α-SMA positive vascular mural cells suppress cyst formation in hemangioblastoma.

Approximately 60% of hemangioblastomas (HBs) have peritumoral cysts adjacent to the tumor, which can cause neurological deficits due to the mass effect, and the management of cyst formation is a clinical challenge. Vascular mural cells surrounding endothelial cells consist of vascular smooth muscle cells (vSMCs) and pericytes, which are essential elements that support blood vessels and regulate permeability. This study investigated the involvement of mural cells in cyst formation. We analyzed the expression of α-smooth muscle actin (α-SMA), platelet-derived growth factor receptor-beta (PDGFRB), and CD31 in 39 consecutive human cerebellar HBs, 20 of cystic and 19 of solid type. Solid type HBs showed stronger diffuse expression of α-SMA in precapillary arterioles and capillaries within the tumor than cystic type HBs (p = 0.001), whereas there was no difference in PDGFRB and CD31 expression. Detailed observation with immunofluorescence demonstrated that α-SMA was expressed in vascular mural cells surrounding capillaries in the solid rather than in the cystic type. Multivariate analysis including various clinical and pathological factors showed that lower α-SMA expression was significantly correlated with cyst formation (p < 0.001). Our data suggested that vascular mural cells from precapillary arterioles to capillaries expressing α-SMA may be pericytes and play a crucial role in HB cystogenesis.

Glioma-derived extracellular vesicles promote tumor progression by conveying WT1.

Glioma persists as one of the most aggressive primary tumors of the central nervous system. Glioma cells are known to communicate with tumor-associated macrophages/microglia via various cytokines to establish the tumor microenvironment. However, how extracellular vesicles (EVs), emerging regulators of cell-cell communication networks, function in this process is still elusive. We report here that glioma-derived EVs promote tumor progression by affecting microglial gene expression in an intracranial implantation glioma model mouse. The gene expression of thrombospondin-1 (Thbs1), a negative regulator of angiogenesis, was commonly downregulated in microglia after the addition of EVs isolated from different glioma cell lines, which endogenously expressed Wilms tumor-1 (WT1). Conversely, WT1-deficiency in the glioma-derived EVs significantly attenuated the Thbs1 downregulation and suppressed the tumor progression. WT1 was highly expressed in EVs obtained from the cerebrospinal fluid of human patients with malignant glioma. Our findings establish a novel model of tumor progression via EV-mediated WT1-Thbs1 intercellular regulatory pathway, which may be a future diagnostic or therapeutic target.

Asymptomatic carotid intraplaque hemorrhage is associated with a high risk of cerebral infarction and death after cardiovascular surgery.

BACKGROUND: There is a lack of information on the natural history of asymptomatic carotid artery stenosis (AsymCS) associated with cardiovascular diseases that require surgery. The aim of this study was to investigate risk factors for postoperative ipsilateral ischemic stroke and all-cause mortality after cardiovascular surgery in patients with AsymCS. METHODS: Among 2158 patients who underwent cardiovascular surgery, 150 patients with AsymCS who didn't undergo carotid revascularization were included. The relationships between preoperative factors, including carotid intraplaque hemorrhage (IPH), and postoperative ipsilateral ischemic stroke and all-cause mortality were analyzed retrospectively. RESULTS: During the median follow-up of 1087 days of 150 patients with 19 IPH, 12 (8.0%) and 21 (14.0%) encountered ipsilateral infarction and all-cause mortality, respectively. Multivariable Cox regression analyses indicated that IPH was significantly predictive of both ipsilateral infarction (hazard ratio [HR] 21.31, 95% confidence interval [CI], 4.98-91.17; P ≤.001) and all-cause mortality (HR 4.64, 95% CI, 1.61-13.34; P = .004). Another significant factor was peak systolic velocity for ipsilateral infarction with the cutoff velocity of 227 cm/s by the receiver-operating characteristic curve. CONCLUSIONS: In this cohort of patients with AsymCS undergoing cardiovascular surgery, IPH had a close connection with a high risk of both postoperative ischemic stroke and mortality after cardiovascular surgery.

Progressively Enlarged Convexity Arachnoid Cysts in Elderly Patients: A Report of 2 Cases.

BACKGROUND: Generally, enlargement of arachnoid cysts (ACs) has been found mostly in cases occurring during early childhood. Therefore, progressively enlarged ACs found to be symptomatic in elderly patients are extremely rare, and the mechanisms have remained unexplored. CASE DESCRIPTION: Our first patient was a 72-year-old woman with memory disturbance, who had presented with a large cyst beneath the right temporal convexity 9 years previously. The annual follow-up magnetic resonance imaging (MRI) studies had revealed that the cyst had progressively enlarged. In addition, her memory disturbance had become advanced. Endoscopic cyst fenestration was performed between the cyst and lateral ventricle, resulting in a reduction of her symptoms. Our second patient was a 79-year-old woman with unsteadiness, who had presented with a large cyst under the right parietal convexity 6 years previously. The annual follow-up MRI studies had shown that the cyst had gradually enlarged. She subsequently developed left hemiparesis. Because the pyramidal tract was located between the cyst and ventricle, a cyst-ventricle shunt was placed to allow the cystic fluid into the lateral ventricle, with complete resolution of her symptoms. In both cases, MRI showed obliteration of the subdural spaces around the cysts. Endoscopic observations revealed that the arachnoid membrane was lined under the surrounding brain, leading to the diagnosis of an AC. CONCLUSION: The establishment of stable communication between a cyst and the normal cerebrospinal fluid space is important to treat symptomatic ACs characterized by progressive enlargement, even in elderly patients. The 1-way entry of the cerebrospinal fluid into the cyst and the closure of the surrounding subdural space might result in AC enlargement internally.

Efficacy of cyst-cisternal shunt for refractory cyst regrowth of cystic vestibular schwannomas.

Vestibular schwannomas (VSs) are generally benign and slow-growing tumors, and microsurgical resection is the commonly recommended treatment. Some reports suggested that inserting a cystoperitoneal shunt was effective for treatment of cystic VSs; however, there was no report of a cyst-cisternal shunt which diverts cyst fluid into cistern. We report a case of cystic VS with repeated cyst regrowth within weeks after repeated surgeries. We prevented further recurrence using cyst-cisternal shunt. This technique may be a new treatment option for refractory cyst regrowth of cystic VSs.

Intratumoral continuous facial nerve stimulation for surgical resection of cystic vestibular schwannoma: Technical note.

BACKGROUND: Cystic vestibular schwannomas (CVSs) account for about 10% of VS. The efficacy of continuous facial nerve stimulation (CFS) was previously reported; however, it is often difficult to place the electrode at the root exit zone (REZ) in the early stage of surgical resection. We proposed a new method of intratumoral CFS (ICFS) by searching for the facial nerve through the cyst wall and leaving the spherically shaped electrode at this point. METHODS: The cyst wall was opened, and the ventral side of the tumor wall was stimulated to search for the positive point of facial nerve stimulation and place the spherically shaped electrode for continuous stimulation at this point through the cyst cavity (intensity: 0.2-1.5 mA, frequency: 1 Hz). Safe surgical resection could be performed under ICFS in all three cases. RESULTS: Good preservation of the facial nerve and extent of resection that was estimated preoperatively was achieved in all cases. CONCLUSION: ICFS is suitable for the preservation of facial nerve function in surgical resection of CVS in cases in which electrode placement at the REZ is difficult.