The systemic drug circulation represents a source of adverse effects during tumor targeting. We studied the binding efficacy of endothelium-specific antibodies after a very short contact with an antigen target, along with assessing the intravascular capture and targeting potential of these antibodies after locoregional injection. Fast-binding anti-CD 146 (clone ME-9F1) and anti-CD31 (clone 390) antibodies were selected based on histological analysis of their binding activity. The efficacy of antibody capture by hepatic endothelium under different conditions was analyzed using an isolated liver perfusion model. The local enrichment of R-phycoerythrin and I-conjugated antibody was studied in vivo in two hepatic tumor models using biodistribution, scintigraphic imaging, and fluorescence microscopy. Upon injection into the tumor-feeding artery, the antibody was immediately captured in the microvasculature during the first passage. At doses not exceeding the saturation level of endothelial epitopes, the capture efficacy was almost 90%. We showed that the efficacy of endothelial capture is controlled by factors such as antibody affinity, number of binding sites on the endothelium, and microvascular flow rate. The targeting potential of endothelial capture was experimentally proven in vivo using scintigraphic imaging and biodistribution analysis after locoregional intra-arterial injection of I-labeled antibodies in hepatic tumor models. Conclusion: The unique phenomenon of endothelial capture can broadly prevent systemic circulation of the antibody or antibody-drug conjugates applied by intravascular injection and may have specific relevance for targeting of hepatic tumors.
Background Vascular malformations are rare diseases that are best managed in multidisciplinary vascular anomaly centers (VAC). So far, there are few published data on the logistic structure, patient allotment, and internal workflow in an interdisciplinary VAC. Purpose To demonstrate the referral structure and patient allotment in a European VAC. Material and Methods A retrospective cohort study was conducted. All patients treated in the VAC since its establishment in April 2014 until June 2020 were identified. A total of 461 patients were included in this study. Results Most often, a venous malformation was diagnosed (49.9%), followed by arteriovenous malformations (8.7%) and syndromal vascular malformations (8.2%). Only 45.1% of referral diagnoses were correct. Of referrals, 35.1% were internal on-campus references, 28.0% were external references through physicians in private practice, and 19.7% came via external cooperating hospitals. Of the patients, 17.1% were self-admissions without a referral. Conclusion The most important referring clinics are internal medicine, pediatric, and vascular surgery. A substantial proportion of referrals came from private practices. Recruiting these cooperation partners should be considered a high priority when establishing a new VAC. The rate of misdiagnosis is high, and more education of fellow clinicians is urgently needed. Therefore, patients with vascular malformations should be referred to and treated in dedicated centers for vascular anomalies.
Late free flap failures due to pedicle obstruction are rare adverse events. The purpose of this report is to present a case in which the near-infrared indocyanine green video angiography (ICG-NIR-VA) was used to evaluate the perfusion in a compromised fasciocutaneous flap in the late postoperative period. A 55-year-old male patient, who initially suffered from an open tibial fracture, developed concurrent osteomyelitis with fistulae of the proximal tibia requiring excision. Reconstruction was achieved using a parascapular flap of 25 × 8 cm, anastomosed to an arterio-venous (AV) Loop in the adductor canal. On the 2nd postoperative day the patient developed a thrombosis of the AV-Loop. After thrombectomy, the postoperative course was uneventful. Seven weeks postoperatively the patient presented with a mottled, partially bluish and cold flap. Anticoagulation prophylaxis was stopped 2 days earlier. Angiography confirmed a thrombus in the arterial pedicle leading to flap ischemia. Near infrared guided fluorescence imaging revealed a delayed recapillarization of the proximal part of the flap closest to the vascular pedicle, albeit flap overall perfusion remained intact. Thus, no surgical intervention was undertaken. However, anticoagulation and prostaglandin therapy was initiated and the flap was salvaged. Genetic analysis uncovered a polymorphism in the prothrombin genes. The flap remained viable and without further complications until the last follow-up visit at 36 weeks after microsurgical reconstruction. The patient was fully mobilized with complete return to function. Near-infrared guided fluorescence imaging may be a viable tool for the assessment of late fasciocutaneous free flap complications and guide the decision-making process.
Aneurysms of the external iliac artery are extremely rare. We present a case of a middle-aged male patient with calf claudication owing to peripheral arterial embolism on the basis of a thrombosed true aneurysm of the external iliac artery caused by cystic media necrosis. Vascular imaging established the diagnosis and we proceeded to removal of the aneurysm via open repair, with excellent surgical and clinical results.
Background: Intraarterial injection into the hepatic artery represents an important route for locoregional administration for the treatment of hepatic tumors. In the present work, we describe microsurgical methodology for injection into the hepatic artery in mice. The technique was recently used for analysis of the phenomenon of endothelial capture in liver tumors. Methods: Two different models of hepatic tumors in C57BL/6 mice were used. Tumors were induced by intrahepatic cell inoculation. The preferential blood supply of tumors was studied using blocking of bioavailability of nontumoral endothelial epitope and the subsequent injection of fluorescent endothelium-specific antibody. The selective intraarterial injection of labeled antibody was performed in tumor-bearing mice. The procedure addressed variations of vascular anatomy of the hepatic artery in mice and used direct intraarterial injection with dispensable catheterization. Results: Both experimental tumor models showed preferential blood supply from the hepatic artery. The technique of hepatic arterial injection was adapted and performed according to two major anatomic variations of the hepatic artery. Using this technique, the selective enrichment of labeled antibody to tumor and liver blood vessels, which were perfused during the first intravascular passage, was demonstrated. Conclusions: The experimental hepatic arterial injection in mice is a feasible but demanding microsurgical procedure. The choice of subsequent operation steps is dependent on the vascular anatomy of the hepatic artery which has two major variations in mice.
Background: Complex scalp defects are regularly reconstructed using microvascular tissue transfer. The latissimus dorsi free flap is one of the workhorse flaps used in scalp reconstruction. These cases necessitate, particularly in the elderly, a close cooperation between plastic surgeons and neurosurgeons. The purpose of this study was to evaluate the suitability of the latissimus dorsi free flap for complex scalp reconstructions and to analyze potential risk factors. Methods: A retrospective study identified 43 patients undergoing complex scalp reconstruction using a latissimus dorsi free flap at our department between 2010 and 2022. Results: The mean patient age was 61 ± 18 years. Defects were mostly caused by oncologic tumor resections (n = 23; 55%), exposure to a cranioplasty (n = 10; 23%) or infection (n = 4; 9%). The most frequent recipient vessels were the superficial temporal artery (n = 28; 65%), external carotid artery (n = 12; 28%) and the venae comitantes (n = 28; 65%), external jugular vein (n = 6; 14%). The reconstructive success rate was 97.7%. There was one total flap loss (2%). Partial flap loss occurred in five cases (12%). Follow-up was 8 ± 12 months. Major complications were seen in 13 cases, resulting in a revision rate of 26%. Multivariate logistic regression identified active tobacco use as the only risk factor for major complications (odds ratio 8.9; p = 0.04). Conclusion: Reconstruction of complex scalp defects using the latissimus dorsi free flap yielded high success rates. Among the potential risk factors, active tobacco use seems to affect the outcome of complex scalp reconstructions.
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