Madoka Inukai

Direct-puncture approach to the extraconal portion of the superior ophthalmic vein for carotid cavernous fistulae

IntroductionThe transvenous approach via the superior ophthalmic vein (SOV) is an available approach for carotid cavernous fistula (CCF), especially in the event that there is no other suitable approach route to the fistula. Surgical exposure of the peripheral roots of the SOV is commonly used; however, often, the SOV is often not accessible because of anatomical problems and/or complications. In this paper, we present and discuss our original direct-puncture approach to the extraconal portion of the SOV.MethodsAn attempt on three patients with traumatic CCF failed with the transarterial approach and the conventional venous approach via the inferior petrosal sinus; therefore, the patients were treated with the direct-puncture approach to the extraconal portion of the SOV using two-dimensional digital subtraction angiography with local anesthesia.ResultsAll cases that had tortuous and partially stenotic division of the SOV were treated successfully with this approach and without complications.ConclusionThis approach will become an alternate approach, especially when the peripheral roots of the SOV are focally narrowed and tortuous, making it impossible to insert a catheter.

Hypoxia-mediated cancer stem cells in pseudopalisades with activation of hypoxia-inducible factor-1α/Akt axis in glioblastoma☆☆☆

Pseudopalisades (Ps) around necrotic foci are severely hypoxic and overexpress hypoxia-inducible factor (HIF) in glioblastoma (GBM). Hypoxic regions have been proposed as one of several distinct niches for cancer stem cells (CSCs) in GBM, but little is known about the association between Ps features and CSC properties. Herein, we focused on the biological role of Ps lesions. In clinical cases of GBM, expression of hypoxia-related molecules including HIF-1α, Glut-1, p27(Kip1), and pAkt was significantly increased in perinecrotic Ps lesions compared with nonnecrotic areas and perinecrotic lesions lacking Ps features. Significantly higher expression levels of several CSC-related markers, including CD133, Sox2, CD44s, and aldehyde dehydrogenase (ALDH) 1, were also observed in Ps lesions, which were positively correlated with expression of hypoxia-related molecules and pAkt. Ps lesions also showed increased number of apoptotic cells and decreased bcl-2 and survivin expression compared with the surrounding tissue. Short-term exposure of astrocytoma cell lines to cobalt chloride, which is known to mimic the effect of hypoxia, caused an increase in expression of both hypoxia- and CSC-related markers, in line with increases in the ALDH(high) cell population and number of spheroids. Inhibition of endogenous Akt by LY294002 resulted in decreased expression of Sox2, ALDH1, and CD133, leading to enhancement of cobalt chloride-mediated apoptotic events due to altered ratio of bcl-2 to bax expression. These findings suggest that Ps lesions within GBM may serve as a specialized hypoxic niche, in which the HIF-1α/pAkt axis is activated, in response to severe hypoxia.

A new transvenous approach to the carotid-cavernous sinus via the inferior petrooccipital vein

OBJECT The transvenous approach via the inferior petrosal sinus (IPS) is commonly used as the most appropriate for carotid-cavernous fistula (CCF) or cavernous sinus sampling. However, sometimes the IPS is not accessible because of anatomical problems and/or complications, therefore an alternative route is needed. In this paper, the authors present and discuss the utility of a transvenous approach to the cavernous sinus via the inferior petrooccipital vein. METHODS Four patients, 3 with dural CCFs and the other with Cushing disease, in whom endovascular surgical attempts failed using a conventional venous approach via the IPS, underwent a transvenous approach to the cavernous sinus via the inferior petrooccipital vein (IPOV). One dural CCF case had only cortical venous drainage, the second CCF also mainly drained into the cortical vein with slight inflow into the superior ophthalmic vein and inferior ophthalmic vein, and the third demonstrated drainage into the superior and inferior ophthalmic veins and IPOV. RESULTS In all cases, the cavernous sinus could be accessed successfully via this route and without complications. CONCLUSIONS The transvenous approach to the cavernous sinus via the IPOV should be considered as an alternative in cases when use of the IPS is precluded by an anatomical problem and there are no other suitable venous approach routes.

Dural Arteriovenous Fistulas in the Cavernous Sinus: Clinical Research and Treatment

Introduction. The purpose of this paper is to clarify the clinical course, with the dural carotid cavernous fistula (CCF), featuring a pallet of symptoms, paying special attention to radiological findings. Methods. Seventy-six consecutive patients with dural CCFs were investigated in detail, all of whom were defined by angiography. Results. The most common initial symptom was diplopia in 47 patients (62%) and the most frequently observed on arrival were type II, featuring cranial nerve palsies followed by the classical triad in 27, and then type I only with cranial nerve palsies. The time until admission with type I (mean: 6.7 W ± 6.0) was significantly shorter than that with type II (mean: 25.1 W ± 23.5). Branches from bilateral carotid arteries widely inflowing into bilateral carotid cavernous sinus were present in 30 (39%), 20 (26%) of which also demonstrated direct inflow into the intercavernous sinus. type I and II had more multiple venous drainage routes as compared with type III (classical triad only on arrival) and IV (initial development of the classical triad followed by cranial nerve palsy). Conclusion. In our series of dural CCF patients, the most common initial symptom was cranial nerve palsy, mostly featuring multiple venous drainage including cortical drainage. Such palsies should be added to the classical triad as indicative symptoms. Bilateral carotid arteries often inflow into cavernous and intercavernous sinuses, which should be taken into account in choice of therapeutic strategy.

Transcriptional regulation of the alpha-1 type II collagen gene by nuclear factor κB/p65 and Sox9 in the chondrocytic phenotype of uterine carcinosarcomas

Uterine carcinosarcomas (U-CSs) are considered monoclonal in origin, but little is known about the mechanisms for establishment of heterologous sarcomatous components. Here, we examine the functional roles of nuclear factor κB (NF-κB)/p65 and Sox9 in the transcriptional regulation of alpha-1 type II collagen (COL2A1), a hallmark of chondrogenesis, during morphologic change in the direction of the chondrocytic phenotype. In 32 cases of U-CS, both phosphorylated p65 and Sox9 expression were colocalized in Col2A1-positive sarcomatous components, particularly in cartilaginous elements, with strongly positive correlation (ρ = 0.72, P = .005). A positive association of Col2A1 expression between protein (immunohistochemistry) and messenger RNA (in situ hybridization) assays was evident in sarcomatous components, whereas 9 cases also showed distinct positive signals for the messenger RNA without protein expression in carcinomatous elements, probably through a posttranscriptional and/or posttranslational modulation mechanism. In the Ishikawa endometrial cancer line, overexpression of p65 could activate transcription of COL2A1 promoter-intron reporters through binding to specific NF-κB sites in the first intron, along with up-regulation of Sox9. Exogenous induction of Sox9 also caused an increase in transcription of COL2A1, in contrast to a repression of the p65-mediated COL2A1 transcription, suggesting the existence of a negative feedback loop. These data, therefore, suggest that NF-κB/p65 signaling, as well as Sox9, may contribute to changes in the morphology of U-CS cells toward the chondrocytic phenotype through modulation of COL2A1 transcription.

Efficacy of endovascular surgery for ruptured aneurysms with vasospasm of the parent artery

Introduction In the presence of vasospasm it is recommended that surgical clipping for a ruptured aneurysm should be delayed until it disappears, but this may be associated with re-rupture of the aneurysm resulting in a poor outcome. The indications for endovascular coil embolization in such cases are discussed. Methods Since November 2002, endovascular coil embolization has been used in 18 consecutive patients with ruptured aneurysm with vasospasm of the parent artery ranging from 2 to 28 days (mean 9 days) after the initial subarachnoid hemorrhage. After successful obliteration of the aneurysm, a microcatheter preceded by a guidewire was introduced into the peripheral vessels with vasospasm of the A2 or M2 portions in order to release the vasospasm mechanically. Results Endovascular procedures were performed successfully in all but one of the cases (94%), resulting in complete occlusion in 14 of 17 patients and mild dilation of the vasospasm in all 17 patients without technical complications or re-rupture of the aneurysm. In the one case of failure because of a tortuous artery, surgical clipping was performed after disappearance of the vasospasm. Cerebral infarction occurred in four patients, but only one correlated with the distribution of catheterization and the neurological deficits had completely disappeared 3 months after the onset. Conclusion Catheterization of parent vessels in cases of vasospasm is safe for coiling and also mechanically releases vasospasm. Vasospasm of M2 and A2 segments can be treated with microcatheterization only.

Effects of Grapefruit Juice Consumption on Pharmacokinetics of Low Dose Simvastatin: Cross-over Study with a Review of the Literature

The effects of consumption of grapefruit juice on the pharmacokinetics of conventional low-dose simvastatin in Japan were investigated. In a randomized cross-over study with two phases, 10 healthy volunteers ingested grapefruit juice 400ml or water for 2 days. On day 3, a single 5mg dose of simvastatin was administered with grapefruit juice 200ml or water. Plasma concentrations of HMG-CoA reductase inhibitor were determined up to 8 h thereafter. Grapefruit juice increased the area under the plasma concentration-time curves from 0 to 8 h of total HMG-CoA reductase inhibitor 1.7- fold (p=0.002) and that of active HMG-CoA reductase inhibitor 1.7-fold (p=0.024). However, the peak concentrations (Cmax) and Tmax of total and active HMG-CoA reductase inhibitors were not significant influenced.Consumption of grapefruit juice with low-dose simvastatin thus resulted in mild increase of the plasma HMG-CoA reductase inhibitor, so that the pharmacokinetic interaction can be labeled as of weak CYP3A type.

ALK signaling cascade confers multiple advantages to glioblastoma cells through neovascularization and cell proliferation

Anaplastic lymphoma kinase (ALK), which is a receptor tyrosine kinase, is essentially and transiently expressed in the developing nervous system. Here we examined the functional role of the ALK gene in glioblastomas (GBMs). In clinical samples of GBMs, high ALK expression without gene rearrangements or mutations was frequently observed in perivascular lesions, in contrast to the relatively low expression in the perinecrotic areas, which was positively correlated with N-myc and phosphorylated (p) Stat3 scores and Ki-67 labeling indices. ALK immunoreactivity was also found to be associated with neovascular features including vascular co-option and vascular mimicry. In astrocytoma cell lines, cells stably overexpressing full-length ALK showed an increase in expression of pStat3 and pAkt proteins, as well as hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) mRNAs, in contrast to cells with knockdown of endogenous ALK which showed decreased expression of these molecules. Transfection of the constitutively active form of Stat3 induced an increase in HIF-1α promoter activity, and the overexpression of HIF-1α in turn resulted in enhancement of VEGF-A promoter activity. In addition, cells with overexpression or knockdown of ALK also showed a tendency toward increased and decreased proliferation, respectively, through changes in expression of pAkt and pStat3. Finally, ALK promoter was significantly activated by transfection of Sox4 and N-myc, which are known to contribute to neuronal properties. These findings therefore suggest that N-myc/Sox4-mediated ALK signaling cascades containing Stat3, Akt, HIF-1α, and VEGF-A confer multiple advantages to tumor growth through alterations in neovascularization and cell proliferation in GBMs.

An Operation in the Park Bench Position Complicated by Massive Tongue Swelling

This paper presents a case of massive tongue swelling as a complication after an operation in the park bench position. A 43-year-old male who had undergone a resection of a mass in the petrous bone of the clivus showed massive tongue swelling after the surgery in the left park bench position. A direct compression of the bite block caused the swelling of tongue. Tongue swelling may become fatal if it progresses to an airway obstruction; therefore the intraoperative and postoperative management is important.

The role of FilGAP, a Rac-specific Rho-GTPase-activating protein, in tumor progression and behavior of astrocytomas

FilGAP, a Rac‐specific Rho‐GTPase‐activating protein (GAP), acts as a mediator of Rho/ROCK‐dependent amoeboid movement, and its knockdown results in Rac‐driven mesenchymal morphology. Herein, we focused on the possible roles of FilGAP expression in astrocytomas. In clinical samples, FilGAP expression was significantly increased in grade (G) II astrocytomas as compared to normal astrocytes, but its expression strongly decreased in a grade‐dependent manner, and was positively associated with isocitrate dehydrogenase 1 (IDH1) mutations and inversely to cytoplasmic Rac1. Patients with astrocytoma showing a high FilGAP score had favorable overall survival as compared to the low score patients. Multivariate Cox regression analysis also showed that a high FilGAP score was a significant and independent favorable prognostic factor. Moreover, patients with high FilGAP score and IDH1 mutant‐type astrocytomas had significantly the best Overall survival (OS) and Progression‐free survival (PFS), in contrast to the patients with low FilGAP score and wild‐type IDH1 tumors who had the worst prognosis. In GIV tumors (GBM: glioblastomas), elongated tumor cells with low FilGAP expression were frequently observed in tumor core lesions, whereas the rounded cells with abundant expression were found in the peripheral areas adjacent to non‐neoplastic brain tissues. In an astrocytoma cell line, suppression of endogenous FilGAP expression by siRNAs caused an increased proportion of mesenchymal elongated cells, probably through increased Rac1 activity. These findings suggest that FilGAP, as well as IDH1 status, may be useful for predicting the behavior of astrocytomas. In addition, the FilGAP/Rac1 axis may serve as an important regulator of tumor progression in GBMs, probably through alteration of cell morphology.