Mesenchymal Stem-Like Cells Derived from the Ventricle More Effectively Enhance Invasiveness of Glioblastoma Than Those Derived from the Tumor

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.

Influence of the Amount of Fresh Specimen on the Isolation of Tumor Mesenchymal Stem-Like Cells from High-Grade Glioma

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.

Influence of the Amount of Fresh Specimen on the Isolation of Tumor Mesenchymal Stem-Like Cells from High-Grade Glioma

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.

Glioblastoma Cellular Origin and the Firework Pattern of Cancer Genesis from the Subventricular Zone

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.

Clinical Significance of Radical Surgery in the Treatment of Silent Corticotroph Adenoma

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.

Clinical Significance of Radical Surgery in the Treatment of Silent Corticotroph Adenoma

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.

Remote Cerebellar Infarction after Supratentorial Craniotomy and Its Management: Two Case Reports

The cerebellar infarction resulting from supratentorial craniotomy is uncommon event and its management has been controversial. After removal of space occupying lesion on right frontal area, two cases of remote cerebellar infarctions occurred. We reviewed each cases and the techniques to manage such complications are discussed. Early extraventricular catheter insertion and midline suboccipital craniectomy were effectively performed in obtunded patients from cerebellar infarction.

Effects of Prophylactic Antiepileptic Drugs on Clinical Outcomes in Patients with a Good Clinical Grade Suffering from Aneurysmal Subarachnoid Hemorrhage

OBJECTIVE: Routine use of prophylactic antiepileptic drugs (AED) has been debated. We retrospectively evaluated the effects of prophylactic AED on clinical outcomes in patients with a good clinical grade suffering from aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: Between September 2012 and December 2014, 84 patients who met the following criteria were included: (1) presence of a ruptured aneurysm; (2) Hunt-Hess grade 1, 2, or 3; and (3) without seizure presentation. Patients were divided into two groups; the AED group (n = 44) and the no AED group (n = 40). Clinical data and outcomes were compared between the two groups. RESULTS: Prophylactic AEDs were used more frequently in patients who underwent microsurgery (84.1%) compared to those who underwent endovascular surgery (15.9%, p < 0.001). Regardless of prophylactic AED use, seizure episodes were not observed during the six-month follow-up period. No statistical difference in clinical outcomes at discharge (p = 0.607) and after six months of follow-up (p = 0.178) were between the two groups. After six months, however, favorable outcomes in the no AED group tended to increase and poor outcomes tended to decrease. CONCLUSION: No difference in the clinical outcomes and systemic complications at discharge and after six months of follow-up was observed between the two groups. However, favorable outcomes in the no AED group showed a slight increase after six months. These findings suggest that discontinuation of the current practice of using prophylactic AED might be recommended in patients with a good clinical grade.

Effects of Prophylactic Antiepileptic Drugs on Clinical Outcomes in Patients with a Good Clinical Grade Suffering from Aneurysmal Subarachnoid Hemorrhage

OBJECTIVE: Routine use of prophylactic antiepileptic drugs (AED) has been debated. We retrospectively evaluated the effects of prophylactic AED on clinical outcomes in patients with a good clinical grade suffering from aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: Between September 2012 and December 2014, 84 patients who met the following criteria were included: (1) presence of a ruptured aneurysm; (2) Hunt-Hess grade 1, 2, or 3; and (3) without seizure presentation. Patients were divided into two groups; the AED group (n = 44) and the no AED group (n = 40). Clinical data and outcomes were compared between the two groups. RESULTS: Prophylactic AEDs were used more frequently in patients who underwent microsurgery (84.1%) compared to those who underwent endovascular surgery (15.9%, p < 0.001). Regardless of prophylactic AED use, seizure episodes were not observed during the six-month follow-up period. No statistical difference in clinical outcomes at discharge (p = 0.607) and after six months of follow-up (p = 0.178) were between the two groups. After six months, however, favorable outcomes in the no AED group tended to increase and poor outcomes tended to decrease. CONCLUSION: No difference in the clinical outcomes and systemic complications at discharge and after six months of follow-up was observed between the two groups. However, favorable outcomes in the no AED group showed a slight increase after six months. These findings suggest that discontinuation of the current practice of using prophylactic AED might be recommended in patients with a good clinical grade.

Localization and Treatment of Unruptured Paraclinoid Aneurysms: A Proton Density MRI-based Study

OBJECTIVE: The purpose of this study was to evaluate the usefulness of proton density magnetic resonance (PD MR) imaging for localization of paraclinoid internal carotid artery aneurysms. MATERIALS AND METHODS: From April 2014 to April 2015, 76 unruptured paraclinoid aneurysms in 66 patients were evaluated using PD MR and angiography (CT/MR angiography or digital subtraction angiography). The locations (extradural, transdural, intradural) in relation to the distal dural ring (DDR) and projection (superior, inferior/posterior, medial, lateral) of the aneurysms were assessed and compared. RESULTS: The most common location of paraclinoid aneurysms was extradural (n = 48, 63.2%), followed by intradural (n = 18, 23.7%), and transdural (n = 10, 13.2%). In the medial projection group (n = 49, 64.5%), 31 were extradural (63.3%), 5 were transdural (10.2%), and 13 were intradural (26.5%). In the inferior/posterior projection group (n = 19, 25.0%), there were 14 extradural (73.7%), 4 transdural (21.0%), and 1 intradural (5.3%). In the superior (n = 4, 5.3%)/lateral (n = 4, 5.3%) projection groups, there were 0/3 extradural (0/75.0%), 1/0 transdural (25.0/0%), and 3/1 intradural (75.0/25.0%). CONCLUSION: PD MR showed sufficient contrast difference to distinguish paraclinoid aneurysms from surrounding dural structures.

Localization and Treatment of Unruptured Paraclinoid Aneurysms: A Proton Density MRI-based Study

OBJECTIVE: The purpose of this study was to evaluate the usefulness of proton density magnetic resonance (PD MR) imaging for localization of paraclinoid internal carotid artery aneurysms. MATERIALS AND METHODS: From April 2014 to April 2015, 76 unruptured paraclinoid aneurysms in 66 patients were evaluated using PD MR and angiography (CT/MR angiography or digital subtraction angiography). The locations (extradural, transdural, intradural) in relation to the distal dural ring (DDR) and projection (superior, inferior/posterior, medial, lateral) of the aneurysms were assessed and compared. RESULTS: The most common location of paraclinoid aneurysms was extradural (n = 48, 63.2%), followed by intradural (n = 18, 23.7%), and transdural (n = 10, 13.2%). In the medial projection group (n = 49, 64.5%), 31 were extradural (63.3%), 5 were transdural (10.2%), and 13 were intradural (26.5%). In the inferior/posterior projection group (n = 19, 25.0%), there were 14 extradural (73.7%), 4 transdural (21.0%), and 1 intradural (5.3%). In the superior (n = 4, 5.3%)/lateral (n = 4, 5.3%) projection groups, there were 0/3 extradural (0/75.0%), 1/0 transdural (25.0/0%), and 3/1 intradural (75.0/25.0%). CONCLUSION: PD MR showed sufficient contrast difference to distinguish paraclinoid aneurysms from surrounding dural structures.