Prediction of atherosclerotic changes in cavernous carotid aneurysms based on computational fluid dynamics analysis: a proof-of-concept study.

PURPOSE: Recent computational fluid dynamics (CFD) studies have demonstrated the concurrence of atherosclerotic changes in regions exposed to prolonged blood residence. In this proof-of-concept study, we investigated a small but homogeneous cohort of large, cavernous carotid aneurysms (CCAs) to establish the clinical feasibility of CFD analysis in treatment planning, based on the association between pathophysiology and hemodynamics. METHODS: This study included 15 patients with individual large CCAs. We identified calcifications, which indicated atherosclerotic changes, using the masking data of digital subtraction angiography. We conducted a CFD simulation under patient-specific inlet flow rates measured using magnetic resonance (MR) velocimetry. In the post-CFD analysis, we calculated the blood residence time ([Formula: see text]) and segmented the surface exposed to blood residence time over 1 s ([Formula: see text]). We measured the decrease in volume after flow diversion using the original time-of-flight MR angiography data. RESULTS: Calcifications were observed in the region with [Formula: see text]. In addition, the ratio of [Formula: see text] to the surface of the aneurysmal domain exhibited a negative relationship with the rate of volume reduction at the 6- and 12-month follow-ups. Post-CFD visualization demonstrated that intra-aneurysmal swirling flow prolonged blood residence time under the condition of a small inlet flow rate, when compared to the aneurysmal volume. CONCLUSION: The results of this study suggest the usefulness of CFD analysis for the diagnosis of atherosclerotic changes in large CCAs that may affect the therapeutic response after flow diversion.

Carotid web leads to new thrombus formation: computational fluid dynamic analysis coupled with histological evidence.

Carotid web has been recognized as a rare cause of ischemic stroke with high recurrence rate. We describe a 48-year-old woman with carotid web who developed embolic stroke. We obtained a fresh thrombus from the internal carotid artery when carotid endarterectomy was performed. A preoperative computational fluid dynamics (CFD) study showed stagnation of blood around the web structure as well as the low wall shear stress. The rheological analysis newly disclosed mechanisms of thrombus formation related to the carotid web. CFD study in the carotid web may determine indication and timing of surgical interventions with further accumulation of clinical evidence.

Enlargement of a Middle Cerebral Artery Aneurysm after Intra-Aneurysmal Embolization with Parent Artery Preservation for an Ipsilateral Large Internal Carotid Artery Aneurysm: A Case Report.

We report a 77-year-old woman with marked enlargement of a middle cerebral artery (MCA) aneurysm 4 years after the successful intra-aneurysmal embolization of an ipsilateral large internal carotid artery (ICA) aneurysm. She intially presented with right third cranial nerve palsy due to a large ICA aneurysm, 20.8 mm in diameter. Initial magnetic resonance angiography (MRA) revealed a signal decrease in the right MCA, suggesting hemodynamic disturbance based on the contrast pooling in the right large ICA aneurysm exhibiting "Windkessel phenomenon". The large ICA aneurysm was successfully managed by intra-aneurysmal embolization with parent artery preservation, and immediate post-treatment MRA demonstrated significant signal recovery in the right MCA. Meticulous follow-up by MRA identified sudden growth in the aneurysmal height within 1 week after embolization, with further growth over the following 4 years, necessitating microsurgical clipping. Enlargement of the ipsilateral distal aneurysm following the treatment of proximal large aneurysm could be altered by marked distal hemodynamic change in view of the sudden amelioration of the "Windkessel phenomenon". Thus, we recommend meticulous follow-up of the associated distal aneurysm after the management of proximal large or giant aneurysms with parent artery preservation.

Convection-enhanced delivery of a hydrophilic nitrosourea ameliorates deficits and suppresses tumor growth in experimental spinal cord glioma models.

BACKGROUND: Convection-enhanced delivery (CED) is a technique allowing local infusion of therapeutic agents into the central nervous system, circumventing the blood-brain or spinal cord barrier. OBJECTIVE: To evaluate the utility of nimustine hydrochloride (ACNU) CED in controlling tumor progression in an experimental spinal cord glioma model. METHODS: Toxicity studies were performed in 42 rats following the administration of 4 µl of ACNU CED into the mid-thoracic spinal cord at concentrations ranging from 0.1 to 10 mg/ml. Behavioral analyses and histological evaluations were performed to assess ACNU toxicity in the spinal cord. A survival study was performed in 32 rats following the implantation of 9 L cells into the T8 spinal cord. Seven days after the implantation, rats were assigned to four groups: ACNU CED (0.25 mg/ml; n = 8); ACNU intravenous (i.v.) (0.4 mg; n = 8); saline CED (n = 8); saline i.v. (n = 8). Hind limb movements were evaluated daily in all rats for 21 days. Tumor sizes were measured histologically. RESULTS: The maximum tolerated ACNU concentration was 0.25 mg/ml. Preservation of hind limb motor function and tumor growth suppression was observed in the ACNU CED (0.25 mg/ml) and ACNU i.v. groups. Antitumor effects were more prominent in the ACNU CED group especially in behavioral analyses (P < 0.05; log-rank test). CONCLUSIONS: ACNU CED had efficacy in controlling tumor growth and preserving neurological function in an experimental spinal cord tumor model. ACNU CED can be a viable treatment option for spinal cord high-grade glioma.

Blood Flow Into Basilar Tip Aneurysms: A Predictor for Recanalization After Coil Embolization.

BACKGROUND AND PURPOSE: Hemodynamic forces may play a role in the recanalization of coiled aneurysms. The purpose of this study was to investigate the influence of presurgical hemodynamics on the efficacy of coil embolization for basilar tip aneurysms. METHODS: We identified 82 patients who underwent endovascular coil embolization for basilar tip aneurysms with a follow-up of >1 year. Presurgical hemodynamics were investigated using computational fluid dynamics with 3-dimensional data derived from rotational angiography. During postprocessing, we quantified the rate of net flow entering the aneurysm through its neck and calculated the proportion of the aneurysmal inflow rate to the basilar artery flow rate. In addition, we investigated the correlation between the basilar bifurcation configuration and the hemodynamics. RESULTS: Twenty-five of the 82 patients were excluded because of difficult vascular geometry reconstruction. Among the 57 examined patients, angiographic recanalization was observed in 19 patients (33.3%). The proportion of the aneurysmal inflow rate to the basilar artery flow rate and a coil packing density <30% were independent and significant predictors for the recanalization of coiled aneurysms. Additional investigation revealed that a small branch angle formed by the basilar artery and the posterior cerebral artery increased blood flow into the aneurysm. CONCLUSIONS: The proportion of the aneurysmal inflow rate to the basilar artery flow rate, influenced by the basilar bifurcation configuration, was an independent and significant predictor for recanalization after coil embolization in basilar tip aneurysms.

Temozolomide reverses doxorubicin resistance by inhibiting P-glycoprotein in malignant glioma cells.

Temozolomide is a standard chemotherapy agent for malignant gliomas, but the efficacy is still not satisfactory. Therefore, combination chemotherapy using temozolomide with other anti-tumor compounds is now under investigation. Here we studied the mechanism of the synergistic anti-tumor effect achieved by temozolomide and doxorubicin, and elucidated the inhibitory effect of temozolomide on P-glycoprotein (P-gp). Temozolomide significantly enhanced sensitivity to P-gp substrate in glioma cells, particularly in P-gp-overexpressed cells. Synergetic effects, as determined by isobologram analysis, were observed by combining temozolomide and doxorubicin. Subsequently, flow cytometry was utilized to assess the intracellular retention of doxorubicin in cells treated with doxorubicin with or without temozolomide. Temozolomide significantly increased the accumulation of doxorubicin in these cells. The P-gp adenosine triphosphatase (ATPase) assay showed that temozolomide inhibited the ATPase activity of P-gp. In addition, temozolomide combined with doxorubicin significantly prolonged the survival of 9L intracranial allografted glioma-bearing rats compared to single agent treatment. Collectively, our findings suggest that temozolomide can reverse doxorubicin resistance by directly affecting P-gp transport activity. Combination chemotherapy using temozolomide with other agents may be effective against gliomas in clinical applications.

The Computational Fluid Dynamics Rupture Challenge 2013--Phase II: Variability of Hemodynamic Simulations in Two Intracranial Aneurysms.

With the increased availability of computational resources, the past decade has seen a rise in the use of computational fluid dynamics (CFD) for medical applications. There has been an increase in the application of CFD to attempt to predict the rupture of intracranial aneurysms, however, while many hemodynamic parameters can be obtained from these computations, to date, no consistent methodology for the prediction of the rupture has been identified. One particular challenge to CFD is that many factors contribute to its accuracy; the mesh resolution and spatial/temporal discretization can alone contribute to a variation in accuracy. This failure to identify the importance of these factors and identify a methodology for the prediction of ruptures has limited the acceptance of CFD among physicians for rupture prediction. The International CFD Rupture Challenge 2013 seeks to comment on the sensitivity of these various CFD assumptions to predict the rupture by undertaking a comparison of the rupture and blood-flow predictions from a wide range of independent participants utilizing a range of CFD approaches. Twenty-six groups from 15 countries took part in the challenge. Participants were provided with surface models of two intracranial aneurysms and asked to carry out the corresponding hemodynamics simulations, free to choose their own mesh, solver, and temporal discretization. They were requested to submit velocity and pressure predictions along the centerline and on specified planes. The first phase of the challenge, described in a separate paper, was aimed at predicting which of the two aneurysms had previously ruptured and where the rupture site was located. The second phase, described in this paper, aims to assess the variability of the solutions and the sensitivity to the modeling assumptions. Participants were free to choose boundary conditions in the first phase, whereas they were prescribed in the second phase but all other CFD modeling parameters were not prescribed. In order to compare the computational results of one representative group with experimental results, steady-flow measurements using particle image velocimetry (PIV) were carried out in a silicone model of one of the provided aneurysms. Approximately 80% of the participating groups generated similar results. Both velocity and pressure computations were in good agreement with each other for cycle-averaged and peak-systolic predictions. Most apparent "outliers" (results that stand out of the collective) were observed to have underestimated velocity levels compared to the majority of solutions, but nevertheless identified comparable flow structures. In only two cases, the results deviate by over 35% from the mean solution of all the participants. Results of steady CFD simulations of the representative group and PIV experiments were in good agreement. The study demonstrated that while a range of numerical schemes, mesh resolution, and solvers was used, similar flow predictions were observed in the majority of cases. To further validate the computational results, it is suggested that time-dependent measurements should be conducted in the future. However, it is recognized that this study does not include the biological aspects of the aneurysm, which needs to be considered to be able to more precisely identify the specific rupture risk of an intracranial aneurysm.

Outflow Occlusion with Occipital Artery-Posterior Inferior Cerebellar Artery Bypass for Growing Vertebral Artery Fusiform Aneurysm with Ischemic Onset: A Case Report.

Surgical treatments should be considered for vertebral artery fusiform aneurysms, which become symptomatic due to cerebral ischemia or mass effect. Ischemic complication is one of the major problems after surgical or endovascular trapping, which is associated with unfavorable outcomes. The authors present a case with growing vertebral artery (VA) fusiform aneurysm with ischemic onset successfully treated with outflow occlusion with occipital artery-posterior inferior cerebellar artery (OA-PICA) bypass. A 50-year-old woman presented with left PICA territory infarction. Left vertebral angiography (VAG) showed occlusion of the left VA at the proximal V4 segment. Right VAG revealed that the distal part of the left V4 segment with fusiform aneurysmal dilatation was reconstituted through vertebrobasilar junction, and the left PICA was the outlet of the blood flow from the fusiform aneurysm. Although the patient was treated conservatively, enlargement of the left VA fusiform aneurysm was observed 8 months after the initial presentation. Considering the potential risks for future stroke or bleeding, we performed clip occlusion of the origin of the left PICA, which could achieve outflow occlusion of the fusiform aneurysm with preservation of the perforators arising around the aneurysm. We created OA-PICA anastomosis for revascularization of the distal PICA. The postoperative course was uneventful, and the postoperative right VAG revealed occlusion of the fusiform aneurysm. Outflow occlusion instead of trapping is an effective surgical option for VA fusiform aneurysm to achieve obliterate the aneurysm with preservation of the perforator at the blind end.

Treatment of children and adolescents with ulcerative colitis by adsorptive depletion of myeloid lineage leucocytes as monotherapy or in combination with low dose prednisolone after failure of first-line medications.

BACKGROUND: Currently available drugs for the treatment of ulcerative colitis (UC) include salicylates, thiopurines, corticosteroids and new anti-tumour necrosis factor (TNF)-α biologics. Among these medications, corticosteroids in children and adolescents may adversely affect the patients' growth and development. Further, UC patients have elevated and activated myeloid lineage leucocytes including the CD14 + CD16+ monocytes, which release TNF-α as a significant exacerbating factor. Accordingly, depletion of these cells by granulocyte/monocyte adsorption (GMA) should alleviate inflammation and promote UC remission. The objective of this study was to evaluate the efficacy of GMA in children and adolescents in whom conventional first-line medications had failed to induce remission. METHODS: In a single centre setting, between 2007 and 2012, a total of 24 consecutive children and adolescents, age 11-19 years were given mesalazine or sulphasalazine as a first-line medication. Seventeen patients relapsed or did not respond to the first-line medications, and received GMA with the Adacolumn, 2 sessions in the first week, and then weekly, up to 11 sessions. Patients who achieved a decrease of ≥5 in the clinical activity index (CAI) were to continue with GMA, while non-responders were to receive 0.5 to 1.0 mg/kg/day prednisolone (PSL) plus additional GMA sessions similar to GMA responder cases. At entry and week 12, patients were clinically and endoscopically evaluated, allowing each patient to serve as her/his own control. RESULTS: Seven patients achieved remission with the first-line medications and did not receive GMA. Five patients did not respond to the first 5 GMA sessions and received PSL plus GMA, while 12 patients responded to the first 5 GMA sessions and received additional sessions. At entry, the average CAI was 12.7 ± 2.5, range 8-17, and the average endoscopic index was 8.5 ± 1.5, range 7-11. The corresponding values at week 12 were 2.1 ± 0.2, range 1-4 (P < 0.001) and 2.4 ± 0.2, range 1-4 (P < 0.001). PSL was tapered to 0 mg within 3 months. CONCLUSIONS: With the strategy we applied in this study, all 24 consecutive patients achieved remission. In growing patients with active UC refractory to first-line medications, GMA was associated with clinical remission and mucosal healing, while in non-responders to GMA monotherapy, addition of a low dose PSL enhanced the efficacy of GMA and tapering of the PSL dose soon after remission was not associated with UC relapse. Therefore, the majority of young corticosteroid naive UC patients in whom first-line salicylates have failed may respond to GMA and be spared from additional drug therapy. Avoiding corticosteroids at an early stage of UC should ensure better long-term clinical course.

Diagnostic Ability and Safety of Repeated Pancreatic Juice Cytology Using an Endoscopic Nasopancreatic Drainage Catheter for Pancreatic Ductal Adenocarcinoma: A Multicenter Prospective Study.

Pathological examination is essential for the diagnosis and treatment of pancreatic ductal adenocarcinoma (PDAC). Moreover, a reliable pathological diagnosis is extremely important for improving prognosis, especially in early-stage PDAC. This study prospectively evaluated the usefulness of repeated pancreatic juice cytology (PJC) using an endoscopic nasopancreatic drainage (ENPD) catheter for the diagnosis of PDAC. We enrolled 82 patients suspected of having resectable PDAC, based on imaging studies, and judged the necessity for cytology. The diagnostic yield of up to six repeated PJCs and the incidence of complications, such as pancreatitis, was evaluated. A total of 60 patients were diagnosed with PDAC. The overall sensitivity and specificity were 46.7% and 95.5%, respectively. The cumulative positivity rate increased with the number of sampling sessions, reaching 58.3% in the sixth session. The sensitivity was significantly higher in the pancreatic head than in the pancreatic tail (p = 0.043). Additionally, it was 100% in four patients with a tumor size ≤10 mm. Pancreatitis occurred in six patients (7.3%), all of whom were treated conservatively. In the diagnosis of PDAC, repeated PJC using an ENPD catheter revealed a cumulative effect of sensitivity up to six times and an excellent diagnostic yield for small PDAC.

Computational hemodynamic analysis of the offending vertebral artery at the site of neurovascular contact in a case of hemifacial spasm associated with subclavian steal syndrome: illustrative case.

BACKGROUND: Hemifacial spasm (HFS) is caused by neurovascular contact along the facial nerve's root exit zone (REZ). The authors report a rare HFS case that was associated with ipsilateral subclavian steal syndrome (SSS). OBSERVATIONS: A 42-year-old man with right-sided aortic arch presented with progressing left HFS, which was associated with ipsilateral SSS due to severe stenosis of the left brachiocephalic trunk. Magnetic resonance imaging showed contact between the left REZ and vertebral artery (VA), which had shifted to the left. The authors speculated that the severe stenosis at the left brachiocephalic trunk resulted in the left VA's deviation, which was the underlying cause of the HFS. The authors performed percutaneous angioplasty (PTA) to dilate the left brachiocephalic trunk. Ischemic symptoms of the left arm improved after PTA, but the HFS remained unchanged. A computational fluid dynamics study showed that the high wall shear stress (WSS) around the site of neurovascular contact decreased after PTA. In contrast, pressure at the point of neurovascular contact increased after PTA. LESSONS: SSS is rarely associated with HFS. Endovascular treatment for SSS reduced WSS of the neurovascular contact but increased theoretical pressure of the neurovascular contact. Physical release of the neurovascular contact is the best treatment option for HFS.

Incomplete stent expansion in flow-diversion treatment affects aneurysmal haemodynamics: a quantitative comparison of treatments affected by different severities of malapposition occurring in different segments of the parent artery.

Incomplete stent expansion (IncSE) is occasionally seen in flow-diversion (FD) treatment of intracranial aneurysms; however, its haemodynamic consequences remain inconclusive. Through a parametric study, we quantify the aneurysmal haemodynamics subject to different severities of IncSE occurring in different portions of the stent. Two patient cases with IncSE confirmed in vivo were studied. To investigate a wider variety of IncSE scenarios, we modelled IncSE at two severity levels respectively located in the proximal, central, or distal segment of a stent, yielding a total of 14 treatment scenarios (including the ideal deployment). We examined stent wire configurations in 14 scenarios and resolved aneurysm haemodynamics through computational fluid dynamics (CFD). A considerable degradation of aneurysm flow-reduction performance was observed when central or distal IncSE occurred, with the maximal elevations of the inflow rate (IR) and energy loss (EL) being 10% and 15%. The underlying mechanism might be the increased resistance for flow to remain within the FD stent, which forces more blood to leak into the aneurysm sac. Counter-intuitively, a slight reduction of aneurysm inflow was associated with proximal IncSE, with the maximal further reduction of the IR and EL being 5% and 8%. This may be due to the disruption of the predominant parent-artery flow by the collapsed wires, which decreased the strength and altered the direction of aneurysmal inflow. The effects of IncSE vary greatly with the location of occurrence, revealing the importance of performing individualised, patient-specific risk assessment before treatment.

Clinical Analysis of Early-Stage Pancreatic Cancer and Proposal for a New Diagnostic Algorithm: A Multicenter Observational Study.

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging but essential for improving its poor prognosis. We established a multicenter study to clarify the clinicopathological features, and to propose new algorithm for early diagnosis of PDAC. Ninety-six patients with stage 0 and IA PDAC were enrolled from 13 high-volume centers. Overall, 70% of the patients were asymptomatic. The serum pancreatic enzyme levels were abnormal in half of the patients. The sensitivity of endoscopic ultrasonography (EUS) for detecting small PDAC was superior to computed tomography and magnetic resonance imaging (MRI) (82%, 58%, and 38%, respectively). Indirect imaging findings were useful to detect early-stage PDAC; especially, main pancreatic duct stenosis on MRI had the highest positive rate of 86% in stage 0 patients. For preoperative pathological diagnosis, the sensitivity of endoscopic retrograde cholangiopancreatography (ERCP)-associated pancreatic juice cytology was 84%. Among the stage IA patients, EUS-guided fine-needle aspiration revealed adenocarcinoma in 93% patients. For early diagnosis of PDAC, it is essential to identify asymptomatic patients and ensure close examinations of indirect imaging findings and standardization of preoperative pathological diagnosis. Therefore, a new diagnostic algorithm based on tumor size and imaging findings should be developed.

Identification and characterization of novel phosphate regulon genes, ecs0540-ecs0544, in Escherichia coli O157:H7.

In response to environmental phosphate limitation, the transcriptional activator PhoB of Escherichia coli (E. coli) activates transcription of the phosphate regulon (pho regulon) genes that are involved in phosphate utilization. At least 31 of pho regulon genes have been identified and well characterized in E. coli by numerous studies using non-pathogenic K-12 derivative strains. In this study, we searched for PhoB-regulated promoters from a lacZ-fused genomic library of the E. coli O157:H7 Sakai in an attempt to find novel pho regulon genes in the strain. A promoter region located upstream of a gene cluster (ecs0540-ecs0544) that mapped within one of the strain-specific chromosomal regions of the E. coli O157:H7 was identified. By further in vivo analysis with various subclones of the 5'-flanking region, it was suggested that the ecs0540 transcription was regulated by at least two promoters, an upstream PhoB-regulated promoter and a downstream constitutive promoter. S1 mapping and footprinting experiments revealed two transcription start sites and a sequence similar to the consensus sequence of PhoB binding, respectively. Bioinformatic analysis of the ecs0540-ecs0544 genes showed that these genes were highly homologous to the Escherichia fergusonii (E. fergusonii) siiCA-DA operon encoding a 718 kDa giant protein (SiiEA) and its cognate type I secretion system. In addition, a highly repetitive region and motifs that are shared among RTX (repeats in toxin) toxin family were found in the amino acid sequence of these giant proteins. Our finding is the first example of a member of the pho regulon identified in the O157:H7 strain-specific chromosomal region.

Convection-enhanced delivery of a synthetic retinoid Am80, loaded into polymeric micelles, prolongs the survival of rats bearing intracranial glioblastoma xenografts.

Prognosis for the patients with glioblastoma, the most common malignant brain tumor, remains dismal. A major barrier to progress in treatment of glioblastoma is the relative inaccessibility of tumors to chemotherapeutic agents. Convection-enhanced delivery (CED) is a direct intracranial drug infusion technique to deliver chemotherapeutic agents to the central nervous system, circumventing the blood-brain barrier and reducing systemic side effects. CED can provide wider distribution of infused agents compared to simple diffusion. We have reported that CED of a polymeric micelle carrier system could yield a clinically relevant distribution of encapsulated agents in the rat brain. Our aim was to evaluate the efficacy of CED of polymeric micellar Am80, a synthetic agonist with high affinity to nuclear retinoic acid receptor, in a rat model of glioblastoma xenografts. We also used systemic administration of temozolomide, a DNA-alkylating agent, which has been established as the standard of care for newly diagnosed malignant glioma. U87MG human glioma cells were injected into the cerebral hemisphere of nude rats. Rats bearing U87MG xenografts were treated with CED of micellar Am80 (2.4 mg/m(2)) on day 7 after tumor implantation. Temozolomide (200 mg/m(2)/day) was intraperitoneally administered daily for 5 days, starting on day 7 after tumor implantation. CED of micellar Am80 provided significantly longer survival than the control. The combination of CED of micellar Am80 and systemic administration of temozolomide provided significantly longer survival than single treatment. In conclusion, temozolomide combined with CED of micellar Am80 may be a promising method for the treatment of malignant gliomas.

Regression of Recurrent Spinal Cord High-Grade Glioma After Convection-Enhanced Delivery of Nimustine Hydrochloride: Case Reports and Literature Review.

BACKGROUND: Spinal cord high-grade glioma has poor prognosis. Especially, no treatment protocols have been established for recurrent cases. OBJECTIVE: To apply a novel treatment method, convection-enhanced delivery (CED), for recurrent high-grade glioma. CED can deliver chemotherapeutic agents directly into the intramedullary lesion and possibly lead to remarkable regression of enlarging tumors that are, otherwise, difficult to control. METHODS: Two patients developed high-grade glioma in the thoracic spinal cord. Partial resection and chemotherapy and radiotherapy induced remission of the disease. However, following the initial treatment, recurrence was noted in the spinal cord at 6 and 12 mo, respectively. No effective treatment was available for these recurrent lesions. Therefore, the authors decided to use CED to infuse nimustine hydrochloride (ACNU) directly into the spinal cord. During the procedure, the infusion cannula was inserted into the spinal cord lesion under intraoperative computed tomography scan. RESULTS: After ACNU CED, successive magnetic resonance imaging confirmed remarkable shrinkages of the tumors in both cases. However, the patient's preinfusion symptoms, including bilateral lower extremity weakness, did not change after the treatment. Importantly, overall survivals of the 2 patients were as long as 67 and 33 mo. CONCLUSION: The authors report the first 2 cases of recurrent spinal cord high-grade glioma. ACNU CED dramatically regressed enhanced mass lesions and provided local tumor controls in the spinal cord.

Therapeutic efficacy of a polymeric micellar doxorubicin infused by convection-enhanced delivery against intracranial 9L brain tumor models.

Convection-enhanced delivery (CED) with various drug carrier systems has recently emerged as a novel chemotherapeutic method to overcome the problems of current chemotherapies against brain tumors. Polymeric micelle systems have exhibited dramatically higher in vivo antitumor activity in systemic administration. This study investigated the effectiveness of CED with polymeric micellar doxorubicin (DOX) in a 9L syngeneic rat model. Distribution, toxicity, and efficacy of free, liposomal, and micellar DOX infused by CED were evaluated. Micellar DOX achieved much wider distribution in brain tumor tissue and surrounding normal brain tissue than free DOX. Tissue toxicity increased at higher doses, but rats treated with micellar DOX showed no abnormal neurological symptoms at any dose tested (0.1-1.0 mg/ml). Micellar DOX infused by CED resulted in prolonged median survival (36 days) compared with free DOX (19.6 days; p = 0.0173) and liposomal DOX (16.6 days; p = 0.0007) at the same dose (0.2 mg/ml). This study indicates the potential of CED with the polymeric micelle drug carrier system for the treatment of brain tumors.

Enhanced antitumor effect of combined-modality treatment using convection-enhanced delivery of hydrophilic nitrosourea with irradiation or systemic administration of temozolomide in intracranial brain tumor xenografts.

OBJECTIVE: Convection-enhanced delivery (CED) is a local infusion technique that delivers chemotherapeutic agents directly to the central nervous system, circumventing the blood-brain barrier and reducing systemic side effects. We previously reported the safety and efficacy of CED of ACNU (nimustine hydrochloride: 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride), a hydrophilic nitrosourea, in rat brain tumor models. This study evaluated the efficacy of combined-modality treatments using CED of ACNU with irradiation or systemic administration of temozolomide. METHODS: Antitumor efficacy and toxicity of the treatment were evaluated using rat 9L intracranial brain tumor models. RESULTS: Combined treatment using CED of ACNU with irradiation produced significantly longer survival time than each treatment alone (versus CED: p<0.001, versus irradiation: p<0.05, log-rank test) or systemic administration of ACNU with irradiation (p<0.001). Long-term survival (120 days) and eradication of tumor occurred only in this combined-treatment group. We also showed that CED of ACNU plus systemic administration of temozolomide significantly enhanced survival rate compared with each treatment alone (versus CED: p<0.001, versus systemic temozolomide: p<0.05). DISCUSSION: Multimodality treatment using CED of ACNU, radiotherapy and systemic chemotherapy with temozolomide is a promising strategy for treatment of brain tumors.

Revascularization of the anterior cerebral artery by Y-shaped superficial temporal artery interposition graft for the treatment of a de novo aneurysm arising at the site of A3-A3 bypass: technical case report.

The most frequently used option to reconstruct the anterior cerebral artery (ACA) is an ACA-ACA side-to-side anastomosis. The long-term outcome and complications of this technique are unclear. The authors report a case of a de novo aneurysm arising at the site of A3-A3 anastomosis. A 53-year-old woman underwent A3-A3 side-to-side anastomosis for the treatment of a ruptured right A2 dissecting aneurysm. At 44 months after surgery, a de novo aneurysm developed at the site of anastomosis. The aneurysm developed in the front wall of the anastomosis site, and projected to the anterosuperior direction. A computational fluid dynamics (CFD) study showed the localized region with high wall shear stress coincident with the pulsation in the front wall of the anastomosis site, where the aneurysm developed. A Y-shaped superficial temporal artery (STA) interposition graft was used successfully to reconstruct both ACAs, and then the aneurysm was trapped. To the authors' knowledge, this is the first case of a de novo aneurysm that developed at the site of an ACA-ACA side-to-side anastomosis. A CFD study showed that hemodynamic stress might be an underlying cause of the aneurysm formation. A Y-shaped STA interposition graft is a useful option to treat this aneurysm. Long-term follow-up is necessary to detect this rare complication after ACA-ACA anastomosis.