Pediatric nonvertebral paraspinal arteriovenous fistulas along the segmental nerve: clinical, imaging, and therapeutic considerations.

OBJECT: The authors characterize the clinical presentation and imaging features of paraspinal nonvertebral arteriovenous fistulas (AVFs) along the segmental nerve and describe their endovascular treatment. METHODS: The authors undertook a retrospective review of medical records, imaging, and treatment of patients with endovascular problems spanning the period from 1985 to 2003. Five pediatric patients (2-3 years of age) received diagnoses of nonvertebral paraspinal AVFs along the segmental nerve. All patients presented with an incidentally discovered continuous murmur over the paraspinal or parasternal regions. All patients were neurologically intact; two patients had cardiomegaly. The AVF was found in the midthoracic level in four patients and at L-3 in one patient. All AVFs were high-flow single-hole fistulas at the neural foramen with venous drainage into paraspinal and epidural veins but without intradural reflux. All fistulas were endovascularly occluded in the same session as diagnostic angiography took place. The fistula was completely occluded, with detachable coils in one case and with N-butyl-cyanoacrylate (NBCA) in four cases. Before NBCA injection, the flow through the fistula was decreased either by placing coils distal to the fistula or by inflating a balloon proximally. No signs of recanalization appeared on short-term follow-up magnetic resonance imaging in all patients. All patients remained neurologically intact at the last available follow-up session (mean 6 years). CONCLUSIONS: Nonvertebral paraspinal AVFs along the segmental nerve are specific disease entities seen in children presenting with bruit and cardiomegaly. Endovascular embolization should be the treatment of choice for this rare disease.

Multiple cerebral aneurysms in a neonate: occlusion and rupture.

Aneurysmal subarachnoid hemorrhage in a neonate is exceedingly uncommon. The authors report the case of a neonate with a large anterior communicating artery aneurysm, accessory left middle cerebral artery aneurysm, and left internal carotid artery (ICA) fusiform aneurysm. The neonate suffered from occlusion of the left ICA and aneurysm rupture. The large aneurysm was treated with detachable coils and the patient made a significant recovery. Of the 15 case reports of cerebral aneurysms in neonates that have been published, none has contained a description of multiple aneurysms or a discussion of endovascular treatment.

Thrombus formation during intracranial aneurysm coil placement: treatment with intra-arterial abciximab.

BACKGROUND AND PURPOSE: The management of thrombus formation during coil placement in an intracranial aneurysm is important in minimizing periprocedural morbidity and mortality. We report on seven cases in which the primary treatment for thrombus formation during such coil placement was intra-arterial abciximab infusion. METHODS: Clinical and radiologic records of 100 consecutive patients who underwent coil placement in intracranial aneurysms at our institution during a 1-year period were reviewed. We identified seven cases (four ruptured aneurysms, three unruptured aneurysms) in which thrombus formation occurred during the procedure. RESULTS: Intra-arterial abciximab infusion, up to 5 mg, completely dissolved the thrombus in four of seven patients and almost completely dissolved it in two. In one patient with distal emboli, recanalization was not achieved. In two patients, an intravenous bolus of abciximab without 12-hour infusion was also given adjunctively. In one patient, leakage of contrast material occurred; this was related to the intra-arterial infusion. Clinically, no new neurologic deficits were directly related to the intra-arterial abciximab infusion. Six patients had good clinical outcome, and one patient died. CONCLUSION: Relatively low-dose, intra-arterial abciximab infusion can immediately dissolve an acute thrombus that forms during intracranial aneurysm coil placement. Although neither the optimal dose of intra-arterial abciximab nor the need to supplement the intra-arterial infusion with intravenous administration was established, we preliminarily found that low-dose intra-arterial abciximab infusion may be relatively effective and safe in this setting, even in patients with acute subarachnoid hemorrhage.

Tissue factor and fibrin in tumor angiogenesis.

The hypercoagulability exhibited by most cancer patients leads to serious complications such as venous thromboembolism and contributes to the pathogenesis of tumor growth and metastasis by promoting angiogenesis. The key player in this vicious cycle is tissue factor (TF), the initiator of blood coagulation. Although TF normally safeguards vascular integrity by inducing hemostasis upon injury, abnormal expression of TF in different tumors and related vascular endothelial cells contributes to unnecessary clot formation in cancer patients. Clotting-dependent induction of tumor angiogenesis is primarily mediated by TF-induced generation of thrombin and subsequent deposition of cross-linked fibrin. A cross-linked fibrin network provides a provisional proangiogenic matrix that facilitates blood vessel infiltration. Clotting-independent mechanisms of TF-induced tumor angiogenesis have also been described, mediated primarily by the cytoplasmic tail of the TF receptor. TF activation could contribute to the venous thromboembolism that has been reported as a complication of the use of novel antiangiogenic agents in combination with chemotherapy. Anticoagulants, such as low-molecular-weight heparin, may act to prevent these complications both by interfering with TF-mediated activation of clotting and by directly down-regulating angiogenesis. Thus, TF may prove to be a novel target for cancer therapy.

Tissue factor, thrombin, and cancer.

In addition to its primary role in hemostasis and blood coagulation, thrombin is a potent mitogen capable of inducing cellular functions. Therefore, it should come as no surprise that thrombin has proved to be of importance in the behavior of cancer. In this review, we focus on the ability of tissue factor (TF) and thrombin to influence tumor angiogenesis. Both exert their influence on angiogenesis through clotting-dependent and clotting-independent mechanisms: (1). directly affecting signaling pathways that mediate cell functions, and (2). mediating clot formation, thereby providing a growth media for tumor cells. Therefore, anticoagulant drugs may prove efficacious in cancer treatment due to their ability to reduce the characteristic hypercoagulability of cancer and alter the fundamental biology of cancer.

Pericytic-like angiotropism of glioma and melanoma cells.

We have identified in malignant melanoma an angiotumoral complex in which tumor cells occupy a pericytic location along the endothelium of microvessels without evidence of intravasation. We have suggested that this pericytic-like angiotropism could be a marker of an extravascular migration of tumor cells along the abluminal surface of vessels. The extravascular migratory metastasis proposed for melanoma has close analogies with glioma migration. To compare our hypothesis of extravascular migration by melanoma with the migration of glioma cells, we have used the B16 murine melanoma cell line and the GL26 murine glioma cell line in an in vivo murine brain tumor model and in vitro using endothelial cells that have formed capillary-like structures and have been cocultivated with tumor cells. In the brain tumors, a clear progression of glioma and melanoma cells was observed along the abluminal surface of vessels, where they occupied a pericytic location along the periendothelial laminin. In vitro, time-lapse videomicroscopy recorded the migration of tumor cells toward endothelial tubules. After 24 hours, both the melanoma cells and the glioma cells were localized along the external surfaces of the vascular tubules, occupying a pericytic-like location. These similarities between glioma and melanoma support the hypothesis of an extravascular migration of melanoma cells, particularly along the abluminal surface of vessels.

Tissue factor and angiogenesis in cancer.

Idiopathic thrombosis often precedes the diagnosis of occult cancer by several years. Whether hypercoagulability predisposes for malignancy or the converse holds true is an unresolved paradigm that stems from the known vicious cycle of clot formation and tumor growth. Central to this paradigm is the interplay between tissue factor (TF), the initiator of coagulation, and angiogenesis, the life support of tumors. Both clotting-dependent and -independent mechanisms of TF-induced angiogenesis have been elucidated that may signal through distinct pathways. This review focuses on the latest studies of TF and angiogenesis and highlights recent applications that have led to the development of promising new TF-targeted cancer therapeutics. Finally a cautionary note is given about unexpected complications arising from antiangiogenic therapy that may potentially involve TF.

Uteroglobin: a potential novel tumor suppressor and molecular therapeutic for prostate cancer.

Currently, there are very few diagnostic or therapeutic strategies targeted at controlling tumor growth and progression towards metastasis. Uteroglobin (UG) is a naturally occurring, small, stable, secretory protein that is normally expressed by most cells of epithelial origin but is known to be lost during the progression of prostate, lung, and uterine cancers to invasive malignancy. Uteroglobin -/- knockout mice appear to be extremely cancer prone. Both pharmacological and transgenic reconstitution of recombinant human UG (rhUG) to prostate, lung, and endometrial tumor cell lines markedly inhibits their invasiveness and antagonizes the neoplastic phenotype. In preliminary studies, rhUG inhibited angiogenesis in the ex vivo rat aorta model and showed antitumor activity against human prostate tumor cells (PC-3) in the chick chorioallantoic membrane assay, reducing both tumor volume and vascularity. A recent in vivo pilot study showed that twice daily dosing with rhUG resulted in a statistically significant increase in survival without evidence of toxicity in severe combined immunodeficient mice challenged with a PC-3 cell metastasizing tumor. Thus, rhUG may slow the progression of cancer by inhibiting both tumor cell invasiveness and tumor angiogenesis. It therefore holds the potential to serve as a new weapon in the arsenal of cytostatic, antimetastatic, adjuvant treatment for cancer. In this paper, we will briefly discuss the therapeutic potential of uteroglobin-based strategies for managing prostate cancer.

Recent advances in cancer research. Highlights of the 92nd annual meeting of the American Association for Cancer Research; held March 24-28, 2001, in New Orleans, LA, U.S.A.

The 92nd Annual Meeting of the American Association for Cancer Research (AACR) was held on March 24-28, 2001, in New Orleans, Louisiana, U.S.A., to discuss the latest advances in basic, translational and clinical cancer research. More than 12,000 scientists representing academia, industry and government attended this international meeting. Over 5,300 proffered papers were presented in a variety of formats. This meeting report highlights a lecture on the antileukemia drug STI-571 (imatinib) and minisymposia that covered the topics of tumor immunity, immunotherapy, pharmacogenetics and novel targets for drug discovery. (c) 2001 Prous Science. All rights reserved.