ラパマイシン内包ナノ粒子による大動脈瘤形成抑制効果の検討

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 國土 典宏, 東京大学准教授 江頭 正人, 東京大学特任准教授 花房 規男, 東京大学講師 中川 徹, 東京大学講師 石原 聡一郎University of Tokyo(東京大学

Clampless In-Situ Immobilized Branching (CLIMB) to Reconstruct the Internal Iliac Artery

Background: Surgical reconstruction of the internal iliac artery (IIA) or its branches is sometimes demanding because of difficulty in distal clamping and suturing in the narrow pelvic space. Here we present a hybrid technique of ClampLess In-situ imMobilized Branching (CLIMB) to reconstruct IIA. Methods: in the CLIMB technique, an 8 mm artificial graft is sutured onto the surface of the common iliac artery (CIA) without clamping. Following puncture of the CIA wall, stent grafts are bridged from IIA to the graft. Finally, the graft is sutured to the ipsilateral external iliac artery (EIA). Concomitant endovascular aneurysm repair or IIA branch embolization can also be performed. We applied this technique to the patients unsuited for other IIA reconstruction. Results: eleven patients underwent the current technique. All but one patient underwent contralateral IIA interruption. Seven patients had a history of aorto-iliac repair before the index surgery. Iliac extender, internal iliac component, Viabahn VBX or Fluency covered stent were used for bridging the graft. Simultaneous IIA branch embolization was performed in 2 patients. Distal landing zones were IIA in 7 grafts, superior gluteal artery in 4 grafts and inferior gluteal artery (IGA) in 1 graft. Technical success was achieved in all cases. No patient complained of buttock claudication or other ischemic symptoms on the treatment side. During a mean follow-up period of 38 months, 11 out of 12 grafts were patent without any related endoleak. One IGA graft occluded at 56 months after surgery. Conclusions: the CLIMB technique is a viable alternative to preserve IIA with an acceptable mid-term durability

Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats.

Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm

Hemodynamic benefits of celiac artery release for ruptured right gastric artery aneurysm associated with median arcuate ligament syndrome: a case report

Abstract Background It has been reported that median arcuate ligament syndrome is closely associated with gastric or pancreaticoduodenal artery aneurysms. Hemodynamic state plays an important role in the formation of the aneurysms. These aneurysms are treated with open resection or endovascular exclusion. However, whether revascularization of the celiac artery can prevent the aneurysm formation is unknown. This report indicated a possibility that prophylactic revascularization for celiac artery stenosis resulted in decreased shear stress on the collaterals, which may otherwise be susceptible to new aneurysms. Case presentation This report describes a 51-year-old man who presented with epigastric pain at our hospital. According to contrast enhanced computed tomography (CT), he was diagnosed with a ruptured right gastric artery aneurysm and celiac artery stenosis caused by the median arcuate ligament (MAL). He had a vascular anomaly of the common hepatic artery arising from the superior mesenteric artery (SMA). His vital signs were stable. We informed him of the situation and he chose open surgery rather than endovascular treatment. Following, we resected the aneurysm and transected the MAL. Intraoperative angiography after transection of the MAL showed the antegrade blood flow to the splenic artery instead of the retrograde flow via the prominent collaterals. Follow-up CT confirmed narrowed collateral vessels between the SMA and the celiac artery without de-novo aneurysms. Conclusion While the necessity of celiac artery release could be questioned, the present case supports the hemodynamic benefits of MAL transection in terms of de-novo aneurysm prevention

Modified adaption of iliac branch endografts in rare congenital anomaly of proximal origin of bilateral internal iliac arteries

We report a case of 55 mm abdominal aortic aneurysm coinciding with a rare congenital anomaly of proximal origin of bilateral internal iliac arteries (IIAs). Because renal to iliac bifurcation lengths were bilaterally short (129 mm and 125 mm), a trunk-ipsilateral leg and an iliac leg were deployed before iliac branch component insertion into the iliac leg. With help of a pull-through wire, internal iliac component was delivered without migration of the main body. The left IIA was embolized, but the right IIA was successfully preserved with commercially available iliac branch endoprosthesis only from femoral approaches, and the patient fully recovered without any complication