5-Aminolevulinic acid fluorescence-guided endoscopic surgery for deep-seated intraparenchymal tumors.

AIM: The usefulness of 5-aminolevulinic acid (5-ALA) fluorescence-assisted surgery for maximum resection of malignant gliomas has been established. However, its usefulness when combined with endoscopic surgery for deep-seated tumors has not been well established. In this study, whether 5-ALA photodynamic diagnosis (PDD) is feasible and useful for endoscopic surgery was investigated. METHODS: A specially designed endoscope for PDD that delivers white light or blue light (375-440 nm) as excitation light was used. The fluorescence emitted by the tumor was evaluated in the cavity during resection or at the tip of the sheath during biopsy. The intensity of fluorescence was classified into three categories: strong, vague, and negative. RESULTS: A total of 30 intraparenchymal tumors were observed with a neuroendoscope and 5-ALA PDD; 16 patients underwent resection, and 14 underwent biopsy. Overall, 67% (20/30) of tumors showed positive fluorescence of protoporphyrin IX. High-grade gliomas (HGGs) including glioblastoma (GBM) and anaplastic astrocytoma (AA) showed strong fluorescence in 47% (7/15), vague fluorescence in 33% (5/15), and negative fluorescence in 20% (3/15) of cases. Low-grade gliomas (LGGs) showed vague fluorescence in 33% (1/3) and negative fluorescence in 67% (2/3). Diffuse large B-cell lymphoma (DLBCL) showed vague fluorescence in 38% (3/8) and negative fluorescence in 63% (5/8). Metastatic tumors showed strong fluorescence in 25% (1/4) and vague fluorescence in 75% (3/4). In the comparison of fluorescence evaluation, a significant difference was observed only in the comparison between HGGs and DLBCL (p = 0.049). CONCLUSION: These results suggest that 5-ALA PDD-assisted endoscopic surgery is feasible and useful for deep-seated intraparenchymal tumors.

A ventricular catheter that migrated into the fourth ventricle successfully removed using a neuroendoscope.

BACKGROUND: In order to remove a foreign body in the ventricle, such as a ventricular drainage catheter, craniotomy and corticotomy are required to access the ventricle. A case in which a catheter in the 4th ventricle was safely removed with a flexible neuroendoscope is reported. CASE DESCRIPTION: A 47-year-old man underwent coil embolization and ventricular drainage for subarachnoid hemorrhage. 10 days after the operation, he tore off the ventricular drainage catheter and the catheter remained intracranially. The tip of the catheter was in the 4th ventricle and the operation to remove remaining catheter with a neuroendoscope was performed. Using a neuroendoscope, we could remove the catheter safely and did not detect the complications. CONCLUSION: To date, there have been no reports of cases in which a drainage catheter in the ventricle was removed using a flexible endoscope. This case suggests that a flexible endoscope is useful for removing a foreign body from the ventricle less invasively.

5-ALA fluorescence-guided endoscopic surgery for mixed germ cell tumors.

5-Aminolevulinic acid (5-ALA) fluorescence-guided surgery is widely used for detection and planning of resection of malignant gliomas and other brain tumors. However, no reports have described 5-ALA fluorescence-guided surgery or direct visualization of germ cell tumors. Here, we report two cases of germ cell tumors in which a positive 5-ALA fluorescent signal was visualized with a neuroendoscope. Both cases had a tumor in the pineal region that was associated with hydrocephalus. The patients underwent surgery after administration of 5-ALA. After ventricular puncture of the anterior horn, we could observe the ventricular wall and tumor using the Karl Storz Photodynamic diagnosis system endoscope. Then, biopsy of the pineal tumor and endoscopic third ventriculostomy were performed in both cases. In case 1, a 22-year-old man, part of the ventricular wall and tumor tissue showed red fluorescence. In case 2, a 16-year-old man, part of the fornix and infundibular recess showed red fluorescence, and the tumor showed relatively weak red fluorescence. The histopathological diagnosis of both cases was pure germinoma. This is the first report of direct visualization of mixed germinomas with 5-ALA fluorescence-guided endoscopic surgery. This method not only allows visualization of the tumor mass, but may also be useful for detailed observation in the ventricular wall.

Establishment of a tumor sphere cell line from a metastatic brain neuroendocrine tumor.

Neuroendocrine tumors are rare, and little is known about the existence of cancer stem cells in this disease. Identification of the tumorigenic population will contribute to the development of effective therapies targeting neuroendocrine tumors. Surgically resected brain metastases from a primary neuroendocrine tumor of unknown origin were dissociated and cultured in serum-free neurosphere medium. Stem cell properties, including self-renewal, differentiation potential, and stem cell marker expression, were examined. Tumor formation was evaluated using intracranial xenograft models. The effect of temozolomide was measured in vitro by cell viability assays. We established the neuroendocrine tumor sphere cell line ANI-27S, which displayed stable exponential growth, virtually unlimited expansion in vitro, and expression of stem-cell markers such as CD133, nestin, Sox2, and aldehyde dehydrogenase. FBS-induced differentiation decreased Sox2 and nestin expression. On the basis of real-time PCR, ANI-27S cells expressed the neuroendocrine markers synaptophysin and chromogranin A. Intracranial xenotransplanted brain tumors recapitulated the original patient tumor and temozolomide exhibited cytotoxic effects on tumor sphere cells. For the first time, we demonstrated the presence of a sphere-forming, stem cell-like population in brain metastases from a primary neuroendocrine tumor. We also demonstrated the potential therapeutic effects of temozolomide for this disease.

Fat necrosis appearing as intraorbital tumour: case report.

A 33-year-old male presented with an extremely rare case of intraorbital fat necrosis. A magnetic resonance imaging scan showed a 10-mm mass lesion within the right lateral rectal muscle. Surgical removal was performed. Histological analysis showed diffuse adipose cells surrounded by macrophage cells. Fat necrosis was diagnosed.

Stent-Assisted Coil Embolization of Ruptured Blood Blister-Like Aneurysm of the Basilar Artery: A Case Report and Literature Review.

Objective: Blood blister-like aneurysms (BBA) often develop on the anterior wall of the internal carotid artery, and few cases have been reported at other sites. We report a case of stent-assisted coil embolization in the acute phase for a ruptured BBA of the basilar artery. Case Presentation: A 53-year-old woman underwent emergency stent-assisted coil embolization for subarachnoid hemorrhage due to a ruptured BBA in the main trunk of the basilar artery. Seven months after the operation, cerebral angiography confirmed no recurrence and a good clinical course. Conclusion: Stent-assisted coil embolization for BBA may be one treatment option.

Rapid deterioration of an asymptomatic lumbosacral lipoma due to formation of an extracanalicular syrinx: case report.

The authors present the case of a 1-month-old girl with a lumbosacral lipoma who then developed an extracanalicular syrinx and experienced rapid deterioration. The patient's initial MRI study, obtained before she became symptomatic, revealed a spinal lipoma with a syrinx in contact with the lipoma-cord interface. She was initially asymptomatic but developed loss of motor function in the left leg 14 days after MRI. Emergency surgery was performed. Intraoperative findings revealed a swollen spinal cord. Lipomatous tissue on the caudal side of the conus was removed subtotally, and the central canal was opened. Expansion of the syrinx was observed intraoperatively. Postoperatively, the patient's left leg paresis remained. Postoperative MRI revealed rostral and extracanalicular expansion of the syrinx. This is the first report on the rapid deterioration of a conus lipoma due to extracanalicular expansion of a syrinx. Careful follow-up and repeat MRI should be considered for patients with spinal lipomas with syringomyelia, especially when the syrinx is attached to the lipoma-cord interface.

ICOSLG-mediated regulatory T-cell expansion and IL-10 production promote progression of glioblastoma.

BACKGROUND: Targeting immune checkpoint proteins has recently gained substantial attention due to the dramatic success of this strategy in clinical trials for some cancers. Inducible T-cell co-stimulator ligand (ICOSLG) is a member of the B7 family of immune regulatory ligands, expression of which in cancer is implicated in disease progression due to regulation of antitumor adaptive immunity. Although aberrant ICOSLG expression has been reported in glioma cells, the underlying mechanisms that promote glioblastoma (GBM) progression remain elusive. METHODS: Here, we investigated a causal role for ICOSLG in GBM progression by analyzing ICOSLG expression in both human glioma tissues and patient-derived GBM sphere cells (GSCs). We further examined its immune modulatory effects and the underlying molecular mechanisms. RESULTS: Bioinformatics analysis and GBM tissue microarray showed that upregulation of ICOSLG expression was associated with poor prognosis in patients with GBM. ICOSLG expression was upregulated preferentially in mesenchymal GSCs but not in proneural GSCs in a tumor necrosis factor-α/nuclear factor-kappaB-dependent manner. Furthermore, ICOSLG expression by mesenchymal GSCs promoted expansion of T cells that produced interleukin-10. Knockdown of the gene encoding ICOSLG markedly reduced GBM tumor growth in immune competent mice, with a concomitant downregulation of interleukin-10 levels in the tumor microenvironment. CONCLUSIONS: Inhibition of the ICOSLG-inducible co-stimulator axis in GBM may provide a promising immunotherapeutic approach for suppressing a subset of GBM with an elevated mesenchymal signature.

Enlarging pediatric ectopic Rathke's cleft cyst in the prepontine cistern: case report.

Rathke's cleft cyst is a cystic disease that occurs in the sella turcica or, occasionally, in the suprasellar area. An ectopic Rathke's cleft cyst is extremely rare, and its nature is less well understood. The authors report the case of a 14-year-old girl who presented with a growing cystic lesion in the prepontine cistern, immediately behind the dorsum sellae. Preoperative imaging and intraoperative investigation showed part of the cyst wall continuing into the dorsum sellae, to the pituitary gland. The cisternal portion of the cyst wall was totally resected via a right subtemporal approach. Histopathological examination of the cyst wall showed a monolayer of ciliated cells, identical to those of Rathke's cleft cyst. To the best of the authors' knowledge, this represents the first pediatric case of Rathke's cleft cyst occurring in the prepontine cistern.

Emergency craniotomy for intraparenchymal massive hematoma after embolization of supratentorial arteriovenous malformations.

OBJECTIVE: We sought to evaluate the efficacy of emergency craniotomy for patients with massive hematoma secondary to endovascular embolization of supratentorial arteriovenous malformations (AVMs) and to investigate relevant factors affecting outcome. METHODS: Within the past 15 years, 605 patients with intracranial AVMs have undergone 1066 endovascular embolizations at our institution. Of these, 24 patients experienced intracranial hemorrhage during or after the procedure. Fourteen patients were demonstrated to have massive intraparenchymal hematomas and deteriorated to a comatose state (Glasgow Come Scale score < or =6). Twelve patients underwent craniotomy within 170 minutes of being diagnosed with intraparenchymal hemorrhage. The surgical procedures performed were hematoma evacuation with total (6 patients) or partial (2 patients) resection of the AVM or hematoma evacuation only (4 patients). The clinical records of these 12 patients were analyzed retrospectively. RESULTS: Nine patients recovered to a favorable condition (good recovery, four patients; moderately disabled, five patients), one patient remained in a persistent vegetative state, and two patients died. The interval between hemorrhage and emergency craniotomy was significantly shorter in patients with favorable outcomes than in those with poor clinical outcomes. Advanced age and a larger volume of intraoperative blood loss were the factors relevant to poor outcome. Temporal lobe location of the AVM and incomplete embolization tended to correlate to poor clinical outcome, but this correlation was not statistically significant. The sizes of the AVM and the hematoma did not correlate to patient outcome. There was no difference in outcomes with regard to the surgical procedure performed. CONCLUSION: In patients with massive postembolization hematomas, emergency craniotomy should be performed as soon as possible to achieve a favorable outcome. Cooperation among interventional neuroradiologists, intensive care physicians, and neurosurgeons is essential to manage AVM patients with critical postembolization hemorrhage. There is no need to persist in performing simultaneous total resection of the AVM at the emergency craniotomy.

Expression of Rb2/p130 protein correlates with the degree of malignancy in gliomas.

It has been reported that there is an inverse correlation between the immunohistochemical expression of Rb2/p130, a member of the retinoblastoma gene family, and the degree of malignancy in at least some histological types. In order to investigate the expression of this protein in gliomas, we evaluated 58 samples from patients with resected gliomas. We focused on the relationship between the degree of malignancy of the glioma and the immunohistochemical detection of Rb2/p130. Expression of Rb2/p130 was observed in 38 glioma specimens (65.5%), including a high expression level in low-grade glioma specimens (> 30% positive cells in 84% of tumors) and a low expression level in high-grade glioma specimens (> 30% positive cells in 12% of tumors). The most aggressive of the gliomas exhibited very low to undetectable levels of Rb2/p130. Moreover, we observed an inverse correlation between Rb2/p130 expression and the degree of malignancy. These findings suggest that the differentiation of gliomas might be partially mediated by the Rb2/p130 gene, and that Rb2/ p130 expression can additionally be an indicator of a better prognosis in patients with gliomas.

Molecular targeting of neuroblastoma with a novel p16INK4a transporter system.

Potential molecular targets in neuroblastoma include ALK mutations, p16 deletion and CDK2A mutations; however, targeted therapeutics have not been developed for these factors. We developed Wr-T, a new system for intracellular peptide and protein delivery with a 30-residue sequence that mediates molecule entrapment and intracellular permeability. Wr-T was used to introduce the p16INK4a functional peptide to restore the tumor suppressor function of p16INK4a. Introduction of Wr-T into rats with subcutaneous grafts of neuroblastoma produced an astonishing 75.6% tumor suppression (p<0.0005). Thus, the p16INK4a functional peptide can be introduced in low doses and, because it exists in vivo, it should produce fewer side-effects than standard chemotherapy. We suggest this system could be used for molecular-targeted peptides other than p16INK4a and should be pursued for further development.

Spontaneous regression of a spinal extradural arteriovenous fistula after delivery by cesarean section.

A 23-year-old Japanese woman presented with a newly developed spinal extradural arteriovenous fistula (AVF) during pregnancy. She had been followed up for a suspected spinal cavernous angioma and became unable to walk during the 29th week of her pregnancy. Magnetic resonance (MR) imaging showed a spinal extradural AVF at the T3 to T4 levels compressing the spinal cord. After delivery by cesarean section, her neurological symptoms gradually began to resolve, and she was able to resume walking without assistance. MR imaging confirmed spontaneous regression of the AVF. This case suggests that exacerbated neurological symptoms and AVF growth triggered by pregnancy can improve after delivery without interventional treatment. Careful follow up of neurological findings is required to prevent unnecessary interventional procedures in pregnant women with spinal AVF.

A case of petrous bone myxoid chondrosarcoma associated with cerebellar hemorrhage.

We report a rare case in which a myxoid chondrosarcoma originated from the petrous bone and invaded the cerebellar hemisphere with hemorrhage. Neuroimaging showed the characteristic feature of multiple small cysts along the solid tumor, and the cystic formation was confirmed as a mucoid secretion by Alcian blue staining and electron microscopic examination. This tumor recurred following partial removal and stereotaxic radiosurgery.