Surgeons' expectations of osteotomies around the knee.

INTRODUCTION: High tibial osteotomy (HTO) is a valid and joint preserving surgical technique to treat medial degenerative osteoarthritis (OA) in young and active patients. A recent study shows that patients' expectations of osteotomy around the knee are high, but OA progression and potential conversion to a total knee arthroplasty (TKA) were underestimated. The aim of this study was to investigate surgeons' expectations of HTO and to compare the results to the patients' expectations and actual outcomes reported in the literature. METHODS: 461 surgeons were questioned online using the 'Hospital for Special Surgery Knee Surgery Expectations Survey (HFSS-KSES)' and a ten-item non-validated questionnaire to investigate the expectations of HTO. Two subgroups were formed to investigate differences regarding the surgeons' experience. Statistical analysis was performed using IBM SPSS Statistics. RESULTS: Surgeons' expectations of HTO were rated between very and little important with pain reduction being the most important item on the HFSS-KSES. Furthermore, 'improving the ability to walk', 'to perform daily activities', 'having confidence in the knee', and 'avoiding future degeneration' were rated of high importance. An important difference regarding the experience was the lower expectations on delay/prevention of TKA of less-experienced surgeons. CONCLUSION: Surgeons' expectations of HTO are high but nevertheless different to the patients' expectations reported in the literature. Also, expectations for the delay/prevention of TKA differed regarding the experience of surgeons. While pain reduction represents one of the most important items for surgeons and patients, the expected outcome regarding the delay/prevention of a TKA and returning to sports differs to the patients' expectations and to the actual outcome reported in the literature. This should be considered when performing the preoperative informed consent.

Concomitant intra-articular glenohumeral injuries in displaced fractures of the lateral clavicle.

PURPOSE: To detect concomitant intra-articular glenohumeral injuries, in acute displaced fractures of the lateral clavicle, initially missed due to unfeasible clinical evaluation of the acutely injured shoulder. METHODS: All patients suffering from an acute displaced lateral clavicle fracture with indication to surgical treatment underwent diagnostic shoulder arthroscopy prior to open reduction and internal fixation. In case of therapy-relevant intra-articular glenohumeral injuries, subsequent surgical treatment was performed. RESULTS: Intra-articular injuries were found in 13 of 28 patients (46.4 %) with initially suspected isolated lateral clavicle fracture. Additional surgical treatment was performed in 8 of 28 cases (28.6 %). Superior labral anterior-posterior (SLAP) lesions were observed in 4 of 28 patients (14.3 %; SLAP II a: 1; II b: 1; III: 1; and IV: 1). Lesions of the pulley system were found in 3 of 28 patients (10.7 %; Habermeyer III°). One partial articular supraspinatus tendon avulsion lesion (3.6 %) and one lesion of the subscapularis tendon (3.6 %; Fox and Romeo II°) were observed. CONCLUSIONS: Traumatic concomitant glenohumeral injuries in lateral clavicle fractures seem to be more frequent than expected in general. Subsequent surgical treatment of these formerly missed but therapy-relevant injuries may increase functional outcome and reduce complication rate. LEVEL OF EVIDENCE: IV.

Single-Bundle Versus Double-Bundle Anterior Cruciate Ligament Reconstruction: A Comparative 2-Year Follow-up.

PURPOSE: To compare anatomic single-bundle (SB) versus double-bundle (DB) anterior cruciate ligament (ACL) reconstruction and to determine possible differences in clinical outcomes. METHODS: In this prospective randomized study, 64 patients were divided into 2 equal groups. Anatomic SB and DB ACL reconstructions were performed using hamstring tendons. A follow-up examination 2 years after surgery comprised International Knee Documentation Committee (IKDC) 2000 assessment, Laxitester (ORTEMA Sport Protection, Markgröningen, Germany) measurement of anteroposterior translation regarding rotational stability, and radiographic evaluation. Statistical analysis and power calculation were performed (P < .05). RESULTS: We examined 62 patients at a mean of 26 months (range, 23.3 to 32.7 months) after surgery. IKDC subjective and objective scores showed no significant differences when both groups were compared. The Laxitester measurements showed no significant differences regarding anteroposterior translation in the neutral position, internal rotation, and external rotation. However, there was a significant improvement in rotational laxity in external rotation in the DB group (P = .02). No differences were seen between the groups regarding osteoarthritic changes and tunnel widening. CONCLUSIONS: There were no differences in IKDC subjective and objective scores between patients who underwent anatomic SB ACL reconstruction and those who underwent anatomic DB ACL reconstruction. LEVEL OF EVIDENCE: Level I, prospective, randomized controlled clinical trial.

The Munich Knee Questionnaire: Development and Validation of a New Patient-Reported Outcome Measurement Tool for Knee Disorders.

PURPOSE: To develop and validate an all-purpose patient-reported outcome questionnaire for a patient-based follow-up examination regarding knee disorders. METHODS: Each scale of the Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score, Lysholm knee score, Western Ontario Meniscal Evaluation Tool (WOMET) score, and Tegner score was analyzed, and after matching of the general topics, the dedicated items underwent a fusion to the final Munich Knee Questionnaire (MKQ) item and a score comprising 33 items was created. In a prospective clinical study, we evaluated validity, reliability, and responsiveness in 152 physical active patients (75 women and 77 men; mean age, 47 years) with traumatic as well as degenerative knee disorders. RESULTS: Test-retest reliability was substantial, with intraclass correlation coefficients of at least 0.91. Construct validity and responsiveness were confirmed by correlation coefficients of 0.78 to 0.86 (P = .01) and 0.41 to 0.71, respectively. Correlation coefficients of the original scores (KOOS, IKDC, Lysholm, WOMET, and Tegner) and the scores calculated from the MKQ were between 0.80 and 0.91 (P = .01). CONCLUSIONS: The MKQ is a reliable and valid patient-reported outcome questionnaire for assessing knee function. It seems to enable the calculation of the original items of the KOOS, IKDC score, Lysholm knee score, WOMET score, and Tegner score. CLINICAL RELEVANCE: The MKQ facilitates the comparison of treatment results in knee disorders and allows the evaluation of treatment efficacy. Identified inadequate treatment concepts could be eliminated, leading to increased patient satisfaction and optimized quality of health care.

Stimulation of bone growth factor synthesis in human osteoblasts and fibroblasts after extracorporeal shock wave application.

BACKGROUND: Nonunion is a common problem in Orthopedic Surgery. In the recent years alternatives to the standard surgical procedures were tested clinically and in vitro. Extracorporeal shock wave therapy (ESWT) showed promising results in both settings. We hypothesized that in target tissue cells from nonunions like fibroblasts and osteoblasts ESWT increases the release of bone growth factors. METHODS: Fibroblasts and osteoblasts were suspended in 3 ml cryotubes and subjected to 250/500 shock waves at 25 kV using an experimental electrohydraulic lithotripter. After ESWT, cell viability was determined and cells were seeded at 1 × 10(5) cells in 12 well plates. After 24, 48, and 72 h cell number was determined and supernatant was frozen. The levels of growth factors FGF-2 and TGF-ß(1) were examined using ELISA. A control group was treated equally without receiving ESWT. RESULTS: After 24 h there was a significant increase in FGF-2 levels (p < 0.05) with significant correlation to the number of impulses (p < 0.05) observed. TGF-ß(1) showed a time-dependent increase with a peak at 48 h which was not significantly different from the control group. CONCLUSIONS: FGF-2, an important growth factor in new bone formation, was shown to be produced by human fibroblasts and osteoblasts after treatment with ESWT. These findings demonstrate that ESWT is able to cause bone healing through a molecular way by inducing growth factor synthesis.

[Extracorporeal high hydrostatic pressure as a new technology for the disinfection of infected bone specimens]]. / Extrakorporale hydrostatische Hochdruckbehandlung als neues Verfahren zur Desinfektion infizierter Knochenpräparate.

BACKGROUND: Allogeneic bone transplantation is at risk of infection, and established disinfection methods typically compromise bone quality. High hydrostatic pressure (HHP) is well established for disinfection in food technology, and also it does protect biomechanical and biological properties of bone. This study is the first investigation of HHP regarding disinfection of bone biopsies. MATERIALS AND METHODS: Bone biopsies of 34 patients with chronic infections were subjected to HHP and assessed for persisting bacterial growth. In series 1, bone biopsies were proceeded directly to HHP (10 min; maximal pressure Pmax 600 MPa). In series 2, HHP was applied after 5-day incubation in growth media (10 min or 2x30 min; Pmax 600 MPa). Furthermore, HHP-induced changes of bacterial morphology on artificially infected bone samples were evaluated by scanning electron microscopy (SEM). RESULTS: For series 1, 71% of the bone samples were sterilised by HHP (n=17), compared to 38% of the untreated control samples, which were obtained during the same surgery (n=8). For series 2, after prior incubation, HHP disinfected 7% of the bone specimens (n=55), all control samples showed bacterial growth (n=33). Destruction of cell wall integrity of Gram-negative strains was observed by SEM. CONCLUSION: The effectiveness of HHP for bone disinfection should be improved by optimising treatment parameters. Infections with barosensitive Gram-negative bacteria or yeast might represent possible clinical indications.

[Standards in rehabilitation following anterior cruciate ligament reconstruction in the German-speaking world]. / Standards in der Nachbehandlung nach vorderem Kreuzbandersatz im deutschsprachigen Raum.

INTRODUCTION: Rehabilitation protocols following anterior cruciate ligament (ACL) reconstruction often differ among orthopaedic surgeons. The primary aim of this study was to investigate which follow-up treatment is recommended by "AGA instructors" certified by the German-speaking Association for Arthroscopic and Open Joint Surgery (AGA). The secondary aim was to compare these findings with the current literature. MATERIAL AND METHODS: A structured anonymous online survey was performed with "AGA instructors" specialised in knee or ACL surgery. All participants were asked about their recommendations for rehabilitation following isolated ACL reconstruction using a questionnaire containing 23 items. RESULTS: 117 out of 218 mail questionnaires were fully completed and analysed. 96.5 % of all surgeons allowed full weight-bearing after 4 weeks or earlier, 52.6 % put a limit on knee flexion, 9.7 % on knee extension after the operation. A brace was prescribed by 82.8 % of all participants. During the first six weeks, isometric training and closed-chain exercises were recommended by the majority of surgeons. Riding a bicycle or driving a car after 6 weeks or earlier was permitted by 78.5 % and 86.2 %, respectively. Jogging (65.5 %) or jumping activities (67.0 %) were allowed after 3 months or earlier. Skiing (53.0 %) or contact/team sport (55.2 % / 46.2 %) was often permitted after 12 months. 82.6 % of all surgeons would like to use return-to-sport test protocols. CONCLUSION: Rehabilitation protocols differ significantly even among experienced knee surgeons working as instructors. Their recommendations are often not evidence-based considering the current literature.

[Does Sports Activity Influence Total Knee Arthroplasty Durability? Analysis with a Follow-Up of 12 Years]. / Beeinflusst sportliche Aktivität die Revisionsrate nach Knietotalendoprothese? Analyse eines 12-Jahres-Follow-up.

Background Total knee replacement is the only surgical option to treat painful degenerative osteoarthritis, restore knee function, improve quality of life, and enable patients to return to sports activity. With an aging population expecting an active life after retirement, patients' expectations of improvement after surgery are increasing as well. In view of the growing demand for higher performance, exercise and athletic activity, clinicians have been increasingly forced to question how much athletic activity a patient may resume after total knee replacement, and what types of athletic activity seem to be acceptable. However, there is currently no consensus on the appropriate intensity of physical activity after total knee arthroplasty or how activity levels affect the rate of revision surgery. Patients, material and methods In a retrospective study with a follow-up period of 12 years, 130 patients were asked about their sport activities 22 months before and after total knee replacement. Based on their answers, the patients were divided into one sports group (group A) and one group without any sports activity (group B). Seven years after surgery the same patients were asked about their sports activity again, and 12 years postoperatively they were additionally asked about whether or not they underwent revision surgery. Results Twenty-two months after total knee replacement 88 (67.7 %) of the 130 patients practiced sports for a minimum of 3 times a week (group A), whereas 42 (32.3 %) patients reported that they practiced no sports (group B). In 2010 - 7 years postoperatively - 60 patients of group A and 27 patients of group B took part in the survey; their levels of sports activity had not changed over the previous 7 years. In 2015, 46 patients out of group A and 21 patients out of group B were questioned. We saw a revision rate of 15.2 % (7 out of 46 patients) in the group with continuous sports activity, whereas we found an increased revision rate of 23.8 % (5 out of 21 patients) in the group without any sports activity 12 years after total knee arthroplasty. Conclusion Our study showed that sports activity after total knee replacement led to a reduced revision rate in the sports group compared with the non-sports group. Therefore, more liberal recommendations should be given to patients regarding athletic activity after total knee arthroplasty. We conclude that moderate sports activities have no negative influence on total knee arthroplasty and may even lead to improved osteointegration with a decrease in osteolytic changes and less prosthesis loosening.

Potential accuracy of navigated K-wire guided supra-acetabular osteotomies in orthopedic surgery: a CT fluoroscopy cadaver study.

BACKGROUND: The aim of this study was to evaluate the accuracy of supra-acetabular pelvic tumor resections in human, full-body cadavers and under realistic operation room conditions with the help of a navigation system and K-wires as guidance for the oscillating saw. METHODS: Seven hemipelvises from fresh, human, male, full-body cadavers were used. A preoperative and a postoperative CT was performed. Under control of the navigation system K-wires were inserted and served as guidance for the oscillating saw to reduce the error by vibration and jerking movements. The accuracy of the computer aided resections was compared with the accuracy of freehand resections in customized 3D printed pelvises with geometries identical to the cadavers used. RESULTS: The mean deviation of the navigated osteotomies was 1.9 mm (standard deviation 1.0 mm) significantly (P < 0.001) lower than the mean deviation of freehand osteotomies at 9.2 mm (standard deviation 3.7 mm). CONCLUSION: Navigated K-wires for supra-acetabular osteotomies allow significantly higher accuracy than freehand procedures under simulated operation room conditions. Copyright © 2016 John Wiley & Sons, Ltd.

Factors regulating bone remodeling processes in aseptic implant loosening.

This study was undertaken to screen periprosthetic tissues (PPTs) under specified conditions for a series of molecular components and describe them in bone remodeling processes within aseptic loosening. PPT samples were obtained from patients undergoing revision surgery of endoprostheses (n = 24) and synovial tissues from patients with OA (control) (n = 18), patients with any form of inflammatory arthritides were excluded. Tissue samples were examined via microbiology, histology (H&E, TRAP), immunohistochemistry (CD68/anti-S100a4), quantitative real-time PCR (ALP, COL1A1, cathepsin K, M-CSF, MMP13, OPG, RANK, RANKL, TNF-α, and TRAP) and an endotoxin-assay. PPT samples contained a variety of cellular components and stained positive for TRAP (56%), CD68 (100%), and S100a4 (100%). Wear debris were found in cells staining positive for CD68 and S100a4. In PPTs significantly higher ALP, COL1A1, MMP-13, RANK, RANKL, and TRAP expression were found along with a significantly higher RANKL/OPG ratio and a significantly lower OPG expression. No significant difference was observed for M-CSF, TNF-α, cathepsin K, and endotoxin levels. In conclusion we found osteogenic proteins (ALP, COL1A1), a proteolytic enzyme (MMP-13), markers for osteoclast differentiation (RANK, RANKL), and osteoclast activity (TRAP) to be increased in PPT, whereas OPG expression decreased significantly in comparison to control. We present data about a large series of molecular components in PPT and describe novel and key findings about their expression levels in regards to aseptic implant loosening. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:248-257, 2017.

Novel temperature-sensitive liposomes with prolonged circulation time.

Hyperthermia increases the efficiency of various chemotherapeutic drugs and is administered as an adjunct to chemotherapy for the treatment of cancer patients. The temperature-dependent effect can be strongly increased by the use of temperature-sensitive liposomes in combination with regional hyperthermia, which specifically releases the entrapped drug in the heated tumor tissue. The novel lipid 1.2-dipalmitoyl-sn-glycero-3-phosphoglyceroglycerol (DPPGOG), which is closely related to the naturally occurring 1.2-dipalmitoyl-sn-glycero-3-phosphoglycerol, in combination with 1.2-dipalmitoyl-sn-glycero-3-phosphocholine and 1.2-distearoyl-sn-glycero-3-phosphocholine provides long-circulating temperature-sensitive liposomes with favorable properties under mildly hyperthermic conditions (41-42 degrees C). DPPGOG facilitates temperature-triggered drug release from these liposomes (diameter, 175 nm) and leads to a substantially prolonged plasma half-life for the encapsulated drug with t(1/2) = 9.6 h in hamsters and t(1/2) = 5.0 h in rats. Quantitative fluorescence microscopy of amelanotic melanoma grown in the transparent dorsal skin fold chamber of hamsters demonstrated a favorable drug accumulation in heated tissue after i.v. application of these liposomes (42 degrees C for 1 h). The mean area under the curve for tissue drug concentration was increased by more than sixfold by application of the new liposomes compared with nonliposomal drug delivery. In summary, we present a new DPPGOG-based liposomal formulation enabling long circulation time combined with fast and efficient drug release under mild hyperthermia. This adds positively to the results with lipid-grafted polyethylenglycol used thus far in temperature sensitive liposomes and widens the possibilities for clinical applications.

Neovascular targeting therapy: paclitaxel encapsulated in cationic liposomes improves antitumoral efficacy.

PURPOSE: Cationic liposomes have been shown to selectively target tumor endothelial cells. Therefore, the encapsulation of antineoplastic drugs into cationic liposomes is a promising tool to improve selective drug delivery by targeting tumor vasculature. It was the aim of our study to evaluate tumor selectivity and antitumoral efficacy of paclitaxel encapsulated in cationic liposomes in comparison with the free drug paclitaxel (Taxol(R)) in vivo. EXPERIMENTAL DESIGN: Experiments evaluating tumor selectivity were carried out in male Syrian golden hamsters bearing the amelanotic hamster melanoma A-Mel-3 in dorsal skinfold preparations. Growth of tumor cells was observed after s.c. inoculation (day 0). On days 5, 7, 9, 12, 14, and 16, animals were treated by continuous i.v. infusion over 90 min with 5% glucose, Taxol(R), unloaded cationic liposomes, or paclitaxel encapsulated into cationic liposomes (LipoPac), respectively (lipid dose, 150 mg/kg body weight; paclitaxel dose, 5 mg/kg body weight). Tumor volumes and presence of regional lymph node metastases were quantified. RESULTS: Vascular targeting of rhodamine-labeled cationic liposomes was maintained after encapsulation of paclitaxel as revealed by in vivo fluorescence microscopy (ratio of dye concentration, tumor:normal tissue = 3:1). The s.c. tumor growth revealed a remarkable retardation of tumor growth after treatment with LipoPac (1.7 +/- 0.3 cm(3)). In contrast, control tumors showed exponential tumor growth [tumor volume at the end of the observation period (mean +/- SE): 5% glucose, 17.7 +/- 1.9 cm(3); unloaded cationic liposomes, 10.0 +/- 1.6 cm(3); Taxol(R), 10.7 +/- 1.7 cm(3)]. In addition, the appearance of regional lymph node metastases was significantly delayed by treatment with paclitaxel encapsulated into cationic liposomes in comparison with all other groups. CONCLUSIONS: The data suggest that cationic liposomes are a powerful tool for selective and efficient drug delivery to tumor microvessels. This may serve as proof of the concept of neovascular tumor targeting therapy by cationic liposomes.

Additional calcar support using a blade device reduces secondary varus displacement following reconstruction of the proximal humerus: a prospective study.

BACKGROUND: Locking plate fixation of displaced fractures of the proximal humerus is still accompanied by a distinct complication rate, especially in case of osteoporotic bone, short-segment fracture length and comminution of the medial calcar. Secondary loss of reduction leading to varus deformity and screw cutout most frequently lead to surgical revision. The aim of the present study was to evaluate the clinical and radiological outcome of a recently developed polyaxial locking plate that allows for the additional placement of a helical blade device, aiming for support of the medial calcar. METHODS: In this prospective study, 17 patients with a mean age of 63.0 ± 16.0 years suffering from displaced fractures of the proximal humerus (Neer type two-, three- and four-part) were enrolled. All patients were surgically treated using a polyaxial locking plate with additional blade device (group PAB, n = 12) or without blade device (group PA, n = 5). Functional outcome was recorded using the Munich Shoulder Questionnaire allowing for qualitative self-assessment of the Shoulder Pain and Disability Index (SPADI), the Disability of the Arm, Shoulder and Hand (DASH score) and the Constant Score. Radiological outcome was assessed by analyzing standardized true anterior-posterior and outlet-view radiographs with respect to radiographic evidence of secondary varus displacement, cutout of screws and hardware failure. Results were compared to an age-, gender- and fracture type-matched collective treated by monoaxial locking plate fixation (group MA, n = 15). RESULTS: The mean follow-up was 12.4 ± 2.9 months after surgery. There were no statistical significant differences in clinical outcome in all three groups. Group MA and group PA revealed significant secondary varus displacement in comparison to group PAB at the final follow-up compared to postoperative analysis (p < 0.001). The distance between the blade and the articular surface showed no significant increase in group PAB at the final follow-up compared to postoperative analysis. Not-implant-related complications were seen in one and implant-related complications were seen in two patients in group PAB. CONCLUSIONS: Polyaxial locking plate fixation with a blade device to restore medial cortical support reduces the risk of secondary varus displacement even in proximal humeral fractures of the elderly in comparison to monoaxial and polyaxial locking plate fixation without blade insertion.

Avascular necrosis following fracture-dislocation of the hip and spontaneous relocation.

Injuries occurring during soccer tend to occur with lower energy transfer than in some other contact sports. Tibial and femoral shaft fractures occasionally occur, but pelvic fractures are rare. We report a case of a missed posterior acetabular rim fracture, caused by a low energy trauma playing soccer, complicated by the development of avascular necrosis (AVN) of the femoral head and subsequent osteoarthritis.

Avascular necrosis of the femoral head: inter- and intraobserver variations of Ficat and ARCO classifications.

Diagnosis of avascular necrosis (AVN) of the femoral head depends on the combination of clinical symptoms and evaluation of radiographs and/or magnetic resonance imaging (MRI). To evaluate the evolution of AVN, the Ficat and the Association Research Circulation Osseous (ARCO) classification are commonly used to assess both imaging modalities. For comparison reasons, these classifications need to be reliable and reproducible to provide sufficient therapy options for the patient. Therefore, the aim of our study was to evaluate the interobserver reliability and the intraobserver reproducibility of these classifications. Patients with suspected AVN were examined using either radiographs or radiographs and MRI. The radiographs and/or MR images were reviewed initially and at 3 months by two general orthopaedic surgeons, two orthopaedic residents, and two general radiologists using the Ficat classification for radiographs and MR images as well as the ARCO classification for MR images only. In all, 38 patients (54 hips) were enrolled. There were 10 patients who presented with radiographs and 28 patients with radiographs and MR scans. Paired comparisons revealed a mean interobserver kappa reliability coefficient of 0.39 for the first and of 0.32 for the second review using the Ficat classification for radiographs, whereas for the MR images a mean of 0.39 in the first and of 0.34 in the second reading resulted. The MRI evaluation using the ARCO classification resulted in a mean interobserver reliability coefficient of 0.37 in the first and of 0.31 in the second reading. The mean kappa value for intraobserver reproducibility using the Ficat classification was 0.52 for radiographs and 0.50 for MR images, whereas a reproducibility of 0.43 resulted for the ARCO classification. This study showed poor interobserver reliability and fair intraobserver variability, diminishing any meaningful comparison of studies using the Ficat as well as the ARCO classification. Thus, the Ficat and ARCO staging systems are still not sufficient to reliably assess the status of AVN alone.

Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels.

Recently, cationic liposomes have been shown to preferentially target the angiogenic endothelium of tumors. It was the aim of our study to investigate the influence of liposomal surface charge on the uptake and kinetics of liposomes into solid tumors and tumor vasculature. Experiments were performed in the amelanotic hamster melanoma A-Mel-3 growing in the dorsal skinfold chamber preparation of male Syrian golden hamsters. Fluorescently labeled liposomes with different surface charge were prepared. Accumulation of i.v. injected liposomes was assessed by quantitative intravital fluorescence microscopy of tumor and surrounding host tissue. The histological distribution of liposomes was analyzed by double-fluorescence microscopy 20 min after application of fluorescently labeled lectin as a vascular marker. After i.v. application of anionic and neutral liposomes, we observed an almost homogeneous distribution of liposome-induced fluorescence throughout the chamber preparation without specific targeting to tumor tissue. In contrast, cationic liposomes exhibited a significantly enhanced accumulation in tumor tissue and tumor vasculature up to 3-fold compared to surrounding tissue (p<0.05). The histological distribution of neutral and anionic liposomes revealed extravasation 20 min after i.v. injection, while cationic liposomes displayed a highly selective accumulation on the vascular endothelium. In conclusion, cationic liposomes exhibited a preferential uptake in angiogenic tumor vessels and therefore may provide an efficient tool for the selective delivery of diagnostic or therapeutic agents to angiogenic blood vessels of solid tumors. On the other hand, anionic and neutral liposomes may be used as carriers of drugs to the extravascular compartment of tumors due to their extravasation.