小林 昌義

Objective: Saphenous varicose veins can be accomplished by various operative techniques that result in stripping, ablation, or ligation of the venous reflux section. Great saphenous vein (GSV) stripping is one of the standard operations for varicose veins to eliminate reflux of the sapheno-femoral junction. The goal of any treatment regimen is to eliminate the junctional varicose reflux to control congestive dysfunction. Endovenous laser ablation (EVLA) is safe and effective with less postoperative pain, bleeding, and peripheral nerve damage than open surgery. In this study, a patient with severe progression of primary saphenous varicose veins is presented. We report the outcome of combined surgical strategy and perioperative treatment for extremely swollen varicose veins of the lower limbs to improve leg symptoms and congestion and/or promote skin ulcer healing. Materials and Methods: The subjects included 42 patients (51 limbs) who underwent EVLA with stripping. The patients comprised 24 males and 18 females, who presented a maximum GSV diameter >15 mm. The Clinical-Etiological-Anatomic-Pathophysiologic classification identified 9, 20, 9, 2, 6, and 5 limbs with C2, C3, C4a, C4b, C5, and C6, respectively, among the 42 patients. Results: EVLA was used to treat GSV with a mean length of 16.1±2.8 cm. The mean of the maximum GSV diameter was 16.8±3.2 mm (14.6-21.8 mm). The preoperative visual analog scale (VAS) score was 82.1±12.1. After operation, the VAS gradually deteriorated to 31.3±17.9 (p<0.0001), 2.8±3.6 (p<0.0001), and 1.2±1.8 (p<0.0001) in 7 days, 1 month, and 3 months, respectively. Conclusion: We obtained a satisfactory outcome from our combined strategy and perioperative treatment for extremely swollen saphenous varicose veins. This approach may show the possibility that lower saphenous varicose veins can induce cosmetic and minimally invasive ameliorated intervention to avoid late-phase incompetent perforating veins.

A venous aneurysm is a relatively rare disease defined by cystic vasodilated lesions in a general vein. Popliteal venous aneurysm (PVA) is a rare clinical entity, and the first signs may be a thromboembolic event. They can cause potentially life-threatening diseases, such as pulmonary embolism and deep venous thrombosis. A left-sided inferior vena cava (IVC) is a common anomaly associated with venous thrombus, resulting in anatomical variations in the venous return from the lower limbs. The general vascular malformation of PVA and left-sided IVC should also be preoperatively understood because of the unpredictable risk of thromboembolic complications.

The treatment tactics for subclavian artery occlusion include the more commonly used endovascular therapy rather than surgical intervention. We present a case of a 61-year-old woman with dialysis-dependent chronic renal failure who experienced left finger necrosis in the left upper extremity. To salvage the limb, we performed femoro-axillary (fem-ax) artery bypass using an autologous saphenous vein graft. However, 10 months later, she experienced coldness in the left forearm. Angiography revealed chronic total occlusion of the venous bypass. Despite emergent thrombectomy, redo fem-ax artery bypass operation was performed using a prosthetic graft. Upper limb salvage can be achieved by fem-ax artery retrograde bypass.

症例は71 歳女性．左足関節痛，両下肢違和感にて当院受診した．両大腿内側から下腿に伏在静脈瘤を認めた．下肢静脈超音波にて両側大腿- 大伏在静脈接合部に逆流を認めたため，全身麻酔にて両下肢に血管内レーザー焼灼術（endovenous laser ablation: EVLA），静脈瘤切除，硬化療法を施行した．術後1 日目病棟歩行時突然の呼吸困難，背部痛にてCT 室搬送となり，心停止により緊急挿管された．ポータブルUS にて右心系収縮不全あり，術後DVT，PTE を疑い緊急下大静脈フィルター留置し，ヘパリン，ウロキナーゼ投与するも全身動態に安定みられず同日夜永眠となった．本邦の文献を調べた限り下肢静脈瘤に対するEVLA 後に肺血栓塞栓症（pulmonary thromboembolism: PTE）を併発した死亡症例の報告はないため，この誌を借りて報告する．

For treatment of deep vein thrombosis and prevention of pulmonary thromboembolism, a retrievable inferior vena cava filter is commonly utilized as an effective bridge to anticoagulation. However, we have experienced difficulties in retrieving inferior vena cava filters. Endovascular retrieval assisted by disposable biopsy forceps is an appropriate approach because it provides a less-invasive low-cost way to remove a migrated filter. We suggest this troubleshooting technique to deal with filter hook migration into the caval wall.

症例は35歳，女性．両下肢の浮腫にて近医受診．タンパク尿も認め，CT検査・エコー検査を施行した．肝・下大静脈へ進展する右副腎腫瘍にて当院紹介となった．精査により，肝右葉・肝部～肝下部下大静脈への浸潤を認める右副腎癌の診断にて，経皮経肝的門脈塞栓術を施行後，右開胸開腹下下大静脈合併右副腎肝右葉尾状葉切除術を施行した．下大静脈はGoreTex graft（リング付き，直径2cm，長さ約10cm）にて再建した．病理組織学的に，下大静脈内腔より発生・増殖しており，免疫組織染色にてS-100・CD34・CD56陰性，αSMA・カルデスモン陽性にて，下大静脈原発平滑筋肉腫と診断した．経過良好で，術後2年6カ月経過し再発は認めていない．下大静脈原発の平滑筋肉腫は比較的稀な疾患であり，今回手術を施行した1例を経験したので報告する．

OBJECTIVES: For treatment and prevention of deep vein thrombosis(DVT) and pulmonary embolism(PE), retrievable inferior vena cava(IVC) filters have commonly been used as an effective bridge to anticoagulation. However, we experienced unexpected difficulty in endovascular retrieval of some IVC filters. Most problems were due to endovascular treatment devices issues, filter intimal migration, filter disintegration, filter-associated thrombosis, and right atrium/ventricle migration. METHODS: Disposable biopsy forceps was used to engage the filter hook and reform the shape of the filter struts. Endovascular retrieval assisted by use of the biopsy forceps via a similar vein was effective and provided a less-invasive, low cost method for removal of problematic IVC filters. RESULTS: We described easily performed methods that uses disposable biopsy forceps for the retrieval of IVC filters that are difficult to remove because of filter hook migration into the caval wall. CONCLUSION: We developed an easily performed method that uses intestine biopsy forceps for the retrieval of IVC filter that are difficult to remove.

Buerger's disease (thromboangiitis obliterans) is considered to be a nonatherosclerotic, inflammatory, and vaso-occlusive disease, although the details of the mechanisms of pathogenesis remain unknown. The occurrence of the disease is strongly related to tobacco abuse and its progression is closely linked to continued smoking. The purpose of this review article is to demonstrate the pathological characteristics of arteries affected with Buerger's disease from a possible immunoreactive point of view. In addition, we present the mechanisms for preserving the architecture of the arterial wall in affected vasculatures. Thereafter, we discuss the possibility that the pathogenesis of Buerger's disease is a type of endarteritis obliterans, deeply connected to the Notch pathway, distinct from arteriosclerosis obliterans and other vasculitides.

BACKGROUND: The autologous saphenous vein graft is currently the most suitable conduit for arterial bypass of the lower limbs. Various approaches have been attempted to control vein graft intimal hyperplasia, and several recent reports have suggested that statin use may be linked to improved patency of vein grafts. In this study, the efficacy of pitavastatin was evaluated on intimal hyperplasia and midkine expression of experimental normocholesterolemic rabbit autologous vein graft. MATERIALS AND METHODS: Rabbits were fed regular rabbit chow, and in half of them, pitavastatin (1 mg/kg/d) was administered. A week after starting the treatment, jugular vein was implanted into the carotid artery. At 2 and 4 wk after the operation, vein grafts were harvested, and intimal hyperplasia of vein grafts were assessed. Cell proliferation in neointima was determined by proliferative cell nuclear antigen and Ki-67 stain 2 wk after implantation. In addition, the effect of pitavastatin on midkine, a heparin-binding growth factor, expressed in vein grafts was analyzed by Western blotting. RESULTS: The intimal hyperplasia in the pitavastatin group was significantly suppressed compared with the control group. Both proliferative cell nuclear antigen and Ki-67 labeling index were significantly lower in the pitavastatin group, and pitavastatin significantly reduced midkine expression of vein graft. CONCLUSIONS: These results demonstrate the efficacy of pitavastatin in reducing the degree of intimal hyperplasia of rabbit autologous vein grafts under normocholesterolemic condition. The mechanism of inhibition of intimal hyperplasia might be associated with midkine suppression.

BACKGROUND: Beta-adrenoceptor antagonist celiprolol has been widely used as an effective antihypertensive agent. Some studies reported that celiprolol enhances nitric oxide production. The purpose of the present study is to examine the effects of celiprolol on vein graft intimal hyperplasia and endothelium-dependent nitric oxide (NO)-mediated relaxation. METHODS: Japanese white rabbits were randomized to a control group that was fed regular rabbit chow or to a celiprolol group that was fed regular rabbit chow supplemented with 100 mg/body celiprolol sodium. The reversed jugular vein was implanted into the carotid artery. At 2 and 4 weeks after the operation, vein grafts in both groups were harvested, and intimal hyperplasia of the vein grafts was assessed. At 4 weeks after the operation, harvested vein grafts from both the groups were examined on the endothelium-dependent relaxation by application of Ach and were examined to detect for endothelial NO synthase (eNOS) expression and superoxide anion production. RESULTS: Celiprolol inhibited intimal hyperplasia of carotid interposition-reversed jugular vein grafts 4 weeks after implantation (Intima/media index of celiprolol group, 0.48 +/- 0.01 vs control group, 1.07 +/- 0.08, P < .05) and suppressed cell proliferation in the neointima 2 weeks after implantation. In addition, celiprolol significantly enhanced endothelium-dependent NO-mediated relaxation in the vein graft with no change in eNOS expression and a reduction in superoxide production. CONCLUSIONS: These novel findings clearly demonstrate that beta-adrenoceptor antagonist celiprolol can suppress intimal hyperplasia of the vein graft, which may be due to the enhancement of nitric oxide function through an inhibition of superoxide production. These results strongly support the clinical usefulness of celiprolol administration for preventing intimal hyperplasia of the vein graft after bypass grafting.

BACKGROUND: Therapeutic angiogenesis using cell transplantation (TACT) is a treatment strategy for no-option patients with critical limb ischemia (CLI). However, because one-third of treated patients fail to respond, the present study was an exploration of the characteristics of responders and non-responders to this treatment regimen. METHODS AND RESULTS: Seven CLI patients (3 with Buerger's disease, 4 with arteriosclerosis obliterans undergoing chronic hemodialysis (ASO-HD)) were treated according to the TACT protocol (n=6: bone marrow-mononuclear cells (MNCs); n=1: peripheral blood-MNCs). Subjective symptoms (visual analog scale) and objective findings (extent of ulcer, ankle-brachial pressure index, transcutaneous oxygen pressure, thermography and angiography) were assessed. Numbers of transplanted CD34+, CD133+ and CD34+ CD133+ cells were counted. Changes in circulating CD34+ and CD133+ cell numbers were also examined before and after the treatment. All responders (n=3) had Buerger's disease, and ASO-HD patients did not respond well. Among the responders, the numbers of circulating CD34+ and CD133+ cells persistently increased for 1 month after the treatment, but not in non-responders. CONCLUSIONS: The TACT regimen improved CLI in patients with Buerger's disease but not in those with ASO-HD in this small study. In responders, post procedural circulating CD34+ and CD133+ cells persistently increased for 1 month (ClinicalTrials.gov Identifier: NCT00145262, TACT-NAGOYA).

Since Buerger's disease was first described by Leo Buerger in 1908, many authors have discussed whether it indeed exists and, if so, is a definite clinical entity. Today, Buerger's disease is accepted as a definite vascular disease with a typical clinical picture, natural history, and histopathology; however, the diagnosis of Buerger's disease has been controversial, and the etiology of this vascular occlusive disease has remained unknown because many authors in different countries have their own criteria. Besides, patients with this disease have decreased in number even in Japan, while there has been no change in the number of arteriosclerosis obliterans patients. Currently, only one or two new patients per year are encountered at our outpatient clinic. The purpose of this review is to examine the current epidemiological, pathological, and clinical aspects of Buerger's disease in Japan based on the 222 patient files of our department between 1980 and 2000 and to discuss the pathogenesis, clinical presentation, and various treatment modalities.

BACKGROUND: Recent studies suggest that statins can protect the vasculature in a manner that is independent of their lipid-lowering activity through inhibition of the small guanosine triphosphate-binding protein, Rho, and Rho-associated kinase. Little information is available on the inhibitory effect of statins on vein graft intimal hyperplasia, the main cause of late graft failure after bypass grafting. We therefore examined the effects of a hydrophilic statin on vein graft intimal hyperplasia in vivo and Rho-kinase activity in vitro. METHODS: In the first experiment, rabbits were randomized to a control group (n = 7) that was fed regular rabbit chow or to a pravastatin group (n = 7) that was fed regular rabbit chow supplemented with 10 mg/kg pravastatin sodium. The branches of the jugular vein were ligated and an approximately 3-cm segment of the jugular vein was taken for an autologous reversed-vein graft. The carotid artery was cut and replaced with the harvested autologous jugular vein. At 2 and 4 weeks after the operation, vein grafts in both groups were harvested, and intimal hyperplasia of the vein grafts was assessed. In the second experiment, human umbilical vein endothelial cells and vascular smooth muscle cells were cultured and then treated with 1 micromol/L and 30 micromol/L pravastatin for 24 hours and harvested. Immunoblotting was performed on the resulting precipitates. Quantitative evaluation of phosphorylated myosin binding subunit and endothelial nitric oxide synthase was performed by densitometric analysis. RESULTS: We demonstrated that oral administration of the hydrophilic statin pravastatin to normocholesterolemic rabbits inhibited intimal hyperplasia of carotid interposition-reversed jugular vein grafts 4 weeks after implantation (pravastatin group, 39.5 +/- 3.5 microm vs control group, 64.0 +/- 7.1 microm; n = 7; P < .05) and suppressed cell proliferation and apoptosis in the neointima 2 weeks after implantation. In addition, we found that pravastatin inhibited Rho-kinase activity and accelerated endothelial nitric oxide synthase expression in human umbilical vein endothelial cells but did not inhibit Rho-kinase activity in vascular smooth muscle cells. CONCLUSIONS: These novel findings clearly demonstrate that a hydrophilic statin can suppress intimal hyperplasia of the vein graft in vivo and also show endothelial cell-tropic inhibition of Rho-kinase in vitro. Furthermore, these results strongly support the clinical use of hydrophilic statins to prevent intimal hyperplasia of the vein graft after bypass grafting. CLINICAL RELEVANCE: Late graft failure caused by neointimal hyperplasia limits the efficacy of vein grafting. Various treatments were examined to reduce neointimal hyperplasia, but a standard clinical treatment has not yet been established. We report here the inhibitory effect of pravastatin on the development of vein graft intimal hyperplasia. In addition, we demonstrate that pravastatin showed endothelial cell-tropic benefits through both the inhibition of Rho-kinase activity and acceleration of eNOS expression in vitro. Because the clinical benefits and safety of pravastatin have been established to a certain extent through long-term clinical usage, pravastatin may soon become standard treatment after vein bypass grafting.

OBJECTIVE: Although some patients with limb ischemia have recently undergone therapeutic angiogenesis by cell transplantation, their angiogenic potential has not been well characterized. It is also important to evaluate endothelial progenitor cell (EPC) contents in different stem cell sources to choose the best material for therapeutic angiogenesis. METHODS AND RESULTS: We quantitated the mRNA expression of EPC-specific molecules (eg, Flk-1, Flt-1, CD133, VE-cadherin, etc) in bone marrow-derived or peripheral blood-derived mononuclear cells obtained from patients with ischemic limbs, using real-time reverse-transcription polymerase chain reaction technique. The mRNA expression level of EPC markers was significantly lower in the patients than in healthy controls, which was consistent with results of flow cytometric analysis. However, the implantation of autologous bone marrow mononuclear cells increased the circulating EPCs in the peripheral blood of patients. We furthermore revealed the different expression pattern of EPC markers in possible sources for stem cell transplantation, including normal bone marrow, peripheral blood obtained from recombinant granulocyte colony-stimulating factor-treated donor, and umbilical cord blood. CONCLUSIONS: Patients with peripheral obstructive arterial diseases may have lower angiogenic potential because of decreased expression of EPC specific molecules in their marrow and blood. Therapeutic angiogenesis by transplantation of autologous marrow mononuclear cells increased circulating EPCs in the patients and improved ischemic symptoms.

We performed 167 femoropopliteal bypass surgeries in 151 patients (95 patients underwent above-knee bypass and 56 below-knee bypass) from December 1985 to December 2000 with the use of prosthetic graft or autologous vein graft. We compared primary patency rates between age, sex, graft material, distal anastomotic site and severity of ischemia, considering their survival rates to elucidate the long-term outcome of above-knee and below-knee femoropopliteal bypass. The 10 year patency rate for above-knee bypass was 47.4%, compared to 36.9% for below-knee ( p < 0.01). Better results were found after bypass surgery for claudicants than for critical ischemia ( p < 0.05). With regard to graft material and age categories, there were unexpectedly no statistical differences in either above-knee or below-knee anastomosis. The survival rate at 10 years in claudicants was 51.2%, compared to 15.9% with critical ischemia ( p < 0.01). Mortality was much influenced by ischemic heart disease ( p < 0.002) and the age of patient ( p < 0.05). The results after above-knee bypass had comparable patency, whereas the results after below-knee bypass were disappointing. Below-knee arterial reconstruction for claudicants should be carefully considered and might be recommended only to patients with critical ischemia.

We report an external iliac venous aneurysm in a young pregnant woman who was diagnosed incidentally by ultrasound scanning. The aneurysm was successfully treated by tangential aneurysmectomy and lateral venorrhaphy. Primary iliac venous aneurysm is a rare vascular abnormality. The clinical significance of the disease is unknown. However, embolism, rupture, and thrombosis might occur as they can occur with popliteal venous aneurysm. In fact, three of four reported patients with iliac venous aneurysms had a thromboembolic event. For those reasons, prophylactic treatment is indicated. This is the first patient with an iliac venous aneurysm to be diagnosed without complication.

We investigated whether fibrin glue (FG) might be useful as a carrier of amikacin (AMK) for prevention of local graft infection. After AMK (4.0 mg)-treated FG (AMK-FG) polyurethane grafts were implanted subcutaneously in the anterior abdominal region of Sprague-Dawley rats, AMK concentrations in tissues surrounding the implantation sites were compared over time with concentrations at the same sites in rats given an intravenous injection of AMK (4.0 mg). In the injection group, AMK concentrations in serum were detectable only for 4 h, whereas AMK released from AMK-FG grafts remained detectable over 24 h. Until 4 h after implantation, AMK concentrations in tissues near implantation sites were significantly higher in the AMK-FG graft group than in the injection group; peak local concentrations during that time were 210 times higher for the AMK-FG graft group than for the injection group. Areas under the tissue concentration-time curve (AUC) for AMK were 171 microg x h/g and 1.35 microg x h/g in the AMK-FG graft and injection groups, respectively. FG therefore was considered to control release of AMK and to maintain a high AMK concentration in tissues surrounding the implantation site. Thus, AMK-FG polyurethane graft delivery may be useful in preventing local infection by local delivery of AMK.

A 42-year-old Japanese man who had undergone amputation of the left leg below the knee because of Buerger disease required emergency thrombectomy 7 months later. He complained of acute abdominal pain after thrombectomy. At aortography the distal superior mesenteric artery and its branches were not well visualized. Emergency laparotomy was performed because of suspected intestinal ischemia, and the terminal ileum and cecum and part of the ascending colon were resected. In total, the patient underwent laparotomy four times. Histopathologic findings revealed that the arteries and veins of the resected small intestine were occluded with organized thrombi. Inflammatory cell infiltration was recognized mainly in the intima. These findings are compatible with Buerger disease.

A 19-year-old female college student had numbness and the sensation of coldness of her left toes. She had a 3-year smoking history. Gangrene of the left foot developed rapidly. Angiography revealed peripheral arterial occlusion of both legs and arms. Detailed laboratory examination excluded collagen disease, a hypercoagulable state, and juvenile atherosclerosis. Below-knee amputation of the left leg was performed. Typical histologic findings of Buerger's disease were observed in the crural arteries and saphenous veins. The clinical course was uneventful after the patient stopped smoking. This is the second case report of Buerger's disease in a woman in the second decade of life. It is important that a correct diagnosis of Buerger's disease be established, because the disease process is benign, compared with collagen disease, if the patient stops smoking.

BACKGROUND: This paper presents an investigation into the expression of endothelial cells and vascular endothelial growth factor (VEGF) in the aortic wall in vascular diseases such as atherosclerotic abdominal aortic aneurysm (AAAA), inflammatory abdominal aortic aneurysm (IAAA), and aortic occlusive disease (AOD) to determine whether the differences in both neovascularization and angiogenic factor expression are related to the pathogenesis of aortic vascular disease. MATERIALS AND METHODS: Surgical specimens of aorta (10 IAAA, 13 AAAA, 6 AOD) were studied pathologically and immunohistochemically. Representative sections of aorta were stained with hematoxylin-eosin, elastica von Gieson, CD34, and VEGF antibody. CD34-positive microvessels and VEGF-positive cells in the media and adventitia were counted, respectively. RESULTS: CD34-positive microvessels were detected in IAAA > AAAA > AOD (one-way analysis of variance (ANOVA), P < 0.0001). VEGF expression was widely detected in macrophages, monocytes, and smooth muscle cells of IAAA and AAAA; however, it was hardly recognized in AOD. VEGF-positive cells were detected in IAAA > AAAA > AOD specimens (ANOVA, P < 0.0001). CONCLUSIONS: VEGF is known to be a regulator of angiogenesis and to simultaneously stimulate elastolytic proteinases. The results of this study suggest that an angiogenic factor, such as VEGF, may play an important role in the degeneration of the aortic wall and could be strongly related to the pathogenesis of IAAA, AAAA, and AOD.

PURPOSE: The diagnosis of Buerger's disease has depended on clinical symptoms and angiographic findings, whereas pathologic findings are considered to be of secondary importance. Arteries from patients with Buerger's tissue were analyzed histologically, including immunophenotyping of the infiltrating cells, to elucidate the nature of Buerger's disease as a vasculitis. METHODS: Thirty-three specimens from nine patients, in whom Buerger's disease was diagnosed on the basis of our clinical and angiographic criteria between 1980 and 1995 at Nagoya University Hospital, were studied. Immunohistochemical studies were performed on paraffin-embedded tissue with a labeled streptoavidin-biotin method. RESULTS: The general architecture of vessel walls was well preserved regardless of the stage of disease, and cell infiltration was observed mainly in the thrombus and the intima. Among infiltrating cells, CD3(+) T cells greatly outnumbered CD20(+) B cells. CD68(+) macrophages or S-100(+) dendritic cells were detected, especially in the intima during acute and subacute stages. All cases except one showed infiltration by the human leukocyte antigen-D region (HLA-DR) antigen-bearing macrophages and dendritic cells in the intima. Immunoglobulins G, A, and M (IgG, IgA, IgM) and complement factors 3d and 4c (C3d, C4c) were deposited along the internal elastic lamina. CONCLUSION: Buerger's disease is strictly an endarteritis that is introduced by T-cell mediated cellular immunity and by B-cell mediated humoral immunity associated with activation of macrophages or dendritic cells in the intima.

Successful aortic stump closure in a patient with Behçet's disease was accomplished with a permanent titanium clamp. In May 1990, a saccular infrarenal abdominal aortic aneurysm was detected in this patient, and prosthetic graft replacement was carried out. One year later, this graft was removed because of perigraft fluid collection; the aortic stump was sutured closed, and a right axillobifemoral bypass was done. In November 1994, the patient was admitted to the hospital because of an aortoenteric fistula. An emergency operation was performed, and the aortic stump was managed successfully with a permanent clamp. In patients with Behçet's disease, use of a permanent clamp may offer an alternative to traditional methods for closing blown-out aortic stumps.

A 77-year-old man with abdominal aortic aneurysm (AAA) was referred to our department. His AAA, which was 6 cm in diameter, was found incidentally with ultrasonography. On admission the diagnosis of hemophilia A was made for the first time in his life because activated partial thromboplastin time was decreased to 32.3% and factor VIII coagulant activity was 2.1% (normal range 40% to 140%). Recombinant factor VIII supplemental therapy was continued during surgery to maintain his factor VIII level within the normal range. His AAA was operated successfully with bifurcated graft replacement. No unusual bleeding complications occurred during his hospitalization. With proper preparation the patient with AAA and hemophilia A can safely undergo surgical treatment. Three other cases of AAA with hemophilia in the English literature were reviewed, and this is the oldest patient with hemophilia who underwent AAA surgery.