Takuro Shirasu

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.

Favorable outcomes of very elderly patients with critical limb ischemia who undergo distal bypass surgery

OBJECTIVE To determine the midterm outcomes of distal bypass surgery for very elderly patients, and to determine the ideal candidates for this procedure. METHODS Of 268 consecutive patients (328 limbs) with critical limb ischemia who were treated between 2006 and 2013, 106 (126 limbs) underwent distal bypass and were retrospectively reviewed. Nineteen patients (22 limbs) were aged ≥80 years (very elderly group) and 87 patients (104 limbs) were aged <80 years (control group). RESULTS The baseline characteristics differed between the 2 groups in terms of regular hemodialysis rate (very elderly group, 4 [21%] vs control group, 60 [69%]; P = .0002) and the Charlson comorbidity index (very elderly group, 3.2 ± 1.7 vs control group, 5.0 ± 2.0; P = .0005). According to the Rutherford category of limb ischemia (4/5/6), the very elderly and control groups were classified as 5/17/0 and 11/87/6, respectively (P = .18). Before the surgery, 17 patients (77%) and 67 patients (64%) were ambulatory in the very elderly and control groups, respectively. At follow-up at 29 ± 22 months, the rates of primary (P = .33) and secondary patency (P = .14), limb salvage (P = .50), survival (P = .26), amputation-free survival (P = .42), major adverse limb event and also perioperative death (P = .11), and major adverse cardiovascular events (P = .36) did not significantly differ between the groups. In multivariate analysis, a history of coronary artery disease (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.3-5.9; P = .005), preoperative nonambulatory status (HR, 4.2; 95% CI, 2.1-8.1; P < .0001), and serum albumin levels <3 g/dL (HR, 2.7; 95% CI, 1.3-5.4; P = .01) were significantly related to poor amputation-free survival. Thirteen patients (59%) remained ambulatory at the latest follow-up. In 91 patients (110 limbs) with tissue loss, the Society for Vascular Surgery lower extremity threatened limb classification system: risk stratification based on Wound, Ischemia, and foot Infection classification stages 3 and 4 negatively affected complete wound healing, according to multivariate analysis (HR, 0.34; 95% CI, 0.20-0.61; P = .0005). CONCLUSIONS A very elderly age should not preclude a patient from undergoing distal bypass surgery. A history of coronary artery disease, a nonambulatory status, and hypoalbuminemia, along with the Wound, Ischemia, and foot Infection classification for patients with tissue loss, should be carefully considered to obtain the most benefit from distal bypass surgery.

Bowel necrosis following endovascular revascularization for chronic mesenteric ischemia: a case report and review of the literature

BackgroundEndovascular revascularization has recently been established as a less invasive treatment method for chronic mesenteric ischemia. However, intestinal necrosis caused by distal embolization following this procedure has not been emphasized.Case presentationThe present report describes a 59-year-old man who was treated with endovascular revascularization for chronic mesenteric ischemia. After the procedure, he was diagnosed with intestinal necrosis caused by distal embolization. Despite emergent bowel resection, he died on postoperative day 109.ConclusionAlthough endovascular revascularization for chronic mesenteric ischemia is less invasive and may be suitable for high-risk patients, attention should be paid to avoid embolic complications that can cause intestinal infarction possibly leading to a fatal condition.

Long-Term Results of Treatment for Critical Limb Ischemia.

From 2001 to 2012, arterial reconstruction was performed in 306 out of 497 limbs (62%) with critical limb ischemia. The reasons for non-vascularization include high operative risk (36%), extended necrosis or infection (20%), and technical issues (15%). Cumulative patency and limb salvage in collagen disease were significantly worse compared to arteriosclerosis obliterans. Cumulative limb salvage, amputation free survival (AFS), and major adverse limb event and perioperative death (MALE + POD) in patients with end-stage renal disease (ESRD) were significantly worse compared to patients without ESRD, but not significant with regards to graft patency. Our finding suggests that aggressive arterial reconstruction provides satisfactory long-term results in critical limb ischemia so long as case selection for revascularization is properly made. (This article is a translation of J Jpn Coll Angiol 2014; 54: 5-11.).

Single-incision laparoscopic cholecystectomy for cholecystolithiasis coinciding with cavernous transformation of the portal vein: report of a case

BackgroundCavernous transformation of the portal vein (CTPV) is a rare vascular deformity. It is thought to be secondary to extra-hepatic portal vein obstruction, with formation of serpiginous collateral vessels around the extra-hepatic bile duct, and even the gallbladder. Surgery is difficult because the vessels have irregular courses, are somewhat fragile and bleed easily. Single-incision laparoscopic cholecystectomy, an emerging procedure for symptomatic cholecystolithiasis, has limitations especially in anatomically complex cases.Case presentationWe describe a 44-year-old woman with symptomatic cholecystolithiasis. Computed tomography revealed a series of tortuous collateral veins at the liver hilum, with the extra-hepatic portal vein occluded at the level of the spleno-portal junction. However, the distended vessels were not particularly close to the cystic duct. We performed single-incision laparoscopic surgery (SILS) for cholecystectomy via a trans-umbilical incision. By pulling the cystic duct out along with neighboring cavernous vessels, we were able to secure detachment of the cystic duct from Calot’s triangle and ligation of the cystic artery. Total operating time was 132 minutes and blood loss was 370 grams. The patient was discharged on postoperative day 2 with no perfusion abnormalities in the liver.ConclusionWe must pay meticulous attention to the area of Calot’s triangle when performing SILS cholecystectomy with CTPV. SILS cholecystectomy might be an option in highly experienced facilities.

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

BackgroundIt 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 presentationThis 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.ConclusionWhile 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.

PC012. Surgical Training of Young Vascular Surgeons for Open Abdominal Aortic Aneurysm Repair Considering the Learning Curve

Objectives: Because endovascular aneurysm repair has become a predominant alternative, it has a high profile how to train young vascular surgeons in open surgery. The objective was to analyze the learning curve and determine the number needed to treat to establish sufficient surgical skills of open surgery for intact abdominal aortic aneurysm. Methods: This was a retrospective study of a prospectively accumulated database at Asahi General Hospital in Japan between 2003 and 2017. A total of 562 consecutive patients who underwent open repair for intact abdominal aortic aneurysm or iliac artery aneurysms either by an attending surgeon or by six young vascular surgeons (>20 experiences) were included. All young vascular surgeons had accomplished general surgery training. Analysis was conducted by every 10-cases experience performed by young vascular surgeons (Y group) to investigate the learning

Pulse volume recordings to identify falsely elevated ankle brachial index.

Background Ankle brachial index can be falsely elevated in cases of medial arterial calcification, and its clinical use should be limited, especially in patients with diabetes. The aim of this study was to evaluate the potential role of pulse volume recording in detecting falsely elevated ankle brachial index. Methods Two parameters of the pulse waveform were automatically calculated: upstroke time and percentage mean artery pressure. Pulse volume recordings were retrospectively evaluated in 171 consecutive patients (342 limbs); 73 (43%) had a diagnosis of diabetes. Results On multivariate analysis, diabetes (hazard ratio = 1.7), ankle brachial index ≤ 0.90 (hazard ratio = 4.4), upstroke time ≥ 180 ms (hazard ratio = 2.1), and percentage mean artery pressure ≥ 45% (hazard ratio = 2.8) were significantly related to toe brachial index < 0.60. Further analysis for falsely elevated ankle brachial index was performed in 196 limbs (146 patients) with ankle brachial index > 0.90. The difference between ankle brachial index and toe brachial index differentiated the limbs of diabetic patients, with percentage mean artery pressure ≥ 45%, from controls (0.45 ± 0.17 vs. 0.35 ± 0.16, p = 0.03); upstroke time was not found to be a discriminating factor. Conclusions Although measurement of ankle brachial index remains the gold standard for diagnosing peripheral arterial disease, percentage mean artery pressure, automatically obtained in ankle brachial index measurement, may be useful to detect falsely elevated ankle brachial index, especially in patients with diabetes.