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Outcomes of abdominal aortic aneurysm (AAA) repair have improved in the 2 decades since the emergence of endovascular aneurysm repair (EVAR). However, EVAR is considered a contraindication for shaggy aorta because of the high risk of shower embolization. Recently, statins have been implicated in preventing embolization in patients with shaggy aorta via its pleiotropic effects, including atheroma reduction and coronary artery stabilization. We selected pitavastatin, a statin with potent effects, discovered and developed by a Japanese company because it has shown excellent pleiotropic effects on atheromatous arteries in the Japanese population. A randomized comparison study of dose-dependent effects of pitavastatin in patients with AAA with massive atheromatous aortic thrombus (PROCEDURE study) has begun. PROCEDURE has an enrollment goal of up to 80 patients with AAA with massive aortic atheroma (excluding intrasac atheroma), randomly allocated into 2 groups receiving pitavastatin at a dose of 1 or 4 mg/day. The endpoints of the PROCEDURE study include change in atheroma volume, major adverse events related to shower embolization after aneurysm repair, and lipid-lowering effects. When complete, results of the PROCEDURE study should provide objective evidence to use statins preoperatively for AAA with massive aortic atheroma. more...

Diabetic foot is one of the challenging diseases in vascular surgery, especially in patients with end-staged renal disease due to diabetic nephropathy. This disease is based on the neuropathic gangrene due to microangiopathy as well as on the macroangiopathy such as peripheral arterial occlusive disease. Therefore, the strategy for diabetic foot is as follows: the first step is the infection control by minor amputation and/or drainage, the second step is the assessment of the limb ischemia, and the final is the complete vascular reconstruction such as distal bypass to the crural arteries. To salvage the diabetic foot, it is important that doctors, who concern to diabetics, understand these strategies and also that they have a settled opinion for the diabetic foot. more...

Antiplatelet therapy is widely performed for arteriosclerosis obliterans (ASO) to relieve ischemic symptoms and prevent cardiovascular events. However, the overall rate of cardiovascular events in patients with ASO under treatment with antiplatelet agents has not been fully investigated in Japan. The SEASON registry is a nationwide observational prospective cohort study designed to compile data from over 2,000 institutions across Japan, whose aims are to (1) understand the current status for the management of ASO and clarify the incidence of cardiovascular events in patients with ASO undergoing antiplatelet therapy, and (2) compare the effectiveness of sarpogrelate, a 5-HT(2A) receptor antagonist, in decreasing the event rate with those of other antiplatelet agents [UMIN ID: UMIN000003385]. The registry will recruit approximately 10,000 patients receiving antiplatelet therapy (8,000 patients for sarpogrelate and 2,000 for other antiplatelet agents), and the patients will be followed every 6 months during a two-year follow-up period. The investigators plan to report all cardiovascular events and exacerbations of ASO. Analysis focusing on the sarpogrelate-treated subgroup will also be performed. Exploratory analysis will be performed to determine the clinical characteristics of the patients and to elucidate the relationships between risk factors and cardiovascular events. The SEASON registry is the first attempt to create a nationwide database regarding the incidence of cardiovascular events in 10,000 ASO patients in Japan. In addition, it ultimately may enable us to conclude that sarpogrelate prevents cardiovascular events. Information on the severity and risk factors in ASO patients in the clinical settings will be applicable to epidemiological analysis. more...

Objectives: True abdominal aortic aneurysm (AAA) in patients with Marfan syndrome is relatively rare because most aortic aneurysms in this disease are dissecting aneurysms in the thoracic area. Therefore, its clinical characteristics and long-term outcome are still unclear., Methods: We examined six patients (3 men, 3 women) with Marfan syndrome who had a true AAA. These patients underwent surgical treatment from 1972 to 2004, and we investigated the clinical and histologic findings., Results: The patients were a median age of 45 years (range, 23-73 years) at the time of operation. The median maximum AAA diameter was 76 mm (range, 30-140 mm). Two AAAs ruptured, one of which had twice undergone stent graft insertion before open repair. There was one anastomotic aneurysm and three aortic dissections with additional repair. Marfan-related cardiac complications, all found perioperatively or postoperatively, comprised three patients with annuloaortic ectasia and four with aortic regurgitation. Three patients died, including one death during the operation. Only slight mural thrombus was seen at nonruptured AAAs, and each surgical specimen of aneurysmal wall demonstrated significant cystic medial necrosis in the tunica media., Conclusions: True AAAs in Marfan syndrome seemed to have several specific features, such as the tendency to occur in relatively young patients, lack of mural thrombus, and susceptibility to dissection and rupture, and the patients have poor life expectancy. Therefore, careful follow-up, keeping these features in mind, is important to treat Marfan syndrome patients with a true AAA. more...

Objective: To analyze the outcome after surgery for critical limb ischemia (CLI) due to tibial artery occlusion in patients with systemic scleroderma., Methods: The medical records of scleroderma patients with CLI due to tibial artery occlusion were reviewed with respect to demographic data and perioperative variables., Results: Eight patients were identified at The University of Tokyo Hospital from 1991 to 2007. The underlying collagen disease was progressive systemic scleroderma in 6 patients and CREST syndrome in 2 patients. The subjects were 1 man and 7 women with a mean age of 68 years. While hypercoagulability including positive anticardiolipin antibodies was found in only 1 patient, all patients were antinuclear antibody (ANA) positive and 6 of 8 patients had a high titer of centromere-type ANA. Five underwent pedal artery bypass and 1 underwent distal peroneal artery bypass, while 2 underwent primary limb amputation. Although 1 patient with bypass had early graft occlusion (with subsequent below-knee amputation), the other 5 patients with patent grafts quickly achieved pain relief and initial wound healing. However, four of the five patent grafts developed graft occlusion several months after surgery, with severe intimal thickening at the anastomosis. As a result, 2 of 6 patients with bypass (totally 4 of 8 patients) underwent limb loss and 1 patient developed persistent recurrent ulcer., Conclusion: Bypass surgery in patients with scleroderma and CLI can be successful in achieving early pain relief and ischemic wound healing. However, the long-term effectiveness is limited with high rates of graft failure and limb loss. more...

Appendiceal cancer is rare and associated with a poor prognosis because it is usually found at an advanced stage. We report a case of appendiceal adenocarcinoma manifesting as a colonic obstruction with a lower abdominal mass. Laparotomy revealed bilateral ovarian tumors and a small appendiceal tumor with peritoneal metastases. We performed ileocecal resection, colectomy, and oophorectomy, following which a histological diagnosis of signet ring cell carcinoma was made. Immunohistochemical analysis revealed positive expression of cytokeratin 7 and 20, and mucin core protein 2 (MUC2), compatible with appendiceal cancer and Kruckenberg metastases. When a patient is found to have disseminated pelvic signet ring cell carcinoma of unknown origin, the appendix should be considered as a possible primary site. more...

Segmental arterial mediolysis (SAM) is a rare condition characterized by splanchnic arterial catastrophe caused by mediolysis. We report a 59-year-old man with a ruptured splenic arterial aneurysm who was successfully treated by coil embolization. He underwent additional resection of large gastroepiploic and residual splenic aneurysms. Pathological examination showed mediolysis and tearing, compatible with SAM. Furthermore, he developed acute dissection of the superior mesenteric artery (SMA) one and a half years later, demonstrated by computed tomography. This report demonstrates that SAM is characterized by multiple lesions of the splanchnic arteries at different times, and requires treatment suited to the lesions, including careful long-term observation. more...

Objectives: Isolated dissection of a splanchnic artery, including the celiac artery, superior mesenteric artery (SMA), and inferior mesenteric artery, and their branches, is a relatively rare condition. This study was conducted to define the characteristics of patients with splanchnic artery dissection and the clinical course of isolated splanchnic artery dissection., Methods: The records of 19 patients were reviewed to survey demographic data, the location of dissection, symptoms, diagnostic modalities, treatment, and long-term outcome., Results: The locations of dissection were the superior mesenteric artery (SMA) in 11 patients, celiac artery in 3, both celiac artery and SMA in 2, and common hepatic artery, celiac artery to splenic artery, and celiac artery to proper hepatic artery in 1 each. In all but one with systemic sclerosis and Sjögren syndrome, the underlying cause of dissection was unclear. There were 12 asymptomatic and seven symptomatic patients. All cases were diagnosed by computed tomography. Surgical treatment was performed in one patient with a large aneurysm of the common hepatic artery, and the remaining 18 patients were followed-up conservatively. The mean follow-up duration was 20.9 +/- 25.4 months (range, 2-116 months). No expansion or progression of the false lumen was observed in these patients., Conclusion: Patients with spontaneous dissection of the splanchnic arteries are often asymptomatic, and in this series, none developed significant end organ ischemia. Most patients with this rare condition can be managed expectantly with clinical follow-up including computed tomography imaging to assess aneurysm formation. more...

Objective: We evaluated the current clinical experience of temporary inferior vena cava (IVC) filter placement and its related complications., Methods: From January 2000 to December 2005, we enrolled 33 patients (8 men and 25 women) who underwent percutaneous insertion of a temporary IVC filter in the Department of Vascular Surgery of Tokyo University Hospital. Deep vein thrombosis (DVT) was proven in 78.8% of the patients. The indications for filter insertion were contraindication to anticoagulation therapy (9.1%), thrombolytic therapy (12.1%), perioperative prophylactic implantation (84.8%), pregnancy with DVT (3.0%), and prophylactic implantation in the absence of DVT (15.2%). A Neuhaus Protect was used in 13 patients, and an Antheor was used in 20 patients., Results: The mean +/- SD duration of filter placement was 10.6 +/- 7.0 days. There was no case of pulmonary embolism during filter protection and retraction. Filter thrombosis (capture of thrombus) was observed in four patients (12.1%), who then received additional thrombolytic therapy. Thrombi were dissolved by thrombolysis in three, one of whom had replacement with a permanent filter. The thrombus was not dissolved in one patient and was removed under venotomy at the insertion site. Major filter-related complications occurred in nine patients (27.3%), including filter dislocation in four patients (12.1%), catheter fracture in three (9.1%), and catheter-related infection in one (3.0%). In a patient with giant ovarian cancer, the IVC was nearly occluded with massive thrombus around the filter 2 days after operation, and the vena cava was then ligated under open laparotomy. No patients died during filter protection and retraction., Conclusions: Temporary IVC filters were effective for the prevention of fatal pulmonary embolism. However, our experience of a high incidence of complications related to temporary filters suggests that this device has limited indications and supports the need for innovative design of temporary filters. more...

Objective: Inflammatory responses are considered to represent a unique property after stent implantation, and we previously demonstrated that inflammatory signaling involving tumor necrosis factor receptor-associated factor 6 (TRAF6) contributes to neointimal formation in a balloon injury model of rabbit carotid artery. The purpose of this study was to examine the role of TRAF6 in in-stent lesion formation after stent implantation in the rabbit carotid artery., Methods: Rabbit carotid arteries were injured with a 2F Fogarty catheter, and 28 days later, the same arteries were implanted with a 3-mm-diameter Palmaz-Schatz stent. A dominant negative (DN) form of TRAF6 (pME-FLAG-T6deltaRZ5) was then transferred using a plasmid-based electroporation method. Its effects were evaluated compared with the findings in arteries treated with control plasmid (pME-FLAG)., Results: Immunostaining with anti-FLAG tag antibody showed that an expression plasmid vector containing the DN-TRAF6 sequence was successfully transferred to the arterial intima and media. Morphometric analyses revealed that the increase of intimal area in in-stent lesions was significantly inhibited by DN-TRAF6 14 days after stent implantation (DN-TRAF6 group, 3.01 +/- 0.25 x 10(5) microm2 vs control group, 4.25 +/- 0.23 x 10(5) microm2, P < .01), and the cell density was increased compared with that in the control group. In the DN-TRAF6 plasmid-treated vessels, cell replication was prevented in both the intima and media, and fewer leukocytes adhered to the luminal surface. Moreover, DN-TRAF6 suppressed macrophage infiltration, activation of proteases, and proteoglycan accumulation in the in-stent intima., Conclusions: These findings suggest that TRAF6 plays an important role in cell replication, inflammatory cell infiltration, protease activity, and extracellular matrix accumulation that contributes to in-stent lesion development. more...

Although the lipoprotein lipase (LPL) activator NO-1886 shows antiobesity effects in high-fat-induced obese animals, the mechanism remains unclear. To clarify the mechanism, we studied the effects of NO-1886 on the expression of uncoupling protein (UCP) 1, UCP2, and UCP3 in rats. NO-1886 was mixed with a high-fat chow to supply a dose of 100 mg/kg to 8-month-old male Sprague-Dawley rats. The animals were fed the high-fat chow for 8 weeks. At the end of the administration period, brown adipose tissue (BAT), mesenteric fat, and soleus muscle were collected and levels of UCP1, UCP2, and UCP3 messenger RNA (mRNA) were determined. NO-1886 suppressed the body weight increase seen in the high-fat control group after the 8-week administration (585 +/- 39 vs 657 +/- 66 g, P < .05). NO-1886 also suppressed fat accumulation in visceral (46.9 +/- 10.4 vs 73.7 +/- 14.5 g, P < .01) and subcutaneous (43.1 +/- 18.1 vs 68.9 +/- 18.8 g, P < .05) tissues and increased the levels of plasma total cholesterol and high-density lipoprotein cholesterol in comparison to the high-fat control group. In contrast, NO-1886 decreased the levels of plasma triglycerides, nonesterified free fatty acid, glucose, and insulin. NO-1886 increased LPL activity in soleus muscle (0.082 +/- 0.013 vs 0.061 +/- 0.016 mumol of free fatty acid per minute per gram of tissue, P < .05). NO-1886 increased the expression of UCP3 mRNA in soleus muscle 3.14-fold (P < .01) compared with the high-fat control group without affecting the levels of UCP3 in mesenteric adipose tissue and BAT. In addition, NO-1886 did not affect the expression of UCP1 and UCP2 in BAT, mesenteric adipose tissue, and soleus muscle. In conclusion, NO-1886 increased the expression of UCP3 mRNA and LPL activity only in skeletal muscle. Therefore, a possible mechanism for NO-1886's antiobesity effects in rats may be the enhancement of LPL activity in skeletal muscle and the accompanying increase in UCP3 expression. more...

Purpose: This study was conducted to evaluate the long-term outcomes of surgical treatment for atypical aortic coarctation due to Takayasu's arteritis and to elucidate the factors that affected outcome., Methods: The outcomes of surgical treatment for atypical aortic coarctation complicating Takayasu's arteritis in 33 consecutive patients over the previous 44 years at our institution were reviewed retrospectively. Preoperatively, 29 patients had coarctation proximal to the renal arteries and hypertension in the upper half of the body. Four hospital deaths occurred, and the remaining 29 patients were followed from 0.5 to 42.0 years (median, 17.9 years). The impacts of several risk factors on survival as well as cardiac and vascular events were analyzed., Results: Among 27 initial survivors who had hypertension preoperatively, 15 did not show normalization of blood pressure. The overall cumulative survival and event-free survival rate at 20 years were 62.3% and 58.4%, respectively. Serious long-term complications were anastomotic aneurysms, congestive heart failure, cerebrovascular accident, graft deterioration, abdominal aortic aneurysms, and renal failure. Among several risk factors analyzed, only the presence of postoperative hypertension had an effect on event-free survival., Conclusions: The long-term survival after surgery for atypical aortic coarctation was satisfactory. However, our study showed that complications associated with cardiovascular system or the operation could occur at any time after surgery; thus, life-long follow-up is mandatory. Further, the absence of normalization of blood pressure after surgery was a poor prognostic factor. Our results demonstrate the need for an intimate preoperative evaluation of renal and carotid artery lesions, which often coexist and may also cause secondary hypertension, to fully manage hypertension by surgery. more...

Objective: Our previous study demonstrated that high flow conditions stimulated cell proliferation in the aortic wall in a rat model of abdominal aortic aneurysm (AAA), and we speculated that there is a possible relation between medial cell density and aortic wall integrity. In the present study we delivered the basic fibroblast growth factor (bFGF) gene to the aortic wall of a rat AAA model and evaluated the effects of growth factor-enhanced smooth muscle cell (SMC) proliferation on aneurysm progression., Methods: AAA was induced in rats by means of infusion of porcine pancreatic elastase. Immediately after elastase infusion the abdominal aorta was filled with an expression plasmid vector containing the bFGF gene (bFGF group) or LacZ gene (control group); then gene transfer to the aortic wall was carried out with an in vivo electroporation method. The animals were killed 7 days after treatment, and the aneurysm was measured. The numbers of SMCs, macrophages, and endothelial cells were counted with immunostaining, and cell replication was evaluated with bromodeoxyuridine (BrdU) staining., Results: Aneurysm diameter in the bFGF group was significantly smaller than that in the control group (4.6 +/- 0.3 mm vs 6.5 +/- 1.4 mm; P <.01). The numbers of medial SMCs and BrdU-incorporated cells in the bFGF group were significantly greater than those in the control group (SMC, 101 +/- 34 per high-power field [hpf] vs 80 +/- 31/hpf; P <.05, BrdU, 107 +/- 63/hpf vs 50 +/- 33/hpf; P <.05), whereas no difference was detected in the numbers of macrophages and endothelial cells between the 2 groups., Conclusions: Delivery of bFGF to the aortic wall induced significant enhancement of medial SMC proliferation, without an increase in inflammatory infiltration, then successfully limited aneurysm enlargement. These findings suggest that increased medial cellularity inhibits aneurysm formation, which possibly offers a clue for developing a new strategy for treatment of AAAs. more...

Purpose: In our previous study, adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor promoted significant collateral vessel development in a rabbit model of hind limb ischemia. The present study examined how to control the efficacy and safety of this gene therapy, and also evaluated the feasibility of repeat application of this procedure., Methods: Modified hFGF gene with the secretory signal sequence was adenovirally transferred to cultured autologous fibroblasts, and various numbers of the cells (2 x 10(5), 1 x 10(6), 5 x 10(6), or 2.5 x 10(7)) or vehicle was injected through the left internal iliac artery in rabbits in whom the left femoral artery had been excised 21 days previously. Twenty-eight days after cell administration, calf blood pressure ratio, angiographic score, blood flow in the internal iliac artery, and capillary density of muscle tissue were measured to analyze collateral vessel development and tissue perfusion in the ischemic limb. To assess delivery efficiency and viral contamination, the distribution of injected cells and the time course of blood anti-adenovirus antibody titer were examined in rabbits treated with various numbers of gene-transduced cells. In addition, animals received two injections, 21 days apart, of fibroblasts infected with adenovirus vector containing the luciferase gene, and luciferase expression was measured to evaluate whether the present therapy is repeatable., Results: At 28 days after cell administration, significant collateral vessel development without detectable side effects was observed in rabbits who received 5 x 10(6) or 2.5 x 10(7) cells, compared with those who received vehicle, and no significant development was detected in animals with fewer than 5 x 10(6) cells (P <.01 for calf blood pressure ratio and capillary density, P <.05 for angiographic score and maximum blood flow). There was no difference in collateral augmentation between rabbits with 5 x 10(6) and 2.5 x 10(7) cells. However, in animals with 2.5 x 10(7) cells a large number of injected cells accumulated in the lungs, anti-adenovirus antibody titer increased significantly, and calf blood pressure in the left hind limb of two rabbits decreased immediately after injection. Luciferase analysis showed very low gene expression after repeated administration., Conclusion: These findings suggest that 5 x 10(6) is a suitable number of cells to induce appropriate collateral vessel development and minimize potential side effects of this procedure. Despite use of ex vivo gene transfer, repeat administration of the cells was not feasible. Clinical relevance Since the present study determined the appropriate conditions for effective and safe stimulation of collateral vessels, the clinical relevance of the ex vivo therapy might be carried forward. However, the findings raised another issue that should be resolved before clinical application; that is, the number of gene-transduced cells able to be injected was strictly limited. To estimate the therapeutic range of cell number in humans, additional experiments using large animals are desirable. more...