Individuals with diabetes have a two- to four-fold increased risk of coronary artery disease (CAD) and higher mortality rates than those without diabetes. Because not only microvascular but also macrovascular disease in patients with diabetes are known to predispose patients to a lower quality of life as well as lead to higher mortality rates, identifying and managing risk factors of CAD is of clinical relevance in diabetes care. A number of antihyperglycemic drugs are currently approved for the treatment of hyperglycemia in patients with type 2 diabetes mellitus (T2DM), with several new drugs having been developed during the last decade. Diabetes-related complications have been substantially reduced worldwide. However, in view of the current situation in which both the prevalence of obesity and glucose abnormality have increased worldwide, including Japan, diet and exercise remain the crucial means of treatment for patients with diabetes. Furthermore, predicting the development of CAD is essential. This review summarizes data from recent studies on cardiovascular disease in patients with T2DM, focusing on clinical trials and big data, including studies involving Japanese individuals.

Carotid artery stenting (CAS) has been recommended as an alternative treatment to carotid endarterectomy for patients with significant carotid stenosis. Only a few studies have analyzed clinical/anatomical and technical variables that affect perioperative outcomes of CAS. Following a comprehensive Medline search, it was reported that clinical factors, including age of >80 years, chronic renal failure, diabetes mellitus, symptomatic indications, and procedures performed within 2 weeks of transient ischemic attack symptoms, are associated with high perioperative stroke and death rates. They also highlighted that angiographic variables, e.g., ulcerated and calcified plaques, left carotid intervention, >90% stenosis, >10-mm target lesion length, ostial involvement, type III aortic arch, and >60°-angulated internal carotid and common carotid arteries, are predictors of increased stroke rates. Technical factors associated with increased perioperative risk of stroke include percutaneous transluminal angioplasty (PTA) without embolic protection devices, PTA before stent placement, and the use of multiple stents. This review describes the most widely quoted data in defining various predictors of perioperative stroke and death after CAS. (This is a review article based on the invited lecture of the 45th Annual Meeting of Japanese Society for Vascular Surgery.)

Several meta-analyses and multicenter trials have shown that chronic limb ischemia did not occur for up to 5 years in 50%–70% of patients who underwent saphenous vein grafts, with limb salvage and perioperative mortality rates of >80% and 3%, respectively. However, open surgical bypass can have limitations, including postoperative morbidity/wound complications of 10%–20% and prolonged length of hospital stay and outpatient care. Several studies have analyzed clinical outcomes for patients with critical limb ischemia treated with endovascular therapies, but they have been mainly retrospective with significant heterogeneity or were single center. Only few randomized trials have compared surgical vs. endovascular therapy. These included the Bypass vs. Angioplasty in Severe Ischemia of the Leg (BASIL) trial, with no differences found in amputation-free or overall survival rates at 1 year; however, late outcomes favored the surgical group. The Bypass or Angioplasty in Severe Intermittent Claudication (BASIC) trial concluded that the 1-year patency rates were 82% and 43% for bypass and angioplasty, respectively. The BEST Endovascular vs. Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) trial is currently enrolling patients. This review analyzed studies comparing open vs. endovascular therapy in patients with femoropopliteal disease. (This is a review article based on the invited lecture of the 45th Annual Meeting of Japanese Society for Vascular Surgery.)

This essay summarizes a lecture presented on October 19th, 2017, during the 58th Annual Meeting of the Japanese College of Angiology in Nagoya, Japan. The lecture summarizes several instances where the absence of relaxations of isolated blood vessels in response to endothelium-dependent vasodilator agonists, which cause activation of endothelial nitric oxide synthase (eNOS) and consequent production of endothelium-derived nitric oxide (NO) and stimulation of soluble guanylyl cyclase (sGC) in underlying vascular smooth muscle, or hypoxia are curtailed or reversed to endothelium-dependent contractions. Chosen examples include selective dysfunction of eNOS activation in regenerated endothelial cells, unresponsiveness of vascular smooth muscle cells to NO during subarachnoid hemorrhage, and biased activation of sGC in vascular smooth muscle cells during acute exposure to hypoxia. The main message of this essay is that absence, blunting, or reversal of endothelium-dependent relaxations in response to vasodilator agonists cannot necessarily be interpreted as a sign of endothelial dysfunction. (This is a review article based on the invited lecture of the 58th Annual Meeting of Japanese College of Angiology.)

Vascular Behçet’s disease (BD) would keep risk of anastomotic pseudoaneurysm due to deterioration of the disease even after vascular surgery was successfully done. Therefore, it is one of the least-welcome diseases for vascular surgeons. There still exist several points on a concept and criteria of the vascular BD which not only general practitioners but also the vascular surgeons do not understand. Clinical findings strongly suspecting vascular BD are follows; saccular aneurysms without atherosclerosis developed in younger than 50-year-old patients, superior vena cava syndrome or deep vein thrombosis in bilateral legs without apparent causes, and multiple superficial thrombophlebitis, etc. It is very difficult to make a diagnosis of BD in the patients whose onset of the disease is a vascular lesion, because vascular BD combines few ocular lesions. In such case, it is very important to find out not only oral and genital ulceration, but also past history of arthritis. To establish the vascular BD, we vascular surgeons have to collect cases of the vascular BD and to revise criteria of the disease. (This is a translation of Jpn J Vasc Surg 2017; 26: 19–23.)

In this seminar, I would like to discuss the recent hybrid operations in patients with peripheral arterial diseases. Hybrid is generally defined as combinations of different types of things. In the surgical community, it is loosely defined as therapy combining open surgery (OS) and endovascular therapy (EVT). In practice, combination surgery of diseased inflow vessels by EVT and outflow vessels by OS is a typical example, namely, the combination therapy of thromboendarterectomy (TEA) for common femoral artery and EVT (PTA and stenting) for iliac artery in patients with PAD (ilio-femoral lesions). Also, there is the potential of various combinations of OS and EVT for complex lesions. Unfortunately, we do not have specific guidelines for hybrid therapy of PAD, but in clinical practices, justified decision-making for surgical indication is strictly required. I emphasize that the cardiovascular surgeon (or vascular specialist) must have the ability of decision-making for suitable combination therapy of OS and EVT which adheres to existing specific guidelines. (This is a translation of Jpn J Vasc Surg 2017; 26: 275–283.)

There were three epoch making events in therapy of varicose veins. The first one is that the endovascular heat ablation (EVHA) using diode laser was authorized by the Ministry of Health Labor and Welfare in January 2011. The second one is that Subfascial Endoscopic Perforator Surgery (SEPS) was also authorized in April 2014. All of the therapies which were covered by the national insurance system had been the procedures for superficial veins but the SEPS is procedure for the perforating veins. The third one is that the foam usage of Polidocasklerol was listed formally at the medical package insert in September 2016. Moreover stub avulsion was introduced as figure-related improvement method with a smaller operation wound instead of conventional varicectomy and the other existing therapies are progressing every day. Therefore, by this education seminar, I lecture mainly on the EVHA, SEPS and foam sclerotherapy in varicose vein treatment. Finally I show one case which you should remember. (This is a translation of Jpn J Vasc Surg 2017; 26: 225–230.)

Immunoglobulin G4-related diseases (IgG4-RD) are systemic inflammatory conditions, characterized by high serum IgG4 concentrations, and pathologically IgG4-positive plasmacytes infiltrations and storiform fibrosis. We described IgG4-related inflammatory abdominal aortic aneurysm in 2008, and revealed the existence of vascular lesions. IgG4-related vascular lesions frequently occur in the aorta and branching medium-sized arteries with or without aneurysmal change. The inflammatory lesion mainly involves in the adventitia, indicating remarkable adventitial fibrous thickening with infiltration of inflammatory cells. Clinical symptoms associated with IgG4-related vascular lesions might be fever, abdominal pain, hydronephrosis, or few subjective symptoms. Comprehensive diagnostic criteria is applied according to image findings of thickening lesions, high serum IgG4 levels, and histopathological findings. As a treatment, open surgical repair or endovascular aneurysm repair is performed for the aneurysmal cases, and steroid administration is used for the cases with strong inflammation. This disease can lead to a lethal situation due to the rupture following aneurysmal formation, thus special attention is needed unlike IgG4-RD occupying in the other organs. (This is a translation of Jpn J Vasc Surg 2017; 26: 129–134.)

Although the therapeutic management of abdominal aortic aneurysms (AAAs) is currently based on the maximum diameter criterion, this has often proved inaccurate and misleading. Conversely, the biomechanical approach, which takes into account the pressure-induced wall stress exerted at every point throughout the aneurysmal surface, has been proven superior in predicting the rupture risk of AAAs, and its value is being increasingly recognized among physicians. More recently, hemodynamic indices, such as flow-induced wall shear stresses, have been indicated as potentially significant determinants of AAA natural history. Ultimately, a statistical model that takes into account all these factors may be relevant for making a sound prediction of the rupture risk of aneurysms and optimizing the management of these patients.

Objective: Abdominal aortic aneurysm (AAA) is characterized by inflammation and destruction of normal tissue architecture. The present study aimed to evaluate the inflammatory signaling cascade by analyzing the cytokines of AAA tissue.

Materials and Methods: We analyzed the comprehensive cytokine secretion profiles of 52 cytokines from human AAA in four patients with AAA using fluorescent beads-based multiplex assay. Further, the effect of janus kinase (JAK) inhibition by pyridone 6 on cytokine profiles was also evaluated.

Results: Cytokine secretion profiles were found to be similar among the four patients. A high level of JAK/signal transducers and activator of transcription (STAT) pathway activity in AAA tissue in culture was maintained, which may be attributed to the secretion of endogenous JAK-activating cytokines. Inhibition of JAK by pyridone 6 resulted in the suppression of STAT3 phosphorylation and secretion of a subset of chemokines and JAK-activating cytokines. However, the inhibition of JAK had no effect on the secretion of matrix metalloproteinase (MMP)-2, MMP-9, or TGF-β family that is responsible for the metabolism of extracellular matrix.

Conclusion: The findings of the present study suggested that AAA tissue exhibits a stereotypical profile of cytokine secretion, where JAK/STAT pathway may play a role in regulating a subset of cytokines. Identification of such a cytokine profile may reveal potential diagnostic markers and therapeutic targets for AAA.

Objective: We evaluated early and mid-term results of endovascular aortic repair (EVAR) using crossed-limb and non-crossed-limb techniques.

Material and Methods: From December 2011 to October 2013, 37 patients (31 men; mean age 75.4 years) were treated with EVAR (crossed-limb, 21 and non-crossed-limb, 16). We compared technical success, maximum short-axis diameter of abdominal aortic aneurysm, iliac angulation, time for catheterization of the short contralateral limb gate of the main body (SCT), and complications between the groups.

Results: The mean follow-up period was 810±230 days. The technical success rate was 100%. There was no significant difference between the groups in terms of mean short-axis diameter. Iliac angulation was significantly wider in the crossed-limb group (53.3±14.6 vs. 39.4±13.0, p=0.0049). There was no significant difference between the groups in terms of SCT. Limb occlusion occurred in two cases (one crossed-limb and one non-crossed-limb). There were no aneurysm-related deaths.

Conclusion: There were no differences between the crossed-limb and non-crossed-limb techniques in terms of early and mid-term results of EVAR. A crossed-limb technique can be performed safely without prolonged SCT even in severely splayed iliac angulation cases.

Background: Recently, reduced serum levels of ω-3 polyunsaturated fatty acids (PUFAs) including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been focused upon as newly recognized risk factors for peripheral artery disease (PAD). The present study investigated the association between disease location and serum levels of ω-3 PUFAs in patients with PAD.

Methods: We retrospectively analyzed the data of patients at Tokyo Medical University between August 2011 and November 2015. The subjects included 98 patients who were categorized into two groups: those with (n=72) and without infrainguinal lesions (n=26).

Results: Univariate analysis revealed that low ankle–brachial pressure index (ABI) values, low EPA levels, low DHA levels, low triglyceride levels, and diabetes mellitus were significant risk factors for infrainguinal lesions. Multivariate analysis indicated that low ABI values [p=0.018; odds ratio, 0.043; 95% confidence interval (CI), 0.003–0.579] and low DHA levels (p=0.003; odds ratio, 0.986; 95%CI, 0.977–0.995) were significant independent risk factors for infrainguinal lesions.

Conclusion: Our study demonstrated that reduced serum level of DHA may underlie the presence of infrainguinal lesions in patients with PAD.

Objective: This study aimed to clarify the selection and determination of appropriate treatment for acute symptomatic spontaneous isolated dissection of the superior mesenteric artery (SIDSMA).

Methods: Data from 10 consecutive patients, who were diagnosed with symptomatic SIDSMA using computed tomography angiography and were managed in our hospital from January 2010 to October 2015, were retrospectively collected and analyzed.

Results: There were nine males and one female; mean patient age was 50.3 (range, 35–64) years. All patients experienced acute abdominal pain, and three patients experienced concomitant vomiting. Only one patient exhibited symptoms of suspected peritonitis and intestinal ischemia. Three patients showed improved abdominal pain before admission to our hospital. One patient experienced severe abdominal pain that could not be managed using morphine; he underwent right external iliac to superior mesenteric artery bypass with a great saphenous vein graft. No patient presented with intestinal necrosis. All patients survived, and no patient developed complications during the follow-up period of up to 42 (24.5±16.5) months.

Conclusion: Conservative management appears to be the most feasible treatment for SIDSMA. However, open surgery can be performed in patients presenting with any symptoms of intestinal ischemia.

Objective: Although deep vein thrombosis (DVT) followed by pulmonary thromboembolism (PE) is a critical complication during pregnancy, there have been few reports about its intrapartum management. We evaluated intrapartum management by using a temporary inferior vena cava filter (IVCF) in pregnant women with PE/DVT.

Materials and Methods: Eleven women with PE/DVT during pregnancy between January 2004 and December 2016 were included. The patients were hospitalized for intravenous unfractionated heparin infusion after acute PE/DVT onset. Seven patients were discharged and continued treatment with subcutaneous injection of heparin at the outpatient unit. IVCF was implanted 1–3 days before delivery in 10 patients. Anticoagulant therapy was discontinued 6–12 h before delivery. We retrospectively analyzed rates of maternal or perinatal death, and recurrence of symptomatic PE/DVT.

Results: One patient was diagnosed as having PE/DVT and 10 had DVT alone. One patient suffered hemorrhagic shock during delivery; however, maternal or perinatal death and recurrence of symptomatic PE/DVT did not occur in any patient.

Conclusion: Maternal or perinatal death and recurrence of symptomatic PE/DVT was not seen in women diagnosed as having PE/DVT during pregnancy and treated with anticoagulant therapy and IVCF.

Objective: Thoracic aortic aneurysm (TAA) reflects the local expansion of the thoracic aorta; the underlying causal molecular mechanism of TAA is not well understood. Recent studies have shown the importance of transforming growth factor beta (TGFβ) signaling in Marfan and Loeys–Dietz syndromes; however, its role in non-familial, non-syndromic TAA remains unclear.

Materials and Methods: We performed histochemical and immunohistochemical analyses for activated (phosphorylated) SMAD2 (P-SMAD2) as an indicator of TGFβ signaling activities in the ascending TAA tissue as well as in the ascending aortic tissue with a normal diameter obtained from 7 patients without any clinical findings suggesting familial or syndromic TAA.

Results: TAA samples showed a higher P-SMAD2-positive area than samples with a normal diameter. P-SMAD2 signal was higher in the outer zone of the aortic and TAA walls. Within the TAA tissue, P-SMAD2 staining showed the following two distinct patterns: layer-like staining at the border of the medial layer and the thickened intima and a spot-like staining within the medial layer surrounding the microvessels.

Conclusion: These findings suggested that TGFβ signaling is activated in several distinct histopathological contexts in TAA, suggesting a complex role of TGFβ.

A man in his 54 was admitted to our hospital owing to progressive postprandial pain for a month. Computed tomography (CT) scan and angiography revealed severe stenosis and calcification of the celiac artery, superior mesenteric artery, and inferior mesenteric artery. Based on the findings of CT scan and angiography, abdominal angina was established and retrograde revascularization was performed only to the superior mesenteric artery using an artificial graft. After the surgery, he remains free of postprandial abdominal pain.

The combination of a double inferior vena cava (IVC), a retroaortic left renal vein, and azygos continuation of the IVC is extremely rare. Here we report the case of a 74-year-old man with this complex venous anomaly associated with a juxtarenal abdominal aortic aneurysm (AAA), who underwent a successful graft implantation with left renal artery reconstruction without injuring the retroaortic venous system. The venous anomaly was diagnosed using preoperative contrast-enhanced computed tomography (CT). Thus, contrast-enhanced CT can provide sufficient information on AAA and anomalous venous anatomy to avoid fatal complications during AAA surgery.

We present the case of a right internal iliac artery aneurysm with arteriovenous fistula in the posterior wall of the right common iliac vein. The fistula would have been difficult to close using endovascular treatment. We strongly anticipated difficulty in controlling bleeding; therefore, we performed cardiopulmonary bypass. Closing the fistula with suture would have been difficult, so we ligated the right common iliac artery and vein around the aneurysm. Femoro–femoral bypass was also performed to preserve blood flow in the lower right leg. The use of cardiopulmonary bypass should be considered in such difficult cases.

We retrospectively examined patients with ultrasonographically occlusive acute proximal deep vein thrombosis (DVT). All patients were categorized into two groups on the basis of whether great saphenous vein (GSV) flow toward the common femoral vein was detected (flow [+]; n=10) or undetected (flow [−]; n=10). We investigated the relationship between the GSV flow pattern and DVT recanalization. Thrombus recanalization, which is defined as diameter reduction to lower than 40% of the vessel diameter, was confirmed in seven of the flow (+), and none of the flow (−). This study proposes that the GSV flow pattern may be a simple marker for the recanalization of proximal occlusive DVT.

An axillary arterial aneurysm is a rare disorder, with few surgical cases reported to date. Here we report the case of a left axillary arterial aneurysm associated with Marfan syndrome. A 44-year-old female with Marfan syndrome presented with numbness of the left upper limb and a pulsatile mass on the left chest. A computed tomography scan revealed a highly enlarged and tortuous left axillary arterial aneurysm. We performed a graft replacement and resection of the aneurysm with two skin incisions. After the surgery, the blood flow to the patient’s left upper limb was confirmed, and the neurological symptoms improved significantly.

A 75-year-old woman was involved in a traffic accident and suffered retrograde type A aortic dissection, multiple rib fractures, and grade II hepatic injury accompanied by intraperitoneal bleeding. We performed total arch replacement using an open stent graft with cardiopulmonary bypass and circulatory arrest. This procedure requires anticoagulation and hypothermia, which are principally contraindicated in severe trauma patients. However, this situation was resolved by managing the patient non-operatively for 7 days, confirming the stabilization of other injured organs, and then performing the surgery. She required prolonged postoperative rehabilitation; however, she recovered steadily.

Primary iliac venous aneurysm is an exceedingly rare abnormality that can be complicated by pulmonary embolism, thrombosis, and rupture. Here we report the case of an otherwise healthy 40-year-old man with a unilateral external iliac vein aneurysm without any evidence of an arteriovenous fistula, proximal stenosis, or obstruction, as reported on computed tomography. Pulmonary embolism was diagnosed using ^99mTc-macroaggregated albumin scintigraphy. To prevent life-threatening complications, we treated the patient with anticoagulant therapy and performed aneurysmectomy with reconstruction using a saphenous vein graft patch. Although postoperative venography showed obstruction of the external iliac vein, the patient remained asymptomatic.

We report our experience of two cases of refractory cellulitis caused by peripheral micro-arteriovenous fistulas (AVFs) in the lower extremity. The micro-AVFs were so small that they could not be located accurately; further, the patients’ symptoms differed markedly from those previously reported for AVF. AVF is known to cause ischemic symptoms. In contrast, micro-AVF causes congestive symptoms and remains undetected in the majority of patients. Identification of this pathology is crucial to enable effective treatment by the ligation of the incompetent perforator vein that increases venous hypertension, leading to congestive symptoms.

We report a case of an aneurysm of the inferior pancreaticoduodenal artery (IPDA), with chronic occlusion of the celiac axis. Both surgical aneurysmectomy and endovascular coil embolization were anticipated to sacrifice IPDA, which could lead to severe acute ischemia in the celiac region. The treatment involved surgical ligation of the aneurysm after bypass grafting from the superior mesenteric artery to the anterior IPDA. A postoperative computed tomography revealed no enhancement of the aneurysm and sufficient collateral blood supply by the patent bypass graft.