Intranodal embolization for lymphocele after revascularization procedure in the groin.

Early postoperative wound complications in revascularization procedures in the groin very often include complications associated with injury to the lymphatic system such as lymphocele and lymphorrhea with subsequent local infectious complications and the risk of infection of prosthetic grafts. We present a case report of successful treatment of postoperative lymphocele with subsequent lymphatic fistula and dehiscence of the surgical wound by intranodal embolization of the injured lymph node with Histoacryl tissue glue.

Efficacy of Preemptive Embolization of Sac Branches During Endovascular Aneurysm Repair Using N-butyl-2-cyanoacrylate.

OBJECTIVE: A type 2 endoleak (T2EL) is the most frequently occurring endoleak type after endovascular aneurysm repair (EVAR). Residual T2ELs may cause aneurysm rupture; however, the management of a T2EL remains controversial. This study evaluated sac branch preemptive embolization using N-butyl-2-cyanoacrylate, aiming to prevent T2ELs and sac shrinkage. METHODS: Twelve consecutive patients underwent elective preemptive embolization during EVAR at our hospital between August 2018 to March 2019. Their demographic information, operative details, and sac diameters were examined at 6 months after EVAR. RESULTS: No procedural complications were observed. There were no in-hospital deaths among the 12 patients. Sac shrinkage was observed in this cohort (53.8-52.1 mm, p = 0.01). A total of 33 lumbar arteries were occluded with this procedure, and 2 patients had residual T2ELs at 6 months. CONCLUSIONS: A T2EL in preemptive sac branch embolization during EVAR has advantages in terms of safety and reduction. Although no clear evidence is available for the management of T2ELs, this study proposes a new standard to prevent it and improve the long-term outcomes after EVAR. However, embolization remains imperfect and further research is necessary.

High-Speed Optical Characterization of Protein-and-Nanoparticle-Stabilized Microbubbles for Ultrasound-Triggered Drug Release.

OBJECTIVE: Ultrasound-triggered bubble-mediated local drug delivery has shown potential to increase therapeutic efficacy and reduce systemic side effects, by loading drugs into the microbubble shell and triggering delivery of the payload on demand using ultrasound. Understanding the behavior of the microbubbles in response to ultrasound is crucial for efficient and controlled release. METHODS: In this work, the response of microbubbles with a coating consisting of poly(2-ethyl-butyl cyanoacrylate) (PEBCA) nanoparticles and denatured casein was characterized. High-speed recordings were taken of single microbubbles, in both bright field and fluorescence. RESULTS: The nanoparticle-loaded microbubbles show resonance behavior, but with a large variation in response, revealing a substantial interbubble variation in mechanical shell properties. The probability of shell rupture and the probability of nanoparticle release were found to strongly depend on microbubble size, and the most effective size was inversely proportional to the driving frequency. The probabilities of both rupture and release increased with increasing driving pressure amplitude. Rupture of the microbubble shell occurred after fewer cycles of ultrasound as the driving pressure amplitude or driving frequency was increased. CONCLUSION: The results highlight the importance of careful selection of the driving frequency, driving pressure amplitude and duration of ultrasound to achieve the most efficient ultrasound-triggered shell rupture and nanoparticle release of protein-and-nanoparticle-stabilized microbubbles.

Feasibility and safety of direct percutaneous embolization of lymphopseudoaneurysm for postoperative lymphatic leakage.

The treatment strategy for refractory postoperative lymphatic leakage is controversial. While the utility of direct percutaneous embolization of lymphopseudoaneurysm has been investigated, only a few reports on this topic exist. The aim of this study was to evaluate the technical and clinical feasibility and safety of direct percutaneous embolization of lymphopseudoaneurysm for refractory postoperative lymphatic leakage. This case series included six consecutive patients who underwent direct percutaneous embolization of lymphopseudoaneurysm for refractory postoperative lymphatic leakage. Technical success (successful percutaneous approach and injection of NBCA glue to the lymphopseudoaneurysm), clinical success (unnecessity of percutaneous drainage tube of the lymphatic leakage), treatment duration (the duration from the treatment to the achievement of clinical success) and procedure-related complications were mainly evaluated. Direct percutaneous embolization of the lymphopseudoaneurysm using NBCA glue was successfully performed in all cases. Clinical success was achieved in five of the six cases (83%). The mean treatment period was 9 days for the cases with clinical success. No major complications occurred postoperatively. In conclusion, direct percutaneous embolization of lymphopseudoaneurysm may become a feasible and safe treatment option for cases of refractory postoperative lymphatic leakage.

An Alternative Endovascular Technique for Treatment of Pulmonary Arteriovenous Malformation: Microballoon-occluded Transcatheter Embolization Using n-butyl-2-cyanoacrylate.

PURPOSE: To investigate the safety and efficacy of microballoon-occluded transcatheter embolization using n-butyl-2-cyanoacrylate (NBCA) in patients with a single pulmonary arteriovenous malformation (PAVM). METHODS: From November 2017 to November 2020, this retrospective study included 38 previously untreated patients with a single PAVM who underwent microballoon-occluded transcatheter embolization using NBCA. All 38 patients had follow-up that included simple chest radiography and contrast-enhanced chest computed tomography (CT). RESULTS: A microballoon was successfully placed in a feeding artery of the PAVM to control the delivery of the NBCA cast in all 38 patients, with complete embolization of sacs and the feeding artery achieved in all cases. The mean diameters of the feeding artery, sac, and draining vein were 3.9 ± 0.9 mm, 7.5 ± 2.6 mm, and 4.6 ± 1.3 mm, respectively. A fixed 1:2 NBCA/Lipiodol ratio was used, and the mean amount of embolic mixture per patient was 1.4 mL (range 0.6-2.2 mL). There were no complications related to microballoon adhesion and non-target embolization of the systemic circulation. Follow-up CT in all 38 patients with a mean delay of 34.5 ± 8.8 months (range 20.7-56.5 months) showed no continued perfusion of the PAVM. CONCLUSION: In our hands, microballoon-occluded n-butyl-2-cyanoacrylate embolization seemed to be safe and appeared to be clinically effective in patients with simple and complex types of single PAVM. Therefore, the present technique has the potential to become a standard treatment for a single PAVM.

Efficacy of Endoscopic Tissue Adhesive in Patients with Gastrointestinal Tumor Bleeding.

BACKGROUND: Gastrointestinal tumors bleeding remains a significantly clinical challenge due to its resistance to conventional endoscopic hemostasis methods. While the efficacy of endoscopic tissue adhesives (ETA) in variceal bleeding has been established, its role in gastrointestinal tumor bleeding (GITB) remains ambiguous. AIMS: This study aims to assess the feasibility and effectiveness of ETA in the treatment of GITB. METHODS: The study enrolled 30 patients with GITB who underwent hemostasis through Histoacryl® tissue glue injection. Hemostasis success rates, ETA-related adverse events, and re-bleeding rates were evaluated. RESULTS: ETA application achieved successful hemostasis at all tumor bleeding sites, with immediate hemostasis observed in all 30 (100.0%) patients. Among the initially hemostasis cases, 5 patients (17.0%) experienced re-bleeding within 30 days, and the 60 day re-bleeding rate was 20.0% (6/30). Expect for one case of vascular embolism, no adverse events related with ETA application were reported. The 6 month survival was 93%. CONCLUSION: ETA demonstrated excellent immediate hemostasis success rate in GITB cases and showed promising outcomes in prevention re-bleeding.

Outcomes of endoscopic sclerotherapy for jejunal varices at the site of choledochojejunostomy (with video): Three case reports.

BACKGROUND: Hemorrhage associated with varices at the site of choledochojejunostomy is an unusual, difficult to treat, and often fatal manifestation of portal hypertension. So far, no treatment guidelines have been established. CASE SUMMARY: We reported three patients with jejunal varices at the site of choledochojejunostomy managed by endoscopic sclerotherapy with lauromacrogol/α-butyl cyanoacrylate injection at our institution between June 2021 and August 2023. We reviewed all patient records, clinical presentation, endoscopic findings and treatment, outcomes and follow-up. Three patients who underwent pancreaticoduodenectomy with a Whipple anastomosis were examined using conventional upper gastrointestinal endoscopy for suspected hemorrhage from the afferent jejunal loop. Varices with stigmata of recent hemorrhage or active hemorrhage were observed around the choledochojejunostomy site in all three patients. Endoscopic injection of lauromacrogol/α-butyl cyanoacrylate was carried out at jejunal varices for all three patients. The bleeding ceased and patency was observed for 26 and 2 months in two patients. In one patient with multiorgan failure and internal environment disturbance, rebleeding occurred 1 month after endoscopic sclerotherapy, and despite a second endoscopic sclerotherapy, repeated episodes of bleeding and multiorgan failure resulted in eventual death. CONCLUSION: We conclude that endoscopic sclerotherapy with lauromacrogol/α-butyl cyanoacrylate injection can be an easy, effective, safe and low-cost treatment option for jejunal varicose bleeding at the site of choledochojejunostomy.

A new agent for contrast-enhanced intravascular ultrasound imaging in vitro: polybutylcyanoacrylate nanoparticles with drug-carrying capacity.

This study prepared and evaluated polymeric polybutylcyanoacrylate (PBCA) nanoparticles (NPs) that can be used as a new agent for contrast-enhanced intravascular ultrasound (IVUS) imaging with drug delivery capacity. The nanoformulation was successfully developed using suspension polymerisation and characterised in terms of size, size distribution, zeta potential, morphology, stability, toxicity effects, imaging effects and drug release study. The results showed that the nanoparticles were round and hollow, with a particle diameter of 215.8 ± 25.3 nm and a zeta potential of -22.2 ± 4.1 mV. In vitro experiments, the nanoparticles were safe, non-toxic, and stable in nature with the capacity to carry and release drug (ant-miR-126). Moreover, the nanoparticles can match the high-frequency probe of commercially IVUS as a contrast agent to improve the resolution of imaging (the mean echo intensity ratio in the vascular wall increased significantly from 10.89 ± 1.10 at baseline, to 24.51 ± 1.91 during injection and 43.70 ± 0.88 after injection, respectively p < .0001). Overall, a new nano agent with drug-carrying capacity was prepared, which can be used in combination with IVUS for simultaneous diagnosis and targeted therapy of coronary atherosclerosis.

Transarterial Embolization of Renal Arteriovenous Malformations: Treatment Outcomes According to Angiographic Classification.

PURPOSE: To assess the different adjunctive catheter techniques required to achieve complete occlusion of renal arteriovenous malformations (rAVMs) of different angioarchitectural types. MATERIALS AND METHODS: Overall, data on 18 patients with rAVM (Type 1, n = 7; Type 2, n = 2; Type 3, n = 9; mean age, 53.8 years) who underwent 25 procedures between 2011 and 2022 were reviewed. The clinical presentations, endovascular techniques, arteriovenous malformation (AVM) occlusion rate, adverse events (including the incidence of renal infarction), and clinical symptoms and outcomes (including recurrence/increase of AVM) were analyzed according to the Cho-Do angioarchitectural classification. Posttreatment renal infarction was classified as no infarction, small infarction (<12.5%), medium infarction (12.5%-25%), and large infarction (>25%) using contrast-enhanced computed tomography or magnetic resonance imaging. RESULTS: Hematuria and heart failure were presenting symptoms in 10 and 2 patients, respectively. The embolic materials used were as follows: Type 1 rAVM, coils alone or with n-butyl-2-cyanoacrylate (nBCA); Type 2 rAVM, nBCA alone or with coils; and Type 3 rAVMs, nBCA alone. Fourteen patients underwent adjunctive catheter techniques, including flow control with a balloon catheter and multiple microcatheter placement, alone or in combination. Immediate postprocedural angiography revealed complete occlusion in 15 patients (83%) and marked regression of rAVM in 3 (17%). Small asymptomatic renal infarctions were observed in 6 patients with Type 3 rAVMs without any decrease in renal function. No major adverse events were observed. All symptomatic patients experienced symptom resolution. Recurrence/increase of rAVM was not observed during the mean 32-month follow-up period (range, 2-120 months). CONCLUSIONS: Transarterial embolization using adjunctive catheter techniques according to angioarchitectural types can be an effective treatment for rAVMs.

Blood-Nanoparticle Interactions Create a Brain Delivery Superhighway for Doxorubicin.

Purpose: This study investigated the brain targeting mechanism of doxorubicin-loaded polybutyl cyanoacrylate (PBCA) nanoparticles, particularly their interactions with the blood-brain barrier (BBB). The BBB protects the brain from drugs in the bloodstream and represents a crucial obstacle in the treatment of brain cancer. Methods: An advanced computer model analyzed the brain delivery of two distinct formulations, Doxil® and surfactant-coated PBCA nanoparticles. Computational learning was combined with in vitro release and cell interaction studies to comprehend the underlying brain delivery pathways. Results: Our analysis yielded a surprising discovery regarding the brain delivery mechanism of PBCA nanoparticles. While Doxil® exhibited the expected behavior, accumulating in the brain through extravasation in tumor tissue, PBCA nanoparticles employed a unique and previously uncharacterized mechanism. They underwent cell hitchhiking, resulting in a remarkable more than 1000-fold increase in brain permeation rate compared to Doxil® (2.59 × 10-4 vs 0.32 h-1). Conclusion: The nonspecific binding to blood cells facilitated and intensified interactions of surfactant-coated PBCA nanoparticles with the vascular endothelium, leading to enhanced transcytosis. Consequently, the significant increase in circulation time in the bloodstream, coupled with improved receptor interactions, contributes to this remarkable uptake of doxorubicin into the brain.

Comparison of outcomes with/without preoperative embolization for meningiomas with diluted N-butyl-2-cyanoacrylate.

BACKGROUND: Preoperative embolization for meningiomas is controversial regarding its effectiveness in reducing intraoperative blood loss and operative time. In contrast, some reports have documented improved surgical outcomes in large meningiomas. In this study, we retrospectively compared the outcomes of craniotomy for meningiomas with/without preoperative embolization with diluted N-butyl-2-cyanoacrylate (NBCA) primarily in a single institution. METHODS: Data (World Health Organization grade, Simpson grade, maximum tumor diameter, intraoperative bleeding, operative time, history of hypertension, and time from embolization to craniotomy) of patients with initial intracranial meningiomas were compared with or without preoperative embolization from January 2015 to April 2022. RESULTS: The embolization group consisted of 56 patients and the nonembolization group included 76 patients. Diluted NBCA (13% concentration for all patients) was used in 51 of 56 patients (91.1%) who underwent transarterial embolization. Permanent neurological complications occurred in 2 (3.6%) patients. Intraoperative bleeding was significantly lower in the embolization group for a maximum tumor diameter ≥40 mm (155 vs. 305 ml, respectively, p < 0.01). In the nonembolization group, for a maximum tumor diameter ≥30 mm, patients with hypertension had more intraoperative bleeding than non-hypertensive ones. CONCLUSIONS: Despite its limitations, the present results showed that, under certain conditions, preoperative embolization for intracranial meningiomas caused less intraoperative bleeding. The safety of treatment was comparable with that reported in the Japan Registry of NeuroEndovascular Therapy 3 (JR-NET3) with a complication rate of 3.7% for preoperative embolization of meningiomas, despite the treatment focused on the liquid embolization material.

Hypersensitivity reactions following vein closure therapy with venasealTM (n-butyl- 2-cyanoacrylate).

VenaSealTM is composed of a cyanoacrylate adhesive compound often utilized for chronic venous stasis treatment. Rare case reports of hypersensitivity reactions to this compound exist. We present the first case of dermatographism and angioedema after utilization of VenaSealTM successfully treated via high dose antihistamines. We also present a case of type IV hypersensitivity to VenaSealTM, a cyanoacrylate, occurring in a patient with known meth(acrylate) allergy indicating a possible cross reactivity between these acrylate groups.

Transcatheter arterial embolization with N-butyl cyanoacrylate for postoperative hemorrhage treatment following pancreatoduodenectomy.

PURPOSE: Postoperative hemorrhage (PPH) is a severe complication of pancreatoduodenectomy (PD) with a mortality rate of 5-20.2% and mortality due to hemorrhage of 11-58%. Transcatheter arterial embolization (TAE) has been widely recommended for PPH, however, TAE with N-butyl cyanoacrylate (NBCA) for PPH treatment has been reported rarely. Therefore, this study aimed to evaluate the safety and efficacy of TAE with NBCA for PPH treatment following PD. METHODS: This retrospective study included 14 male patients (mean age, 60.93 ± 10.97 years) with postoperative hemorrhage following PD treated with TAE using NBCA as the main embolic agent from October 2019 to February 2022. The clinical data, technical and success rate, and complications were analyzed. RESULTS: Among the 14 patients who underwent TAE, the technical and clinical success rates were 100 and 85.71%, respectively. Angiography revealed contrast extravasation in 12 cases and a pseudoaneurysm in 3 cases. One patient developed a serious infection and died 2 days after the TAE. CONCLUSION: TAE with NBCA for PPH treatment following PD, especially for massive hemorrhage caused by a pancreatic fistula, biliary fistula, or inflammatory corrosion, can result in rapid and effective hemostasis with high safety.

mRNA Sonotransfection of Tumors with Polymeric Microbubbles: Co-Formulation versus Co-Administration.

Despite its high potential, non-viral gene therapy of cancer remains challenging due to inefficient nucleic acid delivery. Ultrasound (US) with microbubbles (MB) can open biological barriers and thus improve DNA and mRNA passage. Polymeric MB are an interesting alternative to clinically used lipid-coated MB because of their high stability, narrow size distribution, and easy functionalization. However, besides choosing the ideal MB, it remains unclear whether nanocarrier-encapsulated mRNA should be administered separately (co-administration) or conjugated to MB (co-formulation). Therefore, the impact of poly(n-butyl cyanoacrylate) MB co-administration with mRNA-DOTAP/DOPE lipoplexes or their co-formulation on the transfection of cancer cells in vitro and in vivo is analyzed. Sonotransfection improved mRNA delivery into 4T1 breast cancer cells in vitro with co-administration being more efficient than co-formulation. In vivo, the co-administration sonotransfection approach also resulted in higher transfection efficiency and reached deeper into the tumor tissue. On the contrary, co-formulation mainly promoted transfection of endothelial and perivascular cells. Furthermore, the co-formulation approach is much more dependent on the US trigger, resulting in significantly lower off-site transfection. Thus, the findings indicate that the choice of co-administration or co-formulation in sonotransfection should depend on the targeted cell population, tolerable off-site transfection, and the therapeutic purpose.

Injection of n-Butyl-2-Cyanoacrylate into the Abdominal Aortic Aneurysm Sac during Endovascular Aortic Repair to Prevent Type II Endoleaks Caused by Lumbar Arteries.

PURPOSE: To evaluate midterm results of whether the strategy to occlude target lumbar arteries using n-butyl-2-cyanoacrylate (nBCA) injection during endovascular aneurysm repair (EVAR) reduced the incidence of Type II endoleak (T2EL) after EVAR. MATERIALS AND METHODS: Between 2013 and 2020, 187 patients underwent EVAR; 106 in the treatment group received nBCA injection during EVAR, whereas 81 in the historical control group did not. The incidence of T2EL at 7 days, need for reintervention, and post-EVAR aneurysmal shrinkage were compared between the groups. RESULTS: Between the treatment group and the control group, significant differences were achieved in the incidence of T2EL (2.8% vs 28.4%; P < .0001) and decreased aneurysmal diameter was observed at 1 year after EVAR (-5.2 vs -3.8 mm; P = .034). In multivariate analysis, nBCA injection (odds ratio [OR], 0.04; P = .001) and younger age (OR, 0.92; P = .036) were significantly associated with a reduced incidence of T2EL. As a possible adverse event associated with nBCA injection, 2 cases of transient lower-limb motor dysfunction (1.9%) were observed. Propensity score analysis revealed that the treatment group had a significantly lower incidence of T2EL than that in the control group (P = .0002) even though there was no difference in the incidence of inferior mesenteric artery coil embolization between the groups. The survival rate without aneurysm sac enlargement (100.0% vs 69.8%; P = .014) and the reintervention-free rate (100.0% vs 63.1%; P = .034) in the treatment group were significantly higher than those in the control group. CONCLUSIONS: Concomitant nBCA injection can provide durable EVAR without T2EL, as supported by the avoidance of reintervention associated with aneurysm sac enlargement.

Blocked-flow vs. free-flow cyanoacrylate glue embolization: Histological differences in an in vivo rabbit renal artery model.

PURPOSE: The purpose of this in vivo animal study was to compare the acute histological effects on the arterial vessel wall of free-flow vs. blocked-flow embolization with metacryloxysulfolane-n­butyl cyanoacrylate (MS-NBCA) in several concentrations. MATERIALS AND METHODS: A total of 42 rabbit renal arteries were embolized using MS-NBCA mixed with ethiodized oil. The MS-NBCA concentration was 12.5%, 25%, or 50%. All mixtures were injected under both free-flow and blocked-flow conditions. The rabbits were euthanised 30 min after arterial embolization. Arterial-lumen distension, intimal inflammation and necrosis, peri­arterial edema, and distality of MS-NBCA penetration were assessed histologically. Multivariable regression analyses were performed using a manual backward procedure, with linear, ordinal and logistic regression to search for factors associated with these outcomes RESULTS: Marked or severe dilatation was observed in 36 out of 42 arteries (86%) and marked or transmural intimal arteritis in all 42 arteries (42/42; 100%). Lumen dilatation caused focal vessel-wall flattening, which resulted in intimal necrosis. Multifocal necrosis extending from the intima to the media occurred in 23 out of 42 kidneys (55%) and peri­arterial edema with multifocal vascular leakage in 19 out of 42 kidneys (45%). At multivariable analysis, blocked-flow MS-NBCA injection was associated with greater severity of vessel-wall lesions, including intimal arteritis (P = 0.003) and intimal necrosis (P = 0.014), compared to free-flow injection. Blocked-flow injection was also associated with peri­arterial edema (P = 0.008) and greater distality of MS-NBCA penetration (P = 0.001). CONCLUSION: Blocked-flow MS-NBCA injection during renal artery embolization is significantly associated with more acute arterial-wall damage and greater distality of glue penetration compared to free-flow injection in a rabbit model. These preliminary findings may have clinical implications, as blocked-flow injection is routinely used to treat specific vascular diseases or malformations in human.

Bronchial artery embolization in patients with life-threatening massive hemoptysis: comparison of the efficacy and safety of particulate embolizing agents and n-2-butyl-cyanoacrylate.

OBJECTIVE: Comparing the efficacy and safety of particulate [microspheres/polyvinyl alcohol (PVA)] and non-particulate [n-butyl-2-cyanoacrylate (NBCA)] agents used as the embolic agents for bronchial artery embolization (BAE) intervention in patients experiencing massive hemoptysis. PATIENTS AND METHODS: A total of 58 individuals (47 male, 11 female, standard deviation = 53.9 ± 14.8, age range = 18-84) were recruited for a retrospective study in a single unit. Thirty (51.7%) of the patients underwent BAE intervention with NBCA, and 28 (48.3%) underwent the same procedure with a particulate embolizing agent (microspheres/PVA). The demographic distribution of the patients, the etiological factors, the technical and clinical success rates, and complications were documented, with the two groups subsequently compared. RESULTS: The technical and clinical success rates following the procedure were 100% for both groups. The average follow-up duration was 34 months in the NBCA group and 33.5 months in the particulate embolizing agent group. In comparison, the rate of recurrent hemoptysis was 3.3% in the former and 17.9% in the latter, with the presence of recurrent hemoptysis not statistically different between the two groups (p = 0.097). Major complications and procedural death did not occur in either of the samples. CONCLUSIONS: The use of NBCA in BAE presents a safe and effective method. The combination of NBCA and particulate embolizing agents (PVA/microspheres) achieved equal technical and clinical success and significantly increased the hemoptysis-free survival rates in terms of life-threatening hemoptysis. MAIN POINTS: (1) In managing massive hemoptysis, using NBCA is a safe and effective method similar to using particulate embolizing agents. (2) Although not statistically significant, recurrent hemoptysis is observed less frequently in the NBCA group. (3) Technique and clinical success were relatively high and similar in the groups where NBCA and particulate embolizing agents were used.