Lymphatic dysfunctions are associated with several human diseases, including lymphedema and metastatic spread of cancer. Although it is well recognized that lymphatic capillaries attach directly to interstitial matrix mainly composed of fibrillar type I collagen, the interactions occurring between lymphatics and their surrounding matrix have been overlooked. In this study, we demonstrate how matrix metalloproteinase (MMP)-2 drives lymphatic morphogenesis through Mmp2-gene ablation in mice, mmp2 knockdown in zebrafish and in 3D-culture systems, and through MMP2 inhibition. In all models used in vivo (3 murine models and thoracic duct development in zebrafish) and in vitro (lymphatic ring and spheroid assays), MMP2 blockage or down-regulation leads to reduced lymphangiogenesis or altered vessel branching. Our data show that lymphatic endothelial cell (LEC) migration through collagen fibers is affected by physical matrix constraints (matrix composition, density, and crosslinking). Transmission electron microscopy and confocal reflection microscopy using DQ-collagen highlight the contribution of MMP2 to mesenchymal-like migration of LECs associated with collagen fiber remodeling. Our findings provide new mechanistic insight into how LECs negotiate an interstitial type I collagen barrier and reveal an unexpected MMP2-driven collagenolytic pathway for lymphatic vessel formation and morphogenesis. (Blood. 2012;119(21):5048-5056) IntroductionLymphatic vessels are essential for body fluid balance and immunologic surveillance. Several pathologies manifest abnormal lymphatic vessel growth (lymphangiogenesis), either excessive (inflammatory diseases, tumor metastases, cornea-graft rejection) or defective (lymphedema). [1][2][3] Our understanding of the molecular mechanisms underlying lymphangiogenesis is still in its infancy. Although several key molecular determinants (vascular endothelial growth factor [VEGF]-C/D, VEGF receptor-3, angiopoietin, ephrins, integrins, etc) have been identified, 2,4-7 the importance of cell-matrix interactions during the lymphangiogenic process is not well documented.One of the features that discriminates lymphatic capillaries from blood capillaries is the kind of extracellular matrix (ECM) to which each vessel type is exposed in its natural environment. Blood vascular endothelium is in direct contact with basement membrane components (laminin, type IV collagen), 8 whereas the basal lamina is largely absent in lymphatic capillaries. Lymphatic endothelial cells (LECs) interact intimately with the adjacent interstitial matrix and attach to it through anchorage filaments. 9,10 Therefore, LECs sprouting from preexisting vessels and their migration through the ECM require that they be able to negotiate an interstitial collagen barrier mainly composed of fibrillar type I collagen. Recently, evidence has accumulated demonstrating that integrins, by promoting cell-matrix interaction, influence normal lymphatic function and lymphangiogenesis. 5,10,11 How LECs deal with fibrillar collagens to migrate an...

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Endoscopic spine surgery (ESS) advances the principles of minimally invasive surgery, including minor collateral tissue damage, reduced blood loss, and faster recovery times. ESS allows for direct access to the spine through small incisions and direct visualization of spinal pathology via an endoscope. While this technique has many applications, there is a steep learning curve when adopting ESS into a surgeon’s practice. Two types of navigation, optical and electromagnetic, may allow for widespread utilization of ESS by engendering improved orientation to surgical anatomy and reduced complication rates. The present review discusses these two available navigation technologies and their application in endoscopic procedures by providing case examples. Furthermore, we report on the future directions of navigation within the discipline of ESS.

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Failed back surgery syndrome (FBSS) refers to persistent, chronic pain following spinal surgery. Spinal cord stimulation with dorsal epidural leads can be used to treat back and leg pain in FBSS patients. This paper presents a detailed protocol for using spinal cord stimulation with surgical leads in FBSS patients. In our department, with the patient under general anesthesia, we place the lead in the epidural space by means of a small laminectomy at the 10 thoracic level. Placement of the lead is followed by a 1 month trial period with an externalized lead. If pain relief is greater than 50% at the end of this 1 month stimulation trial (required by Belgian reimbursement criteria), an internal pulse generator is then placed under the skin and connected to the lead in a second surgical procedure. We have demonstrated that using this technique in rigorously selected FBSS patients can significantly improve back pain, leg pain, patient activity, and quality of life for a sustained period of time.