Oklu, Rahmi

Transarterial embolization has shown promise as a safe, effective, and less invasive treatment modality for benign liver lesions (hemangioma, focal nodular hyperplasia (FNH), and hepatic adenoma (HA)) with fewer complications compared to surgical intervention. There is no consensus regarding the most appropriate embolization material(s) for the treatment of benign liver tumors. The purpose of this study was to review the current literature regarding the transarterial embolization of benign liver tumors and to share our single center experience. This was a non-blinded, retrospective, single-institution review of the bland embolization of benign liver tumors. Clinical data and imaging before and after embolization were used to evaluate lesion response to transarterial embolization. Twelve patients were included in the study. Five patients with six hemangiomas were treated. Pain was a presenting complaint in all five of these patients. The median change in tumor volume was −12.4% and ranged from −30.1% to +42.3%. One patient with two FNH lesions was treated, and both lesion volumes decreased by more than 50%. Six patients with 10 adenomas were treated. Pain was a presenting complaint in three patients, and five patients had a lesion >5 cm. The median change in tumor volume was −67.0% and ranged from −92.9% to +65.8%. Bland transarterial embolization of liver hemangiomas, FNH, and HA can be an effective and minimally invasive treatment modality to control the size and/or symptoms of these lesions. There is a variable response depending on tumor type and the embolization materials used.

An ionic liquid formulation ablates tumors, uniformly distributes drugs in the ablation zone, and has synergistic effects with chemotherapy.

Abstract Purpose177Lu-PSMA is a promising therapy for patients with metastatic castration resistant prostate cancer patients (mCRPC). To our knowledge, no study has compared the pharmacokinetic profiles of 177Lu-PSMA therapy delivered intra-arterially. We aimed to compare the feasibility and safety of selective intra-arterial (IA) administration vs conventional intravenous (IV) administration of 177Lu-PSMA in mCRPC. MethodsIn this within-patient pilot study, four patients (median age, 62.5; range, 53-72) with mCRPC who were referred to our clinic between January 2018 and September 2019 for treatment with 177Lu-PSMA. Patients were treated in two visits; in each visit receiving half of the total empiric therapeutic dose of 200 mCi, IV at the first visit and IA at the second visit. They were followed upto 8 weeks using routine parameters such as hematological status, renal function, and serum PSA levels. For each patient, organ biodistribution in lesions, kidneys, liver, bone marrow, prostate, and whole body was calculated for both administration routes according to the Medical Internal Radiation Dose (MIRD) schema. Mean absorbed doses (MAD) across all patients were compared between both administration routes. ResultsThe MAD of all metastatic lesions was significantly higher by IA vs IV administration (1.59 vs 1.20 MGy/MBq; p=0.024). The prostate gland had a lower MAD between IA and IV administrations, but the difference was not significant (0.27 vs 0.36 MGy/MBq; p=0.22). Patients tolerated IA administration very well without unexpected side effects. ConclusionThese preliminary results of an ongoing study showed that IA 177Lu-PSMA therapy is feasible and safe to treat metastatic lesions, potentially having a higher delivery efficacy compared to IV administration.This study is approved by Cerrahpasa Medical Faculty ethics committee on March 5, 2019 and retrospectively registered with file no: 83045809-604.01.02.

Hepatic artery stenosis after liver transplant is often treated with endovascular stent placement. Our institution has adopted use of drug-eluting stents, particularly in small-caliber arteries. We aimed to compare patency rates of drug-eluting stents vs. traditional bare-metal stents. This was a single-institution, retrospective study of liver transplant hepatic artery stenosis treated with stents. Primary patency was defined as time from stent placement to resistive index on Doppler ultrasonography (<0.5), hepatic artery thrombosis, or any intervention including surgery. Fifty-two patients were treated with stents (31 men; mean age, 57 years): 15, drug-eluting stents; 37, bare-metal stents. Mean arterial diameters were 4.1 mm and 5.1 mm, respectively. Technical success was 100% (52/52). At 6 months, 1, 2, and 3 years, primary patency for drug-eluting stents was 80%, 71%, 71%, and 71%; bare-metal stents: 76%, 65%, 53%, and 46% (p = 0.41). Primary patency for small-caliber arteries (3.5–4.5 mm) with drug-eluting stents was 93%, 75%, 75%, and 75%; bare-metal stents: 60%, 60%, 50%, and 38% (p = 0.19). Overall survival was 100%, 100%, 94%, and 91%. Graft survival was 100%, 98%, 96%, and 90%. Stenting for hepatic artery stenosis was safe and effective. While not statistically significant, patency improved with drug-eluting stents compared with bare-metal stents, especially in arteries < 4.5 mm in diameter. Drug-eluting stents can be considered for liver transplant hepatic artery stenosis, particularly in small-caliber arteries.

AbstractEndovascular embolization to treat vascular hemorrhage involves pushing coil‐shaped metal wires into the artery repeatedly until they are densely packed to slow the blood flow and clot. However, coil embolization is associated with high rebleeding rates, unpredictable economics and, most importantly, they rely on the patient's ability to make a clot. These issues are exacerbated when the patient is anticoagulated or coagulopathic. A novel bioengineered tantalum‐loaded nanocomposite hydrogel for gel embolic material (Ta‐GEM) that can be rapidly delivered using clinical catheters for instant hemostasis regardless of the coagulopathic state is reported. Ta‐GEM formulation is visible by most of the clinically available imaging modalities including ultrasound, computed tomography, magnetic resonance imaging, and fluoroscopy without significant artifact. In addition, Ta‐GEM can be retrieved, allowing temporary vascular occlusion, and it can be used to rescue cases of failed coil embolization. Ta‐GEM occlusion of first‐order arteries such as the renal artery and iliac artery in a swine model is found to be safe and durable; by 28 days, 75% of the injected Ta‐GEM in the arterial lumen is replaced by dense connective tissue. Altogether, this study demonstrates that Ta‐GEM has many advantages over the current technologies and has potential applications in clinical practice.

Minimally invasive endovascular interventions have become the cornerstone of medical practice in the treatment of a variety of vascular diseases. Tools developed for these interventions have also opened new avenues for targeted delivery of therapeutics, such as chemotherapy or radiation therapy, using the vessels as highways into remote lesions. A more ambitious move toward an all‐endovascular approach to acute or chronic conditions, however, is fundamentally hindered by a variety of challenges, such as the complexity of the vascular anatomy, access to smaller vessels, the fragility of diseased vessels, emergency procedure requirements, prolonged exposure to ionizing X‐ray radiation, and patient‐specific factors including coagulopathy. These shortcomings necessitate new advances to the current practice. Smart soft‐body robots that fit the smallest vessels with high‐precision wireless control and autonomous capabilities have the potential to set the future standards of minimally invasive endovascular therapies. Herein, the current state of the small‐scale robotics from the viewpoint of endovascular applications is discussed, and their potential advantages to the existing tethered clinical devices are compared. Then, technical challenges and the clinical requirements toward realistic applications of small‐scale untethered robots inside the vasculature are discussed.

AbstractVascular embolization is a life‐saving minimally invasive catheter‐based procedure performed to treat bleeding vessels. Through these catheters, numerous metallic coils are often pushed into the bleeding artery to stop the blood flow. While there are numerous drawbacks to coil embolization, physician expertise, availability of these coils, and their costs further limit their use. Here, a novel blood‐derived embolic material (BEM) with regenerative properties, that can achieve instant and durable intra‐arterial hemostasis regardless of coagulopathy, is developed. In a large animal model of vascular embolization, it is shown that the BEM can be prepared at the point‐of‐care within 26 min using fresh blood, it can be easily delivered using clinical catheters to embolize renal and iliac arteries, and it can achieve rapid hemostasis in acutely injured vessels. In swine arteries, the BEM increases cellular proliferation, angiogenesis, and connective tissue deposition, suggesting vessel healing and durable vessel occlusion. The BEM has significant advantages over embolic materials used today, making it a promising new tool for embolization.

AbstractImmunotherapy is a class of promising anticancer treatments that has recently gained attention due to surging numbers of FDA approvals and extensive preclinical studies demonstrating efficacy. Nevertheless, further clinical implementation has been limited by high variability in patient response to different immunotherapeutic agents. These treatments currently do not have reliable predictors of efficacy and may lead to side effects. The future development of additional immunotherapy options and the prediction of patient‐specific response to treatment require advanced screening platforms associated with accurate and rapid data interpretation. Advanced engineering approaches ranging from sequencing and gene editing, to tumor organoids engineering, bioprinted tissues, and organs‐on‐a‐chip systems facilitate the screening of cancer immunotherapies by recreating the intrinsic and extrinsic features of a tumor and its microenvironment. High‐throughput platform development and progress in artificial intelligence can also improve the efficiency and accuracy of screening methods. Here, these engineering approaches in screening cancer immunotherapies are highlighted, and a discussion of the future perspectives and challenges associated with these emerging fields to further advance the clinical use of state‐of‐the‐art cancer immunotherapies are provided.

AbstractTranscatheter embolization is a minimally invasive procedure that uses embolic agents to intentionally block diseased or injured blood vessels for therapeutic purposes. Embolic agents in clinical practice are limited by recanalization, risk of non‐target embolization, failure in coagulopathic patients, high cost, and toxicity. Here, a decellularized cardiac extracellular matrix (ECM)‐based nanocomposite hydrogel is developed to provide superior mechanical stability, catheter injectability, retrievability, antibacterial properties, and biological activity to prevent recanalization. The embolic efficacy of the shear‐thinning ECM‐based hydrogel is shown in a porcine survival model of embolization in the iliac artery and the renal artery. The ECM‐based hydrogel promotes arterial vessel wall remodeling and a fibroinflammatory response while undergoing significant biodegradation such that only 25% of the embolic material remains at 14 days. With its unprecedented proregenerative, antibacterial properties coupled with favorable mechanical properties, and its superior performance in anticoagulated blood, the ECM‐based hydrogel has the potential to be a next‐generation biofunctional embolic agent that can successfully treat a wide range of vascular diseases.