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Angiogenesis and the development of a vascular network is required for tumor progression, and involves release of angiogenic factors, including vascular endothelial growth factor (VEGF), from both malignant and stromal cell types1. Infiltration by cells of the myeloid lineage is a hallmark of many tumors, and in many cases the macrophages in these infiltrates express VEGF2. Here we show that deletion of inflammatory cell-derived VEGF attenuates the formation of a typical high-density vessel network, thus blocking the angiogenic switch in solid tumors. Vasculature in tumors lacking myeloid cell-derived VEGF was less tortuous, with increased pericyte coverage and decreased vessel length, indicating vascular normalization. In addition, loss of myeloid-derived VEGF decreases VEGFR2 phosphorylation in tumors, even though overall VEGF levels in the tumors are unaffected. However, myeloid deletion of VEGF resulted in an accelerated tumor progression in multiple subcutaneous isograft models and an autochthonous transgenic model of mammary tumorigenesis, with less overall tumor cell death and decreased tumor hypoxia. Furthermore, loss of myeloid cell VEGF increased tumor susceptibility to chemotherapeutic cytotoxicity. This demonstrates that myeloid-derived VEGF is essential for tumorigenic alteration of vasculature and signaling to VEGFR2, and that these changes act to retard, not promote, tumor progression.

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Objective: The lack of readily available branched and fenestrated endovascular aneurysm repair (EVAR) options has created an opportunity for creative deployment of endograft components to treat juxtarenal aneurysms. We present our early experience with "snorkel" or "chimney" techniques in the endovascular management of complex aortic aneurysms. Methods: We retrospectively reviewed planned snorkel procedures for juxtarenal aneurysms performed from September 2009 to August 2011. Our standardized technique included axillary or brachial cutdown for delivery of covered snorkel stents and mostly percutaneous femoral access for the main body endograft. Results: Fifty-six snorkel grafts were successfully placed in 28 consecutive patients (mean age, 75 years) with juxtarenal aneurysms. Mean aneurysm size was 64.8 mm (range, 53-87 mm). The snorkel configuration extended the proximal seal zone from an unsuitable infrarenal neck for standard EVAR (median diameter, 33.5 mm; length, 0.0 mm) to a median neck diameter of 24.5 mm and length of 18.0 mm. Five patients had unilateral renal snorkels, 17 had bilateral renal snorkels, and six had celiac/superior mesenteric artery/renal combinations. Technical success of snorkel placements was 98.2%, with loss of wire access leading to one renal stent deployment failure. Thirty-day mortality was 7.1%: one patient was readmitted 1 week postoperatively with pneumonia and died of sepsis; one patient died at 1 week of a right hemispheric stroke. Other major complications included perinephric hematomas, 7.1%; permanent hemodialysis, 3.6%; iliac artery injury requiring endoconduit placement, 3.6%; and brachial plexus nerve injury, 3.6%. Cardiac complications included self-limited arrhythmias (14.3%) and one non-Q-wave myocardial infarction (3.6%), with all recovering without coronary intervention. Mean follow-up was 10.7 months (range, 3-25 months). One patient died of nonaneurysmalrelated causes at 3 months (89.3% survival). Postoperative imaging revealed one renal snorkel graft occlusion occurring at 3 months (98.2% overall primary patency). Seven (25%) early endoleaks were noted on the first follow-up computed tomography angiography: two type I, three type II, and two type III (25%), leading to one secondary intervention (3.6%) with bridging cuff placement (type III). The small type Ia endoleaks and other type III endoleak resolved at the 6-month scan. Mean sac regression at the latest follow-up was 7.3 mm. No aneurysm has enlarged on postoperative imaging. Conclusions: Early success with the snorkel technique for juxtarenal aneurysms has made it our procedure of choice for complex short-neck to no-neck EVAR. Although long-term follow-up is needed, the flexibility of the snorkel technique and lack of requirement for custom-built devices may make this approach more attractive than branched or fenestrated stent grafts. ( J Vasc Surg 2012;55:935-46.)