Retreatment of Residual and Recurrent Aneurysms After Embolization With the Woven EndoBridge Device: Multicenter Case Series.

BACKGROUND: The Woven EndoBridge (WEB) device (Terumno Corp. [parent company of Microvention]) was approved by the U.S. Food and Drug Administration as the first intrasaccular device for intracranial aneurysm treatment in December 2018. Its use has become more common since then, but both trial results and postmarket experiences have raised questions about the efficacy in achieving complete aneurysm obliteration. Retreatment after WEB embolization has not been extensively discussed. OBJECTIVE: To discuss the incidence and retreatment of aneurysms after initial WEB embolization. METHODS: Retrospective review across 13 institutions identified all occurrences of WEB retreatment within neurovascular databases. Details regarding demographics, aneurysm characteristics, treatment considerations, clinical outcomes, and aneurysm occlusion were obtained and analyzed. RESULTS: Thirty aneurysms were retreated in 30 patients in a cohort of 342 WEB-treated aneurysms. The retreatment rate was 8.8%. Endovascular methods were used for 23 cases, and 7 were treated surgically. Two aneurysms presented with rehemorrhage after initial WEB embolization. Endovascular treatments included stent-assisted coiling (12), flow diversion (7), coiling (2), PulseRider (Johnson & Johnson)-assisted coiling (1), and additional WEB placement (1). Surgical treatments included primary clipping (6) and Hunterian ligation (1). There were no major complications within the study group. CONCLUSION: WEB retreatments were successfully performed by a variety of techniques, including stent-assisted coiling, clipping, and flow diversion as the most common. These procedures were performed safely with subsequent obliteration of most aneurysms. The potential need for retreatment of aneurysms should be considered during primary WEB treatments.

Novel use of robotics and navigation for anterior lumbar total disc replacement surgery.

The ability to navigate the anterior lumbar disc space may improve clinical outcomes and implant longevity. However, no robotic navigation systems are presently authorized by the U.S. Food and Drug Administration to assist with anterior retroperitoneal lumbar interbody surgery. Furthermore, no studies to date have investigated such an application of this technology. This study examines the application of robotic navigation to anterior lumbar total disc replacement surgery to improve retroperitoneal exposure and orientation of the anterior lumbar spine, enhance coronal plane centralization of the implant, optimize surgical trajectory, and mitigate radiologic exposure. Postoperative outcomes of a small cohort of patients undergoing anterior lumbar total disc replacement surgery using robotic navigation were analyzed. The results of the study revealed that a modified use of the aforementioned robot-assisted surgical technology enhances coronal plane centralization and trajectory, all while mitigating radiologic exposure, resulting in more accurate placement of the implant within the intervertebral space at each level.

Endovascular Stenting of Tandem Carotid Artery Origin and Bifurcation Stenotic Lesions Using Flow Reversal.

BACKGROUND: The treatment of tandem lesions involving severe stenosis of the internal carotid artery with concomitant stenosis of the ipsilateral common carotid artery (CCA) origin represents an ongoing challenge. Current options for the treatment of tandem carotid artery origin and bifurcation stenotic lesions include open surgical endarterectomy, endovascular stenting, balloon angioplasty, and hybrid procedures combining both modalities. However, these options are either associated with high peri-operative risks or not always anatomically feasible. CASE DESCRIPTION: We report, for the first time in North America (to the best of our knowledge), an alternative treatment modality that involves obtaining access through a direct carotid cut-down, with serial treatment of the tandem lesions through a combination of retrograde and anterograde endovascular stenting. CONCLUSION: This technique obviates the need for navigating the aortic arch in patients with difficult arch anatomy and permits the use of distal embolic protection devices, thus decreasing the risk of peri-operative ischemic events.

Treatment of iatrogenic V2 segment vertebral artery pseudoaneurysm using Pipeline flow-diverting stent.

BACKGROUND: Iatrogenic injury to the vertebral artery is a rare but potential complication of cervical spine surgery. Previous authors have commented on the use of flow-diverting stents for treatment of aneurysms of the V3 segment of the vertebral artery. CASE DESCRIPTION: Here, we report a case in which injury occurred at the V2 segment of the vertebral artery with the development of a pseudoaneurysm, which was found on angiography. After decompressing the spinal cord from an epidural hematoma, the pseudoaneurysm was treated by deploying two Pipeline flow-diverting stents (Medtronic, Minneapolis, MN). Obliteration of the pseudoaneurysm was noted on follow-up angiography 4 days after the treatment. CONCLUSION: This case highlights a unique treatment at a region which, to our knowledge, has not been mentioned in the literature.

Is bridging with intravenous thrombolysis of any benefit in endovascular therapy for acute ischemic stroke?

OBJECTIVE: Large vessel occlusions with heavy clot burden are less likely to improve with intravenous (IV) thrombolysis alone. The purpose of this study was to show whether a combination of IV thrombolysis and endovascular therapy was superior to endovascular treatment alone. METHODS: Data for 104 patients with acute large artery occlusion treated between 2005 and 2010 were reviewed. Forty-two received endovascular therapy in combination with IV thrombolysis (bridging group), and 62 received endovascular therapy only. Clinical outcome, mortality rate, and symptomatic intracranial hemorrhage (sICH) rate were compared between the two groups. RESULTS: The two groups had similar demographic and vascular risk factor distribution, as well as National Institutes of Health Stroke Scale score on admission (mean±SD: 14.8±4.7 and 16.0±5.3; P=0.23). No difference was found in Thrombolysis in Myocardial Infarction recanalization rates (score of 2 or 3) after combined or endovascular therapy alone (83.33% and 79.03%; P=0.585). Favorable outcome, defined as a modified Rankin Scale score of <2 at 90 days, also did not differ between the bridging group and the endovascular-only group (37.5% and 32.76%; P=0.643). There was no difference in mortality rate (19.04% and 29.03%; P=0.5618) and sICH rate (11.9% and 9.68%; P=0.734). A significant difference was found in mean time from symptom onset to treatment in the bridging group and the endovascular-only group (227±88 min vs. 125±40 min; P<0.0001). CONCLUSION: Combining IV thrombolysis with endovascular therapy resulted in similar outcome, revascularization, sICH, and mortality rates compared with endovascular therapy alone. Prospective clinical studies comparing both treatment strategies in acute ischemic stroke are warranted.

A proposed grading system for standardizing tumor consistency of intracranial meningiomas.

OBJECT: Tumor consistency plays an important and underrecognized role in the surgeon's ability to resect meningiomas, especially with evolving trends toward minimally invasive and keyhole surgical approaches. Aside from descriptors such as "hard" or "soft," no objective criteria exist for grading, studying, and conveying the consistency of meningiomas. METHODS: The authors designed a practical 5-point scale for intraoperative grading of meningiomas based on the surgeon's ability to internally debulk the tumor and on the subsequent resistance to folding of the tumor capsule. Tumor consistency grades and features are as follows: 1) extremely soft tumor, internal debulking with suction only; 2) soft tumor, internal debulking mostly with suction, and remaining fibrous strands resected with easily folded capsule; 3) average consistency, tumor cannot be freely suctioned and requires mechanical debulking, and the capsule then folds with relative ease; 4) firm tumor, high degree of mechanical debulking required, and capsule remains difficult to fold; and 5) extremely firm, calcified tumor, approaches density of bone, and capsule does not fold. Additional grading categories included tumor heterogeneity (with minimum and maximum consistency scores) and a 3-point vascularity score. This grading system was prospectively assessed in 50 consecutive patients undergoing craniotomy for meningioma resection by 2 surgeons in an independent fashion. Grading scores were subjected to a linear weighted kappa analysis for interuser reliability. RESULTS: Fifty patients (100 scores) were included in the analysis. The mean maximal tumor diameter was 4.3 cm. The distribution of overall tumor consistency scores was as follows: Grade 1, 4%; Grade 2, 9%; Grade 3, 43%; Grade 4, 44%; and Grade 5, 0%. Regions of Grade 5 consistency were reported only focally in 14% of heterogeneous tumors. Tumors were designated as homogeneous in 68% and heterogeneous in 32% of grades. The kappa analysis score for overall tumor consistency grade was 0.87 (SE 0.06, 95% CI 0.76-0.99), with 90% user agreement. Kappa analysis scores for minimum and maximum grades of tumor regions were 0.69 (agreement 72%) and 0.75 (agreement 78%), respectively. The kappa analysis score for tumor vascularity grading was 0.56 (agreement 76%). Overall consistency did not correlate with patient age, tumor location, or tumor size. A higher tumor vascularity grade was associated with a larger tumor diameter (p = 0.045) and with skull base location (p = 0.02). CONCLUSIONS: The proposed grading system provides a reliable, practical, and objective assessment of meningioma consistency and facilitates communication among providers. This system also accounts for heterogeneity in tumor consistency. With the proposed scale, meningioma consistency can be standardized as groundwork for future studies relating to surgical outcomes, predictability of consistency and vascularity using neuroimaging techniques, and effectiveness of various surgical instruments.

Feasibility, safety, and periprocedural complications associated with endovascular treatment of selected ruptured aneurysms under conscious sedation and local anesthesia.

BACKGROUND: Endovascular coil embolization of ruptured aneurysms is performed under general anesthesia at most centers for perceived improved image quality and patient safety. OBJECTIVE: To report the feasibility of and outcomes associated with endovascular treatment of subarachnoid hemorrhage (SAH) patients with ruptured cerebral aneurysms performed under conscious sedation with local anesthetics. METHODS: Between January 2005 and December 2009, 187 patients with aneurysmal SAH were treated with coil embolization at the authors' hospital. For each patient, procedural details, mode of anesthesia, and clinical and radiographic outcomes were reviewed retrospectively (retrospective case series). RESULTS: A total of 197 coil embolizations were performed: 112 under general anesthesia, 78 under conscious sedation with local anesthetics, and 7 converted from conscious sedation to general anesthesia. None of the patients who presented with Hunt & Hess grade IV or V were treated under conscious sedation. For patients who presented with Hunt & Hess grades I, II, and III, 79.2%, 66.7%, and 32.6% of patients, respectively, underwent successful completion of treatment under conscious sedation. The symptomatic procedural complication rate was 2.5% overall and 2.4% for the conscious sedation group alone. Among the 14 interventions with intraprocedural perforation, 11 were performed under general anesthesia and 3 were performed under conscious sedation. CONCLUSION: In the authors' experience, conscious sedation with local anesthetics for endovascular treatment of ruptured intracranial aneurysms is feasible and safe in most patients with low-grade SAH. It may allow direct evaluation of the patient's neurological status, potentially leading to earlier detection and response to intraprocedural complications.

Endovascular coil embolization of a very small ruptured aneurysm using a novel microangiographic technique: technical note.

Endovascular treatment of very small aneurysms is technically difficult, although recent advances with coils, microcatheters and adjunctive techniques such as balloon- or stent-assisted coiling have improved the outcomes. The microangiographic fluoroscope (MAF) is a new high-resolution x-ray detector developed for neurointerventional procedures in which superior resolution is required within a small field of view. We report the successful coil embolization of a very small ruptured anterior communicating artery aneurysm using the MAF technique. The use of the MAF facilitated the precision of the coiling procedure and was helpful in preventing catheter- and coil-related intraprocedural complications.

Extent of resection and early postoperative outcomes following removal of cystic vestibular schwannomas: surgical experience over a decade and review of the literature.

OBJECT: Vestibular schwannomas (VSs) are benign tumors of the eighth cranial nerve sheath, representing approximately 6%-8% of all newly diagnosed brain tumors, with an annual incidence of 2000-2500 cases in the US. Although most of these lesions are solid, cystic vestibular schwannomas (CVSs) compose 4%-20% of all VSs and are commonly larger at the time of presentation. The authors present their experience with the operative management of CVSs, including surgical approach, extent of resection, and postoperative facial nerve outcomes. The literature pertaining to clinical and histopathological differences between CVSs and their solid counterparts is reviewed. METHODS: The University of Southern California Department of Neurosurgery database was retrospectively reviewed to identify patients who had undergone resection of a VS between 2000 and 2010. One hundred seventy-nine patients with VS were identified. Patients with CVSs were the subject of the present analysis. Diagnosis of a CVS was made based on MRI findings. Clinical and neuroimaging data, including pre- and postoperative assessments and operative notes, were collected and reviewed. RESULTS: Twenty-three patients, 14 men (61%) and 9 women (39%), underwent 24 operations for CVSs. These patients composed 12.8% of all cases of VS. Patient ages ranged from 28 to 78 years (mean 55 years), and the mean maximal tumor diameter was 3.6 cm (range 2.0-4.0 cm). Patients most frequently presented with headache, hearing loss, vertigo, and dizziness. Preoperative facial numbness was reported in 44% of patients. Among the 24 cases, 13 were treated with retrosigmoid craniotomy and 11 via a translabyrinthine approach. Complete resection was achieved in 11 patients (48%), subtotal resection (STR) in 8 patients (35%), and near-total resection (NTR) in 4 patients (17%). Facial nerve outcomes were available in all except one case. Good facial nerve outcomes (House-Brackmann [HB] Grades I-III) were achieved in 82% of the patients who had undergone either NTR or STR, as compared with 73% of patients who had undergone gross-total resection (GTR; p > 0.05, Fisher exact test). In comparison, 83% of patients with solid VSs had a good HB grade (p = 0.38, Fisher exact test), although this finding did not reach statistical significance. Complications included wound infection (2 patients), delayed CSF leakage (1 patient), and a delayed temporal encephalocele following a translabyrinthine approach and requiring surgical repair (1 patient). CONCLUSIONS: Cystic vestibular schwannoma represents a clinical and surgical entity separate from its solid counterpart, as demonstrated by its more rapid clinical course and early surgical outcomes. Facial nerve grades may correlate with the degree of tumor resection, trending toward poorer grades with more significant resections. Although GTR is recommended whenever possible, performing an STR when facial nerve preservation is in jeopardy to improve facial nerve outcomes is the preferred strategy at the authors' institution.

Treatment and outcomes of acute intracranial vertebrobasilar artery occlusion: one institution's experience.

OBJECT: The treatment of acute intracranial vertebrobasilar artery occlusion (VBO) has been described but often with poor results. The authors of this study set out to evaluate their institution's outcomes following multimodal treatment of VBO. METHODS: They retrospectively reviewed their endovascular database for all patients treated for acute intracranial VBO between December 2004 and June 2010. Twenty-four patients were identified. Two patients were excluded from evaluation-one because of incomplete medical records and one because the etiology was basilar stenosis and not stroke. Occlusion location, hypercoagulable causes, time to endovascular treatment, time to revascularization, comorbidities, devices used, procedural anticoagulation, and outcomes were analyzed. RESULTS: Among the 22 eligible study patients, the mean National Institutes of Health Stroke Scale (NIHSS) score at presentation was 15.3. The mean time from presentation to initiation of the endovascular procedure was 4.77 hours. The mean time for recanalization from the start of angiography was 1.63 hours. In 16 patients (73%), revascularization was successful (Thrombolysis in Myocardial Infarction [TIMI] score of 2 or 3). Thirteen (59%) of the 22 patients were discharged to home or a rehabilitation facility. One patient was transferred to a chronic care facility. The overall survival rate was 64%. The average NIHSS score for the 14 surviving patients at discharge was 3.9. At the follow-up (average 14.5 months, range 1-58 months), 10 patients (71%) had achieved good outcomes (modified Rankin Scale [mRS] score ≤ 2) and 4 (29%) had poor outcomes (mRS Score 3-6). CONCLUSIONS: Published case series have historically shown poor outcomes and high mortality rates in association with the treatment of acute VBO, prompting surgeons to be less aggressive in the treatment of this disease than they might be otherwise. Data in this series show that the revascularization of posterior circulation occlusions is feasible and that good outcomes and lower mortality rates with newer endovascular technologies are possible, and thus more prompt and aggressive treatment of this disease may be warranted.

Perioperative safety of Hydrosoft coils.

OBJECTIVE: Hydrosoft coils were developed to serve as finishing coils to prevent aneurysmal recurrence at the neck. Initial animal studies were encouraging since some studies showed endothelial healing across the neck without recurrence over time. However, theoretical concerns exist regarding the potential threat to parent vessels as the Hydrosoft coils at the neck expand, as well as whether such coils can be adequately supple to safely serve as a true finishing coil. A retrospective review of the initial clinical experience utilizing Hydrosoft coils from three high-volume centers was performed. METHODS: Each center was asked to report angiographic (aneurysmal location, aneurysmal maximal size, neck size, incidence of intraprocedural parent vessel thrombosis, coil herniation, aneurysmal rupture as well as Raymond scale and percent occlusion after coiling) and clinical (rupture status, Hunt and Hess grade, incidence of stroke, hemorrhage, vasospasm and hydrocephalus) data on consecutive patients who underwent placement of Hydrosoft coils. RESULTS: A total of 141 patients were enrolled. Embolization achieved a Raymond scale score of I (complete obliteration) in 79 aneurysms (56%), II (residual neck) in 40 aneurysms (28%) and III (residual dome) in 21 aneurysms (15%); in one case the Hydrosoft coil could not be placed. Procedural morbidity and mortality were 2.1% and 1.4%, respectively. No complications were definitively attributed to the use of Hydrosoft coils. There were three cases (2.1%) of parent vessel thrombosis, two of which resolved after intraprocedural administration of thrombolytic agents and did not lead to neurological sequelae. The incidences of intraprocedural or periprocedural aneurysmal rupture (2.1%), cerebral hemorrhage (3.5%), stroke (4.9%), vasospasm (26.2%) or hydrocephalus (31.1%) were comparable to contemporary literature. CONCLUSION: The use of Hydrosoft coils appears to be safe and does not lead to higher complication rates than are currently accepted in the literature. Further prospective studies are required to determine whether the use of Hydrosoft coils results in a lower incidence of aneurysmal recurrence.

Posterior inferior cerebellar artery to posterior inferior cerebellar artery in situ bypass for the treatment of Bow hunter's-type dynamic ischemia in holovertebral dissection.

BACKGROUND: Bow hunter's syndrome is a rare cause of vertebrobasilar insufficiency arising from mechanical compression of the vertebral artery (VA) during rotation of the head. Surgical treatment usually involves direct decompression of the VA at the site of compression. We describe what is to our knowledge the first reported case of a posterior inferior cerebellar artery (PICA)-to-PICA in situ bypass for treatment of Bow hunter's-type ischemia in a patient with a VA dissection. CASE DESCRIPTION: The patient was a 41-year-old man who developed disabling symptoms of vertebrobasilar insufficiency after trauma when he rotated his head to the right. Dynamic angiography demonstrated a chronic dissection and stasis of flow in the right VA when his head was rotated to the right, with no obvious site of focal compression. The right VA ended in the PICA and the left VA was of good caliber. A single-photon emission computed tomography study with acetazolamide challenge confirmed brainstem ischemia and poor cerebrovascular reserve. He ultimately underwent a PICA-to-PICA in situ bypass to revascularize his right PICA territory with complete symptom resolution. CONCLUSIONS: The PICA-to-PICA in situ bypass is a useful option in the treatment of Bow hunter's-type ischemia in the absence of focal structural compression of the VA or VA stenosis.

Horizontal deployment of an intracranial stent via an antegrade approach for coil embolization of a basilar apex aneurysm: technical note.

The treatment of basilar apex aneurysms has progressively become more minimalistic in nature. Although initial coil embolizations were geared towards those aneurysms with a favorable neck to dome ratio, wide necked aneurysms have also been increasingly treated by the endovascular route. Several techniques have been described in the stent assisted coiling of basilar apex aneurysms, including the Y stent formation, waffle cone technique and horizontal stenting. Thus far, horizontal stenting has required access from a retrograde approach-namely, the posterior communicating artery. The authors describe a novel antegrade technique, through the basilar artery, for the deployment of a Neuroform-EZ stent (Boston Scientific, Natick, Massachusetts, USA) in a horizontal configuration across the neck of a basilar apex aneurysm. This approach allowed for the complete coil embolization of a wide necked basilar apex aneurysm.

Cerebral arteriovenous malformations: issues of the interplay between stereotactic radiosurgery and endovascular surgical therapy.

Intracranial arteriovenous malformations (AVMs) are congenital lesions frequently diagnosed as a result of hemorrhage or other neurological symptoms. Prevention of such devastating neurological injury has promoted a variety of treatment strategies. The rich history of multimodal therapy in the treatment of AVMs includes microsurgery, endovascular embolization, and stereotactic radiosurgery (SRS). This article reviews the biology and natural history of AVMs, as well as their treatment with both SRS and endovascular neurosurgery. It considers various paradigms and goals of endovascular treatment, along with relevant issues such as the features of an AVM to be targeted. Issues of the interplay between SRS and endovascular neurosurgery include the compartments of an embolized AVM to contain within the radiosurgery plan, the radioprotective and radiosensitizing effects of the embolic agent, the durability of embolization, and the sequencing of embolization with respect to the radiosurgical treatment. Published literature on these topics is sparse, and the flimsiness of the data offers limited guidance.

Utility of CT perfusion scanning in patient selection for acute stroke intervention: experience at University at Buffalo Neurosurgery-Millard Fillmore Gates Circle Hospital.

Computed tomography perfusion scanning generates physiological flow parameters of the brain parenchyma, allowing differentiation of ischemic penumbra and core infarct. Perfusion maps, along with the National Institutes of Health Stroke Scale score, are used as the bases for endovascular stroke intervention at the authors' institute, regardless of the time interval from stroke onset. With case examples, the authors illustrate their perfusion-based imaging guidelines in patient selection for endovascular treatment in the setting of acute stroke.

Use of the microangiographic fluoroscope for coiling of intracranial aneurysms.

BACKGROUND: Neurointervention is an ever-evolving specialty with tools including microcatheters, microwires, and coils that allow treatment of pathological conditions in increasingly smaller intracranial arteries, requiring increasing accuracy. As endovascular tools evolve, so too should the imaging. OBJECTIVE: To detail the use of microangiography performed with a novel fluoroscope during coiling of intracranial aneurysms in 2 separate patients and discuss the benefits and potential limitations of the technology. METHODS: The microangiographic fluoroscope (MAF) is an ultra high-resolution x-ray detector with superior resolution over a small field of view. The MAF can be incorporated into a standard angiographic C-arm system for use during endovascular procedures. RESULTS: The MAF was useful for improved visualization during endovascular coiling of 2 unruptured intracranial aneurysms, without adding significant time to the procedure. No significant residual aneurysm filling was identified post-coiling, and no complications occurred. CONCLUSION: The MAF is a high-resolution detector developed for use in neurointerventional cases in which superior image quality over a small field of view is required. It has been used with success for coiling of 2 unruptured aneurysms at our institution. It shows promise as an important tool in improving the accuracy with which neurointerventionists can perform certain intracranial procedures.

Endovascular management of spinal dural arteriovenous fistulas. A review.

OBJECT: Spinal dural arteriovenous fistulas (DAVFs) are the most common spinal vascular malformations and can be a significant cause of myelopathy, yet remain inefficiently diagnosed lesions. Over the last several decades, the treatment of spinal DAVFs has improved tremendously due to improvements in neuroimaging, microsurgical, and endovascular techniques. The aim of this paper was to review the existing literature regarding the clinical characteristics, classification, and endovascular management of spinal DAVFs. METHODS: A search of the PubMed database from the National Library of Medicine and reference lists of all relevant articles was conducted to identify all studies pertaining to spinal DAVFs, spinal dural fistulas, and spinal vascular malformations, with particular attention to endovascular management and outcomes. RESULTS: The ability to definitively treat spinal DAVFs using endovascular embolization has significantly improved over the last several decades. Overall rates of definitive embolization of spinal DAVFs have ranged between 25 and 100%, depending in part on the embolic agent used and the use of variable stiffness microcatheters. The majority of recent studies in which N-butyl cyanoacrylate or other liquid embolic agents were used have reported success rates of 70-90%. Surgical treatment remains the definitive option in cases of failed embolization, repeated recanalization, or lesions not amenable to embolization. Clinical outcomes have been comparable to surgical treatment when the fistula and draining vein remain persistently occluded. Improvements in gait and motor function are more likely following successful treatment, whereas micturition symptoms are less likely to improve. CONCLUSIONS: Endovascular embolization is an increasingly effective therapy in the treatment of spinal DAVFs, and can be used as a definitive intervention in the majority of patients that undergo modern endovascular intervention. A multidisciplinary approach to the treatment of these lesions is required, as surgery is required for refractory cases or those not amenable to embolization. Newer embolic agents, such as Onyx, hold significant promise for future therapy, yet long-term follow-up studies are required.

HoxD10 gene delivery using adenovirus/adeno-associate hybrid virus inhibits the proliferation and tumorigenicity of GH4 pituitary lactotrope tumor cells.

Prolactinoma is one of the most common types of pituitary adenoma. It has been reported that a variety of growth factors and cytokines regulating cell growth and angiogenesis play an important role in the growth of prolactinoma. HoxD10 has been shown to impair endothelial cell migration, block angiogenesis, and maintain a differentiated phenotype of cells. We investigated whether HoxD10 gene delivery could inhibit the growth of prolactinoma. Rat GH4 lactotrope tumor cells were infected with adenovirus/adeno-associated virus (Ad/AAV) hybrid vectors carrying the mouse HoxD10 gene (Hyb-HoxD10) or the beta-galactosidase gene (Hyb-Gal). Hyb-HoxD10 expression inhibited GH4 cell proliferation in vitro. The expression of FGF-2 and cyclin D2 was inhibited in GH4 cells infected with Hyb-HoxD10. GH4 cells transduced with Hyb-HoxD10 did not form tumors in nude mice. These results indicate that the delivery of HoxD10 could potentially inhibit the growth of PRL-secreting tumors. This approach may be a useful tool for targeted therapy of prolactinoma and other neoplasms.