Ayako Nishiyama

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.

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.).

Adequate Selection of a Therapeutic Site Enables Efficient Development of Collateral Vessels in Angiogenic Treatment With Bone Marrow Mononuclear Cells

Background Induction of angiogenic mechanisms to promote development of collateral vessels is considered promising for the treatment of peripheral arterial diseases. Collateral vessels generally develop from preexisting arteriolar connections, bypassing the diseased artery. We speculated that induction of angiogenic mechanisms should be directed to such arteriolar connections to achieve efficient collateral development. The aim of this study was to verify this hypothesis using autologous transplantation of bone marrow mononuclear cells in the rabbit model of chronic limb ischemia. Methods and Results The left femoral artery was excised to induce limb ischemia in male rabbits. In this model, arteriolar connections in the left coccygeofemoral muscle tend to develop into collateral vessels, although this transformation is insufficient to alleviate the limb ischemia. In contrast, arteriolar connections in the closely located adductor muscle do not readily develop into collateral vessels. At 21 days after ischemia initiation, a sufficient number of automononuclear cells were selectively injected in the left coccygeofemoral muscle (coccygeo group) or left adductor muscle (adductor group). Evaluation of calf blood pressure ratios, blood flow in the left internal iliac artery, and angiographic scores at day 28 after injection revealed that collateral development and improvement of limb ischemia were significantly more efficient in the coccygeo group than in the adductor group. Morphometric analysis of the coccygeofemoral muscle at day 14 showed similar results. Conclusions Specific delivery of mononuclear cells to the coccygeofemoral but not the adductor muscle effectively improves collateral circulation in the rabbit model of limb ischemia and suggests that adequate site selection can facilitate therapeutic angiogenesis.

Therapeutic site selection is important for the successful development of collateral vessels

BACKGROUND Induction of collateral development to improve tissue perfusion is a promising approach for the treatment of arterial occlusive diseases. Several growth factors and cells have been reported to increase collateral circulation; however, the appropriate site for the delivery of these factors and cells is unclear. In this study, we identified the delivery site for growth factor in a rabbit model of limb ischemia and evaluated whether specific delivery of basic fibroblast growth factor (bFGF) to this site enhanced collateral augmentation. METHODS The left femoral artery of Japanese white rabbits was excised to induce limb ischemia. Twenty-eight days thereafter, angiograms were obtained to identify the typical pattern of collateral development in this model. Subsequently, bFGF (100 μg) was selectively injected into the left coccygeofemoral muscle (coccygeo group) or adductor muscle (adductor group), major thigh muscles in proximity. Collateral development was evaluated at 28 days after injection, and its mechanism was assessed by immunologic and morphometric analyses of muscle samples. RESULTS Angiographic evaluation of this model revealed that after femoral artery excision, collateral vessels generally developed in the left coccygeofemoral muscle, whereas few collateral vessels were detected in the left adductor muscle. At 28 days after injection, calf blood pressure ratio, defined as left pressure to right pressure, was significantly higher in the coccygeo group than in the adductor group (0.85 ± 0.05 vs 0.69 ± 0.05, respectively; P < .01). Similar results were observed in blood flow through the internal iliac artery (resting: 24.6 ± 6.1 vs 17.4 ± 8.0 mL/min, P < .01; maximum: 47.4 ± 12.3 vs 33.2 ± 10.7 mL/min, P < .01) and in the angiographic score (0.67 ± 0.13 vs 0.39 ± 0.11; P < .01). Immunologic analyses of the coccygeofemoral muscle at day 3 showed marked expressions of Ki-67, monocyte chemotactic protein 1, and FGF receptor 1 in the coccygeo group compared with the adductor group. Morphometric analyses of the same muscle at day 14 also revealed that collateral vessel density and wall thickness were significantly increased in the coccygeal group compared with the adductor group. CONCLUSIONS These findings demonstrated that selective bFGF delivery to the coccygeofemoral muscle markedly improved collateral development and limb perfusion compared with delivery to the adductor muscle, suggesting that site selection is important in increasing therapeutic efficacy.

Targeting ability of self-assembled nanomedicines in rat acute limb ischemia model is affected by size

ABSTRACT Peripheral artery disease (PAD) is one of the most spreading diseases all over the world. The treatment strategies are limited to surgical or endovascular procedures for final stage chronic PAD or acute limb ischemia, and no pharmacological approaches have been achieved to prevent the worsening of chronic PAD or to regenerate the tissues of acute limb ischemia. Therefore, the improvement of therapeutic strategy is strongly demanded in clinics. Here, we adopted an acute hindlimb ischemia model in rats, which provides concomitant inflammatory response, to evaluate the application of drug delivery system against PAD. Through comparative experiments by using different‐sized nanomedicine analogues, polyion complex (PIC) micelles with 30 nm diameter and PIC vesicles with 100‐ and 200‐nm diameter (PICs‐30, −100, −200 respectively), we found the size‐dependent accumulation and retention in the collateral arteries. In contrast to PICs‐30 and ‐200, histological analysis showed that PICs‐100 were around the arterioles and co‐localized with macrophages, which indicates that the PICs‐100 can achieve moderate interaction with phagocytes. Our data suggests that controlling the size of nanomedicines has promise for developing novel angiogenic treatments toward the effective management of collateral arteries. Graphical abstract Figure. No caption available.

Preservation of the accessory renal arteries after endovascular repair of common iliac artery aneurysm using kissing stent grafts

Exclusion of the accessory renal arteries (ARAs) is required during endovascular aneurysm repair if they arise from the sealing zone or aneurysm sac. Here, we report a case of successful endovascular treatment for a common iliac artery aneurysm located close to the aortic bifurcation and associated with nephrotic syndrome in a 51-year-old man. The bilateral ARAs were successfully preserved using kissing stent grafts. During surgery, the proximal ends of endografts inserted from the bilateral femoral arteries were adjusted so that they met at the same level in the aorta, and simultaneous balloon dilatation was performed. This method can be a useful treatment option for common iliac aneurysms in cases with large ARAs.

Long-term results of combined aortoiliac and infrainguinal arterial reconstruction for the treatment of critical limb ischemia.

OBJECTIVE This study was designed to investigate our long-term experience with combined iliac endovascular therapy (EVT) and infrainguinal bypass to treat critical limb ischemia (CLI) and compare outcomes to those of patients who underwent surgery for aortoiliac lesions. MATERIALS AND METHODS From April 2000 to June 2013, 57 patients (58 limbs) underwent an infrainguinal bypass combined with aortoiliac reconstruction to treat CLI. Eighteen limbs were treated by bypass alone and 8 limbs were treated by bypass with EVT for aortoiliac lesions (Bypass group). Thirty-two limbs were subjected to EVT alone for iliac lesions (EVT group). RESULTS Preoperative limb ischemia was more severe in the EVT group. There were no significant differences in major procedure-related complications (χ(2) test, P = 0.853), systemic complications (P = 0.853), and mortality (P = 0.916) between the 2 groups. The limb salvage rates were 92% at 1, 3, and 5 years in the Bypass group and 93% at 1, 3, and 5 years in the EVT group, with no significant difference observed between the groups (Kaplan-Meier, log-rank test, P = 0.616). CONCLUSION Infrainguinal surgical reconstruction combined with an iliac EVT is an acceptable strategy for managing patients with CLI.