Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Tadashi Furuyama Last modified date:2022.05.31

Lecturer / Department of Surgery and Science / Vascular Surgery / Kyushu University Hospital


Papers
1. Koichi Morisaki, Yutaka Matsubara, Shun Kurose, Shinichiro Yoshino, Tadashi Furuyama, Bypass Surgery Provides Better Outcomes Compared with Endovascular Therapy in the Composite Endpoint Comprising Relief from Rest Pain, Wound Healing, Limb Salvage, and Survival after Infra-inguinal Revascularisation in Patients with Chronic Limb Threatening Ischaemia., European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery, 10.1016/j.ejvs.2021.12.043, 63, 4, 588-593, 2022.04, OBJECTIVE: The present study aimed to determine the factors related to relief from rest pain, wound healing, major adverse limb events (MALEs), and prognosis after infrainguinal revascularisation in patients with chronic limb threatening ischaemia (CLTI). METHODS: The data of patients who underwent infrainguinal revascularisation for CLTI between 2010 and 2020 was analysed retrospectively. The endpoint was the composite of relief from rest pain, wound healing, MALE, or death. RESULTS: A total of 234 limbs in 187 patients with CLTI were analysed. Of the 234 limbs, 149 (63.7%) underwent bypass surgery and 85 (36.3%) underwent endovascular therapy (EVT). The event free survival rates with respect to the composite endpoint at two years were 30.4% in the EVT and 48.5% in the bypass groups, respectively (p = .005). The event free survival rates at two years were 56.7% in bypass surgery and 29.5% in EVT in the indeterminate subgroup (p = .051). Multivariable analysis revealed that age (hazard ratio [HR] 1.03; 95% confidence interval [CI] 1.01 - 1.05; p < .001), coronary artery disease (CAD) (HR 1.45; 95% CI 1.01 - 2.07; p = .042), haemodialysis (HR 1.74; 95% CI 1.22 - 2.48; p = .002), Wound, Ischaemia and foot Infection stage (HR 1.34; 95% CI 1.07 - 1.68; p = .012), Global Limb Anatomical Staging System stage (HR 1.31; 95% CI 1.01 - 1.72; p = .043), EVT (HR 1.90; 95% CI 1.31 - 2.74; p < .001), Geriatric Nutritional Risk Index (HR 0.98; 95% CI 0.97 - 0.99; p = .021), and non-ambulatory status (HR 1.89; 95% CI 1.31 - 2.74; p < .001) were risk factors for the composite endpoint. CONCLUSION: Bypass surgery is superior to EVT with respect to the composite endpoint including relief from rest pain, wound healing, MALE, or death. Bypass surgery may be considered as the treatment of choice, instead of EVT, in patients in the indeterminate group according to the Global Vascular Guidelines preferred revascularisation method..
2. Koichi Morisaki, Yutaka Matsubara, Shinichiro Yoshino, Shun Kurose, Sho Yamashita, Tadashi Furuyama, Masaki Mori, Validation of the GLASS Staging Systems in Patients With Chronic Limb-Threatening Ischemia Undergoing De Novo Infrainguinal Revascularization., Annals of vascular surgery, 10.1016/j.avsg.2021.09.054, 81, 378-386, 2022.04, OBJECTIVES: The Global Limb Anatomic Staging System (GLASS) was proposed for evaluating the anatomic complexity of arterial disease in patients with chronic limb-threatening ischemia (CLTI). We aimed to examine the relationship between GLASS stage and treatment outcomes after infrainguinal revascularization in patients with CLTI. METHODS: We retrospectively analyzed data of patients undergoing infrainguinal revascularization for CLTI between 2010 and 2018 to examine whether GLASS stage affects the limb salvage, wound healing, and overall survival (OS). RESULTS: Throughout the study period, 153 CLTI patients and 190 limbs with Fontaine classification III and IV were analyzed for major amputation and OS, and 125 patients and 157 limbs of Fontaine classification IV were analyzed for wound healing. The number of patients with WIfI stage 1, 2, 3, and 4 was 14 (7.4%), 44 (23.2%), 65 (34.2%), and 67 (53.3%), respectively. The number of patients with GLASS stage I, II, and III was 23 (12.1%), 48 (25.3%), and 119 (62.6%), respectively. Among the 190 limbs, the number subject to bypass surgery, endovascular therapy, and hybrid therapy was 132 (69.5%), 39 (20.5%), and 19 (10.0%), respectively. A multivariate analysis showed that only WIfI stage and inframalleolar (IM) disease were risk factors for major amputation and impaired wound healing. There was no relationship between GLASS stage and limb salvage or wound healing. A multivariate analysis revealed that age, geriatric nutritional risk index and GLASS stage were risk factors for 2-year OS (P < 0.01). Patients with all risk factors had a poor prognosis (35.3% at 2 years). CONCLUSION: WIfI stage and IM disease predicted limb salvage and wound healing after infrainguinal revascularization in patients with CLTI. Although GLASS stage did not affect limb salvage or wound healing, it was a prognostic factor for poor OS. The GLASS staging could be useful for deciding between bypass surgery and endovascular therapy in prediction of prognosis..
3. Koichi Morisaki, Yutaka Matsubara, Shun Kurose, Shinichiro Yoshino, Tadashi Furuyama, Effect of abdominal aortic aneurysm sac shrinkage after endovascular repair on long-term outcomes between favorable and hostile neck anatomy., Journal of vascular surgery, 10.1016/j.jvs.2022.03.011, 2022.03, OBJECTIVE: The aim of the present study was to analyze the influence of abdominal aortic aneurysm sac shrinkage on the long-term outcomes after endovascular aneurysm repair (EVAR) between patients with favorable and hostile neck anatomy. METHODS: In the present study, we retrospectively analyzed data from 268 patients with fusiform aneurysm and sac behavior who had been evaluated for ≥1 year after EVAR. Hostile neck anatomy was defined as a proximal aneurysmal neck length of <10 mm or proximal neck angle of ≥60°. The primary end point was sac shrinkage, and the secondary end points included reintervention and a composite of rupture, type Ia endoleak, and late open conversion. RESULTS: No differences were found in sac shrinkage between the patients with favorable and hostile neck anatomy (P = .47). Multivariate analysis revealed that an occluded inferior mesenteric artery (P = .04), the presence of posterior thrombus (P < .01), and no antiplatelet therapy (P = .01) were positive factors for sac shrinkage. The reintervention-free survival rate was better for patients with sac shrinkage compared with those without sac shrinkage regardless of the proximal neck anatomy (P < .01). The event-free survival rate of the composite end point at 5 and 10 years was 97.5% and 83.5% for patients with favorable neck anatomy and 86.8% and 81.0% for those with hostile neck anatomy, respectively (P = .02). In the subgroup with sac shrinkage, the event-free survival rates at 5 and 10 years were 98.7% and 98.7% for those with favorable neck anatomy and 92.7% and 82.4% for those with hostile neck anatomy, respectively (P = .02). In contrast, the event-free survival for patients without sac shrinkage did not differ between those with favorable and hostile neck anatomy (P = .08). Multivariate analysis showed that a hostile neck anatomy (hazard ratio, 3.32; 95% confidence interval, 1.26-8.80; P = .02) and no sac shrinkage (hazard ratio, 3.88; 95% confidence interval, 1.25-12.0; P = .02) were significant risk factors for the composite end point of rupture, type Ia endoleak, and late open conversion. CONCLUSIONS: Proximal neck anatomy did not affect sac shrinkage after EVAR. Sac shrinkage has been a good surrogate marker of better long-term outcomes after EVAR for patients with favorable neck anatomy. In contrast, critical events such as rupture and type Ia endoleak can occur even after sac shrinkage has been achieved in patients with hostile neck anatomy..
4. Ayumi Harada, Koichi Morisaki, Shun Kurose, Shinichiro Yoshino, Sho Yamashita, Tadashi Furuyama, Masaki Mori, Internal Iliac Artery Aneurysm Ruptures with No Visualized Endoleak 2 Years after Endovascular Repair., Annals of vascular diseases, 10.3400/avd.cr.21-00019, 15, 1, 45-48, 2022.03, We report a case of an 83-year-old man with a ruptured internal iliac artery (IIA) aneurysm after endovascular repair, which was treated via the ligation of IIA and tight suture of the aneurysm sac. Although there were no findings of obvious endoleak after endovascular treatment, the IIA aneurysm increased in size and eventually ruptured. We presumed that pressure to IIA aneurysm via the embolized IIA led to rupture. Aneurysm sac expansion may lead to a rupture despite no endoleak being detected; therefore, close follow-up or re-intervention must be considered. Tight embolization of IIA may prevent endotension in the same case..
5. Koichi Morisaki, Yutaka Matsubara, Tadashi Furuyama, Shun Kurose, Shinichiro Yoshino, Sho Yamashita, Masaki Mori, Effects of Antithrombotic Therapy on Abdominal Aortic Aneurysm Sac Size after Endovascular Repair in Patients with Favorable Neck Anatomy., Journal of vascular and interventional radiology : JVIR, 10.1016/j.jvir.2021.10.025, 33, 2, 113-119, 2022.02, PURPOSE: To evaluate the influence of antiplatelet or anticoagulant therapy on sac behavior after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: This study retrospectively analyzed data from patients with favorable neck anatomy who underwent EVAR between 2007 and 2019. Patients with ruptured AAA and ≤1 year of sac behavior evaluation were excluded. Sac shrinkage after 1 year, persistent type II endoleak, and late sac expansion were examined. RESULTS: In total, 182 patients with favorable neck anatomy were included in this study. A multivariable analysis identified an occluded inferior mesenteric artery (IMA; P = .049), the presence of a posterior thrombus (P = .009), and no antiplatelet therapy (P = .012) as factors positively associated with sac shrinkage at 1 year. Persistent type II endoleak was detected in 56 (30.8%) patients, with patent IMA (P = .006), the lack of a posterior thrombus (P = .004), the number of patent lumbar arteries (P = .004), and antiplatelet therapy (P = .039) being identified as significant risk factors. The multivariable analysis identified a larger initial AAA diameter (P < .001), the lack of a posterior thrombus (P = .038), and antiplatelet and anticoagulant therapies (P = .038 and P = .003, respectively) as risk factors for late sac expansion. CONCLUSIONS: After EVAR in patients with favorable neck anatomy, antiplatelet therapy is associated with the lack of sac regression at 1 year, whereas antiplatelet and anticoagulant therapies are risk factors for late sac expansion..
6. Yoshino Shinichiro, Yutaka Matsubara, Tadashi Furuyama, Shun Kurose, Sho Yamashita, Koichi Morisaki, Masaki Mori, Iliac Artery Aneurysms Expand in Quadratically Proportion to the Diameter., Annals of vascular surgery, 10.1016/j.avsg.2021.10.063, 2021.12, BACKGROUND: Iliac artery aneurysms (IAAs) are life-threatening once ruptured. Although some studies have revealed the pathology of IAAs, clinical information on IAAs is still limited. Moreover, previous studies were conducted in Western countries; thus, we aimed to identify the natural history of iliac artery aneurysms in a Japanese cohort. The purpose of this study was to investigate the IAA expansion rate in a Japanese cohort to consider the management of small IAAs and to identify indications for surgical intervention. METHODS: Patients with iliac artery aneurysms were retrospectively reviewed. The primary outcome was the expansion rate of IAAs. We also investigated the correlation between expansion rate and patients' characteristics. Natural histories, including surgical interventions and rupture, were also assessed. RESULTS: The mean expansion rate in our study was 1.59 ± 1.16 mm/year. There was a positive correlation between expansion rate and aneurysm diameter, which was estimated by y = 0.0052 × (X - 23.270)2 + 0.0632 × X - 0.0517, where y is the expansion rate, and X is aneurysm diameter. The freedom from surgical intervention rate of IAAs was 85.5% at 1 year, 54.0% at 3 years, and 41.5% at 5 years. No factors, except initial aneurysm diameter, were revealed as independent predictors of surgical intervention. We experienced one ruptured IAA, which showed unexpected rapid growth from 30.1 mm to 56.3 mm over 15 months during conservative management. This case demonstrated that IAAs ≥30 mm should be carefully followed up and considered for surgical intervention. CONCLUSIONS: We conclude that larger aneurysms have greater expansion rates. Because IAAs ≥30 mm carry a risk of rapid expansion resulting in rupture, careful follow-up, and surgical intervention should be performed if iliac artery aneurysms are ≥30 mm in diameter..
7. Yutaka Matsubara (松原 裕), Luis Gonzalez, Gathe Kiwan, Jia Liu (刘 佳), John Langford, Mingjie Gao (高 明杰), Xixiang Gao (高 喜翔), Ryosuke Taniguchi (谷口 良輔), Bogdan Yatsula, Tadashi Furuyama (古山 正), Takuya Matsumoto (松本 拓也), Kimihiro Komori (古森 公浩), Masaki Mori (森 正樹), Alan Dardik, PD-L1 (Programmed Death Ligand 1) Regulates T-Cell Differentiation to Control Adaptive Venous Remodeling., Arteriosclerosis, thrombosis, and vascular biology, 10.1161/ATVBAHA.121.316380, 41, 12, 2909-2922, 2021.12, OBJECTIVE: Patients with end-stage renal disease depend on hemodialysis for survival. Although arteriovenous fistulae (AVF) are the preferred vascular access for hemodialysis, the primary success rate of AVF is only 30% to 50% within 6 months, showing an urgent need for improvement. PD-L1 (programmed death ligand 1) is a ligand that regulates T-cell activity. Since T cells have an important role during AVF maturation, we hypothesized that PD-L1 regulates T cells to control venous remodeling that occurs during AVF maturation. Approach and results: In the mouse aortocaval fistula model, anti-PD-L1 antibody (200 mg, 3×/wk intraperitoneal) was given to inhibit PD-L1 activity during AVF maturation. Inhibition of PD-L1 increased T-helper type 1 cells and T-helper type 2 cells but reduced regulatory T cells to increase M1-type macrophages and reduce M2-type macrophages; these changes were associated with reduced vascular wall thickening and reduced AVF patency. Inhibition of PD-L1 also inhibited smooth muscle cell proliferation and increased endothelial dysfunction. The effects of anti-PD-L1 antibody on adaptive venous remodeling were diminished in nude mice; however, they were restored after T-cell transfer into nude mice, indicating the effects of anti-PD-L1 antibody on venous remodeling were dependent on T cells. CONCLUSIONS: Regulation of PD-L1 activity may be a potential therapeutic target for clinical translation to improve AVF maturation..
8. Koichi Morisaki, Yutaka Matsubara, Shun Kurose, Shinichiro Yoshino, Sho Yamashita, Ken Nakayama, Tadashi Furuyama, Analysis of prognostic factors for postoperative complications and reinterventions after open surgical repair and endovascular aneurysm repair in patients with abdominal aortic aneurysm., Annals of vascular surgery, 10.1016/j.avsg.2021.05.018, 77, 172-181, 2021.11, OBJECTIVE: A definitive treatment for patients with abdominal aortic aneurysm considering age and comorbidities has not been identified. In the present study, we retrospectively validated treatment outcomes in Japanese patients and proposed the treatment strategy of open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: We retrospectively analyzed data for patients undergoing EVAR or OSR between 2006 and 2017. Patients with ruptured abdominal aortic aneurysm were excluded. We examined post-operative complications, operative mortality, re-intervention and prognosis. RESULTS: Throughout the study period, 405 patients underwent EVAR and 176 patients underwent OSR. The percentage of patients with post-operative complications was 35.8% in the OSR group, compared with 13.1% in the EVAR group (P < 0.01). The operative mortality rate was 0.49% in the EVAR group and 0.57% in the OSR group (P = 1.00). With a multivariate analysis, age, hemodialysis, modified Frailty Index (mFI), and OSR were risk factors for post-operative complications. The 5-year re-intervention free survival rate was 63.0 % with hostile neck EVAR compared with 83.1 % with favorable neck EVAR and 86.1 % with OSR group (P < 0.01). With a multivariate analysis, hemodialysis, mFI, and hostile neck EVAR were risk factors for re-intervention. The 5-year overall survival rate was 51.9 % with hostile neck EVAR compared with 73.2 % with favorable neck EVAR and 79.0 % with OSR group (P < 0.01). With a multivariate analysis, age, mFI, and hostile neck EVAR were poor prognostic factors. CONCLUSION: Age, mFI, hemodialysis and hostile neck anatomy are useful predictors of post-operative complications, re-intervention and overall survival, and could be useful for informing treatment selection between OSR and EVAR..
9. Takuya Matsumoto, Shinichiro Yoshino, Tadashi Furuyama, Koichi Morisaki, Kaku Nakano, Jun-Ichiro Koga, Yoshihiko Maehara, Kimihiro Komori, Masaki Mori, Kensuke Egashira, Pitavastatin-Incorporated Nanoparticles for Chronic Limb Threatening Ischemia: A Phase I/IIa Clinical Trial., Journal of atherosclerosis and thrombosis, 10.5551/jat.58941, 2021.04, AIM: To assess the results of a phase I/IIa open-label dose-escalation clinical trial of 5-day repeated intramuscular administration of pitavastatin-incorporated poly (lactic-co-glycolic acid) nanoparticles (NK-104-NP) in patients with chronic limb threatening ischemia (CLTI). METHODS: NK-104-NP was formulated using an emulsion solvent diffusion method. NK-104-NP at four doses (nanoparticles containing 0.5, 1, 2, and 4 mg of pitavastatin calcium, n=4 patients per dose) was investigated in a dose-escalation manner and administered intramuscularly into the ischemic limbs of 16 patients with CLTI. The safety and therapeutic efficacy of treatment were investigated over a 26-week follow-up period. RESULTS: No cardiovascular or other serious adverse events caused by NK-104-NP were detected during the follow-up period. Improvements in Fontaine and Rutherford classifications were noted in five patients (one, three, and one in the 1-, 2-, and 4-mg dose groups, respectively). Pharmacokinetic parameters including the maximum serum concentration and the area under the blood concentration-time curve increased with pitavastatin treatment in a dose-dependent manner. The area under the curve was slightly increased at day 5 compared with that at day 1 of treatment, although the difference was not statistically significant. CONCLUSIONS: This is the first clinical trial of pitavastatin-incorporated nanoparticles in patients with CLTI. Intramuscular administration of NK-104-NP to the ischemic limbs of patients with CLTI was safe and well tolerated and resulted in improvements in limb function..
10. Yutaka Matsubara, Gathe Kiwan, Jia Liu, Luis Gonzalez, John Langford, Mingjie Gao, Xixiang Gao, Ryosuke Taniguchi, Bogdan Yatsula, Tadashi Furuyama, Takuya Matsumoto, Kimihiro Komori, Alan Dardik, Inhibition of T-Cells by Cyclosporine A Reduces Macrophage Accumulation to Regulate Venous Adaptive Remodeling and Increase Arteriovenous Fistula Maturation., Arteriosclerosis, thrombosis, and vascular biology, 10.1161/ATVBAHA.120.315875, 41, 3, e160-e174, 2021.03, OBJECTIVE: Arteriovenous fistulae (AVF) are the preferred vascular access for hemodialysis, but the primary success rate of AVF remains poor. Successful AVF maturation requires vascular wall thickening and outward remodeling. A key factor determining successful AVF maturation is inflammation that is characterized by accumulation of both T-cells and macrophages. We have previously shown that anti-inflammatory (M2) macrophages are critically important for vascular wall thickening during venous remodeling; therefore, regulation of macrophage accumulation may be an important mechanism promoting AVF maturation. Since CD4+ T-cells such as T-helper type 1 cells, T-helper type 2 cells, and regulatory T-cells can induce macrophage migration, proliferation, and polarization, we hypothesized that CD4+ T-cells regulate macrophage accumulation to promote AVF maturation. Approach and Results: In a mouse aortocaval fistula model, T-cells temporally precede macrophages in the remodeling AVF wall. CsA (cyclosporine A; 5 mg/kg, sq, daily) or vehicle (5% dimethyl sulfoxide) was administered to inhibit T-cell function during venous remodeling. CsA reduced the numbers of T-helper type 1 cells, T-helper type 2, and regulatory T-cells, as well as M1- and M2-macrophage accumulation in the wall of the remodeling fistula; these effects were associated with reduced vascular wall thickening and increased outward remodeling in wild-type mice. However, these effects were eliminated in nude mice, showing that the effects of CsA on macrophage accumulation and adaptive venous remodeling are T-cell-dependent. CONCLUSIONS: T-cells regulate macrophage accumulation in the maturing venous wall to control adaptive remodeling. Regulation of T-cells during AVF maturation may be a strategy that can improve AVF maturation. Graphic Abstract: A graphic abstract is available for this article..
11. Kentaro Inoue, Tadashi Furuyama, Shun Kurose, Shinichiro Yoshino, Ken Nakayama, Sho Yamashita, Koichi Morisaki, Masaki Mori, Platelet Count Recovery after Endovascular Aneurysm Repair for Abdominal Aortic Aneurysm., Annals of vascular diseases, 10.3400/avd.oa.20-00030, 14, 1, 11-18, 2021.03, Objective: To find a new predictor of endoleak (EL) and aneurysm sac expansion after endovascular aneurysm repair (EVAR), we evaluated the platelet count recovery (PCR) process after EVAR. Materials and Methods: Two hundred five patients treated with elective EVAR from 2007 to 2015 were retrospectively analyzed. We compared the platelet count ratio until postoperative day (POD) 7 to the presurgical baseline between patients with and without persistent EL (≥ 6 months). Subsequently, we calculated the optimal platelet count ratio for distinguishing persistent EL using receiver-operating characteristics analysis. A platelet count ratio on POD7 ≥118% was defined as the PCR. We evaluated the PCR's influence on the cumulative aneurysm sac expansion rate. Results: The average platelet count ratio on POD7 rose above baseline (112%), and the ratio was attenuated by persistent EL (103%). Of 205 patients, 126 (61%) were assigned to the disturbed PCR group (PCR(-) group). Cumulative aneurysm sac expansion rate was higher in the PCR(-) group than the PCR(+) group (34.4% vs. 12.8% in 5 years, p=0.01). Conclusion: Disturbed PCR after EVAR may be associated with ELs and eventual aneurysm sac expansion..
12. Shun Kurose, Yutaka Matsubara, Shinichiro Yoshino, Ken Nakayama, Sho Yamashita, Koichi Morisaki, Tadashi Furuyama, Masaki Mori, Influence of Internal Iliac Artery Embolization during Endovascular Aortic Repair Regarding Postoperative Sarcopenia and Midterm Survival., Annals of vascular surgery, 10.1016/j.avsg.2020.10.024, 2020.11, BACKGROUND: Postoperative sarcopenia is a risk factor for postoperative mortality. Internal iliac artery embolization (IIAE) during endovascular aortic repair (EVAR) has ischemic effects on pelvic skeletal muscles because IIAE causes buttock claudication. The long-term effects of IIAE on pelvic skeletal muscle, however, have not been well investigated. We hypothesized that IIAE after EVAR induces a decrease in skeletal muscle, which leads to postoperative sarcopenia. MATERIALS AND METHODS: Patients with abdominal aortic aneurysms who underwent EVAR from 2009 to 2014 were retrospectively reviewed. Skeletal muscle areas (SMAs) at the third lumbar level and the mid-femoral level were measured on transverse computed tomographic images. Postoperative sarcopenia was defined as a >10% decrease in the L3 SMA as established in a previous study. We assessed the association between postoperative sarcopenia and IIAE. RESULTS: Altogether, 102 eligible patients who underwent elective EVAR comprised the study group. The L3 SMA at the 3-year follow-up evaluation was significantly smaller in patients with than without IIAE (P < 0.05). The SMAs of the psoas, lumbar, and thigh muscles were significantly smaller on the IIAE than non-IIAE side (P < 0.05). IIAE was thus revealed as an independent risk factor for postoperative sarcopenia (hazard ratio, 4.69; P = 0.008). In addition, patients who developed postoperative sarcopenia had a lower overall survival rate than those without postoperative sarcopenia (P < 0.001). CONCLUSIONS: IIAE during EVAR is a risk factor for postoperative sarcopenia, which is in turn associated with mortality. Hence, we should preserve the internal iliac artery whenever possible. Alternatively, if IIAE is deemed necessary, we should postoperatively institute protocols to prevent sarcopenia from developing..
13. Koichi Morisaki, Tadashi Furuyama, Yutaka Matsubara, Kentaro Inoue, Shun Kurose, Shinichiro Yoshino, Ken Nakayama, Sho Yamashita, Keiji Yoshiya, Masaki Mori, Thigh sarcopenia and hypoalbuminemia predict impaired overall survival after infrainguinal revascularization in patients with critical limb ischemia., Vascular, 10.1177/1708538120913745, 28, 5, 542-547, 2020.10, OBJECTIVE: This study was performed to determine whether thigh sarcopenia can serve as a clinically relevant predictor of postoperative complications and overall survival after revascularization in patients with critical limb ischemia. METHODS: Patients who underwent preoperative computed tomography followed by infrainguinal revascularization from 2006 to 2015 were retrospectively analyzed. An axial computed tomography image was obtained at the midpoint of a line extending from the superior border of the patella to the greater trochanter of the femur. The thigh muscle area and bone area were measured. Thigh sarcopenia was defined as thigh muscle area/thigh bone area of <9. RESULTS: We included 117 patients with critical limb ischemia who underwent infrainguinal revascularization. The overall survival rates at two years were 86.5% and 55.1% in the thigh sarcopenia (-) and (+) groups, respectively (p < 0.01). The multivariate analysis showed that thigh sarcopenia (hazard ratio, 2.64; 95% confidence interval, 1.11-6.70; p = 0.03), cerebrovascular disease (hazard ratio, 3.18; 95% confidence interval, 1.31-7.36; p = 0.01), and serum albumin level (1 g/dL per increments) (hazard ratio, 0.41; 95% confidence interval, 0.21-0.81; p = 0.01) were the risk factors for overall survival two years after revascularization. CONCLUSION: Thigh sarcopenia is a risk factor for two-year overall survival in patients with critical limb ischemia after infrainguinal revascularization..
14. Naoki Fujimura, Kyousuke Hosokawa, Hideaki Obara, Kimihiro Igari, Daijirou Akamatsu, Hidetoshi Matsumoto, Atsunori Asami, Shintaro Shibutani, Takurin Akiyoshi, Masao Nunokawa, Hirohisa Harada, Kyozo Inoue, Atsuhiro Koya, Tadashi Furuyama, Daisuke Sagara, Tsunehiro Shintani, Terutoshi Yamaoka, Yoshinobu Akiyama, Yoshinori Inoue, Katsuyuki Hoshina, Incidence, diagnosis and treatment of popliteal artery entrapment syndrome in current vascular practice in Japan., Cardiovascular intervention and therapeutics, 10.1007/s12928-020-00710-1, 2020.09, Few data regarding popliteal artery entrapment syndrome (PAES) is available in Japan. In this study, we investigated incidence, diagnosis and treatment of PAES in current vascular practice. A retrospective analysis of all patients with PAES visiting 31 participating institutes between 2003 and 2015 was conducted. Thirty-five limbs (28 patients) were identified during the 13-year study period, and the incidence of PAES was 0.12% of all peripheral artery disease cases revascularized. Mean age was 32.0 ± 16.9 years old, and 60 and more years old was 10.7%. Also, 92.9% were male and 39.3% were athletes. Most frequent initial symptoms were intermittent claudication in 23 limbs (65.7%); 4 limbs (11.4%) had chronic limb-threatening ischemia. CT scan was most frequently (94.3%) used for the diagnostic imaging followed by MRI (45.7%) and duplex ultrasound (45.7%). Stress test such as dorsal flexion during duplex ultrasound was used only in 28.6%. Thirty-two limbs (91.4%) received surgical treatment, including 23 arterial reconstructions (71.9%); there were no major perioperative complications. All patients achieved improvement of their symptoms, and the average ankle brachial index increased from 0.69 ± 0.22 to 1.00 ± 0.14 post-surgery. The average postoperative follow-up period was 26.0 months with only one reintervention during the follow-up. In conclusion, PAES was a rare condition and traditional surgical treatment was solid. However, given a broad spectrum of clinical feature of PAES and less usage of diagnostic duplex ultrasound with stress test, there might be a miss- or delayed diagnosis of PAES even in the current vascular practice..
15. Naoki Fujimura, Tomohiro Imazuru, Hitoshi Matsumura, Tsuyoshi Shibata, Tadashi Furuyama, Kenjiro Kaneko, Hidetoshi Uchiyama, Noriyasu Morikage, Takayuki Uchida, Eiichi Teshima, Terutoshi Yamaoka, Hiroshi Masuhara, Hideki Ueda, Mamoru Arakawa, Togo Norimatsu, Hideaki Obara, Seiji Onitsuka, Two-Year Results of a Multicenter Prospective Observational Study of the Zenith Spiral-Z Limb Deployed in the External Iliac Artery During Endovascular Aneurysm Repair., Circulation journal : official journal of the Japanese Circulation Society, 10.1253/circj.CJ-20-0195, 84, 10, 1764-1770, 2020.09, BACKGROUND: Limited data is available on the use of a polyester graft limb with a helical stent configuration deployed in the external iliac artery (EIA) during endovascular aneurysm repair (EVAR), so we prospectively analyzed the efficacy of the Zenith Spiral-Z limb deployed in the EIA.Methods and Results:Patients undergoing EVAR using a Zenith stent-graft and Spiral-Z limb deployed in the EIA were prospectively registered in 24 Japanese institutions from June 2017 to November 2017. In total, 65 patients (74 limbs) (mean age: 77.1±8.0 years, 87.7% men, mean abdominal aortic aneurysm (AAA) diameter: 51.9±7.2 mm, mean iliac artery aneurysm (IAA) diameter: 38.3±10.0 mm) were registered and followed up. The most common reason for deployment in the EIA was a common IAA (43 limbs, 58.1%), and 8 limbs (10.8%) had a bare nitinol stent placed at the Spiral-Z limb. A total of 61 patients (70 limbs) completed a 24-month follow-up. There were 2 Spiral-Z limb stenoses and 1 occlusion, leading to a primary patency of 95.5% and a secondary patency of 100%, at 24 months. Buttock claudication occurred in 24.3% of the limbs treated at 1 month but decreased to 4.3% at 24 months. CONCLUSIONS: Our multicenter prospective study showed that Spiral-Z limb deployed in the EIA was associated with satisfactory results and seems to be a durable option, even in the era of iliac branch devices..
16. Kentaro Inoue, Tadashi Furuyama, Shun Kurose, Shinichiro Yoshino, Ken Nakayama, Sho Yamashita, Koichi Morisaki, Masazumi Kume, Takuya Matsumoto, Masaki Mori, Platelets reflect the fate of type II endoleak after endovascular aneurysm repair., Journal of vascular surgery, 10.1016/j.jvs.2019.09.062, 72, 2, 541-548, 2020.08, OBJECTIVE: The management of type II endoleak (T2E) remains controversial because of the heterogeneous outcome. For blood-based screening to detect malignant T2E, we focused on platelets after endovascular aneurysm repair (EVAR) and compared them with the prognosis of T2Es. METHODS: From 2007 to 2015, there were 249 patients treated with EVAR for abdominal aortic aneurysm who were evaluated retrospectively. The mean follow-up period was 3.5 ± 0.2 years. T2Es that had aneurysm sac enlargement or converted to type I or type III endoleak were defined as malignant; the other T2Es were considered benign. Cases without any complications, including T2E, were defined as completed. We compared the platelet count on postoperative days (PODs) 1 to 7 with preoperative baseline values among the three groups. Sequentially, we calculated the cutoff of the platelet ratio on POD 7 to the baseline value in relation to malignant T2E using receiver operating characteristic analysis, and the cutoff ratio was 113% (sensitivity, 79%; specificity, 58%). We then reclassified T2E patients into T2E-high platelet (T2E-HP; ≥113%) or T2E-low platelet (T2E-LP; <113%) groups. The influence of platelets on T2E was evaluated with reintervention rate and cumulative aneurysm sac enlargement rate using the Kaplan-Meier method. RESULTS: T2Es were found in 70 patients (28%), and 179 patients were assigned to the completed group. Malignant and benign T2Es were found in 33 and 37 patients, respectively. No difference was found in the preoperative baseline values. On POD 7, the platelet count in the malignant T2E group was significantly lower than that in the completed and benign T2E groups (168 × 103/μL vs 207 × 103/μL and 201 × 103/μL; P = .0124). Then, 27 and 43 patients were assigned to the T2E-HP and T2E-LP groups, respectively. The reintervention-free survival rate in the T2E-LP group was lower than that in the completed group (at 3 years, 66.4% ± 8.0% vs 71.9% ± 4.0%; P = .0031). Among T2E patients, the cumulative aneurysm sac enlargement rates in the T2E-LP group were significantly higher than those in the T2E-HP group (at 3 years, 34.6% ± 8.2% vs 20.6% ± 8.2%; P = .0105). Univariate Cox proportional hazards analysis for the cumulative aneurysm sac enlargement rates among T2E patients showed that sex, dual antiplatelet therapy, and lower platelet ratio (<113%) were significant predictors; multivariate analysis showed that T2E-LP was the only significant predictor (hazard ratio, 2.60; P = .0355). CONCLUSIONS: The platelet count of patients with malignant T2Es on POD 7 was definitively lower than that of patients with completed EVAR or with benign T2Es. The lower platelet count on POD 7 could be a risk factor for aneurysm sac enlargement among patients with T2Es..
17. Takuya Hino, Takeshi Kamitani, Koji Sagiyama, Yuzo Yamasaki, Yuko Matsuura, Soichiro Tsutsui, Yuki Sakai, Tadashi Furuyama, Hidetake Yabuuchi, Detectability of the artery of Adamkiewicz on computed tomography angiography of the aorta by using ultra-high-resolution computed tomography., Japanese journal of radiology, 10.1007/s11604-020-00943-3, 38, 7, 658-665, 2020.07, PURPOSE: To evaluate the detectability of AKA on aortic computed tomography angiography (CTA) using ultra-high-resolution computed tomography (UHRCT). MATERIALS AND METHODS: Twenty-eight patients were enrolled. They underwent aortic CTA with UHRCT (UHRCTA) and had previously undergone aortic conventional CTA (CCTA). The injection protocol of UHRCTA was the same as that of CCTA. The bolus tracking technique was used. UHRCTA images were reconstructed with adaptive iterative dose reduction (strong) and with forward-projected model-based iterative reconstruction solution. The matrix size and slice thickness on UHRCT were 1024 and 0.25 mm, respectively, and those on conventional CT were 512 and 0.5 or 0.67 mm, respectively. The UHRCTA and CCTA images were visually compared by using four scales. A score of 4 or 3 indicated that the AKA was assessable. In this instance, the contrast-to-noise ratios of each UHRCTA were measured. The exposure dose and signal-to-noise ratios were also investigated. RESULTS: The AKA visualization scores obtained with UHRCTA with forward-projected model-based iterative reconstruction solution were significantly higher than those with adaptive iterative dose reduction (p = 0.018) and CCTA (p = 0.0024). CONCLUSION: UHRCT can contribute to the better visualization of the AKA on aortic CTA..
18. Koichi Morisaki, Tadashi Furuyama, Keiji Yoshiya, Shun Kurose, Shinichiro Yoshino, Ken Nakayama, Sho Yamashita, Eisuke Kawakubo, Takuya Matsumoto, Masaki Mori, Frailty in patients with abdominal aortic aneurysm predicts prognosis after elective endovascular aneurysm repair., Journal of vascular surgery, 10.1016/j.jvs.2019.09.052, 72, 1, 138-143, 2020.07, OBJECTIVE: The diagnostic criteria for frailty in patients with abdominal aortic aneurysm (AAA) are undefined. Our purpose was to examine the influence of new diagnostic criteria for frailty on overall survival after endovascular aneurysm repair (EVAR). METHODS: We retrospectively analyzed data for patients undergoing EVAR between 2007 and 2015. Isolated common iliac artery aneurysm and ruptured AAA were excluded. Patients were defined as having frailty when they had at least two of low Geriatric Nutritional Risk Index, sarcopenia, or nonambulatory status. We examined whether frailty affected overall survival, postoperative complications, and reintervention. RESULTS: Over the study period, 349 patients underwent EVAR. Thirty-three patients were excluded. The 5-year overall survival after EVAR was 76.7% for the frailty-negative group vs 43.1% for the frailty-positive group (P < .01). Age, frailty-positive status, and current cancer therapy were risk factors for overall survival. Positive frailty was the only risk factor for postoperative complications. Forty-two patients underwent reintervention. Outside instructions for use was a risk factor for reintervention after EVAR. CONCLUSIONS: Assessing frailty in patients with AAA is useful for determining risk factors for 5-year overall survival and postoperative complications..
19. Tadashi Furuyama, Sho Yamashita, Keiji Yoshiya, Shun Kurose, Shinichiro Yoshino, Ken Nakayama, Kentaro Inoue, Koichi Morisaki, Takuya Matsumoto, Masaki Mori, The Controlling Nutritional Status Score is Significantly Associated with Complete Ulcer Healing in Patients with Critical Limb Ischemia., Annals of vascular surgery, 10.1016/j.avsg.2019.12.031, 66, 510-517, 2020.07, BACKGROUND: It has been reported that the Controlling Nutritional Status (CONUT) score, calculated using the serum albumin concentration, total peripheral lymphocyte count, and total cholesterol concentration, is a valuable nutritional status index. In the present study, we assessed whether the CONUT score was a significant predictor of complete ulcer healing in patients with critical limb ischemia (CLI). METHODS: In this retrospective, single center, cohort study, conducted from January 2013 to June 2018, we treated 112 limbs of 89 patients with Fontaine 4 CLI at the Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan. The primary endpoint of the study was complete ulcer healing after revascularization, and the secondary endpoint was amputation-free survival (AFS). RESULTS: The mean follow-up time was 17.8 months. Complete ulcer healing was achieved during the follow-up period in 91 (81.2%) limbs. The median ulcer healing time was 104 days (range, 16-574 days). In multivariate analysis, improvement of lower skin perfusion pressure ratio of <1, end-stage renal disease, and high CONUT score (>4) were predictive of incomplete ulcer healing in patients with Fontaine 4 CLI. In addition, the AFS rate was significantly better in patients with a CONUT score ≤4 than in those with a CONUT score >4. CONCLUSIONS: The CONUT score was associated with postprocedure ulcer healing and long-term limb retention in patients who underwent revascularization. The management of CLI involving ischemic foot ulcers may require ongoing consideration of nutritional status..
20. Takuya Matsumoto, Sho Yamashita, Shinichiro Yoshino, Shun Kurose, Koichi Morisaki, Kaku Nakano, Jun-Ichiro Koga, Tadashi Furuyama, Masaki Mori, Kensuke Egashira, Therapeutic Arteriogenesis/Angiogenesis for Peripheral Arterial Disease by Nanoparticle-Mediated Delivery of Pitavastatin into Vascular Endothelial Cells., Annals of vascular diseases, 10.3400/avd.ra.19-00130, 13, 1, 4-12, 2020.03, Two decades have passed since therapeutic angiogenesis was proposed to promote reparative collateral growth as an alternative therapy for ischemic diseases in patients for whom neither surgical revascularization nor endovascular therapy was suitable. When therapeutic angiogenesis first began, local administration was conducted using recombinant growth factor proteins or gene-encoding growth factors for endothelial cells. Since then, autologous stem cells and endothelial progenitor cell transplantation therapy have been developed. Although many clinical trials have been performed on patients, most therapies have not yet become standard treatments. We have developed a nanoparticle (NP)-mediated, drug-targeting delivery system using bioabsorbable poly-lactic/glycolic acid (PLGA) NPs. In several animal models, pitavastatin-incorporated (Pitava)-NPs showed significant therapeutic effects on critical limb ischemia. Because PLGA NPs are delivered selectively to vascular endothelial cells after intramuscular administration, it is suggested that therapeutic angiogenesis/arteriogenesis plays an important role in the mechanism by which Pitava-NPs exert beneficial therapeutic effects. To translate this to clinical medicine, we have performed studies and produced Pitava-NPs in compliance with good laboratory practice/good manufacturing practice regulations, and completed a phase I/II clinical trial, reporting the safety and efficacy of Pitava-NP intramuscular injection for patients with critical limb ischemia. This review will focus on therapeutic angiogenesis/arteriogenesis for peripheral arterial disease induced by Pitava-NPs..
21. Kentaro Inoue, Takuya Matsumoto, Sho Yamashita, Ryosuke Yoshiga, Keiji Yoshiya, Yutaka Matsubara, Daisuke Matsuda, Koichi Morisaki, Tadashi Furuyama, Masaki Mori, Malnutrition diagnosed by controlling nutrition status is a negative predictor of life prognosis in aortic arch aneurysm patients treated with thoracic endovascular aneurysm repair, Vascular, 10.1177/1708538119869458, 28, 1, 31-41, 2020.02, Objectives: Controlling Nutritional Status (CONUT) is a useful screening tool for malnutrition in patients with various diseases; however, how CONUT-diagnosed malnutrition affects patients with aortic arch aneurysm is unknown. This study aimed to reveal the utility of CONUT for detecting the patients with high-risk aortic arch aneurysm with malnutrition. Methods: Sixty patients treated for aortic arch aneurysms with elective thoracic endovascular aneurysm repair from 2009 to 2015 were retrospectively analyzed at a single institution. Preoperative nutrition status was evaluated by CONUT, and a CONUT score ≥ 3 was defined as malnutrition. The influence of malnutrition on the patients’ overall survival, aneurysm-related death-free rates, and prevalence of re-interventions were also analyzed. Results: Twenty-three patients were diagnosed with malnutrition. Overall survival was significantly lower in the malnutrition group (P = 0.0036). The multivariate Cox proportional hazard analysis revealed that age (P < 0.0001) and malnutrition (P = 0.0457) were negative predictors of overall survival. Conversely, the two groups did not differ significantly in aneurysm-related death-free rates (P = 0.7879) and the prevalence of re-interventions (P = 0.7879). Conclusions: Malnutrition diagnosed by CONUT as well as age is a negative predictor of survival prognosis in patients with aortic arch aneurysm..
22. Kentaro Inoue, Takuya Matsumoto, Sho Yamashita, Ryosuke Yoshiga, Keiji Yoshiya, Yutaka Matsubara, Daisuke Matsuda, Koichi Morisaki, Tadashi Furuyama, Masaki Mori, Malnutrition diagnosed by controlling nutrition status is a negative predictor of life prognosis in aortic arch aneurysm patients treated with thoracic endovascular aneurysm repair., Vascular, 10.1177/1708538119869458, 28, 1, 31-41, 2020.02.
23. Takuya Hino, Takeshi Kamitani, Koji Sagiyama, Yuzo Yamasaki, Yuko Matsuura, Soichiro Tsutsui, Yuki Sakai, Tadashi Furuyama, Hidetake Yabuuchi, Detectability of the artery of Adamkiewicz on computed tomography angiography of the aorta by using ultra-high-resolution computed tomography, Japanese Journal of Radiology, 10.1007/s11604-020-00943-3, 2020.01, Purpose: To evaluate the detectability of AKA on aortic computed tomography angiography (CTA) using ultra-high-resolution computed tomography (UHRCT). Materials and methods: Twenty-eight patients were enrolled. They underwent aortic CTA with UHRCT (UHRCTA) and had previously undergone aortic conventional CTA (CCTA). The injection protocol of UHRCTA was the same as that of CCTA. The bolus tracking technique was used. UHRCTA images were reconstructed with adaptive iterative dose reduction (strong) and with forward-projected model-based iterative reconstruction solution. The matrix size and slice thickness on UHRCT were 1024 and 0.25 mm, respectively, and those on conventional CT were 512 and 0.5 or 0.67 mm, respectively. The UHRCTA and CCTA images were visually compared by using four scales. A score of 4 or 3 indicated that the AKA was assessable. In this instance, the contrast-to-noise ratios of each UHRCTA were measured. The exposure dose and signal-to-noise ratios were also investigated. Results: The AKA visualization scores obtained with UHRCTA with forward-projected model-based iterative reconstruction solution were significantly higher than those with adaptive iterative dose reduction (p = 0.018) and CCTA (p = 0.0024). Conclusion: UHRCT can contribute to the better visualization of the AKA on aortic CTA..
24. Kentaro Inoue, Tadashi Furuyama, Shun Kurose, Shinichiro Yoshino, Ken Nakayama, Sho Yamashita, Koichi Morisaki, Masazumi Kume, Takuya Matsumoto, Masaki Mori, Platelets reflect the fate of type II endoleak after endovascular aneurysm repair, Journal of Vascular Surgery, 10.1016/j.jvs.2019.09.062, 2020.01, Objective: The management of type II endoleak (T2E) remains controversial because of the heterogeneous outcome. For blood-based screening to detect malignant T2E, we focused on platelets after endovascular aneurysm repair (EVAR) and compared them with the prognosis of T2Es. Methods: From 2007 to 2015, there were 249 patients treated with EVAR for abdominal aortic aneurysm who were evaluated retrospectively. The mean follow-up period was 3.5 ± 0.2 years. T2Es that had aneurysm sac enlargement or converted to type I or type III endoleak were defined as malignant; the other T2Es were considered benign. Cases without any complications, including T2E, were defined as completed. We compared the platelet count on postoperative days (PODs) 1 to 7 with preoperative baseline values among the three groups. Sequentially, we calculated the cutoff of the platelet ratio on POD 7 to the baseline value in relation to malignant T2E using receiver operating characteristic analysis, and the cutoff ratio was 113% (sensitivity, 79%; specificity, 58%). We then reclassified T2E patients into T2E-high platelet (T2E-HP; ≥113%) or T2E-low platelet (T2E-LP; <113%) groups. The influence of platelets on T2E was evaluated with reintervention rate and cumulative aneurysm sac enlargement rate using the Kaplan-Meier method. Results: T2Es were found in 70 patients (28%), and 179 patients were assigned to the completed group. Malignant and benign T2Es were found in 33 and 37 patients, respectively. No difference was found in the preoperative baseline values. On POD 7, the platelet count in the malignant T2E group was significantly lower than that in the completed and benign T2E groups (168 × 103/μL vs 207 × 103/μL and 201 × 103/μL; P =.0124). Then, 27 and 43 patients were assigned to the T2E-HP and T2E-LP groups, respectively. The reintervention-free survival rate in the T2E-LP group was lower than that in the completed group (at 3 years, 66.4% ± 8.0% vs 71.9% ± 4.0%; P =.0031). Among T2E patients, the cumulative aneurysm sac enlargement rates in the T2E-LP group were significantly higher than those in the T2E-HP group (at 3 years, 34.6% ± 8.2% vs 20.6% ± 8.2%; P =.0105). Univariate Cox proportional hazards analysis for the cumulative aneurysm sac enlargement rates among T2E patients showed that sex, dual antiplatelet therapy, and lower platelet ratio (<113%) were significant predictors; multivariate analysis showed that T2E-LP was the only significant predictor (hazard ratio, 2.60; P =.0355). Conclusions: The platelet count of patients with malignant T2Es on POD 7 was definitively lower than that of patients with completed EVAR or with benign T2Es. The lower platelet count on POD 7 could be a risk factor for aneurysm sac enlargement among patients with T2Es..
25. Tadashi Furuyama, Sho Yamashita, Keiji Yoshiya, Shun Kurose, Shinichiro Yoshino, Ken Nakayama, Kentaro Inoue, Koichi Morisaki, Takuya Matsumoto, Masaki Mori, The Controlling Nutritional Status Score is Significantly Associated with Complete Ulcer Healing in Patients with Critical Limb Ischemia, Annals of Vascular Surgery, 10.1016/j.avsg.2019.12.031, 2020.01, Background: It has been reported that the Controlling Nutritional Status (CONUT) score, calculated using the serum albumin concentration, total peripheral lymphocyte count, and total cholesterol concentration, is a valuable nutritional status index. In the present study, we assessed whether the CONUT score was a significant predictor of complete ulcer healing in patients with critical limb ischemia (CLI). Methods: In this retrospective, single center, cohort study, conducted from January 2013 to June 2018, we treated 112 limbs of 89 patients with Fontaine 4 CLI at the Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan. The primary endpoint of the study was complete ulcer healing after revascularization, and the secondary endpoint was amputation-free survival (AFS). Results: The mean follow-up time was 17.8 months. Complete ulcer healing was achieved during the follow-up period in 91 (81.2%) limbs. The median ulcer healing time was 104 days (range, 16–574 days). In multivariate analysis, improvement of lower skin perfusion pressure ratio of <1, end-stage renal disease, and high CONUT score (>4) were predictive of incomplete ulcer healing in patients with Fontaine 4 CLI. In addition, the AFS rate was significantly better in patients with a CONUT score ≤4 than in those with a CONUT score >4. Conclusions: The CONUT score was associated with postprocedure ulcer healing and long-term limb retention in patients who underwent revascularization. The management of CLI involving ischemic foot ulcers may require ongoing consideration of nutritional status..
26. Koichi Morisaki, Tadashi Furuyama, Yutaka Matsubara, Kentaro Inoue, Shun Kurose, Shinichiro Yoshino, Ken Nakayama, Sho Yamashita, Keiji Yoshiya, Masaki Mori, Thigh sarcopenia and hypoalbuminemia predict impaired overall survival after infrainguinal revascularization in patients with critical limb ischemia, Vascular, 10.1177/1708538120913745, 2020.01, Objective: This study was performed to determine whether thigh sarcopenia can serve as a clinically relevant predictor of postoperative complications and overall survival after revascularization in patients with critical limb ischemia. Methods: Patients who underwent preoperative computed tomography followed by infrainguinal revascularization from 2006 to 2015 were retrospectively analyzed. An axial computed tomography image was obtained at the midpoint of a line extending from the superior border of the patella to the greater trochanter of the femur. The thigh muscle area and bone area were measured. Thigh sarcopenia was defined as thigh muscle area/thigh bone area of <9. Results: We included 117 patients with critical limb ischemia who underwent infrainguinal revascularization. The overall survival rates at two years were 86.5% and 55.1% in the thigh sarcopenia (−) and (+) groups, respectively (p < 0.01). The multivariate analysis showed that thigh sarcopenia (hazard ratio, 2.64; 95% confidence interval, 1.11–6.70; p = 0.03), cerebrovascular disease (hazard ratio, 3.18; 95% confidence interval, 1.31–7.36; p = 0.01), and serum albumin level (1 g/dL per increments) (hazard ratio, 0.41; 95% confidence interval, 0.21–0.81; p = 0.01) were the risk factors for overall survival two years after revascularization. Conclusion: Thigh sarcopenia is a risk factor for two-year overall survival in patients with critical limb ischemia after infrainguinal revascularization..
27. Yukihiko Aoyagi, Tadashi Furuyama, Kentaro Inoue, Daisuke Matsuda, Yutaka Matsubara, Arihide Okahara, Tetsuro Ago, Yutaka Nakashima, Masaki Mori, Takuya Matsumoto, Attenuation of Angiotensin II–Induced Hypertension in BubR1 Low-Expression Mice Via Repression of Angiotensin II Receptor 1 Overexpression, Journal of the American Heart Association, 10.1161/JAHA.118.011911, 8, 23, 2019.12, Background: Angiotensin II (Ang II) can cause hypertension and tissue impairment via AGTR1 (Ang II receptor type 1), particularly in renal proximal tubule cells, and can cause DNA damage in renal cells via nicotinamide adenine dinucleotide phosphate oxidase. BubR1 (budding uninhibited by benzimidazole-related 1) is a multifaceted kinase that functions as a mitotic checkpoint. BubR1 expression can be induced by Ang II in smooth muscle cells in vitro, but the relationship between systemic BubR1 expression and the Ang II response is unclear. Methods and Results: Twenty 24-week-old male BubR1 low-expression mice (BubR1L/L mice) and age-matched BubR1+/+ mice were used in this study. We investigated how Ang II stimulation affects BubR1L/L mice. The elevated systolic blood pressure caused by Ang II stimulation in BubR1+/+ mice was significantly attenuated in BubR1L/L mice. Additionally, an attenuated level of Ang II–induced perivascular fibrosis was observed in the kidneys of BubR1L/L mice. Immunohistochemistry revealed that the overexpression of AGTR1 induced by Ang II stimulation was repressed in BubR1L/L mice. We evaluated AGTR1 and Nox-4 (nicotinamide adenine dinucleotide phosphate oxidase-4) levels to determine the role of BubR1 in the Ang II response. Results from in vitro assays of renal proximal tubule cells suggest that treatment with small interfering RNA targeting BubR1 suppressed Ang II-induced overexpression of AGTR1. Similarly, the upregulation in Nox4 and Jun N-terminal kinase induced by Ang II administration was repressed by treatment with small interfering RNA targeting BubR1. Conclusions: Ang II–induced hypertension is caused by AGTR1 overexpression in the kidneys via the upregulation of BubR1 and Nox4..
28. Yukihiko Aoyagi, Tadashi Furuyama, Kentaro Inoue, Daisuke Matsuda, Yutaka Matsubara, Arihide Okahara, Tetsuro Ago, Yutaka Nakashima, Masaki Mori, Takuya Matsumoto, Attenuation of Angiotensin II-Induced Hypertension in BubR1 Low-Expression Mice Via Repression of Angiotensin II Receptor 1 Overexpression., Journal of the American Heart Association, 10.1161/JAHA.118.011911, 8, 23, e011911, 2019.12, Background Angiotensin II (Ang II) can cause hypertension and tissue impairment via AGTR1 (Ang II receptor type 1), particularly in renal proximal tubule cells, and can cause DNA damage in renal cells via nicotinamide adenine dinucleotide phosphate oxidase. BubR1 (budding uninhibited by benzimidazole-related 1) is a multifaceted kinase that functions as a mitotic checkpoint. BubR1 expression can be induced by Ang II in smooth muscle cells in vitro, but the relationship between systemic BubR1 expression and the Ang II response is unclear. Methods and Results Twenty 24-week-old male BubR1 low-expression mice (BubR1L/L mice) and age-matched BubR1+/+ mice were used in this study. We investigated how Ang II stimulation affects BubR1L/L mice. The elevated systolic blood pressure caused by Ang II stimulation in BubR1+/+ mice was significantly attenuated in BubR1L/L mice. Additionally, an attenuated level of Ang II-induced perivascular fibrosis was observed in the kidneys of BubR1L/L mice. Immunohistochemistry revealed that the overexpression of AGTR1 induced by Ang II stimulation was repressed in BubR1L/L mice. We evaluated AGTR1 and Nox-4 (nicotinamide adenine dinucleotide phosphate oxidase-4) levels to determine the role of BubR1 in the Ang II response. Results from in vitro assays of renal proximal tubule cells suggest that treatment with small interfering RNA targeting BubR1 suppressed Ang II-induced overexpression of AGTR1. Similarly, the upregulation in Nox4 and Jun N-terminal kinase induced by Ang II administration was repressed by treatment with small interfering RNA targeting BubR1. Conclusions Ang II-induced hypertension is caused by AGTR1 overexpression in the kidneys via the upregulation of BubR1 and Nox4..
29. Shinichiro Yoshino, Kentaro Inoue, Keiji Yoshiya, Shun Kurose, Ken Nakayama, Koichi Morisaki, Tadashi Furuyama, Takuya Matsumoto, Yoshinao Oda, Masaki Mori, Cystic Arterial Disease Located Only in the Media of the Popliteal Artery: A Case Report., Annals of vascular diseases, 10.3400/avd.cr.19-00057, 12, 4, 530-533, 2019.12, Adventitial cystic disease of the popliteal artery is a rare non-atheromatous peripheral artery disease. In most cases, the cystic lesion is located in the adventitia of the popliteal artery. Herein, we present a rare case of cystic arterial disease in which the cyst was located only in the media of the popliteal artery. We successfully treated the cyst with resection of the affected popliteal artery and reconstruction with an autogenous vein graft..
30. Satoshi Toyota, Kentaro Inoue, Shun Kurose, Shinichiro Yoshino, Ken Nakayama, Sho Yamashita, Koichi Morisaki, Tadashi Furuyama, Masaki Mori, True brachial artery aneurysm after arteriovenous fistula closure following renal transplantation: a case report and literature review., Surgical case reports, 10.1186/s40792-019-0724-4, 5, 1, 188-188, 2019.12, BACKGROUND: A brachial artery aneurysm (BAA) is a rare condition accounting for 5% of all peripheral arterial aneurysms. More cases of true BAAs after arteriovenous fistula (AVF) closure have been reported in the past two decades. CASE PRESENTATION: A 60-year-old man who underwent AVF closure after renal transplantation had a true BAA on his left elbow that had grown within the past 6 months. We successfully performed an open repair with end-to-end anastomosis. No complications occurred for 1 year. CONCLUSIONS: High flow due to AVF and some collateral factors such as the use of steroids and immunosuppressants after renal transplantation, arteriosclerosis, and chronic mechanical stimulation might contribute to BAA formation..
31. Yoshihiko Maehara, Yuji Soejima, Tomoharu Yoshizumi, Naoyuki Kawahara, Eiji Oki, Hiroshi Saeki, Tomohiko Akahoshi, Toru Ikegami, Yo ichi Yamashita, Tadashi Furuyama, Keishi Sugimachi, Noboru Harada, Tetsuzo Tagawa, Norifumi Harimoto, Shinji Itoh, Hideto Sonoda, Koji Ando, Yuichiro Nakashima, Yoshihiro Nagao, Nami Yamashita, Yuta Kasagi, Takafumi Yukaya, Takeshi Kurihara, Ryosuke Tsutsumi, Shinkichi Takamori, Shun Sasaki, Tetsuo Ikeda, Yoshikazu Yonemitsu, Takasuke Fukuhara, Hiroyuki Kitao, Makoto Iimori, Yuki Kataoka, Takeshi Wakasa, Masami Suzuki, Koji Teraishi, Yasuto Yoshida, Masaki Mori, The evolution of surgical treatment for gastrointestinal cancers, International Journal of Clinical Oncology, 10.1007/s10147-019-01499-7, 24, 11, 1333-1349, 2019.11, Introduction: According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them. Materials and methods, and results: Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery. Conclusion: We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival..
32. Yoshihiko Maehara, Yuji Soejima, Tomoharu Yoshizumi, Naoyuki Kawahara, Eiji Oki, Hiroshi Saeki, Tomohiko Akahoshi, Toru Ikegami, Yo-Ichi Yamashita, Tadashi Furuyama, Keishi Sugimachi, Noboru Harada, Tetsuzo Tagawa, Norifumi Harimoto, Shinji Itoh, Hideto Sonoda, Koji Ando, Yuichiro Nakashima, Yoshihiro Nagao, Nami Yamashita, Yuta Kasagi, Takafumi Yukaya, Takeshi Kurihara, Ryosuke Tsutsumi, Shinkichi Takamori, Shun Sasaki, Tetsuo Ikeda, Yoshikazu Yonemitsu, Takasuke Fukuhara, Hiroyuki Kitao, Makoto Iimori, Yuki Kataoka, Takeshi Wakasa, Masami Suzuki, Koji Teraishi, Yasuto Yoshida, Masaki Mori, The evolution of surgical treatment for gastrointestinal cancers., International journal of clinical oncology, 10.1007/s10147-019-01499-7, 24, 11, 1333-1349, 2019.11, INTRODUCTION: According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them. MATERIALS AND METHODS, AND RESULTS: Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery. CONCLUSION: We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival..
33. Koichi Morisaki, Tadashi Furuyama, Yutaka Matsubara, Kentaro Inoue, Shun Kurose, Shinichiro Yoshino, Ken Nakayama, Sho Yamashita, Keiji Yoshiya, Ryosuke Yoshiga, Yoshihiko Maehara, External validation of CLI Frailty Index and assessment of predictive value of modified CLI Frailty Index for patients with critical limb ischemia undergoing infrainguinal revascularization, Vascular, 10.1177/1708538119836005, 27, 4, 405-410, 2019.08, Objectives: CLI Frailty is a useful diagnostic criterion of frailty in patients with critical limb ischemia (CLI). It is important to evaluate not only comorbidities but also frailty in decision making to select the type of treatment for CLI patients. The purposes of our study were to externally validate the CLI Frailty Index and to evaluate the modified CLI Frailty Index by measurement of skeletal muscle mass using computed tomography. Methods: Patients who underwent preoperative computed tomography examination and infrainguinal revascularization between 2002 and 2015 were retrospectively analyzed. A patient was defined as CLI Frailty (+), if two or more of the following criteria were present: low Geriatric Nutritional Risk Index (GNRI), low skeletal muscle mass index (SMI) evaluated by prediction equations, and non-ambulatory status. For the modified CLI Frailty Index, skeletal muscle area was measured by computed tomography instead of prediction equations. Results: During the study period, 226 patients with CLI underwent revascularization; we included 127 patients and excluded 99 patients who were treated only with iliac revascularization or did not undergo CT scans. The overall survival at two years after revascularization was 83.6% for the CLI Frailty (−) group versus 63.2% for the CLI Frailty (+) group (P =.02). The overall survival at two years after revascularization was 89.7% for the modified CLI Frailty (−) group versus 60.5% for the modified CLI Frailty (+) group (P <.01). Multivariate analysis 1 including CLI Frailty revealed that hemodialysis (HR, 3.71; 95% CI, 1.58–8.83; P <.01), CLI Frailty (HR, 3.22; 95% CI, 1.35–7.47; P <.01) and cerebrovascular disease (HR, 2.58; 95% CI, 1.09–5.91; P =.03) were risk factors for overall survival two years after revascularization. In multivariate analysis 2 including modified CLI Frailty, modified CLI Frailty (HR, 5.92; 95% CI, 2.49–15.7; P <.01), hemodialysis (HR, 4.03; 95% CI, 1.65–10.0; P <.01) and diabetes mellitus (HR, 0.41; 95% CI, 0.16–0.99; P =.05) were risk factors for overall survival two years after revascularization. Conclusions: Both the CLI Frailty and the modified CLI Frailty Indexes were useful in predicting the two-year overall survival of patients with CLI after infrainguinal revascularization. Although the measurement of skeletal muscle mass using computed tomography may accurately predict two-year overall survival, SMI prediction is effective for patients with CLI who did not undergo preoperative CT..
34. Koichi Morisaki, Tadashi Furuyama, Yutaka Matsubara, Kentaro Inoue, Shun Kurose, Shinichiro Yoshino, Ken Nakayama, Sho Yamashita, Keiji Yoshiya, Ryosuke Yoshiga, Yoshihiko Maehara, External validation of CLI Frailty Index and assessment of predictive value of modified CLI Frailty Index for patients with critical limb ischemia undergoing infrainguinal revascularization., Vascular, 10.1177/1708538119836005, 27, 4, 405-410, 2019.08.
35. Shun Kurose, Kentaro Inoue, Shinichiro Yoshino, Ken Nakayama, Sho Yamashita, Keiji Yoshiya, Ryosuke Yoshiga, Koichi Morisaki, Keizo Kaku, Yasuhiro Okabe, Tadashi Furuyama, Yoshihiko Maehara, Successful Bridge Therapy with Initial Endovascular Repair for Arterioenteric Fistula Resulting from Pseudoaneurysm Rupture with Massive Gastrointestinal Hemorrhage after Pancreas Transplantation, Annals of Vascular Surgery, 10.1016/j.avsg.2018.10.028, 58, 379.e15-379.e22, 2019.07, Pseudoaneurysm after pancreas transplantation has a reported incidence of 1.4 to 8.0% and may be caused by perioperative infection. Subsequent pseudoaneurysm rupture is a rare cause of arterioenteric fistula. Only 28 cases of arterioenteric fistula after pancreas transplantation have been reported in the past 20 years. We experienced a rare case of arterioenteric fistula resulting from pseudoaneurysm rupture after pancreas transplantation. We successfully treated the arterioenteric fistula with multistaged bridge therapy composed of initial endovascular aneurysm repair, secondary isolation of the fistula, and definitive open repair with extraanatomic bypass. No complications occurred in 1 year of follow-up; this staged therapy seems feasible for patients with arterioenteric fistula..
36. Shun Kurose, Kentaro Inoue, Shinichiro Yoshino, Ken Nakayama, Sho Yamashita, Keiji Yoshiya, Ryosuke Yoshiga, Koichi Morisaki, Keizo Kaku, Yasuhiro Okabe, Tadashi Furuyama, Yoshihiko Maehara, Successful Bridge Therapy with Initial Endovascular Repair for Arterioenteric Fistula Resulting from Pseudoaneurysm Rupture with Massive Gastrointestinal Hemorrhage after Pancreas Transplantation., Annals of vascular surgery, 10.1016/j.avsg.2018.10.028, 58, 379.e15-379.e22, 2019.07, Pseudoaneurysm after pancreas transplantation has a reported incidence of 1.4 to 8.0% and may be caused by perioperative infection. Subsequent pseudoaneurysm rupture is a rare cause of arterioenteric fistula. Only 28 cases of arterioenteric fistula after pancreas transplantation have been reported in the past 20 years. We experienced a rare case of arterioenteric fistula resulting from pseudoaneurysm rupture after pancreas transplantation. We successfully treated the arterioenteric fistula with multistaged bridge therapy composed of initial endovascular aneurysm repair, secondary isolation of the fistula, and definitive open repair with extraanatomic bypass. No complications occurred in 1 year of follow-up; this staged therapy seems feasible for patients with arterioenteric fistula..
37. Toshihiro Onohara, Ryoichi Kyuragi, Kentaro Inoue, Shohei Yoshida, Takuya Matsumoto, Tadashi Furuyama, Late-Onset Malignant Neoplasms and Their Prognostic Factors after Abdominal Aortic Aneurysm Repair, Annals of Vascular Surgery, 10.1016/j.avsg.2018.08.095, 56, 194-201, 2019.04, Background: Little is known about late-onset primary malignant neoplasms after repair of abdominal aortic aneurysms (AAAs) despite malignancy being one of the primary causes of late death. We investigated the incidence and prognostic factors related to the occurrence of malignancy after AAA repair. Methods: We performed a retrospective analysis of 589 patients who underwent AAA repair, including 264 endovascular AAA repairs and 325 open surgical repairs; 482 patients had no history of previous malignancy or concomitant malignancy, 72 had previous malignancy, and 35 had concomitant malignancy in remission at the time of AAA repair. The cumulative incidence rates of late-onset malignancy occurrence and cancer death were estimated using the cumulative incidence function in the presence of competing risks, that is, noncancer death, and prognostic factors were investigated using the Fine-Gray hazard model. Results: After hospital discharge, 128 malignancies occurred in 116 patients. Overall cumulative incidence rates of late-onset malignancy occurrence at 1, 3, 5, and 10 years were 4.0%, 11.7%, 18.2%, and 38.1%, respectively. Multivariate analysis revealed that significant prognostic factors for late-onset malignancy included history of previous malignancy, current smoker, higher intraoperative blood loss, absence of allogeneic blood transfusion, lower C-reactive protein levels, and lower serum high-density lipoprotein-cholesterol levels. The type of surgical procedures for AAA repair did not affect the occurrence of malignancy. In addition, current smoker and higher intraoperative blood loss significantly increased the risk of cancer death. Conclusions: Current smoker and higher intraoperative blood loss were independent risk factors for late-onset malignancy after AAA repair. Late-onset malignancy after AAA repair should be monitored among patients at high risk and requires aggressive management to improve long-term survival..
38. Toshihiro Onohara, Ryoichi Kyuragi, Kentaro Inoue, Shohei Yoshida, Takuya Matsumoto, Tadashi Furuyama, Late-Onset Malignant Neoplasms and Their Prognostic Factors after Abdominal Aortic Aneurysm Repair., Annals of vascular surgery, 10.1016/j.avsg.2018.08.095, 56, 194-201, 2019.04, BACKGROUND: Little is known about late-onset primary malignant neoplasms after repair of abdominal aortic aneurysms (AAAs) despite malignancy being one of the primary causes of late death. We investigated the incidence and prognostic factors related to the occurrence of malignancy after AAA repair. METHODS: We performed a retrospective analysis of 589 patients who underwent AAA repair, including 264 endovascular AAA repairs and 325 open surgical repairs; 482 patients had no history of previous malignancy or concomitant malignancy, 72 had previous malignancy, and 35 had concomitant malignancy in remission at the time of AAA repair. The cumulative incidence rates of late-onset malignancy occurrence and cancer death were estimated using the cumulative incidence function in the presence of competing risks, that is, noncancer death, and prognostic factors were investigated using the Fine-Gray hazard model. RESULTS: After hospital discharge, 128 malignancies occurred in 116 patients. Overall cumulative incidence rates of late-onset malignancy occurrence at 1, 3, 5, and 10 years were 4.0%, 11.7%, 18.2%, and 38.1%, respectively. Multivariate analysis revealed that significant prognostic factors for late-onset malignancy included history of previous malignancy, current smoker, higher intraoperative blood loss, absence of allogeneic blood transfusion, lower C-reactive protein levels, and lower serum high-density lipoprotein-cholesterol levels. The type of surgical procedures for AAA repair did not affect the occurrence of malignancy. In addition, current smoker and higher intraoperative blood loss significantly increased the risk of cancer death. CONCLUSIONS: Current smoker and higher intraoperative blood loss were independent risk factors for late-onset malignancy after AAA repair. Late-onset malignancy after AAA repair should be monitored among patients at high risk and requires aggressive management to improve long-term survival..
39. Yutaka Matsubara, Takuya Matsumoto, Keiji Yoshiya, Ayae Yoshida, Seiichi Ikeda, Tadashi Furuyama, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Masatoshi Nomura, Yoshihiko Maehara, Budding Uninhibited by Benzimidazole-1 Insufficiency Prevents Acute Renal Failure in Severe Sepsis by Maintaining Anticoagulant Functions of Vascular Endothelial Cells, Shock, 10.1097/SHK.0000000000001147, 51, 3, 364-371, 2019.03, Severe sepsis is critical to health and can result in acute renal failure (ARF). Tissue factor (TF) and thrombomodulin (TM) play key roles in vascular endothelial functions by helping maintain microcirculation in the kidney. Budding uninhibited by benzimidazole-1 (Bub1) plays a role in Akt and JNK signaling, which control TF and TM, respectively. We hypothesized that Bub1 could control vascular endothelial function in sepsis. The aim of this study was to determine the role of Bub1 in septic ARF. We used Mouse cecum ligation and puncture (CLP) using low Bub1 expressing (Bub1L/L) and wild-type (Bub1+/+) mice in vivo and lipopolysaccharide (LPS) stimulation of human aortic endothelial cell (HAEC) in vitro. Bub1L/L mice had a higher survival rate after CLP than Bub1+/+. Bub1+/+ mice had more severe ARF after CLP than Bub1L/L with blood biochemical and pathological analyses. TF expression in Bub1+/+ mice and control HAEC (control) significantly increased in the septic model compared with Bub1L/L and Bub1 silenced HAEC (siBub1). TM expression in the control significantly decreased after LPS stimulation compared with siBub1. Akt and JNK phosphorylation of siBub1 were attenuated after LPS stimulation. Associations of Bub1 with Akt or JNK after LPS stimulation of HAEC were detected using immunoprecipitation, suggesting that Bub1 is involved in the phosphorylation of Akt and JNK after LPS stimulation. Bub1 insufficiency attenuates TF expression and reduces TM suppression by blocking Akt and JNK phosphorylation, respectively, thus leading to the prevention of ARF and death caused by sepsis..
40. Yutaka Matsubara, Takuya Matsumoto, Keiji Yoshiya, Ayae Yoshida, Seiichi Ikeda, Tadashi Furuyama, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Masatoshi Nomura, Yoshihiko Maehara, Budding Uninhibited by Benzimidazole-1 Insufficiency Prevents Acute Renal Failure in Severe Sepsis by Maintaining Anticoagulant Functions of Vascular Endothelial Cells., Shock (Augusta, Ga.), 10.1097/SHK.0000000000001147, 51, 3, 364-371, 2019.03, Severe sepsis is critical to health and can result in acute renal failure (ARF). Tissue factor (TF) and thrombomodulin (TM) play key roles in vascular endothelial functions by helping maintain microcirculation in the kidney. Budding uninhibited by benzimidazole-1 (Bub1) plays a role in Akt and JNK signaling, which control TF and TM, respectively. We hypothesized that Bub1 could control vascular endothelial function in sepsis. The aim of this study was to determine the role of Bub1 in septic ARF. We used Mouse cecum ligation and puncture (CLP) using low Bub1 expressing (Bub1) and wild-type (Bub1) mice in vivo and lipopolysaccharide (LPS) stimulation of human aortic endothelial cell (HAEC) in vitro. Bub1 mice had a higher survival rate after CLP than Bub1. Bub1 mice had more severe ARF after CLP than Bub1 with blood biochemical and pathological analyses. TF expression in Bub1 mice and control HAEC (control) significantly increased in the septic model compared with Bub1 and Bub1 silenced HAEC (siBub1). TM expression in the control significantly decreased after LPS stimulation compared with siBub1. Akt and JNK phosphorylation of siBub1 were attenuated after LPS stimulation. Associations of Bub1 with Akt or JNK after LPS stimulation of HAEC were detected using immunoprecipitation, suggesting that Bub1 is involved in the phosphorylation of Akt and JNK after LPS stimulation. Bub1 insufficiency attenuates TF expression and reduces TM suppression by blocking Akt and JNK phosphorylation, respectively, thus leading to the prevention of ARF and death caused by sepsis..
41. Tadashi Furuyama, Toshihiro Onohara, Ryosuke Yoshiga, Keiji Yoshiya, Yutaka Matsubara, Kentaro Inoue, Daisuke Matsuda, Koichi Morisaki, Takuya Matsumoto, Yoshihiko Maehara, Functional prognosis of critical limb ischemia and efficacy of restoration of direct flow below the ankle, Vascular, 10.1177/1708538118798886, 27, 1, 38-45, 2019.02, Objective: Patients with critical limb ischemia have serious systemic comorbidities and are at high risk of impairment of limb function. In this study, we assessed the prognostic factors of limbs after revascularization. Methods: In this retrospective single-center cohort study, from April 2008 to December 2012, we treated 154 limbs of 121 patients with critical limb ischemia by the endovascular therapy-first approach based on the patients’ characteristics. The primary end point was amputation-free survival. Secondary end points were patency of a revascularized artery, major adverse limb events, or death. Furthermore, we investigated the ambulatory status one year after revascularization as prognosis of limb function. Results: Endovascular therapy was performed in 85 limbs in 65 patients as the initial therapy (endovascular therapy group) and surgical reconstructive procedures (bypass group) were performed in 69 limbs in 56 patients. Early mortality within 30 days was not observed in either group. The primary patency rate was significantly better in the bypass group than in the endovascular therapy group (p < 0.0001). Furthermore, the secondary patency rate was similar between the two groups (p = 0.0096). There were no significant differences in amputation-free survival and major adverse limb event between the two groups. Univariate analysis showed that ulcer healing (p < 0.0001), no hypoalbuminemia (p = 0.0019), restoration of direct flow below the ankle (p = 0.0219), no previous cerebrovascular disease (p = 0.0389), and Rutherford 4 (p = 0.0469) were predictive factors for preservation of ambulatory status one year after revascularization. In multivariate analysis, ulcer healing (p < 0.0001) and restoration of direct flow below the ankle (p = 0.0060) were significant predictors. Conclusions: Ulcer healing and restoration of direct flow below the ankle are independently associated with prognosis of limb functions in patients who undergo infrainguinal arterial reconstruction..
42. Tadashi Furuyama, Toshihiro Onohara, Ryosuke Yoshiga, Keiji Yoshiya, Yutaka Matsubara, Kentaro Inoue, Daisuke Matsuda, Koichi Morisaki, Takuya Matsumoto, Yoshihiko Maehara, Functional prognosis of critical limb ischemia and efficacy of restoration of direct flow below the ankle., Vascular, 10.1177/1708538118798886, 27, 1, 38-45, 2019.02, OBJECTIVE: Patients with critical limb ischemia have serious systemic comorbidities and are at high risk of impairment of limb function. In this study, we assessed the prognostic factors of limbs after revascularization. METHODS: In this retrospective single-center cohort study, from April 2008 to December 2012, we treated 154 limbs of 121 patients with critical limb ischemia by the endovascular therapy-first approach based on the patients' characteristics. The primary end point was amputation-free survival. Secondary end points were patency of a revascularized artery, major adverse limb events, or death. Furthermore, we investigated the ambulatory status one year after revascularization as prognosis of limb function. RESULTS: Endovascular therapy was performed in 85 limbs in 65 patients as the initial therapy (endovascular therapy group) and surgical reconstructive procedures (bypass group) were performed in 69 limbs in 56 patients. Early mortality within 30 days was not observed in either group. The primary patency rate was significantly better in the bypass group than in the endovascular therapy group ( p < 0.0001). Furthermore, the secondary patency rate was similar between the two groups ( p = 0.0096). There were no significant differences in amputation-free survival and major adverse limb event between the two groups. Univariate analysis showed that ulcer healing ( p < 0.0001), no hypoalbuminemia ( p = 0.0019), restoration of direct flow below the ankle ( p = 0.0219), no previous cerebrovascular disease ( p = 0.0389), and Rutherford 4 ( p = 0.0469) were predictive factors for preservation of ambulatory status one year after revascularization. In multivariate analysis, ulcer healing ( p < 0.0001) and restoration of direct flow below the ankle ( p = 0.0060) were significant predictors. CONCLUSIONS: Ulcer healing and restoration of direct flow below the ankle are independently associated with prognosis of limb functions in patients who undergo infrainguinal arterial reconstruction..
43. Koichi Morisaki, Tadashi Furuyama, Keiji Yoshiya, Shun Kurose, Shinichiro Yoshino, Ken Nakayama, Sho Yamashita, Eisuke Kawakubo, Takuya Matsumoto, Masaki Mori, Frailty in patients with abdominal aortic aneurysm predicts prognosis after elective endovascular aneurysm repair, Journal of Vascular Surgery, 10.1016/j.jvs.2019.09.052, 2019.01, Objective: The diagnostic criteria for frailty in patients with abdominal aortic aneurysm (AAA) are undefined. Our purpose was to examine the influence of new diagnostic criteria for frailty on overall survival after endovascular aneurysm repair (EVAR). Methods: We retrospectively analyzed data for patients undergoing EVAR between 2007 and 2015. Isolated common iliac artery aneurysm and ruptured AAA were excluded. Patients were defined as having frailty when they had at least two of low Geriatric Nutritional Risk Index, sarcopenia, or nonambulatory status. We examined whether frailty affected overall survival, postoperative complications, and reintervention. Results: Over the study period, 349 patients underwent EVAR. Thirty-three patients were excluded. The 5-year overall survival after EVAR was 76.7% for the frailty-negative group vs 43.1% for the frailty-positive group (P < .01). Age, frailty-positive status, and current cancer therapy were risk factors for overall survival. Positive frailty was the only risk factor for postoperative complications. Forty-two patients underwent reintervention. Outside instructions for use was a risk factor for reintervention after EVAR. Conclusions: Assessing frailty in patients with AAA is useful for determining risk factors for 5-year overall survival and postoperative complications..
44. Yutaka Matsubara, Tadashi Furuyama, Ken Nakayama, Keiji Yoshiya, Kentaro Inoue, Koichi Morisaki, Masazumi Kume, Yoshihiko Maehara, High intramuscular adipose tissue content as a precondition of sarcopenia in patients with aortic aneurysm, Surgery today, 10.1007/s00595-018-1697-9, 48, 12, 1052-1059, 2018.12, Purpose: Sarcopenia is a major problem of the elderly. Although little is known about the cause of sarcopenia, the intramuscular adipose tissue content (IMAC) is known to be a cause of sarcopenia. The aim of this study was to investigate the significance of IMAC as a cause of sarcopenia. Methods: We evaluated patients who underwent aneurysm repair and were monitored preoperatively and 3 years postoperatively by computed tomography (CT). The skeletal muscle area and IMAC were measured on preoperative L3 CT images. The clinical characteristics and risk factors for skeletal muscle wasting were assessed. Results: Among the 155 patients, 38 (24.5%) had > 10% skeletal muscle wasting 3 years after the operation. Patients with > 10% skeletal muscle wasting had higher IMACs of the iliopsoas (− 0.31 ± 0.01 vs. −0.45 ± 0.01, P < 0.001) muscles and higher rates of cerebrovascular infarctions (7.7 vs. 23.7%, P = 0.0068), lung cancer (0 vs. 10.5%, P < 0.001), and urgent operations (0.9 vs. 10.5%, P = 0.029) and a longer postoperative fasting period (1.3 ± 0.1 vs. 3.1 ± 0.9 days, P < 0.001) than those without > 10% skeletal muscle wasting. The IMAC of the iliopsoas muscle correlated strongly with skeletal muscle wasting (P < 0.05, r = 0.70). Conclusions: A high IMAC of the iliopsoas muscle may cause sarcopenia and thus be a clinical target in disease prevention..
45. Tadashi Furuyama, Toshihiro Onohara, Sho Yamashita, Ryosuke Yoshiga, Keiji Yoshiya, Kentaro Inoue, Koichi Morisaki, Ryoichi Kyuragi, Takuya Matsumoto, Yoshihiko Maehara, Prognostic factors of ulcer healing and amputation-free survival in patients with critical limb ischemia, Vascular, 10.1177/1708538118786864, 26, 6, 626-633, 2018.12, Objective: A multidisciplinary approach is required to treat critical limb ischemia. We determined the poor prognostic factors of ischemic ulcer healing after optimal arterial revascularization, and assessed the efficacy of the medication therapy using cilostazol, which is a selective inhibitor of phosphodiesterase 3. Methods: In this retrospective, single-center, cohort study, 129 limbs that underwent infrainguinal arterial revascularization for Rutherford class 5 critical limb ischemia were reviewed. The primary end point was the ulcer healing time after arterial revascularization. The secondary end point was the amputation-free survival rate. Results: Of the 129 limbs, endovascular therapy was performed in 69 limbs, and surgical reconstructive procedures were performed in 60 limbs for initial therapy. Complete ulcer healing was achieved in 95 limbs (74%). The median ulcer healing time was 90 days. In multivariate analysis, no cilostazol use significantly inhibited ulcer healing (p = 0.0114). A white blood cell count >10,000 (p = 0.0185), a major defect after debridement (p = 0.0215), and endovascular therapy (p = 0.0308) were significant poor prognostic factors for ulcer healing. Additionally, ischemic heart disease (p < 0.0001), albumin levels <3 g/dl (p = 0.0016), no cilostazol use (p = 0.0078), and a major defect after debridement (p = 0.0208) were significant poor prognostic factors for amputation-free survival rate. Conclusions: Ulcer healing within 90 days after arterial revascularization is impaired by no cilostazol use, a white blood cell count >10,000, a major defect after debridement, and endovascular therapy. Furthermore, cilostazol improves amputation-free survival rate in patients with critical limb ischemia..
46. Yutaka Matsubara, Tadashi Furuyama, Ken Nakayama, Keiji Yoshiya, Kentaro Inoue, Koichi Morisaki, Masazumi Kume, Yoshihiko Maehara, High intramuscular adipose tissue content as a precondition of sarcopenia in patients with aortic aneurysm., Surgery today, 10.1007/s00595-018-1697-9, 48, 12, 1052-1059, 2018.12, PURPOSE: Sarcopenia is a major problem of the elderly. Although little is known about the cause of sarcopenia, the intramuscular adipose tissue content (IMAC) is known to be a cause of sarcopenia. The aim of this study was to investigate the significance of IMAC as a cause of sarcopenia. METHODS: We evaluated patients who underwent aneurysm repair and were monitored preoperatively and 3 years postoperatively by computed tomography (CT). The skeletal muscle area and IMAC were measured on preoperative L3 CT images. The clinical characteristics and risk factors for skeletal muscle wasting were assessed. RESULTS: Among the 155 patients, 38 (24.5%) had > 10% skeletal muscle wasting 3 years after the operation. Patients with > 10% skeletal muscle wasting had higher IMACs of the iliopsoas (- 0.31 ± 0.01 vs. -0.45 ± 0.01, P < 0.001) muscles and higher rates of cerebrovascular infarctions (7.7 vs. 23.7%, P = 0.0068), lung cancer (0 vs. 10.5%, P < 0.001), and urgent operations (0.9 vs. 10.5%, P = 0.029) and a longer postoperative fasting period (1.3 ± 0.1 vs. 3.1 ± 0.9 days, P < 0.001) than those without > 10% skeletal muscle wasting. The IMAC of the iliopsoas muscle correlated strongly with skeletal muscle wasting (P < 0.05, r = 0.70). CONCLUSIONS: A high IMAC of the iliopsoas muscle may cause sarcopenia and thus be a clinical target in disease prevention..
47. Tadashi Furuyama, Toshihiro Onohara, Sho Yamashita, Ryosuke Yoshiga, Keiji Yoshiya, Kentaro Inoue, Koichi Morisaki, Ryoichi Kyuragi, Takuya Matsumoto, Yoshihiko Maehara, Prognostic factors of ulcer healing and amputation-free survival in patients with critical limb ischemia., Vascular, 10.1177/1708538118786864, 26, 6, 626-633, 2018.12, OBJECTIVE: A multidisciplinary approach is required to treat critical limb ischemia. We determined the poor prognostic factors of ischemic ulcer healing after optimal arterial revascularization, and assessed the efficacy of the medication therapy using cilostazol, which is a selective inhibitor of phosphodiesterase 3. METHODS: In this retrospective, single-center, cohort study, 129 limbs that underwent infrainguinal arterial revascularization for Rutherford class 5 critical limb ischemia were reviewed. The primary end point was the ulcer healing time after arterial revascularization. The secondary end point was the amputation-free survival rate. RESULTS: Of the 129 limbs, endovascular therapy was performed in 69 limbs, and surgical reconstructive procedures were performed in 60 limbs for initial therapy. Complete ulcer healing was achieved in 95 limbs (74%). The median ulcer healing time was 90 days. In multivariate analysis, no cilostazol use significantly inhibited ulcer healing ( p = 0.0114). A white blood cell count >10,000 ( p = 0.0185), a major defect after debridement ( p = 0.0215), and endovascular therapy ( p = 0.0308) were significant poor prognostic factors for ulcer healing. Additionally, ischemic heart disease ( p < 0.0001), albumin levels <3 g/dl ( p = 0.0016), no cilostazol use ( p = 0.0078), and a major defect after debridement ( p = 0.0208) were significant poor prognostic factors for amputation-free survival rate. CONCLUSIONS: Ulcer healing within 90 days after arterial revascularization is impaired by no cilostazol use, a white blood cell count >10,000, a major defect after debridement, and endovascular therapy. Furthermore, cilostazol improves amputation-free survival rate in patients with critical limb ischemia..
48. Eisuke Kawakubo, Takuya Matsumoto, Keiji Yoshiya, Sho Yamashita, Tomoko Jogo, Hiroshi Saeki, Eiji Oki, Tadashi Furuyama, Yoshinao Oda, Yoshihiko Maehara, BUBR1 insufficiency is correlated with eNOS reduction experimentally in vitro and in vivo, and in gastric cancer tissue, Anticancer research, 10.21873/anticanres.12960, 38, 11, 6099-6106, 2018.11, Background/Aim: Budding uninhibited by benzimidazole-related 1 (BUBR1) and endothelial nitric oxide synthase (eNOS) are related to aging and angiogenesis. This study examined the effect of low BUBR1 expression on eNOS expression in vivo, in vitro, and human gastric cancer tissues. Materials and Methods: Human umbilical vein endothelial cells (HUVECs) were passaged to investigate the effect of aging on BUBR1 and eNOS expression; expression of eNOS and phospho-eNOS protein was assessed in BUBR1 siRNAtransfected HUVECs. Additionally, guanosine 3′,5′ cyclic monophosphate (cGMP) and eNOS protein levels were measured in BUBR1-insufficient mice (Bubr1L/-). BUBR1 and eNOS expression levels were also evaluated in human gastric cancer tissues. Results: BUBR1 and eNOS, but not p-eNOS, levels were reduced significantly in aged and BUBR1 siRNAtransfected HUVECs. Additionally, cGMP production and the eNOS protein level were reduced in Bubr1L/- mice. Human gastric cancer tissues with low BUBR1 expression showed no eNOS expression. Conclusion: A decrease in BUBR1 reduced eNOS bioavailability through a pathway other than eNOS phosphorylation..
49. Eisuke Kawakubo, Takuya Matsumoto, Keiji Yoshiya, Sho Yamashita, Tomoko Jogo, Hiroshi Saeki, Eiji Oki, Tadashi Furuyama, Yoshinao Oda, Yoshihiko Maehara, BUBR1 Insufficiency Is Correlated with eNOS Reduction Experimentally In Vitro and In Vivo, and in Gastric Cancer Tissue., Anticancer research, 10.21873/anticanres.12960, 38, 11, 6099-6106, 2018.11, BACKGROUND/AIM: Budding uninhibited by benzimidazole-related 1 (BUBR1) and endothelial nitric oxide synthase (eNOS) are related to aging and angiogenesis. This study examined the effect of low BUBR1 expression on eNOS expression in vivo, in vitro, and human gastric cancer tissues. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were passaged to investigate the effect of aging on BUBR1 and eNOS expression; expression of eNOS and phospho-eNOS protein was assessed in BUBR1 siRNA-transfected HUVECs. Additionally, guanosine 3',5' cyclic monophosphate (cGMP) and eNOS protein levels were measured in BUBR1-insufficient mice (Bubr1L/-). BUBR1 and eNOS expression levels were also evaluated in human gastric cancer tissues. RESULTS: BUBR1 and eNOS, but not p-eNOS, levels were reduced significantly in aged and BUBR1 siRNA-transfected HUVECs. Additionally, cGMP production and the eNOS protein level were reduced in Bubr1L/- mice. Human gastric cancer tissues with low BUBR1 expression showed no eNOS expression. CONCLUSION: A decrease in BUBR1 reduced eNOS bioavailability through a pathway other than eNOS phosphorylation..
50. Jin Okazaki, Daisuke Matsuda, Kiyoshi Tanaka, Masaru Ishida, Sosei Kuma, Koichi Morisaki, Tadashi Furuyama, Yoshihiko Maehara, Analysis of wound healing time and wound-free period as outcomes after surgical and endovascular revascularization for critical lower limb ischemia, Journal of Vascular Surgery, 10.1016/j.jvs.2017.07.122, 67, 3, 817-825, 2018.03, Background: Traditional end points, such as amputation-free survival, used to assess the clinical effectiveness of lower limb revascularization have shortcomings because they do not account independently for wound nonhealing and recurrence or patient survival. Wound healing process and maintenance of a wound-free state after revascularization were not well-studied. The aim of this study was to elucidate the long-term clinical course of ischemic wounds after revascularization. We focused on initial wound healing process as well as the maintenance of a wound-free state after achievement of wound healing. We introduced a wound-free period (WFP; the period during which limbs maintained an ulcer-free state) and Wound Recurrence and Amputation-free Survival (WRAFS) as parameters and tested their effectiveness in evaluating clinical outcomes of limbs treated using endovascular therapy (EVT) and surgical revascularization. Methods: The medical records of patients developing lower critical limb ischemia with tissue loss who underwent surgical or endovascular revascularization of the infrainguinal vessels between 2009 and 2013 were reviewed retrospectively. The risk factors for achieving wound healing and WRAFS were analyzed using Kaplan-Meier survival curves and Cox regression model. Risk factors to prolong wound healing time (WHT) and reduce WFP were determined by the least squares method. Results: In total, 233 patients underwent 278 limb revascularizations; 138 endovascular and 140 surgical procedures were performed as first treatments. The proportion of healed wounds 1, 2, and 3 years after primary revascularization was 64.0%, 69.7%, and 70.5%, respectively. Significant risk factors for wound healing were an EVT-first strategy (risk ratio [RR], 2.47), congestive heart failure (RR, 2.05), and wound, ischemia, and foot infection wound grade (RR, 1.59). The mean WHT was 143.7 days. An EVT-first strategy and wound infection contributed to significantly longer WHT. The mean WFP was 711.0 days. An EVT-first strategy, history of coronary artery disease, and dialysis dependence were associated with significantly shorter WFPs. WRAFS at 1 and 2 years after achievement of wound healing were 76.9% and 64.2%, respectively. Significant risk factors against WRAFS were a history of coronary artery disease (RR, 1.68), dialysis dependence (RR, 2.03), and being wheel chair bound (RR, 1.64). Conclusions: EVT revascularization was associated with longer WHT, reduced wound healing rate, and a shorter WFP compared with surgical revascularization. wound, ischemia, and foot infection grade was associated with longer WHT and reduced wound healing rate, but not associated with a shorter WFP. Systemic conditions such as dialysis dependence, congestive heart failure, and being wheel chair bound were associated with reduced wound healing rate and shorter WFP, presumably because they limited life expectancy. WHT and WFP are useful criteria for evaluating limb outcomes in patients with critical limb ischemia..
51. Jin Okazaki, Daisuke Matsuda, Kiyoshi Tanaka, Masaru Ishida, Sosei Kuma, Koichi Morisaki, Tadashi Furuyama, Yoshihiko Maehara, Analysis of wound healing time and wound-free period as outcomes after surgical and endovascular revascularization for critical lower limb ischemia., Journal of vascular surgery, 10.1016/j.jvs.2017.07.122, 67, 3, 817-825, 2018.03, BACKGROUND: Traditional end points, such as amputation-free survival, used to assess the clinical effectiveness of lower limb revascularization have shortcomings because they do not account independently for wound nonhealing and recurrence or patient survival. Wound healing process and maintenance of a wound-free state after revascularization were not well-studied. The aim of this study was to elucidate the long-term clinical course of ischemic wounds after revascularization. We focused on initial wound healing process as well as the maintenance of a wound-free state after achievement of wound healing. We introduced a wound-free period (WFP; the period during which limbs maintained an ulcer-free state) and Wound Recurrence and Amputation-free Survival (WRAFS) as parameters and tested their effectiveness in evaluating clinical outcomes of limbs treated using endovascular therapy (EVT) and surgical revascularization. METHODS: The medical records of patients developing lower critical limb ischemia with tissue loss who underwent surgical or endovascular revascularization of the infrainguinal vessels between 2009 and 2013 were reviewed retrospectively. The risk factors for achieving wound healing and WRAFS were analyzed using Kaplan-Meier survival curves and Cox regression model. Risk factors to prolong wound healing time (WHT) and reduce WFP were determined by the least squares method. RESULTS: In total, 233 patients underwent 278 limb revascularizations; 138 endovascular and 140 surgical procedures were performed as first treatments. The proportion of healed wounds 1, 2, and 3 years after primary revascularization was 64.0%, 69.7%, and 70.5%, respectively. Significant risk factors for wound healing were an EVT-first strategy (risk ratio [RR], 2.47), congestive heart failure (RR, 2.05), and wound, ischemia, and foot infection wound grade (RR, 1.59). The mean WHT was 143.7 days. An EVT-first strategy and wound infection contributed to significantly longer WHT. The mean WFP was 711.0 days. An EVT-first strategy, history of coronary artery disease, and dialysis dependence were associated with significantly shorter WFPs. WRAFS at 1 and 2 years after achievement of wound healing were 76.9% and 64.2%, respectively. Significant risk factors against WRAFS were a history of coronary artery disease (RR, 1.68), dialysis dependence (RR, 2.03), and being wheel chair bound (RR, 1.64). CONCLUSIONS: EVT revascularization was associated with longer WHT, reduced wound healing rate, and a shorter WFP compared with surgical revascularization. wound, ischemia, and foot infection grade was associated with longer WHT and reduced wound healing rate, but not associated with a shorter WFP. Systemic conditions such as dialysis dependence, congestive heart failure, and being wheel chair bound were associated with reduced wound healing rate and shorter WFP, presumably because they limited life expectancy. WHT and WFP are useful criteria for evaluating limb outcomes in patients with critical limb ischemia..
52. Yutaka Matsubara, Takuya Matsumoto, Kentaro Inoue, Daisuke Matsuda, Ryosuke Yoshiga, Keiji Yoshiya, Tadashi Furuyama, Yoshihiko Maehara, Sarcopenia is a risk factor for cardiovascular events experienced by patients with critical limb ischemia, Journal of Vascular Surgery, 10.1016/j.jvs.2016.09.030, 65, 5, 1390-1397, 2017.05, Background Prognosis is poor for patients with critical limb ischemia (CLI), and the most frequent cause of death is cardiovascular disease. Low grip strength is a risk factor for cardiovascular events, and sarcopenia may be associated as well. Thus, we hypothesized that sarcopenia is a risk factor for cardiovascular events experienced by patients with CLI. If this is true and appropriate therapy becomes available, the prognosis of patients with CLI will improve with appropriate risk management strategies to prevent cardiovascular events. Therefore, the aim of this study was to verify this hypothesis. Methods We studied 114 patients who underwent revascularization and computed tomography between January 2002 and December 2012 in the Department of Surgery and Sciences at Kyushu University in Japan. Sarcopenia was defined as skeletal muscle area measured by L3-level computed tomography scan <114.0 cm2 and <89.8 cm2 for men and women, respectively. Clinical characteristics, cardiovascular event-free survival, <2-year death, causes of death, and effective treatments for sarcopenia were investigated. Results We identified 53 (46.5%) patients with sarcopenia. Three-year cardiovascular event-free survival rates were 43.1% and 91.2% for patients with and without sarcopenia, respectively (P <.01). During follow-up, cardiovascular disease caused the deaths of 4 and 15 patients without and with sarcopenia (P <.01), respectively, and in particular, ischemic heart disease caused the deaths of 0 and 5 patients without or with sarcopenia (P <.05), respectively. Single antiplatelet therapy (SAPT; hazard ratio, 0.46; 95% confidence interval, 0.24-0.82; P <.01) and statin therapy (hazard ratio, 0.38; 95% confidence interval, 0.16-0.78; P <.01) were independent factors associated with improved cardiovascular event-free survival. Three-year cardiovascular event-free survival rates for patients with sarcopenia who received SAPT, dual antiplatelet therapies, and no antiplatelet therapy were 75.3%, 21.1%, and 29.5%, respectively (P <.01). Conclusions Sarcopenia is a risk factor for worse cardiovascular event-free survival, and SAPT and statin therapy reduced this risk for patients with CLI. Furthermore, SAPT but not dual antiplatelet therapy increased cardiovascular event-free survival in patients with sarcopenia..
53. Yutaka Matsubara, Takuya Matsumoto, Kentaro Inoue, Daisuke Matsuda, Ryosuke Yoshiga, Keiji Yoshiya, Tadashi Furuyama, Yoshihiko Maehara, Sarcopenia is a risk factor for cardiovascular events experienced by patients with critical limb ischemia., Journal of vascular surgery, 10.1016/j.jvs.2016.09.030, 65, 5, 1390-1397, 2017.05, BACKGROUND: Prognosis is poor for patients with critical limb ischemia (CLI), and the most frequent cause of death is cardiovascular disease. Low grip strength is a risk factor for cardiovascular events, and sarcopenia may be associated as well. Thus, we hypothesized that sarcopenia is a risk factor for cardiovascular events experienced by patients with CLI. If this is true and appropriate therapy becomes available, the prognosis of patients with CLI will improve with appropriate risk management strategies to prevent cardiovascular events. Therefore, the aim of this study was to verify this hypothesis. METHODS: We studied 114 patients who underwent revascularization and computed tomography between January 2002 and December 2012 in the Department of Surgery and Sciences at Kyushu University in Japan. Sarcopenia was defined as skeletal muscle area measured by L3-level computed tomography scan <114.0 cm2 and <89.8 cm2 for men and women, respectively. Clinical characteristics, cardiovascular event-free survival, <2-year death, causes of death, and effective treatments for sarcopenia were investigated. RESULTS: We identified 53 (46.5%) patients with sarcopenia. Three-year cardiovascular event-free survival rates were 43.1% and 91.2% for patients with and without sarcopenia, respectively (P < .01). During follow-up, cardiovascular disease caused the deaths of 4 and 15 patients without and with sarcopenia (P < .01), respectively, and in particular, ischemic heart disease caused the deaths of 0 and 5 patients without or with sarcopenia (P < .05), respectively. Single antiplatelet therapy (SAPT; hazard ratio, 0.46; 95% confidence interval, 0.24-0.82; P < .01) and statin therapy (hazard ratio, 0.38; 95% confidence interval, 0.16-0.78; P < .01) were independent factors associated with improved cardiovascular event-free survival. Three-year cardiovascular event-free survival rates for patients with sarcopenia who received SAPT, dual antiplatelet therapies, and no antiplatelet therapy were 75.3%, 21.1%, and 29.5%, respectively (P < .01). CONCLUSIONS: Sarcopenia is a risk factor for worse cardiovascular event-free survival, and SAPT and statin therapy reduced this risk for patients with CLI. Furthermore, SAPT but not dual antiplatelet therapy increased cardiovascular event-free survival in patients with sarcopenia..
54. Yuko Miyazaki, Tadashi Furuyama, Yutaka Matsubara, Keiji Yoshiya, Ryosuke Yoshiga, Kentaro Inoue, Daisuke Matsuda, Yukihiko Aoyagi, Masaaki Kato, Takuya Matsumoto, Yoshihiko Maehara, Thoracic endovascular aortic repair for complicated chronic type B aortic dissection in a patient on hemodialysis with recurrent ischemic colitis., Surgical case reports, 10.1186/s40792-016-0165-2, 2, 1, 38-38, 2016.12, We present a successful case of thoracic endovascular aortic repair (TEVAR) for chronic Stanford type B aortic dissection (B-AD) with recurrent ischemic colitis. The patient was a 56-year-old woman with abdominal pain as the main complaint who had two operations previously: the total arch replacement 8 years ago and the Bentall 7 years ago for acute Stanford type A aortic dissection. Her abdominal pain worsened as her blood pressure became low during her hemodialysis treatment. An enhanced computed tomography scan was performed on the patient and showed chronic B-AD that occurred from the distal anastomotic part of the total arch graft to the bilateral common iliac arteries. The celiac artery and superior mesenteric artery (SMA) arose from the true lumen, and these were compressed by the expanded false lumen. Her complicated chronic B-AD was treated with the Zenith Dissection Endovascular System, and its procedure was performed as her proximal entry tear was covered by a proximal tapered Zenith TX2 stent graft, supplemented by a noncovered aortic stent extending across both renal arteries, the SMA, and the celiac artery. Seven days after this operation, enhanced computed tomography showed that the patient's true lumen was expanded and her blood flow to the true lumen and SMA was improved. On the other hand, her false lumen tended to be thrombosed. Consequently, she was discharged 10 days after the operation without any postoperative complications as she had no abdominal complaints even though she underwent hemodialysis three times per week after the operation. We believe that TEVAR supplemented by a noncovered aortic stent is an effective treatment, even for highly chronic B-AD in dialysis patients..
55. Daisuke Matsuda, Takuya Matsumoto, Kenichi Honma, Ayae Ikawa-Yoshida, Mitsuho Onimaru, Tadashi Furuyama, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Yoshihiko Maehara, BUBR1 insufficiency in mice increases their sensitivity to oxidative stress, In Vivo, 10.21873/invivo.10993, 30, 6, 769-776, 2016.11, Background/Aim: Budding uninhibited by benzimidazole-related 1 (BUBR1) plays an important role in the spindle assembly checkpoint to prevent chromosome missegregation and aneuploidy during mitosis. We previously generated mutant mice that express BUBR1 at only 20% of the normal level (BubR1L/L mice). Here, we examined the effect of low BUBR1 expression on oxidative stress-induced carcinogenesis in mice. Materials and Methods: We orally administered either a potassium bromate (KBrO3) solution (2 g/l) or tap water to BubR1L/L and wild-type (BubR1+/+) mice for 16 weeks and examined the subsequent incidence of tumours. Results: KBrO3-treated BubR1L/L mice showed significantly higher mortality than the KBrO3-treated BubR1+/+ and control tap water-treated mice (p=0.0082). Histopathological and immunohistochemical analyses revealed that the spleens of surviving BubR1L/L mice were occupied by non-B-, non-T-cells with high proliferative potential. Conclusion: Our results indicate that low BUBR1 expression increases oxidative stress-induced mortality in mice, possibly caused by splenic neoplasms..
56. Kentaro Inoue, Toshihiro Onohara, Keita Mikasa, Tadashi Furuyama, Early-phase wound healing and long-term outcomes of a selective endovascular-first approach for treating Rutherford 5 critical limb ischemia with infrainguinal lesions, Surgery today, 10.1007/s00595-016-1332-6, 46, 11, 1301-1309, 2016.11, Purpose: To evaluate the validity of a selective endovascular-first approach for Rutherford 5 critical limb ischemia (CLI). Methods: We analyzed, retrospectively, 51 limbs in 46 patients treated for Rutherford 5 CLI with infrainguinal lesions between 2010 and 2012. Endovascular therapy (EVT) and open surgical revascularization (OSR) were performed initially in 28 and 23 limbs, respectively. The interventions were assigned according to the systemic condition and femoropopiliteal TransAtlantic Inter-Society Consensus (TASC) II classification. We investigated early wound healing rates (defined as healing within 90 days) and amputation-free survival (AFS) rates in the EVT and OSR groups. Results: The OSR group had more TASC D lesions (P < 0.0001). The early wound healing rate was significantly higher in the OSR group (OSR 46.1 % vs. EVT 14.3, P = 0.0205); however, the AFS rates did not differ significantly between the groups (P = 0.4031). Preoperative walking ability significantly influenced AFS (P < 0.0001). Conclusions: Our selective endovascular-first approach did not worsen AFS; however, OSR yielded better early wound healing rates. Preoperative walking ability strongly influenced AFS; hence, patients with good walking ability were good candidates for primary OSR. The indications for EVT for earlier wound healing still require better clarification..
57. Kentaro Inoue, Toshihiro Onohara, Keita Mikasa, Tadashi Furuyama, Early-phase wound healing and long-term outcomes of a selective endovascular-first approach for treating Rutherford 5 critical limb ischemia with infrainguinal lesions., Surgery today, 10.1007/s00595-016-1332-6, 46, 11, 1301-9, 2016.11, PURPOSE: To evaluate the validity of a selective endovascular-first approach for Rutherford 5 critical limb ischemia (CLI). METHODS: We analyzed, retrospectively, 51 limbs in 46 patients treated for Rutherford 5 CLI with infrainguinal lesions between 2010 and 2012. Endovascular therapy (EVT) and open surgical revascularization (OSR) were performed initially in 28 and 23 limbs, respectively. The interventions were assigned according to the systemic condition and femoropopiliteal TransAtlantic Inter-Society Consensus (TASC) II classification. We investigated early wound healing rates (defined as healing within 90 days) and amputation-free survival (AFS) rates in the EVT and OSR groups. RESULTS: The OSR group had more TASC D lesions (P < 0.0001). The early wound healing rate was significantly higher in the OSR group (OSR 46.1 % vs. EVT 14.3, P = 0.0205); however, the AFS rates did not differ significantly between the groups (P = 0.4031). Preoperative walking ability significantly influenced AFS (P < 0.0001). CONCLUSIONS: Our selective endovascular-first approach did not worsen AFS; however, OSR yielded better early wound healing rates. Preoperative walking ability strongly influenced AFS; hence, patients with good walking ability were good candidates for primary OSR. The indications for EVT for earlier wound healing still require better clarification..
58. Ayae Ikawa-Yoshida, Takuya Matsumoto, Shinji Okano, Yukihiko Aoyagi, Yutaka Matsubara, Tadashi Furuyama, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Mitsuho Onimaru, Tomoko Ohkusa, Masatoshi Nomura, Yoshihiko Maehara, BubR1 Insufficiency Impairs Liver Regeneration in Aged Mice after Hepatectomy through Intercalated Disc Abnormality, Scientific reports, 10.1038/srep32399, 6, 2016.08, A delay in liver regeneration after partial hepatectomy (PHx) leads to acute liver injury, and such delays are frequently observed in aged patients. BubR1 (budding uninhibited by benzimidazole-related 1) controls chromosome mitotic segregation through the spindle assembly checkpoint, and BubR1 down-regulation promotes aging-associated phenotypes. In this study we investigated the effects of BubR1 insufficiency on liver regeneration in mice. Low-BubR1-expressing mutant (BubR1L/L) mice had a delayed recovery of the liver weight-to-body weight ratio and increased liver deviation enzyme levels after PHx. Microscopic observation of BubR1L/L mouse liver showed an increased number of necrotic hepatocytes and intercalated disc anomalies, resulting in widened inter-hepatocyte and perisinusoidal spaces, smaller hepatocytes and early-stage microvilli atrophy. Up-regulation of desmocollin-1 (DSC1) was observed in wild-type, but not BubR1L/L, mice after PHx. In addition, knockdown of BubR1 expression caused down-regulation of DSC1 in a human keratinocyte cell line. BubR1 insufficiency results in the impaired liver regeneration through weakened microstructural adaptation against PHx, enhanced transient liver failure and delayed hepatocyte proliferation. Thus, our data suggest that a reduction in BubR1 levels causes failure of liver regeneration through the DSC1 abnormality..
59. Ayae Ikawa-Yoshida, Takuya Matsumoto, Shinji Okano, Yukihiko Aoyagi, Yutaka Matsubara, Tadashi Furuyama, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Mitsuho Onimaru, Tomoko Ohkusa, Masatoshi Nomura, Yoshihiko Maehara, BubR1 Insufficiency Impairs Liver Regeneration in Aged Mice after Hepatectomy through Intercalated Disc Abnormality., Scientific reports, 10.1038/srep32399, 6, 32399-32399, 2016.08, A delay in liver regeneration after partial hepatectomy (PHx) leads to acute liver injury, and such delays are frequently observed in aged patients. BubR1 (budding uninhibited by benzimidazole-related 1) controls chromosome mitotic segregation through the spindle assembly checkpoint, and BubR1 down-regulation promotes aging-associated phenotypes. In this study we investigated the effects of BubR1 insufficiency on liver regeneration in mice. Low-BubR1-expressing mutant (BubR1(L/L)) mice had a delayed recovery of the liver weight-to-body weight ratio and increased liver deviation enzyme levels after PHx. Microscopic observation of BubR1(L/L) mouse liver showed an increased number of necrotic hepatocytes and intercalated disc anomalies, resulting in widened inter-hepatocyte and perisinusoidal spaces, smaller hepatocytes and early-stage microvilli atrophy. Up-regulation of desmocollin-1 (DSC1) was observed in wild-type, but not BubR1(L/L), mice after PHx. In addition, knockdown of BubR1 expression caused down-regulation of DSC1 in a human keratinocyte cell line. BubR1 insufficiency results in the impaired liver regeneration through weakened microstructural adaptation against PHx, enhanced transient liver failure and delayed hepatocyte proliferation. Thus, our data suggest that a reduction in BubR1 levels causes failure of liver regeneration through the DSC1 abnormality..
60. Toshihiro Onohara, Kentaro Inoue, Tadashi Furuyama, Tomokazu Ohno, Preoperative Cardiovascular Assessment and Late Cardiovascular Events after Elective Abdominal Aortic Aneurysm Repair., Annals of vascular surgery, 10.1016/j.avsg.2015.05.026, 29, 8, 1533-42, 2015.11, BACKGROUND: Cardiovascular evaluation is performed before elective repair of abdominal aortic aneurysm (AAA) because of the high prevalence of cardiovascular disease. We investigated the association between preoperative cardiovascular evaluation and the incidence of late cardiovascular events after AAA repair. METHODS: We retrospectively analyzed 438 patients who underwent elective repair of AAA. Echocardiography, serial coronary assessment using functional myocardial scanning or coronary angiography, and carotid ultrasound scanning were performed preoperatively. Coronary revascularization after serial coronary assessment was performed preoperatively or simultaneously in 21 patients, and 54 patients had a remote history of coronary revascularization. RESULTS: The 5-year survival rate, incidence rate of cardiovascular events (myocardial infarction or stroke), and incidence rate of major adverse cardiovascular events (MACE; cardiovascular death or cardiovascular events) were 86.0%, 5.7%, and 11.5%, respectively. Carotid stenosis was associated with these long-term outcomes, and hypokinesis, determined by echocardiography, increased the incidence of cardiovascular events and MACE. Serial coronary assessment findings and history of previous or preoperative coronary revascularization were not associated with these long-term outcomes. CONCLUSIONS: Preoperative cardiovascular evaluation and treatment are beneficial for reducing not only perioperative risk but also late cardiovascular events..
61. Toshihiro Onohara, Kentaro Inoue, Tadashi Furuyama, Tomokazu Ohno, Preoperative Cardiovascular Assessment and Late Cardiovascular Events after Elective Abdominal Aortic Aneurysm Repair, Annals of Vascular Surgery, 10.1016/j.avsg.2015.05.026, 29, 8, 1533-1542, 2015.01, Background Cardiovascular evaluation is performed before elective repair of abdominal aortic aneurysm (AAA) because of the high prevalence of cardiovascular disease. We investigated the association between preoperative cardiovascular evaluation and the incidence of late cardiovascular events after AAA repair. Methods We retrospectively analyzed 438 patients who underwent elective repair of AAA. Echocardiography, serial coronary assessment using functional myocardial scanning or coronary angiography, and carotid ultrasound scanning were performed preoperatively. Coronary revascularization after serial coronary assessment was performed preoperatively or simultaneously in 21 patients, and 54 patients had a remote history of coronary revascularization. Results The 5-year survival rate, incidence rate of cardiovascular events (myocardial infarction or stroke), and incidence rate of major adverse cardiovascular events (MACE; cardiovascular death or cardiovascular events) were 86.0%, 5.7%, and 11.5%, respectively. Carotid stenosis was associated with these long-term outcomes, and hypokinesis, determined by echocardiography, increased the incidence of cardiovascular events and MACE. Serial coronary assessment findings and history of previous or preoperative coronary revascularization were not associated with these long-term outcomes. Conclusions Preoperative cardiovascular evaluation and treatment are beneficial for reducing not only perioperative risk but also late cardiovascular events..
62. Nobuhiro Handa, Masafumi Yamashita, Toshiki Takahashi, Toshihiro Onohara, Minoru Okamoto, Tsuyoshi Yamamoto, Yasushi Shimoe, Masahiro Okada, Yoshimitsu Ishibashi, Fuminori Kasashima, Jyunji Kishimoto, Akihiro Mizuno, Jyun Ichi Kei, Mikizou Nakai, Hitoshi Suhara, Masamitsu Endo, Takeshi Nishina, Tadashi Furuyama, Masakazu Kawasaki, Yoichirou Ueno, Impact of introducing endovascular aneurysm repair on treatment strategy for repair of abdominal aortic aneurysm - National hospital organization network study in Japan, Circulation Journal, 10.1253/circj.CJ-14-0131, 78, 5, 1104-1111, 2014, Background: The objective of the present study was to assess the hypothesis that the introduction of endovascular aneurysm repair (EVAR) into Japan has expanded the indication of abdominal aortic aneurysm (AAA) repair without increasing surgical mortality. Methods and Results: From 10 national hospitals, we registered a total of 2,154 consecutive patients (Open surgery [OS]: n=1,577, EVAR: n=577) over 8 years, divided into 4 time periods: Group I (2005-2006: n=522), Group II (2007-2008: n=475), Group III (2009-2010: n=551), Group IV, (2011-2012: n=606). Mean age increased over the 4 time periods (P<0.0001). The incidences of COPD, smoking history, history of abdominal surgery and concomitant malignancy significantly increased as well, while the numbers of patients with preoperative shock or high ASA status reduced over time. The proportion of EVAR in AAA repair increased from: 0% in Group I, 11.6% in Group II, 41.0% in Group III, to 48.8% in Group IV (P<0.0001). Early mortality was 0.8% in the EVAR and 3.4% in the OS (P<0.001) groups. Survival rates among the 4 groups free of all-cause death and aneurysm-related death at 1 year were 92.1-96.3% (P=0.1555) and 95.5-96.8% (P=0.9891), respectively. Multiple logistic regression analysis for surgical death failed to demonstrate survival advantage of EVAR over OS. Conclusions: Introduction of EVAR expanded the indication of AAA repair without increasing mortality, while high risk for anesthesia and emergency cases reduced over time..
63. Haidi Hu, Takeshi Takano, Atsushi Guntani, Toshihiro Onohara, Tadashi Furuyama, Hiroyuki Inoguchi, Maki Takai, Yoshihiko Maehara, Treatment of solitary iliac aneurysms
Clinical review of 28 cases, Surgery today, 10.1007/s00595-007-3598-1, 38, 3, 232-236, 2008.03, Purpose. The clinical characteristics and long-term results of patients with solitary iliac aneurysms (SIAs) were investigated. Methods. 28 consecutive patients who underwent repair of SIAs between 1985 and 2004 were reviewed retrospectively, and compared with those of 536 patients who underwent elective repair of an abdominal aortic aneurysm (AAA) during the same period. Results. The incidence of SIAs among all aorto-iliac aneurysms was 5.0%. The 28 patients with SIAs were men with a mean age of 69.1 years. There were a collective total of 42 iliac aneurysms in the 28 patients, with 12 patients having multiple aneurysms. Thirty aneurysms involved the common iliac artery, and 12 involved the internal iliac artery. Twenty-two patients had symptoms, although none of the SIAs ruptured. Four patients had coexistent iliac occlusive disease and two patients had femoral occlusive disease. The 5-and 10-year survival rates of the patients with SIAs were 90.5% and 75.4%, whereas those of the patients with AAAs were 76.3% and 54%, respectively (P = 0.089). Conclusion. Routine imaging is necessary not only to evaluate the SIAs, but also to detect multiple aneurysms or arterial occlusive disease. Close and long-term followup is mandatory for the early detection of the formation of new aneurysms..
64. Tadashi Furuyama, Kimihiro Komori, Hiroaki Shimokawa, Yasuharu Matsumoto, Toyokazu Uwatoku, Katsuya Hirano, Yoshihiko Maehara, Long-term inhibition of Rho kinase suppresses intimal thickening in autologous vein grafts in rabbits, Journal of Vascular Surgery, 10.1016/j.jvs.2006.02.035, 43, 6, 1249-1256, 2006.06, Background: Rho kinase plays an important role in vascular smooth muscle cell (VSMC) contraction and other cellular functions, such as proliferation, migration, and apoptosis. Recent studies have demonstrated that long-term inhibition of Rho kinase suppresses coronary artery spasm and vascular lesion formation after arterial injury. In the cardiovascular surgery field, intimal thickening in vein grafts is the major cause of late graft failure, for which no effective treatment has yet been developed. In this study, we examined whether long-term inhibition of Rho kinase suppresses intimal thickening in autologous vein grafts in rabbits. Methods: Male rabbits were randomly divided into two groups and received normal chow (control group) or a special chow containing 0.09% fasudil (fasudil group). After oral administration, fasudil is metabolized to a specific Rho kinase inhibitor, hydroxyfasudil. Each group underwent reversed autologous vein graft surgery with the internal jugular vein into the left common carotid artery. At 1, 2, and 4 weeks after the operation, we examined the extent of intimal thickening of the graft and VSMC proliferation and apoptosis. Results: The intimal thickening was significantly suppressed in the fasudil group compared with the control group at 2 and 4 weeks after the operation. In the fasudil group, VSMC proliferation was suppressed at 1 and 2 weeks after the operation, whereas VSMC apoptosis was enhanced at 2 weeks after the procedure. Conclusions: These results indicate that Rho kinase is substantially involved in the pathogenesis of intimal thickening of vein grafts and that it is an important therapeutic target for the prevention of graft failure..
65. Tadashi Furuyama, Kimihiro Komori, Hiroaki Shimokawa, Yasuharu Matsumoto, Toyokazu Uwatoku, Katsuya Hirano, Yoshihiko Maehara, Long-term inhibition of Rho kinase suppresses intimal thickening in autologous vein grafts in rabbits., Journal of vascular surgery, 43, 6, 1249-56, 2006.06, BACKGROUND: Rho kinase plays an important role in vascular smooth muscle cell (VSMC) contraction and other cellular functions, such as proliferation, migration, and apoptosis. Recent studies have demonstrated that long-term inhibition of Rho kinase suppresses coronary artery spasm and vascular lesion formation after arterial injury. In the cardiovascular surgery field, intimal thickening in vein grafts is the major cause of late graft failure, for which no effective treatment has yet been developed. In this study, we examined whether long-term inhibition of Rho kinase suppresses intimal thickening in autologous vein grafts in rabbits. METHODS: Male rabbits were randomly divided into two groups and received normal chow (control group) or a special chow containing 0.09% fasudil (fasudil group). After oral administration, fasudil is metabolized to a specific Rho kinase inhibitor, hydroxyfasudil. Each group underwent reversed autologous vein graft surgery with the internal jugular vein into the left common carotid artery. At 1, 2, and 4 weeks after the operation, we examined the extent of intimal thickening of the graft and VSMC proliferation and apoptosis. RESULTS: The intimal thickening was significantly suppressed in the fasudil group compared with the control group at 2 and 4 weeks after the operation. In the fasudil group, VSMC proliferation was suppressed at 1 and 2 weeks after the operation, whereas VSMC apoptosis was enhanced at 2 weeks after the procedure. CONCLUSIONS: These results indicate that Rho kinase is substantially involved in the pathogenesis of intimal thickening of vein grafts and that it is an important therapeutic target for the prevention of graft failure..
66. Satoru Funahashi, Ichiro Masaki, Tadashi Furuyama, Hypereosinophilic syndrome accompanying gangrene of the toes with peripheral arterial occlusion
A case report, Angiology, 10.1177/000331970605700215, 57, 2, 231-234, 2006.03, The authors herein report the case of a teenage boy who presented with peripheral arterial occlusion of both upper and lower extremities associated with hypereosinophilia. During a 10-year follow-up, corticosteroid therapy was continued for the treatment of hypereosinophilia. The patient underwent bilateral lumbar sympathectomies because of severe ischemia of the bilateral lower extremities with gangrene of the toes. Based on the progress of his disease over the past 10 years, he was suspected to have idiopathic hypereosinophilic syndrome (HES) accompanied by peripheral arterial obstruction. Idiopathic HES is a disease characterized by unexpected hypereosinophilia, which may lead to organ damage. This is a very rare case of peripheral arterial occlusion associated with idiopathic HIS..
67. Kimihiro Komori, T. Furuyama, Y. Maehara, Renal artery clamping and left renal vein division during abdominal aortic aneurysm repair, European Journal of Vascular and Endovascular Surgery, 10.1016/S1078-5884(03)00408-8, 27, 1, 80-83, 2004.01, Objectives. To determine whether renal artery clamping and division of the left renal vein affects renal function in the patients who undergo repair of infrarenal abdominal aortic aneurysm (AAA). Methods. Between 1992 and 2000, 267 patients had open surgery for infrarenal AAA. Of these, 22 (8%) required temporary bilateral (15) or unilateral (7) renal artery clamping. 8 also had the left renal vein divided, three of which were reanastomosed. Results. Renal artery clamping and/or renal vein divisions did not affect the incidence of complications and long term renal failure. Conclusions. Clamping of the renal arteries and/or renal vein division during AAA surgery does not in itself compromise short or long term renal function..
68. Masazumi Kume, Kimihiro Komori, Hiroyuki Inoguchi, Tetsuya Shoji, Tadashi Furuyama, Akio Sakamoto, Keizo Sugimachi, Solitary fibrous tumor in the retroperitoneal space
Report of a case, Surgery today, 10.1007/s005950200223, 32, 12, 1099-1101, 2002.12, Solitary fibrous tumors (SFTs) are spindle-cell neoplasms originally described in the pleura. It is now known that these tumors can develop in many sites. This report describes the case of a well-circumscribed tumor located around the superior mesenteric artery (SMA), which was initially thought to be either a superior SMA aneurysm, a lymphoma, or a neurogenic tumor. Histological examination demonstrated the tumor to be composed of a cellular proliferation of ovoid to spindle cells with a fine collagenous matrix in the short fascicles. Immunohistochemical staining was strongly positive for CD34 and negative for factor VIII, cytokeratin, desmin, and muscle-specific actin (HHF-35). These findings suggested a diagnosis of SFT in the retroperitoneal space. To our knowledge, this is the first report of an SFT located around the SMA. Based on the above findings, it is important to include SFT in the differential diagnosis of retroperitoneal tumors located around the SMA..
69. T. Matsumoto, K. Komori, T. Furuyama, T. Shoji, M. Kume, T. Yamaoka, E. Mori, K. Sugimachi, Alternative approach to endoluminal treatmet of an anastomotic aneurysm, Journal of Cardiovascular Surgery, 43, 3, 403-406, 2002.07, Conventional surgical treatment of patients with an anastomotic aneurysm can be a surgical challenge if severe adhesions are present. We report here effective treatment of an anastomotic aneurysm using an endoluminal stent graft. A 71-year-old man had undergone an aorto-bifemoral bypass for Leriche's syndrome in 1989 and partial gastrectomy for cancer in 1996. He was admitted to our department with a pseudoaneurysm of a proximal anastomosis located at the aorta below both renal arteries. Based on his medico-surgical history, we considered that an endovascular stent should be placed. This graft composed of an UBE(UBE-WOVEN GRAFT) graft and self-expandable Z stents were introduced through the right limb of the bifurcated graft previously implanted, then were placed using the delivery system while advancing under fluoroscopic control, using a pusher rod. Endoleakage was not evident and the post-operative course was uneventful. An endovascular graft is one alternative approach for treating patients with an anastomotic aneurysm as it is less invasive. This procedure proved satisfactory for this patient..
70. Emiko Mori, Kimihiro Komori, Masazumi Kume, Terutoshi Yamaoka, Tetsuya Shoji, Tadashi Furuyama, Hiroyuki Inoguchi, Comparison of the long-term results between surgical and conservative treatment in patients with intermittent claudication, Surgery, 10.1067/msy.2002.119966, 131, 1 SUPPL., 2002.01, Background. The optional therapeutic strategy for patients with intermittent claudication remains controversial. In this study, we investigated the influence of surgical and conservative therapies on improving the quality of life in patients with intermittent claudication. Methods. We analyzed 427 patients who were admitted to our hospital with intermittent claudication in their legs during a 15-year period from January 1984 to December 1999. We separated them into 2 groups; 259 patients (362 legs) were treated surgically and 168 patients were treated conservatively. Results. At the suprainguinal and infrainguinal (above knee) region, the surgery group showed significantly better rate of improvement than did the conservative group, but in the infrainguinal (below knee) region, there was no significant difference between the 2 groups. The 3-year and 5-year patency rates for the arterial reconstruction of the suprainguinal and infrainguinal region was satisfactory, but that of the infrainguinal region was not very good even if an auto vein graft was used. Conclusions. Aggressive surgical treatment is therefore recommended in patients whose distal anastomotic region is above the knee, because there are great benefits from surgical reconstruction. However, in patients whose distal anastomotic region is below the knee, conservative treatment might be just as effective as surgery..
71. Kimihiro Komori, Hiroyuki Inoguchi, Masazumi Kume, Tetsuya Shoji, Tadashi Furuyama, Differences in endothelial function and morphologic modulation between canine autogenous venous and arterial grafts
Endothelium and intimal thickening, Surgery, 10.1067/msy.2002.119797, 131, 1 SUPPL., S249-S255, 2002.01, Background. Late graft failure is still a problem for vascular surgeons. A previous study showed superior patency of arterial grafts compared with venous grafts. In this review we discuss the differences in functional and morphologic modulation of experimental autogenous venous and arterial grafts. Results. In canine venous grafts, the endothelium of the graft was denuded and recovered within 3 or 4 weeks. In contrast, in arterial grafts, denudation of the endothelium was minimal, and no platelet adherence was observed. Instead, nearly normal intact endothelial cell surface had covered the intima within 3 days after grafting. The histologic findings for arterial grafts thus were quite different from those for venous grafts. Different responses to flow changes between venous and arterial grafts were observed. In the venous grafts, pronounced intimal thickening was associated with impairment of endothelial responses, whereas in the arterial grafts, intact endothelial function and no intimal thickening were observed. Conclusions. The intact endothelial function and absence of intimal thickening under the arterial grafts may explain the superior patency of autogenous arterial grafts in comparison with venous grafts..
72. Emiko Mori, Kimihiro Komori, Masazumi Kume, Terutoshi Yamaoka, Tetsuya Shoji, Tadashi Furuyama, Hiroyuki Inoguchi, Comparison of the long-term results between surgical and conservative treatment in patients with intermittent claudication., Surgery, 131, 1 Suppl, S269-74, 2002.01, BACKGROUND: The optional therapeutic strategy for patients with intermittent claudication remains controversial. In this study, we investigated the influence of surgical and conservative therapies on improving the quality of life in patients with intermittent claudication. METHODS: We analyzed 427 patients who were admitted to our hospital with intermittent claudication in their legs during a 15-year period from January 1984 to December 1999. We separated them into 2 groups; 259 patients (362 legs) were treated surgically and 168 patients were treated conservatively. RESULTS: At the suprainguinal and infrainguinal (above knee) region, the surgery group showed significantly better rate of improvement than did the conservative group, but in the infrainguinal (below knee) region, there was no significant difference between the 2 groups. The 3-year and 5-year patency rates for the arterial reconstruction of the suprainguinal and infrainguinal region was satisfactory, but that of the infrainguinal region was not very good even if an auto vein graft was used. CONCLUSIONS: Aggressive surgical treatment is therefore recommended in patients whose distal anastomotic region is above the knee, because there are great benefits from surgical reconstruction. However, in patients whose distal anastomotic region is below the knee, conservative treatment might be just as effective as surgery..
73. Kimihiro Komori, Hiroyuki Inoguchi, Masazumi Kume, Tetsuya Shoji, Tadashi Furuyama, Differences in endothelial function and morphologic modulation between canine autogenous venous and arterial grafts: endothelium and intimal thickening., Surgery, 131, 1 Suppl, S249-55, 2002.01, BACKGROUND: Late graft failure is still a problem for vascular surgeons. A previous study showed superior patency of arterial grafts compared with venous grafts. In this review we discuss the differences in functional and morphologic modulation of experimental autogenous venous and arterial grafts. RESULTS: In canine venous grafts, the endothelium of the graft was denuded and recovered within 3 or 4 weeks. In contrast, in arterial grafts, denudation of the endothelium was minimal, and no platelet adherence was observed. Instead, nearly normal intact endothelial cell surface had covered the intima within 3 days after grafting. The histologic findings for arterial grafts thus were quite different from those for venous grafts. Different responses to flow changes between venous and arterial grafts were observed. In the venous grafts, pronounced intimal thickening was associated with impairment of endothelial responses, whereas in the arterial grafts, intact endothelial function and no intimal thickening were observed. CONCLUSIONS: The intact endothelial function and absence of intimal thickening under the arterial grafts may explain the superior patency of autogenous arterial grafts in comparison with venous grafts..
74. Kimihiro Komori, Tadashi Furuyama, Tetsuya Shoji, Masazumi Kume, Emiko Mori, Terutoshi Yamaoka, Keizo Sugimachi, Inhibitory effect of prostaglandin E1 on intimal thickening caused by poor runoff conditions in the canine autologous vein grafts, Journal of Cardiovascular Pharmacology, 10.1097/00005344-200111000-00005, 38, 5, 686-692, 2001.10, The efficacy of ONO-1608, a newly developed liposomal formulation of prostaglandin E1 prodrug, was evaluated on intimal hyperplasia of experimental canine autologous vein grafts under distal poor runoff conditions. The femoral vein was implanted into the femoral artery, preparing a distal poor runoff canine model. After 4 weeks of preparing the poor runoff model, the femoral vein was implanted into the femoral artery. They were then divided into two groups consisting of the control group and the ONO-1608 group. At 4 weeks, the grafts were harvested and intimal hyperplasia of the graft was measured with an ocular cytometer. Intimal cell proliferation was determined by bromodeoxyuridine incorporation 2 weeks after surgery. In addition, the effect of ONO-1608 on the proliferation of platelet-derived growth factor (PDGF)-stimulated human aortic smooth muscle cells (HASMCs) in culture was also investigated. At 4 weeks, the degree of intimal hyperplasia of the graft in the ONO-1608 group was significantly less than that of the control group. The bromodeoxyuridine labeling index 2 weeks after grafting was significantly lower in the ONO-1608 group compared with that in the control group. In addition, ONO-1608 significantly inhibited the proliferation of PDGF-stimulated HASMCs in culture. These results demonstrate the efficacy of ONO-1608 in reducing the degree of intimal hyperplasia of canine autogenous vein grafts under poor runoff conditions. The mechanism of reducing the intimal hyperplasia may be that ONO-1608 inhibited PDGF-stimulated proliferation of the smooth muscle cell. These results suggest that the administration of ONO-1608 may be beneficial in patients who have undergone gone arterial reconstruction..
75. T. Matsumoto, K. Komori, T. Shoji, S. Kuma, M. Kume, T. Yamaoka, E. Mori, T. Furuyama, Y. Yonemitsu, K. Sugimachi, Successful and optimized in vivo gene transfer to rabbit carotid artery mediated by electronic pulse, Gene Therapy, 10.1038/sj.gt.3301502, 8, 15, 1174-1179, 2001.09, Several gene transfer methods, including viral or nonviral vehicles have been developed, however, efficacy, safety or handling continue to present problems. We developed a nonviral and plasmid-based method for arterial gene transfer by in vivo electronic pulse, using a newly designed T-shaped electrode. Using rabbit carotid arteries, we first optimized gene transfer efficiency, and firefly luciferase gene transfer via electronic pulse under 20 voltage (the pulse length: Pon time 20 ms, the pulse interval: Poff time 80 ms, number of pulse: 10 times) showed the highest gene expression. Exogenous gene expression was detectable for at least up to 14 days. Electroporation-mediated gene transfer of E. coli lacZ with nuclear localizing signal revealed successful gene transfer to luminal endothelial cells and to medial cells. Histological damage was recognized as the voltage was increased but neointima formation 4 weeks after gene transfer was not induced. In vivo electroporation-mediated arterial gene transfer is readily facilitated, is safe and may prove to be an alternative form of gene transfer to the vasculature..
76. K. Komori, T. Shoji, T. Furuyama, Y. Yonemitsu, E. Mori, T. Yamaoka, T. Matsumoto, K. Sugimachi, Non-penetrating vascular clips anastomosis inhibited intimal thickening under poor runoff conditions in canine autogenous vein grafts, European Journal of Vascular and Endovascular Surgery, 10.1053/ejvs.2001.1297, 21, 3, 241-247, 2001.01, Objective: Late graft failure is still a significant problem, particularly in cases with poor runoff vessels. The main cause of late graft failure is intimal thickening of the anastomotic region. Vascular closure system (VCS) clips may provide ideal anastomosis, since they do not penetrate the wall. Therefore, we examined whether the VCS clips affect intimal thickening under poor runoff conditions in the canine autogenous vein grafts. Methods: A canine poor runoff model was prepared at both femoral veins. Four weeks after the first surgical procedure, two groups were established according to the two different methods of anastomosis employed. The right femoral vein graft was performed using polypropylene sutures, conventional surgical anastomosis (control group), while the left femoral vein graft was performed using VCS clips anastomosis (VCS group). Four weeks after grafting, the vein grafts were removed and the intimal thickening of proximal, distal anastomosis and midportion of the vein grafts were examined histologically. Results: In the control group, flow rate and variation were 26 ± 8 ml/min and 51 ± 10 dynes/cm2, respectively. In the VCS group, the flow rate and variation were 23 ± 11 ml/min and 44 ± 14 dynes/cm2, respectively. There were no significant differences between the two groups. The average value of intimal thickening of both the anastomotic region and the midportion of the vein graft in the VCS group was significantly inhibited compared to that of the control group. The number of positive cells of masson trichrome stain in the VCS group was significantly less than that of the control group. Conclusions: These experiments indicate that VCS clips significantly inhibit intimal thickening under poor runoff conditions in canine autogenous vein grafts to a greater extent compared to suture-constructed anastomosis. One mechanism that may account for the decreased intimal thickening is the inhibition of the expression of transforming growth factor-β (TGF-β), because the number of positive cells of masson trichrome stain in the VCS group was significantly less than that of the control group..