Troubleshooting the bypass: intraoperative management of initially failed anastomosis in direct cerebral revascularization surgery.

OBJECTIVE: Direct cerebral revascularization is considered as one of the most technically challenging operations in neurosurgery. Technical errors are often not identified during the case, but only after the recirculation stage, making management crucial at that time of the procedure. In this study, the authors sought to describe troubleshooting of the technical errors encountered in initially failed bypass cases. METHODS: A retrospective analysis describing a single-surgeon, single-institution experience between 2014 and 2021 was performed, based on operative reports and videos, including a 30-day follow-up period. Initially failed bypass was defined if the bypass was not patent or had a significant leak after recirculation, irrespective of the final result. RESULTS: One hundred thirty-eight bypass cases were reviewed for complex aneurysms (n = 49), moyamoya disease (n = 59), and atherosclerosis (n = 30). Fifty-one initially failed anastomoses were identified; 43 of these were the result of a technical error. Etiologies of these failed anastomoses included a clot (n = 14), vessel kinking (n = 4), spasm (n = 5), suture-related cause (n = 5), inappropriate donor or recipient (n = 3), or lack of demand (n = 8). A major leak was attributed to an uncoagulated side branch (n = 4), vessel injury due to suture/clip placement (n = 1), or inadequate suture line coverage (n = 7). Thirty-seven (86%) of 43 cases were troubleshot successfully, as salvage maneuvers included papaverine vessel massage, donor repositioning, re-anastomosis for occlusion in select cases, local hemostatic agents, and suturing or coagulating side branches in a leak. Thirty-day follow-up revealed similar rates of patency between successfully troubleshot patients (35/37) and the rest of the cases (80/87, p = 0.6). CONCLUSIONS: Three major patterns of a noncompatible bypass were found: a major leak, an acute occlusion, or a delayed occlusion. Based on the authors' experience, salvage strategies proved successful, showing an eventual high patency rate. The authors suggest a gradual, structured algorithm to address this stage in surgery that may contribute specifically to cerebrovascular neurosurgeons at the beginning of their careers.

Radiographic and clinical outcomes with particle or liquid embolic agents for middle meningeal artery embolization of nonacute subdural hematomas.

BACKGROUND: Middle meningeal artery (MMA) embolization is an apparently efficacious minimally invasive treatment for nonacute subdural hematomas (NASHs), but how different embolisates affect outcomes remains unclear. Our objective was to compare radiographic and clinical outcomes after particle or liquid MMA embolization. METHODS: Patients who had MMA embolization for NASH were retrospectively identified from a multi-institution database. The primary radiographic and clinical outcomes-50% NASH thickness reduction and need for surgical retreatment within 90 days, respectively-were compared for liquid and particle embolizations in patients treated 1) without surgical intervention (upfront), 2) after recurrence, or 3) with concomitant surgery (prophylactic). RESULTS: The upfront, recurrent, and prophylactic subgroups included 133, 59, and 16 patients, respectively. The primary radiographic outcome was observed in 61.8%, 61%, and 72.7% of particle-embolized patients and 61.3%, 55.6%, and 20% of liquid-embolized patients, respectively (p = 0.457, 0.819, 0.755). Hazard ratios comparing time to reach radiographic outcome in the particle and liquid groups or upfront, recurrent, andprophylactic timing were 1.31 (95% CI 0.78-2.18; p = 0.310), 1.09 (95% CI 0.52-2.27; p = 0.822), and 1.5 (95% CI 0.14-16.54; p = 0.74), respectively. The primary clinical outcome occurred in 8.0%, 2.4%, and 0% of patients who underwent particle embolization in the upfront, recurrent, and prophylactic groups, respectively, compared with 0%, 5.6%, and 0% who underwent liquid embolization (p = 0.197, 0.521, 1.00). CONCLUSIONS: MMA embolization with particle and liquid embolisates appears to be equally effective in treatment of NASHs as determined by the percentage who reach, and the time to reach, 50% NASH thickness reduction and the incidence of surgical reintervention within 90 days.

BRAINterns 2.0: Durability of Webinar-Based Education and Social Media Beyond the Coronavirus Disease 2019 Pandemic.

BACKGROUND: Webinars offer novel educational opportunities beyond those of traditional, in-person experiences. BRAINterns is an open-access webinar-based education platform created to replace opportunities lost during the coronavirus disease 2019 pandemic. This program previously showed the efficacy of webinars to expand access to careers in medicine, and in particular, neurosurgery. BRAINterns 2.0 was established to assess the durability of Web-based learning. METHODS: A modified 4-week webinar series was held during July 2021. A retrospective exit survey was distributed to participants and responses analyzed. RESULTS: A total of 16,045 people registered for BRAINterns 2.0, representing 103 countries. Survey responses were received from 3765 participants (23% response rate). New, first-time registrants comprised 66% of participants, with the rest being returning participants. A total of 342 students participated in a dedicated module delivered entirely in Spanish. Females represented 81% of respondents. Participants identified that desirable elements of the program were opportunities to hear from women (53%) and people of color (44%) in health care. Participants heard about the series through TikTok (n = 1251; 33%), Instagram (n = 1109; 29%), Facebook (n = 637; 17%), and word of mouth (n = 708; 19%) with assistance from an ambassador program. CONCLUSIONS: Webinar-based education programs continue to be of interest to students in an increasingly digital world. Social media, and specifically the use of educational ambassadors, are effective to improve visibility of educational programs across a diverse population of students. Understanding the desires of participants is critical to building a successful online education platform.

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: A Multi-Center Experience of 154 Consecutive Embolizations.

BACKGROUND: Middle meningeal artery (MMA) embolization has emerged as a promising treatment for chronic subdural hematoma (cSDH). OBJECTIVE: To determine the safety and efficacy of MMA embolization. METHODS: Consecutive patients who underwent MMA embolization for cSDH (primary treatment or recurrence after conventional surgery) at 15 centers were included. Clinical details and follow-up were collected prospectively. Primary clinical and radiographic outcomes were the proportion of patients requiring additional surgical treatment within 90 d after index treatment and proportion with > 50% cSDH thickness reduction on follow-up computed tomography imaging within 90 d. National Institute of Health Stroke Scale and modified Rankin Scale were also clinical outcomes. RESULTS: A total of 138 patients were included (mean age: 69.8, 29% female). A total of 15 patients underwent bilateral interventions for 154 total embolizations (66.7% primary treatment). At presentation, 30.4% and 23.9% of patients were on antiplatelet and anticoagulation therapy, respectively. Median admission cSDH thickness was 14 mm. A total of 46.1% of embolizations were performed under general anesthesia, and 97.4% of procedures were successfully completed. A total of 70.2% of embolizations used particles, and 25.3% used liquid embolics with no significant outcome difference between embolization materials (P > .05). On last follow-up (mean 94.9 d), median cSDH thickness was 4 mm (71% median thickness reduction). A total of 70.8% of patients had >50% improvement on imaging (31.9% improved clinically), and 9 patients (6.5%) required further cSDH treatment. There were 16 complications with 9 (6.5%) because of continued hematoma expansion. Mortality rate was 4.4%, mostly unrelated to the index procedure but because of underlying comorbidities. CONCLUSION: MMA embolization may provide a safe and efficacious minimally invasive alternative to conventional surgical techniques.

Fusiform superior cerebellar artery aneurysm treated with flow diversion: A case report.

BACKGROUND: Fusiform aneurysms of the distal superior cerebellar artery are rare and challenging to treat. Due to the rarity of these lesions, there is little consensus regarding their management. Treatment options have traditionally included parent artery sacrifice with either an endovascular approach or microsurgical clipping. Given the small diameter of the superior cerebellar artery, flow diversion has not been typically considered as a viable treatment option for these aneurysms. CASE DESCRIPTION: A 67-year-old female presented complaining of severe sudden onset headache. Noncontrast head CT demonstrated no intracranial hemorrhage. Head CT angiogram demonstrated a 4.2 mm fusiform aneurysm in the distal right superior cerebellar artery. The patient underwent treatment with the Pipeline embolization device which was deployed in the right superior cerebellar artery covering the aneurysm. Six-month posttreatment follow-up angiogram demonstrated resolution of the aneurysm with patency of the parent vessel. CONCLUSION: To the best of our knowledge, this is the first report of a distal superior cerebellar artery aneurysm treated with the Pipeline embolization device. The use of a Pipeline stent to create flow diversion should be considered in a case of a fusiform aneurysm of the right superior cerebellar artery. Treatment with flow diversion may allow for the treatment of the aneurysm while preserving patency of the parent vessel.

Middle meningeal artery embolization treatment of nonacute subdural hematomas in the elderly: a multiinstitutional experience of 151 cases.

OBJECTIVE: The incidence of already common chronic subdural hematomas (CSDHs) and other nonacute subdural hematomas (NASHs) in the elderly is expected to rise as the population ages over the coming decades. Surgical management is associated with recurrence and exposes elderly patients to perioperative and operative risks. Middle meningeal artery (MMA) embolization offers the potential for a minimally invasive, less morbid treatment in this age group. The clinical and radiographic outcomes after MMA embolization treatment for NASHs have not been adequately described in elderly patients. In this paper, the authors describe the clinical and radiographic outcomes after 151 cases of MMA embolization for NASHs among 121 elderly patients. METHODS: In a retrospective review of a prospectively maintained database across 15 US academic centers, the authors identified patients aged ≥ 65 years who underwent MMA embolization for the treatment of NASHs between November 2017 and February 2020. Patient demographics, comorbidities, clinical and radiographic factors, treatment factors, and clinical outcomes were abstracted. Subgroup analysis was performed comparing elderly (age 65-79 years) and advanced elderly (age > 80 years) patients. RESULTS: MMA embolization was successfully performed in 98% of NASHs (in 148 of 151 cases) in 121 patients. Seventy elderly patients underwent 87 embolization procedures, and 51 advanced elderly patients underwent 64 embolization procedures. Elderly and advanced elderly patients had similar rates of embolization for upfront (46% vs 61%), recurrent (39% vs 33%), and prophylactic (i.e., with concomitant surgical intervention; 15% vs 6%) NASH treatment. Transfemoral access was used in most patients, and the procedure time was approximately 1 hour in both groups. Particle embolization with supplemental coils was most common, used in 51% (44/87) and 44% (28/64) of attempts for the elderly and advanced elderly groups, respectively. NASH thickness decreased significantly from initial thickness to 6 weeks, with additional decrease in thickness observed in both groups at 90 days. At longest follow-up, the treated NASHs had stabilized or improved in 91% and 98% of the elderly and advanced elderly groups, respectively, with > 50% improvement seen in > 60% of patients for each group. Surgical rescue was necessary in 4.6% and 7.8% of cases, and the overall mortality was 8.6% and 3.9% for elderly and advanced elderly patients, respectively. CONCLUSIONS: MMA embolization can be used safely and effectively as an alternative or adjunctive minimally invasive treatment for NASHs in elderly and advanced elderly patients.

Method for Safely Excising a Large Head and Neck Arteriovenous Malformation in the Hybrid Operating Room.

Large head and neck arteriovenous malformations are notoriously difficult to manage given their location and propensity for extreme hemorrhage. We propose a unique approach utilizing a Hyperform balloon and percutaneous Surgiflo sclerotherapy to provide intraoperative hemostatic stability during the excision of a left-sided scalp arteriovenous malformation. In a hybrid operating room a microcatheter balloon was fed into the left external carotid artery for occlusion of the malformation's main blood supply, and subsequently followed with digital subtraction angiography guided sclerotherapy of selective vessels. A split thickness graft was used to reconstruct the site of excision. This method offered optimal hemostatic control with a blood loss less than 120 cc. Our approach may offer safety advantages over traditional modalities and allow resection of head and neck lesions previously thought to be inoperable.

Monitoring Treatment Effectiveness in Intracranial Arteriovenous Shunt Lesions: Emerging Role of Quantitative Magnetic Resonance Venography for Intracranial Arteriovenous Shunts.

BACKGROUND: Quantitative magnetic resonance angiography (qMRA) using noninvasive optimal vessel analysis (NOVA) is a novel noninvasive imaging technique that is being increasingly used to measure blood flow in extracranial and intracranial arteries. By providing important quantitative flow data, NOVA qMRA can facilitate the management of cerebrovascular disease. While the same technology can also be applied to measure flow in intracranial and extracranial veins, NOVA quantitative MRV (qMRV) is only rarely used in neurovascular practice. CASE DESCRIPTION: We report interesting qMRV data in 2 patients with symptomatic intracranial arteriovenous shunts: a 61-year-old man with a left transverse-sigmoid dural arteriovenous fistula and a 40-year-old woman with a left parietal arteriovenous malformation. In each patient, NOVA qMRV demonstrated significant reduction of intracranial venous outflow after therapeutic obliteration of the shunt lesion, heralding marked clinical improvement. CONCLUSIONS: To the best of our knowledge, this is the first report of successful clinical application of NOVA qMRV in adult patients with intracranial arteriovenous malformations or dural arteriovenous fistulas. We propose that NOVA qMRV is a promising technique for noninvasive measurement of intracranial and extracranial venous blood flow and for monitoring treatment effectiveness in patients with intracranial arteriovenous shunt lesions.

Moyamoya-Related Stroke Risk During Pregnancy: An Evidence-Based Reappraisal.

BACKGROUND: Moyamoya is a rare, yet classic etiology of stroke in young adults, affecting predominately women of childbearing age. The impact of pregnancy on the natural history of symptomatic moyamoya remains a matter of extensive debate, however. METHODS: In October 2017, a MEDLINE search was performed using 14 keywords. A total of 12 original articles reporting on cohorts of at least 5 patients were retrieved and reviewed. Individual study data were extracted, pooled, and analyzed. RESULTS: A total of 736 pregnancies in 483 patients were included in our analysis. The mean age at delivery was 31 years, and the mean age at diagnosis (before pregnancy) was 22.6 years. Clinical presentation was ischemic stroke in 50.8%, hemorrhagic stroke in 45.9%, headaches in 2.1%, and ischemic-hemorrhagic stroke in 1.2%. After excluding patients first diagnosed during or after pregnancy (n = 283) and those who had been revascularized before pregnancy (n = 183), a total of 270 pregnancies in 188 patients were analyzed. During 224.6 patient-years of follow-up, 22 moyamoya-related neurologic events occurred (annual event rate 9.8%), more than two-thirds of which were transient (12 transient ischemic attacks and 3 seizures). Seven strokes occurred (6 hemorrhagic and 1 ischemic), yielding an annual stroke risk of 3.1%. As a result, 1 patient died and 2 were permanently disabled (annual death/disability rate 1.3%). All remaining patients experienced favorable functional outcomes. CONCLUSIONS: The risk of moyamoya-related stroke during pregnancy, delivery, and the postpartum period appears to be similar to or lower than that suggested by published natural history studies in symptomatic patients. A neuroprotective effect of pregnancy in moyamoya patients cannot be excluded.

Intracranial Aneurysm: Diagnostic Monitoring, Current Interventional Practices, and Advances.

PURPOSE OF REVIEW: Cerebral aneurysms are commonly diagnosed incidentally with non-invasive neuro-imaging modalities (i.e., brain MRA and/or head CTA). The first decision to be made in the management of patients with unruptured cerebral aneurysms is to determine if the aneurysm should undergo treatment as any intervention carries a risk of morbidity and mortality. RECENT FINDINGS: The multiple risk factors that are associated with increased risk of aneurysm rupture should be evaluated (size, shape, and location of aneurysm; history of hypertension and cigarette smoking and family history of cerebral aneurysms). With the advent and rapid evolution of less traumatic neuro-endovascular surgery techniques in the past two decades, many more patients are undergoing treatment of cerebral aneurysms. The neuro-endovascular surgeon has multiple options for the treatment of aneurysms including coiling, with or without balloon/stent assistance, and flow diversion. A number of intrasaccular devices for the neuro-endovascular treatment of cerebral aneurysms are being evaluated. The percentage of patients with cerebral aneurysms treated with craniotomy and clip ligation is decreasing. This is controversial as it has direct impact in neurosurgical training and the aneurysms that are usually recommended for microsurgical clipping are the ones with challenging anatomy that cannot be treated safely with endovascular approaches. The best outcomes are achieved with management by experienced, high-volume practitioners at specialized cerebrovascular treatment centers that consist of individuals with dedicated training in neuro-endovascular surgery as well as individuals trained in open cerebrovascular neurosurgery.

Cerebral Hyperperfusion Syndrome by the Numbers: Transient Focal Neurological Deficit, Imaging-Proven Focal Hyperperfusion, and High Graft Flow Rate Following Superficial Temporal Artery-Middle Cerebral Artery bypass in a Patient With Symptomatic Carotid Occlusion-Case Report.

BACKGROUND AND IMPORTANCE: Cerebral hyperperfusion syndrome (CHS) is a well-known complication of superficial temporal artery (STA) to middle cerebral artery (MCA) bypass for ischemic cerebrovascular disease. While this argues against "low flow" in the bypass construct, flow rates in the graft have not been previously quantified in the setting of CHS. CLINICAL PRESENTATION: A 58-yr-old man presented with recurrent left hemispheric ischemic strokes and fluctuating right hemiparesis and aphasia. Vascular imaging revealed left cervical internal carotid artery occlusion and perfusion imaging confirmed left hemispheric hypoperfusion. After failing to respond to maximal medical therapy, the patient underwent single-barrel STA-MCA bypass. Postoperatively, his symptoms resolved and blood pressure (BP) was strictly controlled within normal range. However, 2 d later, he developed severe expressive aphasia. CTA demonstrated a patent bypass graft and SPECT showed focal hyperperfusion in Broca's speech area. Seizure activity was ruled out. A high graft flow rate of 52 mL/min was documented by quantitative magnetic resonance angiography (MRA). Thus, the diagnosis of CHS was made and managed with strict BP control. The patient exhibited complete recovery of speech over a period of days and was discharged home. Repeat SPECT at 4 mo showed resolution of hyperperfusion and quantitative MRA demonstrated reduction of graft flow rate to 34 mL/min. CONCLUSION: This is the first case of perfusion imaging-proven CHS after STA-MCA bypass, where high graft flow rates are objectively documented. Our observations constitute irrefutable evidence challenging the classic belief that the STA-MCA bypass is a low-flow construct.

Combined Surgery and Intraoperative Sclerotherapy for Vascular Malformations of the Head/Neck: The Hybrid Approach.

Vascular malformations (VMs) of the head and neck can lead to aesthetic problems as well as cranial nerve damage, airway compromise, and vision loss. Large VMs are typically managed surgically, with sclerotherapy or embolization performed in the perioperative period to decrease the risk of excessive blood loss and minimize the size of the VM. However, this initial treatment is frequently insufficient leading to excessive blood loss intraoperatively, poorer margin visualization for the surgeon, and decreased likelihood of complete resection. As a result, resections of large VMs are often performed in a multistage approach. This article introduces a new hybrid approach for the management of head and neck VMs entailing the use of an endovascular operating room where a neuroendovascular surgeon performs embolization or sclerotherapy intraoperatively as needed in conjunction with surgical excision. Three patients with large VMs in the facial region underwent successful use of the hybrid approach. The hybrid approach improved visualization, leading to complete resection in 1 patient and nearly complete resections (70% and 90%) in the other patients. The technique also helped minimize blood loss because only the youngest patient (23 months old) required a blood transfusion. Implications of these findings include the transition from a multistaged approach for large VMs to a single-stage approach. In addition, decreases in blood loss may allow for the development and use of minimal access techniques, leading to a decrease in visible scarring for patients. We suggest the consideration of the hybrid approach for large head and neck VMs.

Intracranial Bypass of Posterior Inferior Cerebellar Artery Aneurysms: Indications, Technical Aspects, and Clinical Outcomes.

BACKGROUND: For some posterior inferior cerebellar artery (PICA) aneurysms, there is no constructive endovascular or direct surgical clipping option. Intracranial bypass is an alternative to a deconstructive technique. OBJECTIVE: To evaluate the clinical features, surgical techniques, and outcome of PICA aneurysms treated with bypass and obliteration of the diseased segment. METHODS: Retrospective review of PICA aneurysms treated via intracranial bypass was performed. Outcome measurements included postoperative stroke, cranial nerve deficits, gastrostomy/tracheostomy requirement, bypass patency, modified Rankin scale (mRS) at discharge, and mRS at 6 mo. RESULTS: Seven patients with PICA aneurysms treated with intracranial bypass were identified. Five had fusiform aneurysms (4 ruptured, 1 unruptured), 1 had a giant partially thrombosed saccular aneurysm (unruptured), and 1 had a dissecting traumatic aneurysm (ruptured). Two aneurysms were at the anteromedullary segment, 4 at the lateral medullary segment, and 1 at the tonsillomedullary segment. Three patients underwent PICA-to-PICA side to side anastomoses, 2 PICA-to-PICA reanastomosis, 1 vertebral artery-to-PICA bypass, and 1 occipital artery-PICA bypass. Six out of 7 aneurysms were obliterated surgically and 1 with additional endovascular occlusion after the bypass. All bypasses were patent intraoperatively; 2 were later demonstrated occluded without radiological signs or symptoms of stroke. No patients had new cranial nerve deficit postoperatively. With the exception of 1 death due to pulmonary emboli 3 mo postoperatively, all others remain at a mRS ≤ 2. CONCLUSION: Constructive bypass and aneurysm obliteration remains a viable alternative for treatment of PICA aneurysms not amenable to direct surgical clipping or to a vessel-preserving endovascular option.

Sphingosine-1-Phosphate Receptor-3 Supports Hematopoietic Stem and Progenitor Cell Residence Within the Bone Marrow Niche.

Hematopoietic stem and progenitor cells (HSPCs) egress from bone marrow (BM) during homeostasis and at increased rates during stress; however, the mechanisms regulating their trafficking remain incompletely understood. Here we describe a novel role for lipid receptor, sphingosine-1-phosphate receptor 3 (S1PR3), in HSPC residence within the BM niche. HSPCs expressed increased levels of S1PR3 compared to differentiated BM cells. Pharmacological antagonism or knockout (KO) of S1PR3 mobilized HSPCs into blood circulation, suggesting that S1PR3 influences niche localization. S1PR3 antagonism suppressed BM and plasma SDF-1, enabling HSPCs to migrate toward S1P-rich plasma. Mobilization synergized with AMD3100-mediated antagonism of CXCR4, which tethers HSPCs in the niche, and recovered homing deficits of AMD3100-treated grafts. S1PR3 antagonism combined with AMD3100 improved re-engraftment and survival in lethally irradiated recipients. Our studies indicate that S1PR3 and CXCR4 signaling cooperate to maintain HSPCs within the niche under homeostasis. These results highlight an important role for S1PR3 in HSPC niche occupancy and trafficking that can be harnessed for both rapid clinical stem cell mobilization and re-engraftment strategies, as well as the opportunity to design novel therapeutics for control of recruitment, homing, and localization through bioactive lipid signaling. Stem Cells 2017;35:1040-1052.

Forearm Cephalic Vein Graft for Short, "Middle"-Flow, Internal Maxillary Artery to Middle Cerebral Artery Bypass.

BACKGROUND: The cervical carotid system has been used as a source of donor vessels for radial artery or saphenous vein grafts in cerebral bypass. Recently, internal maxillary artery to middle cerebral artery bypass has been described as an alternative, with reduction of graft length potentially correlating with improved patency. OBJECTIVE: To describe our experience using the forearm cephalic vein grafts for short segment internal maxillary artery to middle cerebral artery bypasses. METHODS: All vein grafts were harvested from the volar forearm between the proximal cubital fossa where the median cubital vein is confluent with the cephalic vein and the distal wrist. RESULTS: Six patients were treated with internal maxillary artery to middle cerebral artery bypass. In 4, the cephalic vein was used. Postoperative angiography demonstrated good filling of the grafts with robust distal flow. There were no upper extremity vascular complications. All but 1 patient (mortality) tolerated the procedure well. The other 3 patients returned to their neurological baseline with no new neurological deficit during follow-up. CONCLUSION: The internal maxillary artery to middle cerebral artery "middle" flow bypass allows for shorter graft length with both the proximal and distal anastomoses within the same microsurgical field. These unique variable flow grafts represent an ideal opportunity for use of the cephalic vein of the forearm, which is more easily harvested than the wider saphenous vein graft and which has good match size to the M1/M2 segments of the middle cerebral artery. The vessel wall is supple, which facilitates handling during anastomosis. There is lower morbidity potential than utilization of the radial artery. Going forward, the cephalic vein will be our preferred choice for external carotid-internal carotid transplanted conduit bypass.

Internal maxillary artery-middle cerebral artery bypass: infratemporal approach for subcranial-intracranial (SC-IC) bypass.

BACKGROUND: Internal maxillary artery (IMax)-middle cerebral artery (MCA) bypass has been recently described as an alternative to cervical extracranial-intracranial bypass. This technique uses a "keyhole" craniectomy in the temporal fossa that requires a technically challenging end-to-side anastomosis. OBJECTIVE: To describe a lateral subtemporal craniectomy of the middle cranial fossa floor to facilitate wide exposure of the IMax to facilitate bypass. METHODS: Orbitozygomatic osteotomy is used followed by frontotemporal craniotomy and subsequently laterotemporal fossa craniectomy, reaching its medial border at a virtual line connecting the foramen rotundum and foramen ovale. The IMax was identified by using established anatomic landmarks, neuronavigation, and micro Doppler probe (Mizuho Inc. Tokyo, Japan). Additionally, we studied the approach in a cadaveric specimen in preparation for microsurgical bypass. RESULTS: There were 4 cases in which the technique was used. One bypass was performed for flow augmentation in a hypoperfused hemisphere. The other 3 were performed as part of treatment paradigms for giant middle cerebral artery aneurysms. Vein grafts were used in all patients. The proximal anastomosis was performed in an end-to-side fashion in 1 patient and end-to-end in 3 patients. Intraoperative graft flow measured with the Transonic flow probe ranged from 20 to 60 mL/min. Postoperative angiography demonstrated good filling of the graft with robust distal flow in all cases. All patients tolerated the procedure well. CONCLUSION: IMax to middle cerebral artery subcranial-intracranial bypass is safe and efficacious. The laterotemporal fossa craniectomy technique resulted in reliable identification and wide exposure of the IMax, facilitating the proximal anastomosis.

Nano-engineering of 5-fluorouracil-loaded magnetoliposomes for combined hyperthermia and chemotherapy against colon cancer.

The present investigation aimed to develop magnetoliposome nanoparticles loaded with 5-fluorouracil by following a reproducible thin film hydration technique. The physicochemical characterization (including electron microscopy analysis, dynamic light scattering, infrared spectrometry, X-ray diffractometry, electrophoresis, and surface thermodynamics) suggested that superparamagnetic magnetite nuclei were successfully embedded into a multilamellar lipid vesicle. Magnetic responsiveness of these nanocomposites was quantitatively analyzed by determining the hysteresis cycle and qualitatively confirmed by microscopic visualizations. A high frequency alternating electromagnetic field was further used to define their heating properties. The absence of cytotoxicity in human colon fibroblast CCD-18 and in human colon carcinoma T-84 cell lines and excellent hemocompatibility of these core/shell particles were demonstrated. Additionally, 5-fluorouracil incorporation was investigated by two procedures: (i) entrapment into the nanoparticulate matrix and (ii) surface deposition onto already formed magnetoliposome particles. The former method reported greater drug loading values and a sustained release profile. Interestingly, 5-fluorouracil release was also triggered by the heating properties of the nanoparticles (hyperthermia-triggered drug release). Hence, we put forward that magnetoliposome particles hold important properties, that is, magnetically targeted delivery, hyperthermia inducing capability, high 5-fluorouracil loading capability, and hyperthermia-triggered burst drug release, suggestive of their potential for a combined antitumor therapy against colon cancer.

Synthesis of a biodegradable magnetic nanomedicine based on the antitumor molecule tegafur.

The introduction of magnetic nanocarriers in chemotherapy aims to enhance the anticancer activity of antitumor molecules whereas keeping their toxicity to a very minimum. Magnetite/poly(hexylcyanoacrylate) (core/shell) nanoplatforms were synthesized by an emulsion/polymerization procedure. An exhaustive physicochemical characterization (including infrared spectrometry, electrophoresis, and thermodynamic analysis) suggested that the magnetite nuclei were embedded into a polymeric nanomatrix. The very good magnetic responsiveness of such core/shell nanoparticles was defined by the hysteresis cycle. To improve the intravenous delivery of tegafur to cancer, we investigated its incorporation into the nanoplatform. Compared to surface adsorption, drug entrapment into the polymeric shell yielded higher tegafur loading values, and a much slower release profile. A high frequency alternating magnetic gradient was used to elucidate the heating characteristics of the nanoparticles: a stable maximum temperature of 46 °C was successfully achieved within 32 min. Thus, we put forward that such kind of multifunctional nanomedicine hold very important characteristics (i.e., high drug loading, little burst release, hyperthermia, and magnetically targeted tegafur delivery), suggestive of its potential for combined antitumor therapy against cancer.