the most challenging lesions for surgical treatment. In this study, we describe our surgical strategy for falcotentorial meningiomas and provide a review of our experience.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Dura Mater/pathology , Meningeal Neoplasms/pathology , Meningioma/pathologyABSTRACT
Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare condition with a fatal outcome, characterized by diffuse infiltration of the leptomeninges by neoplastic glial cells without evidence of primary tumor in the brain or spinal cord parenchyma. In particular, PDLG histologically diagnosed as gliosarcoma is extremely rare, with only 2 cases reported to date. We report a case of primary diffuse leptomeningeal gliosarcomatosis. A 68-year-old man presented with fever, chilling, headache, and a brief episode of mental deterioration. Initial T1-weighted post-contrast brain magnetic resonance imaging (MRI) showed diffuse leptomeningeal enhancement without a definite intraparenchymal lesion. Based on clinical and imaging findings, antiviral treatment was initiated. Despite the treatment, the patient's neurologic symptoms and mental status progressively deteriorated and follow-up MRI showed rapid progression of the disease. A meningeal biopsy revealed gliosarcoma and was conclusive for the diagnosis of primary diffuse leptomeningeal gliosarcomatosis. We suggest the inclusion of PDLG in the potential differential diagnosis of patients who present with nonspecific neurologic symptoms in the presence of leptomeningeal involvement on MRI.
Subject(s)
Aged , Humans , Biopsy , Brain , Diagnosis , Diagnosis, Differential , Fatal Outcome , Fever , Follow-Up Studies , Gliosarcoma , Headache , Magnetic Resonance Imaging , Meningeal Carcinomatosis , Meningoencephalitis , Neuroglia , Neurologic Manifestations , Spinal CordABSTRACT
OBJECTIVE: Endovascular treatment with stent placement or stent-assisted coiling was recently introduced as an alternative to parent artery occlusion for treating intracranial vertebral artery dissections. However, complete aneurysm obliteration after single stent placement is often not accomplished. The aim of the study was to evaluate the safety and efficacy of placing multiple stents in intracranial vertebral dissecting aneurysms. METHODS: We retrospectively reviewed 8 patients who underwent stent angioplasty with placing multiple stents for treating intracranial vertebral dissecting aneurysms. There were 5 male patients and 3 female patients with a mean age of 54 years (age range, 37-71 years). Three patients presented with subarachnoid hemorrhage (SAH), 1 presented with ischemic events and 4 presented with headache. Follow-up angiogram was performed in 8 patients within 6~12 months to determine whether or not the affected segment was occluded. RESULTS: Eight patients with intracranial vertebral artery dissections were treated by placing multiple stents, 6 were treated by double stent placement and the others were treated by triple and quadruple stent placement. Although immediate complete occlusion was not shown in any cases, the follow-up angiogram revealed complete occlusion in 5 cases (62.5%) within 6-12 months. There were 2 complications (25%, temporary vasospasm during the procedure and acute thrombosis). On the modified Rankin scale applied during follow-up, 6 patients were ssessed as functionally improved or of a stable clinical status, 1 patient expired due to cardiopulmonary complications, and 1 was lost to follow-up). CONCLUSION: Intracranial vertebral artery dissections can be treated by the endovascular method with placing multiple stents and the morbidity is acceptable. However, further study is needed since the treatment of patients presenting with SAH using multiple stent placement can be controversial.