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Purpose: To determine safety and efficacy of yttrium-90 ((90)Y) transarterial radioembolization (TARE) in patients who have undergone chemoembolization for hepatocellular carcinoma.Materials and Methods: A retrospective study identified 40 patients (median age 61 y; range, 44-84 y) who underwent (90)Y mapping angiography and had undergone ≥ one prior chemoembolizations. There were 4 (10%) patients in Barcelona Clinic Liver Cancer stage A, 7 (17.5%) in stage B, and 29 (72.5%) in stage C; 28 (70%) were Child-Pugh class A and 12 (30%) were class B. Median tumor diameter was 4.2 cm (range, 1-11.6 cm). The most common indications for changing to TARE were tumor progression (35/40; 86%) and development of portal vein thrombus (15/40; 37.5%).Results: Of 40 patients, 29 (72.5%) underwent TARE; the most common reasons for not undergoing TARE were attenuated hepatic arteries (5/11), high pulmonary shunt (4/11), and poor arterial flow (2/11). Patients who underwent ≤ 4 chemoembolizations to the TARE target tended to be more likely to undergo TARE after mapping than patients who had > 4 chemoembolizations (P = .056). Most common grade ≥ 3 toxicities were fatigue (9/29; 31%) and biochemical alterations (bilirubin [3/29; 10.3%], albumin [4/29; 13.8%], aspartate aminotransferase [5/29; 17.2%]). Of 27 patients treated with TARE with follow-up, responses were 11 (41%) complete response, 5 (19%) partial response, 2 (7%) stable disease, and 9 (33%) progressive disease. Median progression-free survival and overall survival were 90 days and 257 days.Conclusions: TARE is safe and effective salvage therapy in patients after chemoembolization. In patients who have undergone > 4 chemoembolizations to the (90)Y target, feasibility of TARE tends to be decreased. [ABSTRACT FROM AUTHOR]

Intra- and extra-muscular hematomas result from repetitive injury as well as sharp and blunt limb trauma. The clinical consequences can be serious, including debilitating pain and functional deficit. There are currently no short-term treatment options for large hematomas, only lengthy conservative treatment. The goal of this work was to evaluate the feasibility of a high intensity focused ultrasound (HIFU)-based technique, termed histotripsy, for rapid (within a clinically relevant timeframe of 15-20 min) liquefaction of large volume (up to 20 mL) extra-vascular hematomas for subsequent fine-needle aspiration. Experiments were performed using in vitro extravascular hematoma phantoms-fresh bovine blood poured into 50 mL molds and allowed to clot. The resulting phantoms were treated by boiling histotripsy (BH), cavitation histotripsy (CH) or a combination in a degassed water tank under ultrasound guidance. Two different transducers operating at 1 MHz and 1.5 MHz with f-number = 1 were used. The liquefied lysate was aspirated and analyzed by histology and sized in a Coulter Counter. The peak instantaneous power to achieve BH was lower than (at 1.5 MHz) or equal to (at 1 MHz) that which was required to initiate CH. Under the same exposure duration, BH-induced cavities were one and a half to two times larger than the CH-induced cavities, but the CH-induced cavities were more regularly shaped, facilitating easier aspiration. The lysates contained a small amount of debris larger than 70 μm, and 99% of particulates were smaller than 10 μm. A combination treatment of BH (for initial debulking) and CH (for liquefaction of small residual fragments) yielded 20 mL of lysate within 17.5 minutes of treatment and was found to be most optimal for liquefaction of large extravascular hematomas. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To assess the safety and efficacy of yttrium-90 (90Y) radioembolization when performed in a superselective fashion for patients with unresectable hepatocellular carcinoma (HCC). Materials and Methods: This retrospective study included 20 patients with unresectable HCC. Median Model for End-Stage Liver Disease score was 10.5 (range, 6–25), with 8 of 20 patients (40%) classified Child-Pugh class B and 1 of 20 patients (5%) classified class C cirrhosis. Segmental tumor-associated portal vein thrombus was present in 12 patients (60%), and a transjugular intrahepatic portosystemic shunt was present in 4 patients (20%). Median tumor diameter was 3.9 cm (range, 2.5–7.1 cm). All patients underwent superselective 90Y radioembolization targeted to a single liver segment using glass microspheres. Results: Median dose to the treated segment was 254 Gy, and median dose to the tumor was 536 Gy. No grade 3–4 hepatotoxicity occurred. The most common clinical toxicities were fatigue (30%), abdominal pain (10%), and postembolization syndrome (10%). Follow-up imaging demonstrated complete European Association for the Study of the Liver response of the index tumor in 19 of 20 patients (95%) and stable disease in 1 of 20 patients (5%). In patients with complete response, local tumor recurrence rate was 5.3% (1 of 19 patients). Median time to progression was 319 days. Overall survival was 90% (18 of 20 patients) with a median follow-up period of 275 days (range, 32–677 d). Conclusions: When performed in a segmental fashion, 90Y radioembolization demonstrates high response rates and low local tumor recurrence rates. Complete imaging response can be achieved in patients with locally aggressive disease. This study demonstrates no clinically significant hepatotoxicity, despite moderate liver dysfunction in many patients. [Copyright &y& Elsevier]

The aim of this review was to describe quality of life (QoL) questionnaires relevant to interventional radiology. Interventional radiologists perform a large number of palliative procedures. The effect of these therapies on QoL is important. This is particularly true for cancer therapies where procedures with marginal survival benefits may result in tremendous QoL benefits. Image-guided minimally invasive procedures should be compared to invasive procedures, with respect to QoL, as part of comparative effectiveness assessment. A large number of questionnaires have been validated for measurement of overall and disease-specific quality of life. Use of applicable QoL assessments can aid in evaluating clinical outcomes and help to further substantiate the need for minimally invasive image-guided procedures. [Copyright &y& Elsevier]

The etiology of arteriovenous (AV) malformations remains incompletely understood. Two cases of acquired AV malformations wholly located within the thrombosed lumen of the femoral and external iliac veins are presented here. The patients presented with symptoms of high venous pressure: pigmented skin and chronic pain. Such AV malformations have been rarely described in the extracranial circulation. The associated pain was successfully treated with catheter-based embolization of the lesions. The induction of the AV malformations in the peripheral circulatory system raises questions regarding the nature of angiogenesis and its possible triggers. [Copyright &y& Elsevier]

Congenital vascular anomalies of pelvis and lower limb arteries are rare. During embryologic development, the sciatic artery represents the dominant supplier of blood to the lower limb. The external iliac and femoral arteries appear later in the process and take over as the sciatic artery regresses. Failure of the sciatic artery to regress creates a persistent sciatic artery malformation. Failure of the external iliac artery to properly bud may lead to similar vascular malformations. The authors present a patient with atresia of the left external iliac artery with an associated atresia of the left common iliac vein, duplication of the infrarenal inferior vena cava, and absence of the left S1 bony arch. The left-sided single iliac artery supplies both pelvic structures and the lower limb. The “pelvic” external iliac artery may result from embryologic budding at a lower segmental level than the usual fifth lumbar segmental artery. This combination of anomalies suggests an abnormality of segmentation on left at the first sacral level. [Copyright &y& Elsevier]

Purpose: To assess the incidence of long- and short-term complications following internal iliac artery (IIA) embolization after blunt pelvic trauma. Materials and Methods: One hundred trauma patients with pelvic fractures underwent pelvic angiography from 1994 through 2006. Sixty-seven patients underwent IIA embolization. These patients were retrospectively identified for medical record review. Short- and long-term complications were defined as those occurring at less than or greater than 30 days, respectively. Complications and outcomes were assessed through chart review and, when possible, a standardized questionnaire. Patients who underwent IIA embolization were compared with matched control patients with blunt pelvic trauma who did not undergo pelvic arteriography. Individuals were matched by age, sex, year of admission, and injury scores. Results: There were no significant differences in skin necrosis, sloughing, pelvic perineal infection, or nerve injury between embolized and nonembolized patients within 30 days. There was no significant difference in claudication, skin ulceration, or regional pain at a mean of 18.4 months follow-up. In the long term, buttock, thigh, and perineal paresthesia occur at a significantly higher rate in embolized patients. Skin sloughing in the embolized patient group is an important but rare complication. Conclusions: IIA embolization is an important means of controlling pelvic arterial hemorrhage. There is no significant increase in the risk of most evaluated long- and short-term complications in trauma patients who underwent IIA embolization versus those who did not. However, IIA embolization is associated with a marginally significantly increased rate of buttock, thigh, or perineal paresthesia. [Copyright &y& Elsevier]

The purpose of this pilot study was to determine if two-dimensional perfusion angiography can be used to quantify tumor perfusion during mapping prior to Yttrium-90 (Y-90) transarterial radio-embolization (TARE) treatment and whether perfusion metrics correlate with tumor response and prognosis. Table 1 summarizes pre-TARE tumor perfusion in tumors with and without CR. 2D perfusion angiography can be used to assess tumor perfusion during Y-90 mapping procedures. [Extracted from the article]

Feasibility of angiography-free robotic endovascular procedures The purpose of this study was to demonstrate feasibility of using a robotic system to remotely steer an angiographic catheter, with electromagnetic sensors (EM), through a 3D printed model of the arterial vasculature while visualizing a holographic dynamic 3D representation of the catheter and co-registered vascular anatomy in virtual reality (VR). A trakSTAR EM tracking system (Northern Digital Inc.) was used to track the catheter in the 3D physical model and the catheter position coordinates were co-registered with the VR display. [Extracted from the article]

Bacterial loads can be effectively reduced using cavitation-mediated focused ultrasound, or histotripsy. In this study, gram-negative bacteria (Escherichia coli) in suspension were used as model bacteria to evaluate the effectiveness of two regimens of histotripsy treatments: cavitation histotripsy (CH) and boiling histotripsy (BH). Ten-milliliter volumes of Escherichia coli were treated at different negative focal pressure amplitudes and over time periods up to 40 min. Cavitation activity was characterized with coaxial passive cavitation detection (PCD) and synchronized plane wave B-mode imaging. CH treatments exhibited a threshold behavior that was consistent with PCD metrics of cavitation. Above the threshold, bacterial inactivation followed a monotonically increasing log-linear relationship that indicated an exponential inactivation rate. BH exhibited no threshold, but instead followed a different monotonically increasing inactivation rate. Inactivation rates were larger for BH at or below the CH threshold, and larger for CH substantially above the threshold. CH studies performed at different pulse lengths at the same duty cycle had similar inactivation rates, suggesting that at any given pressure amplitude, the "on time" was the most important variable for inactivating E. coli. The maximum inactivation was produced by CH at the highest pressure amplitudes used, leading to a log reduction >4.2 for a 40 min treatment. The results of this study suggest that both CH and BH can be used to inactivate E. coli in suspension, with the optimal regimen depending on the attainable peak negative focal pressure at the target. [ABSTRACT FROM AUTHOR]

Purpose: To compare segmental radioembolization with segmental chemoembolization for localized, unresectable hepatocellular carcinoma (HCC) not amenable to ablation.Materials and Methods: In a single-center, retrospective study (2010-2015), 101 patients with 132 tumors underwent segmental radioembolization, and 77 patients with 103 tumors underwent segmental doxorubicin-based drug-eluting embolic or conventional chemoembolization. Patients receiving chemoembolization had worse performance status (Eastern Cooperative Oncology Group 0, 76% vs 56%; P = .003) and Child-Pugh class (class A, 65% vs 52%; P = .053); patients receiving radioembolization had larger tumors (32 mm vs 26 mm; P < .001), more infiltrative tumors (23% vs 9%; P = .01), and more vascular invasion (18% vs 1%; P < .001). Toxicity, tumor response, tumor progression, and survival were compared. Analyses were weighted using a propensity score (PS).Results: Toxicity rates were low, without significant differences. Index and overall complete response rates were 92% and 84% for radioembolization and 74% and 58% for chemoembolization (P = .001 and P < .001). Index tumor progression at 1 and 2 years was 8% and 15% in the radioembolization group and 30% and 42% in the chemoembolization group (P < .001). Median progression-free and overall survival were 564 days and 1,198 days in the radioembolization group and 271 days and 1,043 days in the chemoembolization group (PS-adjusted P = .002 and P = .35; censored by transplant PS-adjusted P < .001 and P = .064).Conclusions: Segmental radioembolization demonstrates higher complete response rates and local tumor control compared with segmental chemoembolization for HCC, with similar toxicity profiles. Superior progression-free survival was achieved. [ABSTRACT FROM AUTHOR]

Due to the increasing needs on the performance of satellites, in particular optical satellites, microvibrations have become more and more important over the last years. Microvibrations affect a large number of satellites for both Earth observation and space observation missions. Further, microvibrations are also a concern for other missions with sensitive instruments like Fourier spectrometers, high-precision accelerometers or reference oscillators. In classical fields like structural dynamic engineering, management approaches have been established and implemented in all space projects. This paper presents a corresponding approach for the area of microvibrations. Focus is on the definition of all key elements needed to establish a microvibration control approach. This includes the establishment of microvibration budgets and associated summation rules. A systematic way for microvibration disturbance minimization is presented and rules for the application are defined. Specific emphasis is given to the definition of microvibration interface requirements and the associated control process. The concepts provided in this paper have been verified by tests performed in the frame of various satellite programs and studies. Tests related to the superposition of different noise sources are presented in here. • Spacecraft performance budgets related to microvibrations are established using adaptation of standard ECSS rules. • Microvibration interface requirements are defined using an optimized margin approach. • Microvibration requirement definition and verification concepts are defined for typical satellite architectures. • Assuming linear summation of different microvibration noise sources overestimates the performance impact. [ABSTRACT FROM AUTHOR]

Purpose: Yttrium-90 (Y90) microsphere radioembolization is a well-accepted treatment strategy for unresectable hepatocellular carcinoma (HCC). It is usually performed in patients with extensive tumors, necessitating lobar infusions. This study assessed the safety and efficacy of Y90 radioembolization when performed in a superselective fashion. Materials and Methods: In this retrospective cohort study, 20 patients with unresectable HCC were included. Median age was 61 years. Many had advanced liver dysfunction, with 8 (40%) Child-Pugh class B and 1 (5%) Child-Pugh class C cirrhosis. Twelve patients (60%) had segmental tumor-associated portal vein thrombus, and 4 (20%) had an indwelling transjugular intrahepatic portosystemic shunt. Median tumor diameter was 39 mm. During mapping angiography, 1 patient required prophylactic embolization of the right gastric artery. All patients underwent superselective Y90 radioembolization targeted to a single segment of the liver using glass microspheres. Results: A total of 20 patients were followed for a median of 225 days (range 26-677 days). Median dose to the treated tissue was 251 gray. There was no grade 3 or 4 hepatotoxicity. The most common clinical toxicities were fatigue (30%) and abdominal pain (10%). Follow-up imaging demonstrated complete local EASL response of the index tumor in 19/20 patients (95%) and stable disease in 1/20 (5%). Median time to response was 33 days. In patients with complete response, local tumor recurrence rate was 5% (1/20). Seven (35%) patients eventually developed a second tumor outside the treatment area. Overall survival was 90% (18/20) during the follow-up period. One patient died on day 123 as a result of extrahepatic tumor progression. A second patient died on day 126 as a result of trauma. Conclusion: When performed in a superselective fashion, Y90 radioembolization demonstrates high response rates, low local tumor recurrence rates, and no hepatotoxicity. Complete imaging response can be achieved even in patients with advanced disease. It can be safe in the setting of moderate liver dysfunction. Further comparative studies with other treatment modalities would better define the role of this technique in the treatment algorithm for HCC. [Copyright &y& Elsevier]

Abscesses are walled-off collections of infected fluids that often develop as complications in the setting of surgery and trauma. Treatment is usually limited to percutaneous catheterization with a course of antibiotics. As an alternative to current treatment strategies, a histotripsy approach was developed and tested in a novel porcine animal model. The goal of this article is to use advanced ultrasound imaging modes to extract sonographic features associated with the progression of abscess development in a porcine model. Intramuscular or subcutaneous injections of a bi-microbial bacteria mixture plus dextran particles as an irritant led to identifiable abscesses over a 2 to 3 wk period. Selected abscesses were imaged at least weekly with B-mode, 3-D B-mode, shear-wave elastography and plane-wave Doppler imaging. Mature abscesses were characterized by a well-defined core of varying echogenicity surrounded by a hypoechoic capsule that was highly vascularized on Doppler imaging. 3-D imaging demonstrated the natural history of abscess morphology, with the abscess becoming less complex in shape and increasing in volume. Furthermore, shear-wave elastography demonstrated variations in stiffness as phlegmon becomes abscess and then liquefies, over time. These ultrasound features potentially provide biomarkers to aid in selection of treatment strategies for abscesses. [ABSTRACT FROM AUTHOR]

Infected abscesses are walled-off collections of pus and bacteria. They are a common sequela of complications in the setting of surgery, trauma, systemic infections and other disease states. Current treatment is typically limited to antibiotics with long-term catheter drainage, or surgical washout when inaccessible to percutaneous drainage or unresponsive to initial care efforts. Antibiotic resistance is also a growing concern. Although bacteria can develop drug resistance, they remain susceptible to thermal and mechanical damage. In particular, short pulses of focused ultrasound (i.e., histotripsy) generate mechanical damage through localized cavitation, representing a potential new paradigm for treating abscesses non-invasively, without the need for long-term catheterization and antibiotics. In this pilot study, boiling and cavitation histotripsy treatments were applied to subcutaneous and intramuscular abscesses developed in a novel porcine model. Ultrasound imaging was used to evaluate abscess maturity for treatment monitoring and assessment of post-treatment outcomes. Disinfection was quantified by counting bacteria colonies from samples aspirated before and after treatment. Histopathological evaluation of the abscesses was performed to identify changes resulting from histotripsy treatment and potential collateral damage. Cavitation histotripsy was more successful in reducing the bacterial load while having a smaller treatment volume compared with boiling histotripsy. The results of this pilot study suggest focused ultrasound may lead to a technology for in situ treatment of acoustically accessible abscesses. [ABSTRACT FROM AUTHOR]

Large intra-abdominal, retroperitoneal and intramuscular hematomas are common consequences of sharp and blunt trauma and post-surgical bleeds, and often threaten organ failure, compartment syndrome or spontaneous infection. Current therapy options include surgical evacuation and placement of indwelling drains that are not effective because of the viscosity of the organized hematoma. We have previously reported the feasibility of using boiling histotripsy (BH)-a pulsed high-intensity focused ultrasound method-for liquefaction of large volumes of freshly coagulated blood and subsequent fine-needle aspiration. The goal of this work was to evaluate the changes in stiffness of large coagulated blood volumes with aging and retraction in vitro, and to correlate these changes with the size of the BH void and, therefore, the susceptibility of the material to BH liquefaction. Large-volume (55-200 mL) whole-blood clots were fabricated in plastic molds from human and bovine blood, either by natural clotting or by recalcification of anticoagulated blood, with or without addition of thrombin. Retraction of the clots was achieved by incubation for 3 h, 3 d or 8 d. The shear modulus of the samples was measured with a custom-built indentometer and shear wave elasticity (SWE) imaging. Sizes of single liquefied lesions produced with a 1.5-MHz high-intensity focused ultrasound transducer within a 30-s standard BH exposure served as the metric for susceptibility of clot material to this treatment. Neither the shear moduli of naturally clotted human samples (0.52 ± 0.08 kPa), nor their degree of retraction (ratio of expelled fluid to original volume 50%-58%) depended on the length of incubation within 0-8 d, and were significantly lower than those of bovine samples (2.85 ± 0.17 kPa, retraction 5%-38%). In clots made from anticoagulated bovine blood, the variation of calcium chloride concentration within 5-40 mmol/L did not change the stiffness, whereas lower concentrations and the addition of thrombin resulted in significantly softer clots, similar to naturally clotted human samples. Within the achievable shear modulus range (0.4-1.6 kPa), the width of the BH-liquefied lesion was more affected by the changes in stiffness than the length of the lesion. In all cases, however, the lesions were larger compared with any soft tissue liquefied with the same BH parameters, indicating higher susceptibility of hematomas to BH damage. These results suggest that clotted bovine blood with added thrombin is an acceptable in vitro model of both acute and chronic human hematomas for assessing the efficiency of BH liquefaction strategies. [ABSTRACT FROM AUTHOR]

This study addresses inactivation of E. coli in either 5- or 10-mL volumes, which were 50- to 100-fold greater than used in an earlier study (Brayman et al. 2017). Cells were treated with 1-MHz pulsed high-intensity focused ultrasound (10 cycles, 2-kHz repetition frequency, +65/-12.8 MPa focal pressures). The surviving fraction was assessed by coliform assay, and inactivation demonstrated curvilinear kinetics. The reduction of surviving fraction to 50% required 2.5 or 6 min in 5- or 10-mL samples, respectively. Exposure of 5 mL for 20 min reduced the surviving fraction to ∼1%; a similar exposure of 10-mL samples reduced the surviving fraction to ∼10%. Surviving cells from 5-min exposures appeared normal under light microscopy, with minimal debris; after 20 min, debris dominated. Transmission electron microscopy images of insonated samples showed some undamaged cells, a few damaged but largely intact cells and comminuted debris. Cellular damage associated with substantive but incomplete levels of inactivation can be variable, ranging from membrane holes tens of nanometers in diameter to nearly complete comminution. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively assess the threshold dose for objective response of hepatocellular carcinoma (HCC), using 90Y internal pair-production positron emission tomography (PET) to quantify the radiation dose delivered to hepatic tumors after radioembolization.Methods and Materials: A prospective study was performed under institutional review board approval from 2012 to 2014. Thirty-five patients with primary and secondary liver tumors undergoing 90Y treatment were recruited. Eight patients did not meet inclusion criteria, and 27 patients with HCC were included for analysis. Time-of-flight PET imaging was performed immediately after radioembolization and voxel values converted into 90Y activity. The radioembolization dose was calculated from PET images, and image segmentation was performed with volumetric analysis of dose deposition within tumors. Radiographic response was assessed on follow-up imaging.Results: Treated HCC showed 84% objective response, 11% stable disease, and 5% progressive disease according to modified RECIST 1.1 response criteria. Responders had a higher median 90Y tumor dose than nonresponders (225 Gy vs 83 Gy, P < .01). Logistic regression models show tumor dose (P = .002) strongly predicted objective response. All nonresponders had tumor dose <200 Gy. No statistical difference for patient age, tumor volume, multifocal or extrahepatic disease, portal vein invasion, or injected 90Y activity was found between responders and nonresponders.Conclusions: Hepatocellular carcinoma that resulted in objective response after radioembolization had a greater median tumor dose of 225 Gy, compared with 83 Gy in nonresponders. Delivered tumor dose can be assessed by PET and significantly impacts treatment response in HCC. [ABSTRACT FROM AUTHOR]

This study was motivated by the desire to develop a non-invasive means to treat abscesses, and represents the first steps toward that goal. Non-thermal, high-intensity focused ultrasound (HIFU) was used to inactivate Escherichia coli (∼1 × 109 cells/mL) in suspension. Cells were treated in 96-well culture plate wells using 1.95-MHz ultrasound and incident focal acoustic pressures as high as 16 MPa peak positive and 9.9 MPa peak negative (free field measurements). The surviving fraction was assessed by coliform culture and the alamarBlue assay. No biologically significant heating was associated with ultrasound exposure. Bacterial inactivation kinetics were well described by a half-life model, with a half-time of 1.2 min. At the highest exposure levels, a 2log inactivation was typically achieved within 10 min. The free field-equivalent peak negative acoustic pressure threshold for inactivation was ∼7 MPa. At the highest acoustic pressures used, inactivation efficacy was insensitive to reciprocal changes in pulse length and pulse repetition frequency at constant duty factor. Although treated volumes were very small, proof of principle was provided by these experiments. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) has been implicated in the pathologic angiogenesis observed in psoriasis and other chronic inflammatory skin diseases that are characterized by enhanced expression of VEGF by epidermal keratinocytes and of VEGF receptors by tortuous microvessels in the upper dermis. To investigate the functional importance of chronic VEGF overexpression in vivo , we used a keratin 14 promoter expression cassette containing the gene for murine VEGF164 to selectively target VEGF expression to basal epidermal keratinocytes in transgenic mice. These mice demonstrated an increased density of tortuous cutaneous blood capillaries with elevated expression levels of the high affinity VEGF receptors, VEGFR‐1 and VEGFR‐2, most prominently during the neonatal period. In contrast, no abnormalities of lymphatic vessels were detected. In addition, the number of mast cells in the upper dermis was significantly increased in transgenic skin. Intravital fluorescence microscopy revealed highly increased leukocyte rolling and adhesion in postcapillary skin venules that were both inhibited after injection of blocking antibodies against E‐ and P‐selectin. Combined blocking antibodies against intercellular adhesion molecule‐1 and lymphocyte function‐associated antigen‐1 were without effect, whereas an anti‐vascular cell adhesion molecule‐1/VLA‐4 antibody combination almost completely normalized the enhanced leukocyte adhesion in transgenic mice. This study reveals VEGF as a growth factor specific for blood vessels, but not lymphatic vessels, and demonstrates that chronic orthotopic overexpression of VEGF in the epidermis is sufficient to induce cardinal features of chronic skin inflammation, providing a molecular link between angiogenesis, mast cell accumulation, and leukocyte recruitment to sites of inflammation. [ABSTRACT FROM AUTHOR]